December 2, 2024
Copper-Catalyzed Asymmetric Nucleophilic Substitutions of TsSCF3: Synthesis of Chiral SCF3-Containing Compounds
Yan Zhao - ,
Tian Cao - ,
Huaxin Lin - ,
Wei Jiao - ,
Min Wang *- , and
Jian Liao *
By employing electrophilic TsSCF3 as an efficient SCF3 source, we reported Cu/SOP (chiral sulfoxide-phosphine ligand)-catalyzed enantioselective nucleophilic substitutions. Under this protocol, α-pyridyl-α-fluoro esters as latent carbon nucleophiles, compounds containing a C-SCF3 stereocenter along with azacycles and fluorine atoms, were obtained in good yields and enantioselectivities under mild conditions (up to 68% yield, 92% ee).
Stereoselective Synthesis of (±)-Tetraponerine-2 and -4 via the Gold(I)-Catalyzed Intramolecular Dehydrative Amination of Allylic Alcohols
Soyun Lee - ,
Da Mi Kim - , and
Jae-Sang Ryu *
The concise and efficient total synthesis of (±)-tetraponerine-2 (T2) and (±)-tetraponerine-4 (T4) was achieved in 9% and 14% overall yield, respectively. The key step included the diastereoselective gold(I)-catalyzed intramolecular dehydrative amination of an allylic alcohol-tethered sulfamide to produce the cis-1,3-diamine moiety. The resulting olefinic side chain was then elaborated by cross-metathesis and cyclized to a five-membered pyrrolidine or a six-membered piperidine ring by intramolecular Mitsunobu N-alkylation. The unique tricyclic core of the (±)-tetraponerines was completed through cyclic sulfamide cleavage followed by aminal formation using 4-bromobutanal. This flexible synthetic strategy allows for the variation of the ring size, C-5 alkyl side chain length, and stereochemistry, which enables the preparation of diverse tetraponerine analogs for biological study.
α,β-Epoxy Ketone Rearrangements for the Practical Synthesis of Cephalotaxine and the Stereodivergent Synthesis of Azaspiro Allylic Alcohols
Cui-Cui Wang - ,
Huai-Yuan Yang - ,
Chang Liu - ,
Yu-Mo Geng - ,
Xiao-Bin Yang - ,
Dong-Sheng Xu - ,
Shouxin Liu *- ,
Juan Wang - ,
Pengfei Jia *- , and
Zhi-Wei Zhang *
We report herein that three facile rearrangements of epoxy ketones can be employed for the efficient and practical synthesis of cephalotaxine, the parent member of the family of Cephalotaxus alkaloids. The Meinwald rearrangement of epoxy ketone (90%) was used for the preparation of the dense functional groups in the cyclopentane ring of cephalotaxine. A novel acid-catalyzed umpolung SN2′ rearrangement and the Wharton transposition reaction of epoxy ketones were also developed to synthesize the Mori intermediate via the key azaspiro allylic alcohols in a stereodivergent manner.
Regioselective Synthesis of N-Aryl Pyrazoles from Alkenyl Sulfoxonium Ylides and Aryl Diazonium Salts
Ramesh Kumar Vishwakarma - ,
Raju Sen - ,
Shalu Deshwal - , and
Janakiram Vaitla *
A convenient and practical method has been developed for synthesizing various N-aryl pyrazoles from vinyl sulfoxonium ylides and diazonium salts. When using 1,3-disubstituted vinyl sulfoxonium ylides, the reaction selectively yields 1,3,5-trisubstituted pyrazoles. On the other hand, employing 2,3-disubstituted vinyl sulfoxonium ylides results in the formation of 1,3,4-trisubstituted pyrazoles. The reaction proceeds through the novel aryl diazene-derived vinyl sulfoxonium ylide. Furthermore, this method efficiently produces pyrazoles from aniline derivatives in a one-pot transformation. The reaction takes place under transition metal-free, mild conditions using easily accessible starting materials, making it a practical approach for generating pyrazoles in pharmaceutical chemistry.
November 30, 2024
Amplified Light-Induced pKa Modulation with Diarylethene Photoswitches
Marc Villabona - ,
Arnau Marco - ,
Rosa M. Sebastián - ,
Gonzalo Guirado *- , and
Jordi Hernando *
This publication is Open Access under the license indicated. Learn More
The reversible modulation of acidity using molecular photoswitches enables the remote control of a variety of (bio)chemical processes with light. Herein we investigated the structural features that allow amplifying photoinduced pKa variation in phenol-diarylethene conjugates, which toggle between low- and high-acidity states by switching the conjugation between the ionizable moiety and electron-withdrawing groups upon photoisomerization. By tuning the structure of these conjugates, high pKa modulation amplitudes were accomplished that surpass those previously reported.
DFT Studies on the Mechanism of Ligand-Regulated Palladium-Catalyzed Iodide-Assisted Hydrocarbonylation of Olefins with Formic Acid: Favored Reaction Routes and Selectivities
Jingjing Li *- and
Xiaoyu Ning
DFT calculations have been performed to gain insight into the mechanism of hydrocarbonylation of olefins and the origin of regio- and chemoselectivity. It is shown that the most feasible mechanism involves five steps: (i) decomposition of acetic formic anhydride, (ii) hydropalladation of olefins, (iii) CO migratory insertion, (iv) iodide-assisted acetate-formate exchange, and (v) formylation or carboxylation. Importantly, carboxylation proceeds via the decomposition of anhydride, followed by reductive elimination instead of direct hydrolysis of anhydride. For phosphine-ligated palladium catalysis, on one hand, the lower stability of the transition state leading to 1,2-hydropalladation could be attributed to H···H steric hindrance. On the other hand, the high chemoselectivity for the aldehyde is ascribed to increased π back-donation effect and ligand-substrate noncovalent interactions, which stabilize the transition state and hence reduce the energy barrier. For ferrocenyl phosphine-ligated palladium catalysis, significant C–H···π interaction between the substrate and proximal phenyl moiety of the phenylphosphine and π–π interaction between formate and phenyl moiety can facilitate the carboxylation process. This in-depth mechanistic insight can account for reactivity and selectivity at an atomistic level and have implications for designing new generations of palladium catalysts.
Generation of Quaternary Carbons in Cycloalkanones and Lactones with Arynes through a Domino Process
Jih Ru Hwu *- ,
Khagendra Prasad Bohara - ,
Mohit Kapoor - ,
Animesh Roy - ,
Shu-Yu Lin - ,
Chun-Cheng Lin - ,
Kuo-Chu Hwang - ,
Wen-Chieh Huang - , and
Shwu-Chen Tsay
This publication is Open Access under the license indicated. Learn More
A synthetic method was developed for the generation of a quaternary carbon center in carbonyl compounds. This innovative process involved the reaction of α-thiolate lactones and cycloalkanones with two equivalents of arynes in acetonitrile to give α,α-diarylated products in 63–85% yields at 25 °C. The reaction unfolds through an unconventional domino process, encompassing sequential 1,2-elimination, 1,2-nucleophilic addition, 1,4-proton transfer, the second 1,2-nucleophilic addition, interrupted Pummerer rearrangement, intramolecular spirocyclization, and sulfonium ring-opening. The potential of this “single-flask” reaction was systematically investigated and found well-suited to generate diarylated carbonyl compounds, incorporating naphthalene, pyridine, quinoline, or isoquinoline rings adorned with various substituents.
Photoinduced Aromatization-Driven Deconstructive Fluorosulfonylation of Spiro Dihydroquinazolinones
Wen-Peng Yang - ,
Hong-Jie Miao - ,
Gang Wang - ,
Xiaoyu Yang - ,
Xianjun Wang - ,
Le Liu - ,
Xin-Hua Duan *- , and
Li-Na Guo *
A catalyst-free photoinduced deconstructive fluorosulfonylation cascade of spiro dihydroquinazolinones with DABSO and NFSI is reported. This protocol features mild reaction conditions, good yields and excellent functional group tolerance, providing a practical approach to the quinazolin-4(1H)-one-functionalized aliphatic sulfonyl fluorides. In addition, the ease of gram-scale synthesis and the versatility of the SuFEx exchange highlight the application potential of this protocol.
November 29, 2024
Direct Continuous Flow Synthesis of Two Difficult Polypeptides Using β-Cyclodextrins
Szebasztián Szaniszló - ,
Gitta Schlosser - ,
Viktor Farkas - , and
András Perczel *
This study focuses on investigating the use of β-cyclodextrin (β-CyD) derivatives as additives in continuous flow peptide synthesis, with particular emphasis on challenging sequences such as the Jung-Redemann decapeptide and the 42-residue amyloid β polypeptide [Aβ(1–42)]. The efficacy of the OH-free β-CyD and two of its derivatives (Ac-β-CyD and HP-β-CyD) is compared with alternative, state-of-the-art synthetic methods, including the widely used and recently improved pseudoproline monomer technique, e.g., Ser(ΨPro). Our results show that the use of β-CyD as an additive results in a significant (8–19%) increase in the purity of the crude polypeptide compared to that determined by our reference method. The chromatograms determined by LC-MS were deconvoluted to estimate the more precise purity of the crude products, and we found that the improvement is greater when the free OH β-CyD is used and moderate when the acetyl-β-CyD or the 2-hydroxypropyl-β-CyD derivatives are used. We have found that the free CyD gives an improvement comparable to that achieved with the Ser(ΨPro) derivative.
Analysis of Interaction Features of Cyclo[13]carbon with Small Molecules and Formation Mechanism of Its Dimer
Yongkang Lyu *- ,
Yonglin Cui - ,
He Xu - ,
Changzhe Zhang - , and
Qingtian Meng *
The newly discovered cyclo[13]carbon, the first artificially synthesized odd-numbered carbon ring, is an intriguing carbon isomer that provides a valuable subject for studying low-symmetry carbon materials. In this work, we employed first-principles calculations to explore the geometric structure and electronic properties of cyclo[13]carbon through various techniques such as vibrational mode analysis, bond order analysis, spin density analysis, electron localization analysis, electrostatic potential and van der Waals potential analysis, visualization of weak interactions, and energy decomposition analysis. We investigated the interaction characteristics of cyclo[13]carbon with small molecules and examined its dimer formation mechanism and dynamics features using ab initio molecular dynamics. Our study reveals the unique physicochemical properties of this novel carbon ring system. The antiaromaticity of the low-symmetry cyclo[13]carbon sets it apart from previously synthesized even-numbered carbon rings, with van der Waals interactions playing a crucial role in its binding with small molecules and in the formation of C13 dimers. This research provides theoretical insights that complement experimental observations and theoretical studies, aiding further investigation into the diverse properties of fresh carbon material isomers and promoting the synthesis and application of novel molecular materials in molecular electronics and nanotechnology.
Advancements in Loop Cyclization Approaches for Enhanced Peptide Therapeutics for Targeting Protein–Protein Interactions
Lucia Lombardi *- ,
Luke A. Granger - ,
Robin J. Shattock - , and
Daryl R. Williams
This publication is Open Access under the license indicated. Learn More
Protein–protein interactions (PPIs) are pivotal in regulating cellular functions and life processes, making them promising therapeutic targets in modern medicine. Despite their potential, developing PPI inhibitors poses significant challenges due to their large and shallow interfaces that complicate ligand binding. This study focuses on mimicking peptide loops as a strategy for PPI inhibition, utilizing synthetic peptide loops for replicating critical binding regions. This work explores turn-inducing elements and highlights the importance of proline in promoting favorable conformations for lactamization, yielding high-purity cyclic peptides. Notably, our one-pot method offers enhanced versatility and represents a robust strategy for efficient and selective macrolactamization, expanding the scope of peptide synthesis methodologies. This approach, validated through the synthesis of AAV capsid-derived loops, offers a robust platform for developing peptide-based therapeutics and highlights the potential of peptide macrocycles in overcoming PPI drug discovery challenges and advancing the development of new therapeutics.
Dibromomethane-Triggered Electrochemical Cyclization of Enaminones with Amidines for the Synthesis of 5-Acylimidazoles
Peng Xu - ,
Xing-Wang Hu - ,
Zeng-Yang He *- ,
Luan-Ting Wu - ,
Si-Qi Chen - ,
Pinhua Li - ,
Ze Zhang *- , and
Hui Xu *
An electrochemical tandem cyclization of enaminones with amidines has been reported for the first time using dibromomethane as an initiating agent in an undivided cell. Following this protocol, a vast variety of polysubstituted 5-acylimidazoles were obtained in moderate to good yields without the use of external oxidants. Mechanistic studies indicate that the bromide anion, electroreductively generated from dibromomethane, acts as a redox mediator to complete the catalytic cycle.
November 28, 2024
Cu–ABNO Catalyst for the Synthesis of Quinolines and Pyrazines via Aerobic Double Dehydrogenation of Alcohols
Shivali Hans - ,
Mohd Adham - ,
Manas Khatua - , and
Subhas Samanta *
In this report, a new imidazole- and amide-functionalized pincer-like Cu(II) complex (1) was synthesized and characterized. By employing 1 and 9-azabicyclo[3.3.1]nonane NH-Oxyl (ABNOH), a catalytic protocol for alcohol oxidation and the subsequent alcohol oxidation-triggered synthesis of quinolines and pyrazines were explored. Alcohols such as 2-aminoaryl alcohols were also oxidized efficiently. As carbonyls from 2-arylaminobenzyl alcohols and secondary alcohols are synthons for quinolines, we explored their synthesis directly from alcohols. The protocol was quite efficient and completed the reaction in only ∼5–10 h. Combinations such as (a) primary 2-arylaminobenzyl alcohols with secondary alcohols or their ketones and (b) secondary 2-arylaminobenzyl alcohols with secondary alcohols or their ketones were found to be very effective for the synthesis of quinolines. The protocol was also successful for the synthesis of various pyrazines from 1,2-diols and 1,2-diaminobenzenes in 10 h. Mechanistic investigations showed that the generated complex acted as an active catalyst: it activated O2 and subsequently with the cooperation of 9-azabicyclo[3.3.1]nonane N-Oxyl (ABNO•) activated the α-CH hydrogen of coordinated alkoxide. Then, Cu(II)/Cu(I) reduction led to the formation of carbonyl compounds, which via successive C–C/C–N coupling reactions resulted in heterocycles in the presence of KOtBu and 1.
Synthesis of Functionalized Indoles by an Iridium-Catalyzed N–H Insertion Cascade: Nucleophilic Cyclization of Naphthylamines with α-Diazocarbonyl Compounds
Xiaogang Wang *- ,
Chi Yang - ,
Di Chen - ,
Pu Chen - ,
Yishou Wang - ,
Baoyue Cao - ,
Chengfang Qiao - , and
Michal Szostak *
A novel iridium-catalyzed [3 + 2] annulation of naphthylamines and α-diazocarbonyl compounds was developed for the rapid assembly of densely functionalized indoles. This new catalytic process represents the first example of a cascade intramolecular nucleophilic cyclization by the N–H insertion of amines. Various naphthylamines and α-diazocarbonyl compounds could be obtained in high yields with excellent functional group tolerance. The reaction affords valuable indole derivatives, enabling expedient access to novel heterocyclic analogues not easily accessible by other methods.
Palladium-Catalyzed Oxidative Cyclization of O-Aryl Cyclic Vinylogous Esters: Synthesis of Benzofuran-Fused Cyclohexenones
Ko-Wang Yen - ,
Chia-Chen Chein - ,
Shih-Hsun Wung - ,
Li-Ching Shen - , and
Yen-Ku Wu *
This publication is Open Access under the license indicated. Learn More
This study presents a method for synthesizing functionalized hydrodibenzofuran derivatives. Using palladium catalysis, O-aryl cyclic vinylogous esters undergo dehydrogenative intramolecular arylation at the vinylic carbon. Preliminary kinetic isotope effect studies suggest that the C(aryl)–H bond cleavage may be the rate-determining step.
November 27, 2024
N-Hydroxyphthalimides as Nitrogen Radical Precursors in the Copper-Catalyzed Radical Cross-Coupling Amination of Arylboronic Acids: Synthesis of Arylamines
Hafiz Noor - ,
Shuwei Zhang - ,
Xiaodong Jia - ,
Pan Gao *- , and
Yu Yuan *
A new and practical approach for the synthesis of arylamines via copper-catalyzed radical cross-coupling amination of arylboronic acids has been developed. The key enabling advance in this protocol is the design of N-hydroxyphthalimides as precursors to generate nitrogen-based radical intermediates for cross-coupling with arylboronic acids, providing the corresponding arylamines of a high yield of up to 98%. In addition, the procedure successfully demonstrated remarkable efficiency across a wide range of functional group tolerances. Mechanistic investigations suggested that a nitrogen radical cross-coupling pathway is possible via phosphite-mediated N–O bond scission.
Selective Synthesis of Vinyl Sulfides or 2-Methyl Benzothiazoles from Disulfides and CaC2 Mediated by a Trisulfur Radical Anion
Shuyi Li - ,
Siliu Cheng - ,
Yunzhe Du - ,
Ligang Yan - ,
Jiakai Wu - ,
Limin Han *- , and
Ning Zhu *
In this report, we have established a novel and efficient method for selectively synthesizing either vinyl sulfides or 2-methylbenzothiazoles from the reaction of CaC2 and disulfides. The selective synthesis of these two distinct products can be controlled by simply adjusting the amount of K2S. The underlying reaction mechanism has been thoroughly investigated through control experiments, HRMS, and FTIR, which collectively support the pivotal role of a trisulfur radical anion. This radical species, generated in situ from K2S, is essential for the homolytic cleavage of the S–S bonds in a catalytic manner. Additionally, the trisulfur radical anion also acts as an effective mediator for activating the vinyl group of 2-aminophenyl vinyl sulfides, facilitating the crucial intramolecular cyclization required to produce 2-methylbenzothiazoles. Moreover, CaC2 not only serves as an acetylene source but also creates the basic conditions essential for the selective formation of vinyl sulfides. This methodology demonstrates broad substrate compatibility and excellent functional group tolerance, significantly enhancing its practical utility in diverse synthetic applications.
Synthesis of 4-Hydroxy-5-phenylaminoimidazoles through a Three-Component Reaction of Sulfur Ylides, Nitrosobenzenes, and Amidines
Chaowei Xiang - ,
Gongruixue Zeng - ,
Yi Hao - ,
Yunlong Pan - ,
Linghui Zeng - ,
Chong Zhang - ,
Jiankang Zhang *- ,
Huajian Zhu *- , and
Jiaan Shao *
A novel annulation reaction of amidines with sulfur ylides and nitrobenzenes has been developed, affording various novel 4-hydroxy-5-phenylaminoimidazoles in moderate to excellent yields. The 4-hydroxy-5-phenylaminoimidazoles have been further converted into α-ketoamide and imidazol-4-imine derivatives. Moreover, a plausible mechanism for this multicomponent reaction is proposed.
Cascade Annulation for Synthesizing Chromenopyrrolones from o-Hydroxyphenyl Enaminones and 2-Halo-N-alkyloxyacetamides
Wei-Min Zhang - ,
Qing-Sheng Zhao - ,
Si-Yi Chen - ,
Cong-Hai Zhang *- , and
Sheng-Jiao Yan *
A cascade cyclization reaction comprising two halogenation reactions and a Michael addition was developed for the synthesis of chromeno[2,3-c]pyrrole-3-ones 4. Additionally, another cascade cyclization reaction, which involves a halogenation reaction followed by two intramolecular Michael additions, was established for the synthesis of chromeno[2,3-b]pyrrole-2-ones 5. Both types of compounds were synthesized from o-hydroxyphenyl enaminones and 2-halo-N-alkyloxyacetamides through a process that facilitated the intramolecular formation of C–C, C–O, and C–N bonds to effectively establish two fused rings in a single operation. This novel protocol is efficient, uses readily accessible starting materials, and operates under mild conditions, demonstrating tolerance for various functional groups while achieving good yields.
Visible-Light-Induced Divergent Oxygenation of Methylbenzene Utilizing Aryl Halides
Jianing Li - ,
Zongyi Yu - ,
Jingnan Zhao *- ,
Cunfei Ma - ,
Liyuan Duan - ,
Zunchao Liu - ,
Huinan Sun - ,
Guofeng Zhao - ,
Qilei Liu - , and
Qingwei Meng *
The selective oxidation of methylbenzene to value-added products is of indisputable importance in organic synthesis. Although photocatalytic oxidation reactions of toluene have achieved great success for the preparation of its oxidative products, such as carboxylic acids, benzaldehyde, and benzoate, there remains a lack of a unified photocatalytic system for the selective preparation of these oxidation products. Herein, we report a metal- and additive-free photocatalytic protocol enabled by aryl halides using O2 as a green oxidant for the selective synthesis of the above-mentioned three oxidation products by adjusting the reaction solvent. This strategy features many advantages, including environmentally friendly and mild reaction conditions, broad substrate applicability and functional group tolerance, and potential practical application for the synthesis of aromatic carboxylic drugs and polymer materials and degradation of polystyrene waste. The continuous-flow system was utilized for the oxidation of toluene, which resulted in a reduced reaction time and increased production efficiency. Detailed mechanistic investigation revealed that the hydrogen atom transfer process was facilitated by the bromine radical from aryl halides for further oxidation, and an electron donor–acceptor complex of methylbenzene and aryl halides may exist.
Investigation of a Highly Selective Asymmetric Synthesis Strategy for cis-2-Fluorocyclopropanecarboxylic Acid: The Key Component of Sitafloxacin
Ling-Xi Zhang - ,
Yu Gao - ,
Jing Zheng - ,
Bing-Tong Li - ,
Dong Ding - ,
Chao Tan - ,
Ao Wen - , and
Lin Dong *
A high-precision asymmetric synthetic route for cis-2-fluorocyclopropanecarboxylic acid with excellent stereoselectivity and regioselectivity was developed from commercially available starting materials, namely, fluoromethylphenylsulfone and chiral glycidyl derivatives, on a 100 g scale at the start. Despite the high overall yield, the synthetic route is remarkable for its brevity. This strategy forms the basis for further production of sitafloxacin on an industrial scale and provides an affordable and high-quality product.
Synthesis of Janus All-Cis Tetrafluorocyclohexanes Carrying 1,4-Diether Motifs
Thomas J. Poskin - ,
Bruno A. Piscelli - ,
Aidan P. McKay - ,
David B. Cordes - ,
Yuto Eguchi - ,
Shigeyuki Yamada - ,
Rodrigo A. Cormanich *- , and
David O’Hagan *
This publication is Open Access under the license indicated. Learn More
Nucleophilic aromatic substitutions (SNAr) of alkoxides on pentafluoroaryl ethers are explored as a first step in a synthesis sequence to generate all-cis 2,3,5,6-tetrafluorocyclohexyl-1,4-dialkyl ethers 1. The SNAr reaction was explored both experimentally and theoretically to rationalize ortho/para/meta selectivities. tert-Butyl deprotection of products followed by phenol alkylations introduces versatility to the synthesis. The final Rh(CAAC) 3 catalyzed aryl hydrogenation step of intermediate tetrafluoroaryl-1,4-diethers generated cyclohexane products 1. This chemistry introduces a new class of Janus fluorocyclohexane derivatives with ether substituents placed 1,4- to each other.
Diversity Oriented Routes to Thiopeptide Antibiotics: A Solution to the “Thiazole Problem”
Mai Lam Ferguson - and
Marco A. Ciufolini *
The Goossen decarboxylative coupling reaction enables the union of thiazole-2-carboxylic acids with a 2-pyridyl triflate, leading to the formation of pyridine-thiazole clusters of the kind found in thiopeptide antibiotics. The method avoids problematic or technically challenging reaction sequences involving 2-thiazolyl organometallics, facilitating the investigation of the structure–activity relationship of the thiopeptides.
Silver-Catalyzed Thio-Claisen Rearrangement of Aryl Sulfoxides with AIBN
Guoqing Yang - and
Hanmin Huang *
The Pummerer reaction represents a well-known transformation of sulfoxides. Mechanistically, this reaction is initiated by the generation of the thionium ion, whereas forming such intermediates typically requires the use of a stoichiometric amount of activating reagent. In this regard, we report the activator-free Pummerer-type transformation, a silver-catalyzed thio-Claisen rearrangement of aryl sulfoxides with AIBN. Facilitated by silver catalyst, AIBN is transformed into highly reactive ketenimine in situ, which directly captures the sulfoxides to generate thionium ion intermediates.
November 26, 2024
Triphenylamine-Based Push–Pull Dyes for Chromogenic Detection of HSO4– Ion in Water: The Role of Anion in the Formation of Fluorescent Organic Nanoparticles
Rikitha S Fernandes - ,
Suvendu Paul - ,
Jiří Tydlitát - ,
Filip Bureš *- , and
Nilanjan Dey *
Optical detection of the HSO4– ion in pure aqueous medium is rare, owing to the very high Gibbs free energy of hydration and ambiguity to distinguish with the isostructural H2PO4– ion. Herein, a pair of triphenylamine-based push–pull dyes with different numbers of terminal pyridine fragments, connected via an acetylenic linker, were synthesized by Sonogashira cross-coupling reaction. These two dyes displayed highly selective (LOD = 15.1/8.3 ppb), dual-mode color-changing responses toward the HSO4– ion in pure aqueous medium without any interference. Despite the halochromic behavior, both compounds exhibited very distinct optical responses with the HSO4– ion. The mechanistic investigation indicated that HSO4– was engaged in a bifurcated intermolecular hydrogen bonding interaction (leading to proton transfer) with pyridine nitrogen atoms that altered the extent of intramolecular charge transfer (ICT). The self-assembly of such protonated species was found to be prominent when sulfate was present as the counteranion. The extent of self-assembly was found to be more prominent for the trisubstituted, Y-shaped quadrupolar derivative than that observed for the linear, monosubstituted one. Furthermore, the present system was utilized for the detection of HSO4– ions in commercially available samples with satisfactory responses.
Catalyst-Free Construction of Imidazole-Pyrrolo[1,2-a]pyrazine Hybrid, 2,6-Disubstituted Imidazo[1,2-a]pyrrolo[2,1-c]pyrazine via Regioselective Annulative Functionalizations
Hyunjin Oh - ,
Dohui Ku - ,
Myungho Jung - ,
Sunhee Lee - , and
Ikyon Kim *
Highly efficient catalyst-free annulative functionalization approaches to a novel imidazole-pyrrolo[1,2-a]pyrazine hybrid structure were devised from the reaction of β-enaminone with propargylamine where regioselective conjugate substitution of β-enaminone with propargylamine followed by cycloisomerization proceeded smoothly in a domino fashion to construct two heterocyclic moieties (pyrazine and imidazole) via successive formation of three C–N bonds, leading to the target tricyclic skeleton.
Construction of Isochromanones via Hemin-Catalyzed Phenol-Enamine Oxidative Annulation
Muhammad Adnan Bashir - ,
Tie Wang - ,
Hui Guo - ,
Jianguo Sun - ,
Xinye Bao - ,
Hai-Jun Zhang *- , and
Hongbin Zhai *
We have developed a hemin-catalyzed biomimetic oxidative annulation of 2,3-dihydroxybenzoic acid with an array of cyclic enamines to form isochromanones in good to excellent yields and high regioselectivity. This formal [4+2] cycloaddition protocol showed high efficiency and remarkable functional group tolerance. Mechanistic studies indicate the involvement of a single-electron oxidation pathway. Preliminary biological investigations showed that isochromanones 3ag and 3ca exhibited antineoplastic activities against MCF-7 cell lines with IC50 values of 25.21 and 29.09 μM, respectively.
Macrocyclic Bridgehead Fluorophores, Pyrrolyl-diazabicyclo[8.3.1]tetradecadienones, with Giant Stokes Shifts
Boris A. Trofimov *- ,
Lyubov N. Sobenina - ,
Olga V. Petrova - ,
Elena F. Sagitova - ,
Konstantin B. Petrushenko - ,
Denis N. Tomilin - ,
Elena G. Martyanova - ,
Vladimir F. Razumov - ,
Ludmila A. Oparina - ,
Igor A. Ushakov - ,
Denis V. Korchagin - ,
Alexandra M. Belogolova - , and
Alexander B. Trofimov
A previously unknown class of fluorophores was discovered, which represents 14-membered bridgehead heterocycles, pyrrolyl-diazabicyclo[8.3.1]tetradecadienones, herein referred to as PY-14-ONEs. The new fluorophores are characterized by giant Stokes shifts of ∼8000–10,250 cm–1 and virtually zero overlap of the absorption and emission bands. They exhibit fluorescence maxima in the blue-green region (454 ≤ λem ≤ 513 nm, MeCN), which shift to the red side when converted to their water-soluble salts by alkylation with MeI (478 ≤ λem ≤ 516 nm, water). PY-14-ONEs were obtained by an original synthesis from DBU, 1,8-diazabicyclo[5.4.0]undec-7-ene, which reacts with acylethynylpyrroles without catalysts under mild conditions to afford PY-14-ONEs in a 34–58% yield. The reaction represents a ring expansion of DBU. Since acylethynylpyrroles are readily available, the discovered reaction opens promising possibilities for the development of new fluorophores. The results of our time-dependent DFT calculations indicate that the pyrrole ring in PY-14-ONEs plays an important role in the formation of the Stokes shifts, which can be further enhanced by attaching appropriate substituents to it, capable of creating in S1 an extended conjugated system and causing a substantial alternation of the molecular structure via its planarization.
Brønsted Acid-Catalyzed, Asymmetric Allenoate Claisen Reaction
Rachael E. Hamilton - ,
Ellen A. Berkley - ,
Iain K. Laufer - ,
Madeline E. Ruos - ,
Brandon Smith - ,
Anthony N. Dahi - ,
Timothy J. Gallagher - ,
Vanessa Justo - ,
Flannery Warner - , and
Anna G. Wenzel *
This publication is Open Access under the license indicated. Learn More
An auxiliary-based protocol is described for an asymmetric allenoate Claisen rearrangement. Silicated tosic acid (10 mol %) was used as an inexpensive, user-friendly catalyst. Stereochemical analysis revealed a preferential attack at the si face of prostereogenic olefin. The amine auxiliary was readily hydrolyzed and can be isolated from the reaction mixture (85–87% recovery). The resulting unsaturated β-keto esters were isolated in ≤99% yield and 98% ee. Diastereoselective examples provided a 96:4 syn:anti ratio of the resulting vicinal stereocenters.
Three-Component Synthesis of Multiply Functionalized 5,6-Dehydroisoquinuclidines through Dearomatization of Pyridine
Kenshin Sano - ,
Atsunori Mori - , and
Kentaro Okano *
A three-component synthesis of multiply functionalized 5,6-dehydroisoquinuclidines is described. After the formation of an N-alkylpyridinium salt, Grignard addition led to the formation of the corresponding 1,2-dihydropyridine bearing an alkyl, alkene, aryl, or alkynyl group. Subsequent Diels–Alder reaction with a dienophile provided functionalized dehydroisoquinuclidines in high yields (up to 93%) with endo selectivities (73:27 to >99:1). This reaction was applicable to the synthesis of an N-(4-methoxybenzyl)pyridinium salt, where the 4-methoxybenzyl group was switched to a benzyloxycarbonyl group after the formation of the dehydroisoquinuclidine.
Nontraditional Synthesis of Disaccharides via Acyclic Vinylic Ether Intermediates: Catalytic C–O Cross-Coupling as the Enabling Link
Taehee Kim - ,
Eric J. Meindl - , and
Frank E. McDonald *
This publication is Open Access under the license indicated. Learn More
We describe complementary methods for synthesizing acyclic vinylic ethers from two carbohydrate-derived synthons. We compare a nonstereoselective olefination approach with a stereoselective catalytic C–O cross-coupling method, preparing 1,2-disubstituted vinylic ethers with complexity on both sides of the ether linkage. Upon epoxidation/in situ oxacyclization of acyclic vinylic ethers, we synthesized disaccharides with α-d-galacto-, α-d-talo-, β-d-allo-, and α-d-altropyranoside stereochemistry, from d-lyxose and d-ribose precursors. Stereoselective CuI/CyDMEDA-catalyzed C–O cross-couplings offer considerable potential for broadly implementing this nontraditional strategy for glycoside synthesis.
4-Azaspiro[2.3]hexane, an Overlooked Piperidine Isostere: Multigram Synthesis and Physicochemical and Structural Evaluation
Sergiy Galavskyy - ,
Anton Chernykh - ,
Oleksandr Liashuk - ,
Dmytro Lesyk - ,
Svitlana V. Shishkina - ,
Denys Kliukovskyi - ,
Dmytro M. Volochnyuk - ,
Serhiy V. Ryabukhin - , and
Oleksandr O. Grygorenko *
An expedient approach to the synthesis of 4-azaspiro[2.3]hexane derivatives is described. The synthetic scheme consists of Tebbe olefination of N-Boc-protected 2-azetidinone (including the first use of the deuterated Petasis reagent Cp2Ti(CD3)2 in the building block preparation) and cyclopropanation of the resulting intermediate. The developed protocols allowed for the preparation of target building blocks on a multigram scale (up to 52 g). To illustrate the potential of the obtained 4-azaspiro[2.3]hexane derivatives for isosteric replacements in drug discovery, their physicochemical and structural characterization was performed, i.e., basicity (pKa) and lipophilicity (Log P) measurements, X-ray diffraction studies, and exit vector plot (EVP) analysis.
November 25, 2024
Exploring and Regulating Heteroatom-Electronegativity-Associated with Ring Aromaticity and Excited State Intramolecular Proton Transfer Mechanism for Benzothiazole-Based Fluorophore
Jing Zhang - and
Hua Fang *
A novel fluorophore 2-(2′-hydroxy-5′-benzaldehyde phenyl) benzothiazole (HBBT) with excited state intramolecular proton transfer (ESIPT) characteristics, showing good selectivity for Cu+/Cu2+ ions had been synthesized experimentally (Molecules 2022, 27, 7678). However, its ESIPT mechanism and fluorescent performance related to atomic substituents have not been investigated systematically. In this work, two HBBT derivatives, 2-(2′-hydroxy-5′-benzaldehyde phenyl)benzoimidazole (HBBI) and 2-(2′-hydroxy-5′-benzaldehyde phenyl)benzopyrrole (HBBP), were obtained by respectively using −NH and −CH2 groups in place of the sulfur atom in the thiazole ring. The absorption/emission spectra and ring aromaticity as well as ESIPT processes of HBBT and its derivatives were studied using density functional theory (DFT) and time-dependent DFT (TD-DFT). The simulated absorption and fluorescence wavelengths of HBBT agreed well with the corresponding values obtained in the experiment. According to the analyses of geometry structures, electron densities, and infrared vibration frequencies, the intramolecular hydrogen bond becomes stronger upon light excitation. The frontier molecular orbitals were analyzed via establishing potential energy curves, and the ESIPT behavior was described deeply. Obviously, the NH–substitution makes ring 4 more aromatic, while the CH2–substitution changes ring 4 from aromatic to antiaromatic. The ESIPT process helps to alleviate the excited state antiaromaticity. The greater the antiaromaticity of the S1 state normal form, the higher the barrier of ESIPT.
Microwave Mediated Acylation of Alcohols, Phenols and Thiophenols in Neat Acetic Anhydride
Mark H. S. Troftgruben - ,
Isabella Oldenburg - ,
Alyssa M. Pama - ,
Bryce Igawa - ,
Salvatore Deguara - ,
Maya Shields - ,
Neil K. Viswanathan - ,
Joshua X. Silverio - ,
Cameron Gleason - ,
Justin Shan-Min Wang - ,
Jordan S. Ford - ,
Horacio Lazaro - , and
Scott Eagon *
This publication is Open Access under the license indicated. Learn More
A microwave-based method for the acylation of alcohols, phenols, and thiols has been developed without the need of a catalyst or base additives. The reaction is far more rapid than previously reported acylation methods, tolerates a wide variety of functional groups, and provides easy isolation of products in excellent yields without the need for chromatography. Most products can be isolated directly via evaporation under reduced pressure or by pouring the reaction mixture into water and filtering.
Self-Catalyzed Sono-Photoinduced Arylation of Quinoxalin-2(1H)-ones with Arylhydrazines
Yao-Dan Xu - ,
Yu-Mai Xing - ,
Hong-Tao Ji - ,
Li-Juan Ou *- ,
Wei-Bao He - ,
Jia Peng - ,
Jia-Sheng Wang - ,
Jun Jiang - , and
Wei-Min He *
Herein, the first example of self-catalyzed sono-photoinduced carbon–carbon bond formation was described. Combining the advantages of phototriggered self-catalysis and ultrasonic catalysis, a wide range of 3-arylquinoxalin-2(1H)-ones can be efficiently synthesized in good yields with high functional-group compatibility under mild and eco-friendly conditions.
Three-Component Regioselective Aryl- and Alkenyl-Aminoalkylation of Alkenes via Cooperative Photoredox/Nickel Catalysis
Fu Ye - and
Weiming Yuan *
Recently, metallaphotoredox-catalyzed alkene dicarbofunctionalization reactions have been extensively investigated. Most cases are related to alkyl-arylation processes by conjugate coupling of alkyl radical precursors and aryl electrophiles across alkenes. By contrast, reported examples of alkylvinylation by coupling of vinyl electrophiles are largely limited. Herein, we represent a three-component aminoalkyl-vinylation of alkenes enabled by photoredox/nickel catalysis. This redox-neutral protocol exhibits broad substrate scope and good chemo-, regio- and E/Z-stereoselectivity. A series of valuable α-vinyl γ-amino acid derivatives are conveniently synthesized by the assembly of readily available starting materials.
Alkylthiolation of Aryl Halides under Electrochemical Conditions
Yingsibing Fan - ,
Tan Zhang - ,
Mengyun Wu - ,
Ping Liu *- , and
Peipei Sun *
An electrochemical protocol for the alkylthiolation of aryl halides was developed. By using dialkyl disulfides as the alkylthio sources, Mg plate as the sacrificial anode and graphite felt (GF) as the cathode, a series of aryl sulfides were obtained in moderate to good yields. The approach was also suitable for the synthesis of aryl selenides. This method has the features such as simple reaction conditions and good functional group compatibility, which makes it have a good application prospect in organic synthesis and drug synthesis.
November 24, 2024
Regioselective Copper(I)-Catalyzed Direct C(3)-H (Hetero)arylation of 6-(Hetero)arylated 1,2,4-Triazolo[4,3-b]pyridazines: Ligand-Free Approach
Chaimae Hourma - ,
Badr Jismy - ,
Wafa Blancou - ,
Mohsine Driowya - ,
Khalid Bougrin - ,
Gérald Guillaumet - , and
Mohamed Abarbri *
The first efficient Cu(I) catalyzed regioselective C3-(hetero)arylation of 6-(hetero)arylated 1,2,4-triazolo[4,3-b]pyridazines has been developed to streamline the synthesis of pharmaceutically important 3,6-diarylated 1,2,4-triazolo[4,3-b]pyridazines. This direct (hetero)arylation is compatible with a range of aryl iodides and tolerates a variety of functional groups (23 examples). A series of new 3,6-diarylated 1,2,4-triazolo[4,3-b]pyridazines were synthesized with good to excellent yields (up to 98%). The reactivity varied depending on the nature of the aryl iodide and the substituent in position 6 of the starting substrate. The procedure is experimentally simple, cost-effective, and free of additional ligands and cocatalysts.
Computational Library Enables Pattern Recognition of Noncovalent Interactions and Application as a Modern Linear Free Energy Relationship
Jacquelyne A. Read *- ,
Tyler E. Ball - ,
Beck R. Miller - ,
Eric N. Jacobsen *- , and
Matthew S. Sigman *
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ACS Editors' Choice® is a collection designed to feature scientific articles of broad public interest. Read the latest articles
A quantitative and predictive understanding of how attractive noncovalent interactions (NCIs) influence functional outcomes is a long-standing goal in mechanistic chemistry. In that context, better comprehension of how substituent effects influence NCI strengths, and the origin of those effects, is still needed. We sought to build a resource capable of elucidating fundamental origins of substituent effects in NCIs and diagnosing NCIs in chemical systems. To accomplish this, a library of 893 NCI energies was calculated encompassing cation−π, anion−π, CH−π, and π–π interactions across 60 different arenes and heteroarenes. The interaction energies (IEs) were calculated using symmetry-adapted perturbation theory (SAPT), which identifies electrostatic, inductive, exchange-repulsive, and dispersive contributions to total IE. This descriptor library provides a comprehensive platform for evaluating substituent effect trends beyond traditional molecular descriptors such as Hammett values, frontier molecular orbital energies, and electrostatic potential, thereby expanding the tools available to analyze modern chemical processes that involve NCIs. To demonstrate the application of this library, three case studies in asymmetric catalysis and supramolecular chemistry are presented. These case studies informed the development of an automated NCI analysis tool, which employs statistical analyses to diagnose a particular NCI in a chemical system of interest.
Pd-Catalyzed Decarbonylative Suzuki–Miyaura Cross-Coupling of Pyramidalized N-Mesyl Amides by a Tandem N–C(O)/C–C Bond Activation
Pengcheng Gao - ,
Yawei Zhu - ,
Tongliang Zhou - ,
Greta Utecht-Jarzyńska - ,
Roman Szostak - , and
Michal Szostak *
The Suzuki–Miyaura biaryl cross-coupling is the pivotal technology for carbon–carbon coupling in pharmaceutical, polymer, and agrochemical fields. A long-standing challenge has been the development of efficient precursors for the decarbonylative cross-coupling of amide bonds. Herein, we report a highly chemoselective palladium-catalyzed Suzuki–Miyaura cross-coupling of N-mesyl amides for the synthesis of biaryls by a tandem N–C(O)/C–C bond activation with high selectivity for decarbonylative cleavage. The results demonstrate the first example of a decarbonylative coupling (−CO) of amide bonds activated by an atom-economic, low-cost, and benign N-pyramidalized mesyl group (>30 examples). The reaction shows high generality and functional group tolerance and can be applied in late-stage functionalization of pharmaceuticals. Notably, N-mesyl amides are significantly more reactive than other classes of amides in the decarbonylative Suzuki cross-coupling manifold. Density functional theory (DFT) studies demonstrate considerably lower barrier for rate-limiting transmetalation using N-mesyl amides. The study establishes N-mesyl amides as versatile precursors for Suzuki–Miyaura cross-coupling to afford valuable biaryls and opens the door to deploy N-mesyl amides in challenging cross-couplings of amides by decarbonylation.
November 23, 2024
Direct Synthesis of Sulfinylated Phenanthrenes via BF3-Promoted Annulation of 2-Alkynyl Biaryls with Arylsulfinic Acids
Tingting Pu - ,
Han Yue - ,
Zhen Zhang - ,
Hui Gao *- ,
Pei-Long Wang - , and
Tao Miao *
A novel approach to sulfinylated phenanthrenes has been developed by BF3-promoted annulation of 2-alkynyl biaryls with arylsulfinic acids. This approach utilizes readily available arylsulfinic acids as a sulfinyl source and affords a variety of sulfinylated phenanthrenes in good to excellent yields under simple and mild reaction conditions.
November 22, 2024
Copper-Catalyzed Three-Component Tandem Cyclization for One-Pot Synthesis of Indole-Benzofuran Bis-Heterocycles
Peng Ma - ,
Yuhang Wang - , and
Jianhui Wang *
A one-pot, three-component synthesis of indole-benzofuran bis-heterocycles from terminal alkynes, salicylaldehydes, and indoles has been developed via copper-catalyzed tandem annulation. This catalytic system utilizes readily available starting materials, enabling predictable synthesis of indole-benzofuran bis-heterocycles with broad substrate versatility, excellent regiocontrol, and gram-scale amenability. The reaction proceeds via a sequential pathway involving A3 coupling, 1,4-conjugate addition, and 5-exo-dig cyclization.
A Tool for Reaction Monitoring in Real Time, the Development of a “Walk-Up Automated Reaction Profiling” System
Muhammad Alimuddin - ,
Louise Bernier - ,
John F. Braganza *- ,
Michael R. Collins - ,
Martha Ornelas - ,
Paul F. Richardson - ,
Neal Sach - ,
Deszra Shariff - ,
Wei Wang - , and
Alex Yanovsky
Optimization of chemical reactions requires a thorough analysis of reaction products and intermediates over a given time course. Chemical reactions are often analyzed by liquid chromatography-mass spectrometry (LC-MS), but generating LC-MS samples and data analysis is time-consuming and produces a significant amount of waste. We sought to remove the sample preparation and data analysis steps by implementing an iChemExplorer/Agilent LC-MS instrument as our reactor and analysis tool, coupled with an automated report generator of reaction progress over time. Herein, we show that our easy-to-use walk-up automated reaction profiling (WARP) system can sample chemical reactions multiple times to produce a data-rich report of reaction progress over time.
Photocatalytic Consecutive Photoinduced Electron Transfer-Enabled C(sp3)–H Pyridylation of Dihydroquinoxalin-2-ones
Changduo Pan *- and
Dongdong Chen
A photocatalytic decyanative C(sp3)–H pyridination of dihydroquinoxalin-2-ones with 4-cyanopyridines was developed by utilizing 4CzIPN as the photocatalyst. Mechanism studies show that this organophotocatalytic direct C(sp3)–H pyridination undergoes a radical–radical cross-coupling pathway promoted by consecutive photoinduced electron transfer.
Site-Specific Dehydrogenative Hydroxyfluoroalkylation of Indoles with Hexafluoroisopropanol
Xia Chen - and
Xiao-Yu Zhou *
An efficient and convenient method for the synthesis of C3-hydroxytrifluoroalkylated indoles and pyrroles was described in this paper. The copper-catalyst-free site-specific cross-dehydrogenative coupling reaction of various indoles and pyrroles with hexafluoroisopropanol proceeded smoothly by using MnO2 as oxidant to furnish a hydroxytrifluoroalkylated electron-rich N-heterocycle in satisfactory to excellent yields. Various groups, including the synthetically useful functional groups Cl, NO2, and CN, were tolerated well. The mechanistic study revealed that a radical pathway accommodated the formation of a hexafluoroacetone intermediate.
Asymmetric Synthesis of Taiwaniaquinone H via a Late-Stage Oxidative Decarboxylation
Debgopal Jana - ,
Suman Noskar - ,
Souvik Pal - ,
Sovan Niyogi - , and
Alakesh Bisai *
The asymmetric syntheses of naturally occurring biologically relevant abeo-abietane diterpenoids, (−)-taiwaniaquinone G (1a), and H (1b) have been reported via a chiral pool strategy starting from commercially available abietic acid. A ring contraction of the middle ring of the [6,6,6]-carbotricyclic abietane diterpenoid core was carried out under the Wolff rearrangement. Finally, the synthesis of (−)-taiwaniaquinone H (1b) was completed via a one-pot CAN-mediated oxidative decarboxylation.
Cu/Pd-Catalyzed Domino Carbonylative Synthesis of Polycyclic Carbonyl-Containing Quinolin-2(1H)-one Scaffolds from α-Bromocarbonyls
Jianwei Wang - ,
Shangyuan Wang - ,
Shuwei Li - ,
Jiajun Zhao - , and
Jun Ying *
A novel Cu/Pd-catalyzed domino radical cyclization and C–H carbonylation of α-bromocarbonyls has been developed, which enables the rapid incorporation of CO unit into polycyclic quinolin-2(1H)-one scaffolds. By using Mo(CO)6 as the CO source, the reaction proceeded smoothly to furnish various polycyclic carbonyl-containing quinolin-2(1H)-one derivatives in high yields. Notably, this method could be used in the late-stage modification of biologically active molecules such as estrone.
November 21, 2024
Launching Graphene into 3D Space: Symmetry, Topology, and Strategies for Bottom-Up Synthesis of Schwarzites
Alexey V. Ignatchenko *
Schwarzites are hypothetical carbon allotropes in the form of a continuous negatively curved surface with three-dimensional periodicity. These materials of the future attract interest because of their anticipated large surface area per volume, high porosity, tunable electric conductivity, and excellent mechanical strength combined with light weight. A three-decade-long history attempting schwarzite synthesis from gas-phase carbon atoms went without success. Design of schwarzites is both a digital art and the science of placing tiles of sp2-carbon polygons on mathematically defined triply periodic minimal surfaces. The knowledge of how to connect polygons in sequence using the rules of symmetry unlocks paths for the bottom-up synthesis of schwarzites by organic chemistry methods. Schwarzite tiling by heptagons is systematically analyzed and classified by symmetry and topology. For the first time, complete plans for the bottom-up synthesis of many schwarzites are demonstrated. A trimer of heptagons is suggested as the key building block for most synthetic schemes.
Synthesis of Substituted Tetralins via Nitrogen Deletion/Diels–Alder Cascade Reaction
Zixuan Zang - ,
Wen Ye - ,
Kehang Cheng - ,
Xiaotai Wang - , and
Xiaodong Jin *
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Skeletal editing is an important approach for the modification and diversification of biologically active molecules. The utilization of nitrogen deletion strategies in skeletal editing has recently emerged as a new method for compound modification. Here, we report an unexpected nitrogen deletion in isoindolines. Contrary to the anticipated outcome of cyclobutane formation via intramolecular radical couplings, the nitrogen deletion of isoindoline triggers a Diels–Alder cycloaddition facilitated by the in situ formation of ortho-xylylene to yield tetraline. Inspired by this reaction, we developed a new strategy for synthesizing substituted tetralins, employing isoindoline, nitrogen deletion reagent (anomeric amide), and dienophiles. This methodology demonstrates a new pathway for tetralin synthesis and the modification and diversification of isoindolines.
Synthesis of Pyranocoumarin through MCRs: Modulation of this Approach as a Function of Substituent Effect Forms the Furocoumarin and 4-Hydroxy-3-styryl Coumarin as a Function of Solvent Effect1
Simra Faraz - ,
Kriti Mehta - ,
Prasad V. Bharatam - , and
Abu Taleb Khan *
The synthesis of pyranocoumarin is reported from 4-hydroxycoumarin, styrene oxide, and DMSO in the presence of p-TSA·H2O at 110 °C using a three-component reaction. Interestingly, a CH2 moiety from DMSO gets inserted in this reaction to form the pyranocoumarin ring. The plausible mechanism for this interesting reaction was proposed and validated using quantum chemical methods. Interestingly, when the reactions were performed with 7-methoxy-4-hydroxycoumarin and styrene oxides, having an electron-withdrawing group, the reaction followed a two-component pathway, and furocoumarins were obtained in good yields. Switching the solvent from DMSO to CH3CN for the same reactants results in the exclusive formation of the novel monomeric product 4-hydroxy-3-styryl-2H-chromen-2-one (5) instead of the expected furocoumarins. Interestingly, one of the novel monomeric products, 4-hydroxy-3-styryl-2H-chromen-2-one, directly undergoes unexpected cyclization to provide a more interesting and complex tricyclic product. The salient features of the present strategy are its easy handling, commercial availability of starting material, metal-free synthesis, inexpensive catalysts, environmentally benign, and high atom economy.
Samarium Diiodide/Samarium-Mediated Deoxygenative Hydrosilylation of Ketones
Ruxing Li - ,
Yilin Ma - ,
Jianwen Zhang - , and
Chengwei Liu *
The first deoxygenative hydrosilylation of ketones promoted by samarium diiodide and samarium has been reported. In this approach, secondary alkyl silanes are synthesized from unactivated ketones and chlorosilanes in one step. The carbonyl group of ketones is activated by SmI2-mediated single-electron transfer process, which follows a deoxygenative elimination of O=Sm. Broad substrate scope and excellent functional group tolerance has been demonstrated.
Photoredox-Catalyzed C–H Methylation of N-Heteroarenes Enabled by N,N-Dimethylethanolamine
Jiayang Wang - ,
Yun Wang - ,
Wenjing Lin - ,
Anyi Yang - ,
Ying Wang - ,
Jingran Wang - ,
Haizhen Zheng - , and
Haixia Ge *
A visible-light-driven radical C–H methylation of N-heteroarenes that is efficient and additive- and catalyst-free and employs readily available N,N-dimethylethanolamine as the methyl source has been developed. The transformation offers the benefits of broad substrate scope, mild reaction conditions, and operational simplicity. A photoactive electron donor–acceptor (EDA) complex between N-heteroarenes and N,N-dimethylethanolamine is essential for this transformation, as revealed by mechanistic investigations.
Synthesis of Nucleoside Analogs Containing Sulfur or Selenium Replacements of the Ribose Ring Oxygen or Carbon
Caecilie M. M. Benckendorff *- ,
Peter Sunde-Brown - ,
Aisling Ní Cheallaigh - , and
Gavin J. Miller *
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Nucleoside analogs have proven highly successful in many pharmaceutical intervention strategies, and continued exploration of next generation structural motifs is required. Herein we discuss recent advances toward the chemical synthesis of heteroatom-modified nucleosides, where this is constituted by the chalcogens sulfur or selenium. Paying specific focus to the organic chemistry to incorporate these heteroatoms, we consider developments toward ribose ring oxygen and ring carbon replacements alongside chalcogen-modified heterobases.
Stereoselective Aminomethylation of β,β-Disubstituted Enesulfinamides: Asymmetric Construction of Less Accessible Acyclic α,α-Disubstituted α-Aminomethylated Ketimines
Tao Liu - ,
Zhi-Yao Huang - ,
Yi Li - , and
Chong-Dao Lu *
β,β-Disubstituted enesulfinamides undergo stereoselective nucleophilic addition to the formaldehyde imines, in situ formed from tosylmethylcarbamates, affording α-aminomethylated ketimines bearing a challenging acyclic quaternary stereocenter substituted by two sterically and electronically similar groups (e.g., Me and Et). The defined geometry of the C═C bond in the enesulfinamides, combined with the strong chiral induction offered by their chiral sulfinyl group, ensures precise stereocontrol during the formation of the new C–C bond.
November 20, 2024
Stoichiometry Dependence in the Consecutive, Competing Reduction, Halogenation, or Deoxygenation of Aryl Carbonyls
P. Veeraraghavan Ramachandran *- ,
Henry J. Hamann - , and
Abdulkhaliq A. Alawaed
Six fundamental chemical transformations of aryl carbonyls are achieved by properly adjusting the stoichiometry of the borane-amine and titanium tetrachloride reagent system. This set of reagents acts collectively as a hydride donor, Lewis acid catalyst, and halogen source for the reduction of carbonyls to alcohols, reductive halogenation of carbonyls to halides, deoxygenation of carbonyls to alkanes, dehydroxyhalogenation of alcohols to halides, deoxygenation of alcohols to alkanes, and hydrodehalogenation of halides to alkanes. While the carbonyl reduction is broadly applicable to both aromatic and aliphatic substrates, the remaining reactions are dependent on the stability of the proposed carbocationic intermediates, enabling highly selective reactions at the substrates’ benzylic position. This unique selectivity allows benzylic dehalogenation in the presence of aryl and alkyl halides in addition to highly selective dehydroxyhalogenation of alcohols even for tertiary versus secondary aliphatic and secondary versus primary benzylic substrates using only titanium tetrachloride as the chlorinating agent.
A Pyridinium Ylide-Alkylation Strategy for the Structural Diversification of N-Carbamoylpyridinium Salts
Akash M. Sarkar - ,
Benjamin Gossett - , and
Michael T. Taylor *
A pyridinium ylide-alkylation strategy has been developed for selectively accessing N,N-disubstituted pyridinium salts from monosubstituted pyridinium salts possessing ambident nucleophiles. The method was shown to be tolerant toward an array of different pyridinium scaffolds and common electrophiles, enabling access to structurally diverse pyridinium salts. The potential versatility of the approach was demonstrated through the synthesis of chemically complex, heterotrifunctional pyridinium salts containing a pyridinium warhead, a click chemistry handle, and a third, high-value, payload.
Synthesis of 2-(3,5-Dinitrophenyl)-5-(trinitromethyl)-1,3,4-oxadiazole
Yu-Cong Chen - ,
Qiong Yu *- ,
Ning Liu - ,
Tao Li - , and
Wenbin Yi *
The trinitromethyl group plays a crucial role in the energetic material industry due to its high oxygen balance and energetic properties. This study focuses on the synthesis of dinitrophenyl-substituted trinitromethyl-1,3,4-oxadiazole. The introduction of dinitrophenyl groups to trinitromethyl-1,3,4-oxadiazole aims to improve its stability against heat-induced decomposition, a critical factor in ensuring the safe and reliable performance of energetic materials. Consequently, 2-(3,5-dinitrophenyl)-5-(trinitromethyl)-1,3,4-oxadiazole (6) was designed and synthesized. Compound 6 exhibited a remarkable thermal decomposition temperature of 117 °C, surpassing that of all other 1,3,4-oxadiazoles bearing the trinitromethyl group. This research highlights the incorporation of the dinitrophenyl ring to elevate the thermal decomposition temperature of the trinitromethyl group attached to the 1,3,4-oxadiazole ring, thereby presenting novel strategies for enhancing the thermal stability of these compounds.
Rhodium(III)-Catalyzed Regioselective C4 Alkylation of Indoles with Nitroalkenes
Ru Zhao - ,
Xulin Lv - ,
Hao-Ran Yang - ,
Lijun Gao - ,
Liming Zhou *- ,
Shaoming Fang *- , and
Shuang-Liang Liu *
The Rh(III)-catalyzed indole C4–H bond addition to nitroalkenes is disclosed under mild and redox-neutral reaction conditions, offering straightforward access to various 4-(2-nitroalkyl)indoles (34 examples) with excellent chemo- and regioselectivity. Furthermore, late-stage diversifications and mechanistic studies were also performed.
Adjusting the Coordination Configuration by Changing Electrostatic Potential: Introducing N/O/S Heteroatoms Based on the Electronic Effect
Chao Zhang - ,
Tingwei Wang - ,
Shaoqun Li - ,
Zujia Lu - ,
Meiqi Xu - ,
Cong Li - ,
Qiyao Yu *- , and
Jianguo Zhang *
Energetic coordination compounds (ECCs) have demonstrated unique advantages in regulating the physicochemical properties of energetic materials through the design of organic ligands. The fundamental approach involves altering the electron cloud density distribution of organic ligands to modify the characteristics of coordination sites and, thus, achieve new coordination configurations. In this study, Mulliken charge distribution and surface electrostatic potential analysis were used to elucidate the effects of pyridinic N, pyrrolic N, oxazolic O, and thiazolic S on the electron cloud density of carbohydrazide groups through the induction effect and conjugate effect. Furthermore, three AgClO4-based ECCs were synthesized based on 1H-imidazole-4-carbohydrazide, oxazole-4-carbohydrazide, and thiazole-4-carbohydrazide. Single-crystal X-ray diffraction analysis revealed that [Ag(IZ-4-CA)ClO4]n has a one-dimensional (1D) chain structure, while Ag2(OZCA)2(ClO4)2 and Ag2(SZCA)2(ClO4)2 exhibit zero-dimensional structures. The 1D structure, with good planarity, results in [Ag(IZ-4-CA)ClO4]n having lower mechanical sensitivity (IS = 21 J, FS = 80 N). The introduction of oxazolic O enhances oxygen balance (OB), leading to a higher predicted detonation velocity and pressure for Ag2(OZCA)2(ClO4)2 (D = 6.4 km s–1, P = 23.6 GPa). Although the introduction of thiazolic S is unfavorable for improving oxygen balance, Ag2(SZCA)2(ClO4)2 exhibits the highest initial decomposition temperature among the three, at 232 °C. Additionally, initiation tests demonstrated that three ECCs can successfully detonate cyclotrimethylenetrinitramine (RDX), indicating good initiation capabilities.
Au(PPh3)Cl/AgOTf/TsOH-Catalyzed Cascade Reaction between 1-(2-Hydroxyphenyl)-propargyl Alcohols and β-Oxoketones (Amides, Acid): Diastereoselective Construction of cis-3a,8a-Dihydrofuro[2,3-b]benzofuran Framework
Yangyi Zhang - and
Guisheng Deng *
In the Au(PPh3)Cl/AgOTf/TsOH/MeCN/N2/25 °C system, diastereoselective synthesis of cis-3a,8a-dihydrofuro[2,3-b]benzofuran derivatives with a substituent at the 8a-position has been achieved by using 1-(2-hydroxyphenyl)-3-arylprop-2-yn-1-ols and β-oxoketones (amides, acid) as starting materials. The studies revealed that the acidity of methylene in substrates plays a key role in the differential reactions. A stronger acidity of the methylene is favorable in the desired conversion. The unique role of TsOH as an additive acid in the synthesis strategy has been rationalized. 2-Oxo-phosphonate, 2-oxo-sulfonate, and 3-oxobutanoate are suitable for the conversion.
Synthesis of Rapicone Based on Acyl Ketene–Alkyne Cycloaddition
Erandi Liyanage Perera - and
Daesung Lee *
We report herein a concise route for the total synthesis of rapicone. The key strategy to form the ynone intermediate involves an Fe(III)/TEMPO-catalyzed aerobic oxidation of a 1,3-dihydroisobenzofuran moiety. This ether oxidation for the simultaneous installation of the keto aldehyde allowed the effective formation of the required ynone intermediate. The concise total synthesis of rapicone is substantiated by the unique formal [4 + 2] cycloaddition of acyl ketene with alkynone and is completed in 7 steps with 9.4% overall yield.
November 19, 2024
Cobalt-Catalyzed Intramolecular Enantioselective Reductive Heck Reaction toward the Synthesis of Chiral 3-Trifluoromethylated Oxindoles
Qiang Wang - ,
Zi-Sheng Ruan - ,
Hong-Peng Wang - ,
Ren-Xiao Liang - ,
Yuan-Yuan Hu *- , and
Yi-Xia Jia *
Herein, a cobalt-catalyzed intramolecular enantioselective reductive Heck reaction is disclosed. Starting from N-ortho-iodoaryl-2-(trifluoromethyl)acrylamides, a plethora of chiral oxindoles bearing trifluoromethylated quaternary stereogenic centers at the C3-position are achieved in moderate to good yields (up to 88% yield) and good to excellent enantioselectivities (up to 94% ee) by employing zinc/silane as reducing agent. Other than the trifluoromethyl group, a number of chiral oxindoles bearing alkyl, aryl, and ester groups at C3-position were also obtained albeit in relatively lower enantioselectivities (68–78% ee).
Molecular Dynamics of the Davies Ambimodal C–H Functionalization/Cope Rearrangement Reaction
Yaling Zhang - ,
Chaoqin Cao - ,
Yuanbin She - ,
Huw M. L. Davies *- ,
Yun-Fang Yang *- , and
K. N. Houk *
The mechanism of the dirhodium-catalyzed combined C–H functionalization/Cope rearrangement (CH/Cope) reaction discovered by the Davies group has been investigated with density functional theory (DFT) calculations and quasi-classical molecular dynamics (MD) simulations. Computations from the Davies group previously showed that there is a post-transition state bifurcation leading to a direct CH reaction and also to the CH/Cope product. While this work was in preparation, the Tantillo group and the Ess group independently reported quantum mechanical and molecular dynamics studies on the dirhodium-tetracarboxylate-catalyzed diazoester CH/Cope and CH insertion reactions with 1,3-cyclohexadiene and 1,4-cyclohexadiene, respectively. The Tantillo group cited “dynamic mismatching” to explain the origins of the low yield of CH/Cope products in some experiments; the Ess group explained the origins of product selectivity from the perspective of TS vibrational modes and their synchronization that occurs at the entropic intermediates. We report quasi-classical trajectories for the reaction of the carbene with 1-methylcyclohexene that afford both the CH/Cope and C–H insertion products. After passing through the transition state that involves mostly hydrogen transfer, momentum drives the reaction trajectories toward the CH/Cope products.
A Method for the Preparation of Fused Dinitromethyl High-Energy-Density Materials
Chengchuang Li - ,
Teng Zhu - ,
Luyao Chen - ,
Caijin Lei - ,
Jie Tang - ,
Guangbin Cheng *- ,
Chuan Xiao *- , and
Hongwei Yang *
This work investigates a simple synthetic method for producing fused dinitromethyl energetic compounds. Fused compound 2 has a high detonation velocity (9358 m s–1) close to that of the well-known high-energy-density explosive CL-20 (9455 m s–1), an extremely high density (1.97 cm–1), and acceptable sensitivity (IS = 8 J). The good thermal stability of 2 (Td = 181 °C) is rarely reported in the field of dinitromethyl-based high explosives. The results show that compound 2 is a promising candidate for high explosives and provide new insight into the synthesis of dinitromethyl compounds.
Copper-Catalyzed Cascade Cyclization of 2-Nitrochalcones with NH-Heterocycles
Thang M. Ly - ,
Tan N. Huynh - ,
Nhi H. Y. Phan - ,
Phuong T. Dinh - , and
Tung T. Nguyen *
We developed a method for allowing cascade cyclization of 2-nitrochalcones with pyrazoles, imidazole, and indazole in the presence of CuI catalyst, DBU base, and THF solvent. The conditions were tolerant of an array of useful functionalities including ester, nitro, cyano, halogen groups. A mechanistic consideration was also provided, as H2O2 was presumably a byproduct. Our method appears to be a rare example to directly prepare C3-heterocyclic unprotected indoles.
Protecting Group Control of Hydroxyketone-Hemiketal Tautomeric Equilibrium Enables the Stereoselective Synthesis of a 1′-Azido C-Nucleoside
Subhankar Panda - ,
Moyosore O. Orimoloye - ,
Tej Narayan Poudel - ,
Steven De Jonghe - ,
Dirk Jochmans - ,
Johan Neyts - , and
Courtney C. Aldrich *
The synthesis of 1′-azido C-nucleosides is described to expand the set of azide-functionalized nucleosides for bioorthogonal applications and as potential antiviral drugs. Lewis acid-promoted azidation of a nucleoside hemiketal resulted in the formation of a tetrazole through a Schmidt reaction manifold. Conformational control to prevent ring–chain tautomerism enabled efficient 1′-azidation with complete β-diastereoselectivity. The unique reactivity and further derivation of the 1′-azido C-nucleosides are also reported.
Correction to “Chemical Bonding and Aromaticity in Furan, Pyrrole, and Thiophene: A Magnetic Shielding Study”
Kate E. Horner - and
Peter B. Karadakov *
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November 18, 2024
C2-Arylated Indoles and Benzofurans through Formal (4 + 1) Annulation of N-Sulfonyl-2-aminobenzaldehydes and Salicylaldehyde Derivatives with Electron-Deficient Benzyl Chlorides
Lillian A. de Ceuninck van Capelle - ,
Kimia Rahmannia - ,
James M. Macdonald - ,
Christopher Richardson - ,
Michael G. Gardiner - ,
John H. Ryan - ,
Rasool Babaahmadi - ,
Steven M. Wales *- , and
Christopher J. T. Hyland *
A two-step formal (4 + 1) annulation-dehydration reaction offers a convenient route to C2-arylated indoles and benzofurans. This reaction exploits the bifunctional reactivity of electron-deficient benzyl chlorides with N-sulfonyl-2-aminobenzaldehydes or salicylaldehyde derivatives. The reaction tolerates both electron-withdrawing and donating groups on the substituted aldehydes, as well as variation of electron-withdrawing groups at the para position of the benzyl chloride reagent. This work also identifies interesting byproducts resulting from the self-reaction of these benzyl chlorides under basic conditions.
Synthesis of Sulfinamidines via Iron-Catalyzed Nitrene Transfer Reaction with Sulfenamides
Zhi-Kun Zhang - ,
Yin Yuan - ,
Huiling Peng - ,
Yidan Han - ,
Junliang Zhang *- , and
Junfeng Yang *
An iron-catalyzed nitrene transfer reaction for the rapid synthesis of sulfinamidines from readily available sulfenamides is reported. This method features mild conditions, short reaction times, and a broad substrate scope, allowing the preparation of a variety of sulfinamidines in good to excellent yields. The synthetic utility of the sulfinamidine products was further demonstrated through their conversion to other valuable sulfur(VI) compounds, such as sulfondiimidoyl fluorides, sulfinamidiate esters, and sulfonimidamides. Preliminary efforts in the development of an asymmetric variant showed moderate enantioselectivity.
Cobalt-Catalyzed Regioselective C8–H Sulfoxamination of 1-Naphthylamine Derivatives with NH-Sulfoximines
Nileshkumar B. Rathod - ,
Raj N. Patel - ,
Sachinkumar D. Patel - ,
Dharmik M. Patel - ,
Mahesh A. Sonawane - ,
Dinesh Gopichand Thakur - , and
Subhash Chandra Ghosh *
A simple cobalt-catalyzed, picolinamide-directed C8–H sulfoxamination of 1-naphthalamides with NH-sulfoximines has been developed. This cross-dehydrogenative C–H/N–H coupling reaction offers a facile route to N-arylated sulfoximines, exhibiting high yields, a broad substrate scope, and excellent functional group tolerance and scalability.
November 17, 2024
Development of a Highly Enantioselective Catalytic Di-π-methane Rearrangement
Samuel B. Cahoon - ,
Steven J. Chapman - ,
Tahoe A. Fiala - ,
Matthew J. Genzink - , and
Tehshik P. Yoon *
The di-π-methane (DPM) rearrangement is an important organic photorearrangement that converts 1,4-diene-containing compounds to vinyl cyclopropanes, often resulting in extensive, synthetically valuable restructuring of the substrate’s carbon framework. We investigated the influence of Lewis and Brønsted acids on the DPM rearrangement of dibenzobarrelenes. These studies have culminated in the identification of a dual chiral Brønsted acid–iridium photosensitizer system that enables the first highly enantioselective catalytic all-carbon DPM rearrangement.
November 16, 2024
Lewis Acid Promotes Three-Component Cyclization to Construct Dithioxazole Derivatives
Kai Zou - ,
Anquan Li - ,
Yitong Chen - ,
Gao Cao *- , and
Baofu Zhu *
A simple and effective strategy for the construction of disulfide-substituted oxazole derivatives from amides, ynals, and acetyl disulfides via a Lewis acid-promoted three-component reaction has been reported. In addition, this reaction possesses other unique advantages, such as transition-metal-free catalysis, the production of disulfides, good functional group tolerance, and good regioselectivity.
Chemoselective Dehydrogenation and Hetero-Arylation of Amides via Radical Translocation Enabled by Photoexcited Triplet Ketone Catalysis
Akash Bisoyi - ,
Amit Behera - ,
Alisha Rani Tripathy - ,
Vijay Kumar Simhadri - , and
Veera Reddy Yatham *
We herein report the chemoselective dehydrogenation and heteroarylation of amides through photoexcited triplet ketone catalysis. Under mild reaction conditions, the generated aryl radical through the halogen atom transfer (XAT) process further undergoes an intramolecular 1,5-HAT event to generate an α-amido alkyl radical, which then intercepted with either cobalt or a reduced cyano arene radical leads to dehydrogenated and heteroarylated products, respectively, in good yields.
Robust Organocatalytic Three-Component Approach to 1,3-Diarylallylidene Pyrazolones via Consecutive Double Condensation Reactions
Ashvani K. Patel - and
Sampak Samanta *
A robust pyrrolidine-BzOH salt-catalyzed one-pot three-component reaction involving 4-unsubstituted pyrazolones, aryl/heteroarylaldehydes, and aryl methyl ketones is reported for the first time. This catalytic process fortifies an efficient method, allowing for the practical synthesis of a wide array of synthetically useful 1,3-diarylallylidene pyrazolones in good to high yields exclusively in their single geometrical isomer forms. Furthermore, this catalyst facilitates a sequential double condensation reaction under thermal conditions, thereby enabling two consecutive C═C bonds through displacement of aryl groups. Moreover, this organocatalytic technique achieves a 100% carbon atom economy, marking a significant step forward toward efficient and sustainable synthesis.
November 15, 2024
Access to Ketones via Nickel-Catalyzed Coupling between S-2-Pyridyl Thioesters and Redox-Active Esters Using an Organic Reductant
Jiang-Hong Liu - ,
Ze-Yu Tian - ,
Zhen-Ye Wu - ,
Tian-Le Huang - ,
Zheng Lin - ,
Le Zhang - ,
Jian Chen - ,
Li Hai - ,
Li Guo *- , and
Yong Wu *
A nickel-catalyzed coupling between S-2-pyridyl thioesters and redox-active esters has been reported. Diludine was used as a reductant in this strategy. Our method rapidly achieves the target ketone products in moderate to good yield. The construction of nonanomeric C-acyl glycosides was realized through the approach as well.
Asymmetric Vinylogous Michael/Oxa-Michael Tandem Reaction between β,γ-Unsaturated Amides and Isatin-Derived β,γ-Unsaturated α-Ketoesters
Shan-Shan Xu - ,
Zi-Yu Li - ,
Meng-Yu Liu - ,
Feng Sha - , and
Xin-Yan Wu *
An organocatalytic asymmetric vinylogous Michael/oxa-Michael tandem reaction between β,γ-unsaturated pyrazoleamides and isatin-derived β,γ-unsaturated ketoesters has been developed with excellent regio-, diastereo-, and enantioselectivities. The methodology provides an effective approach to construct enantiomerically pure 3,4′-pyranyl spirooxindole derivatives containing three contiguous chiral centers. Moreover, the transformations of the chiral products, including the removal and reduction of the pyrazole group, have been investigated.
Highly Regioselective Dehydrogenative Hydrazination of Tropones
Yan Wang - ,
Muliang Zhang *- , and
Shi-Kai Tian *
Direct C(sp2)–H bond functionalization of the tropone skeleton constitutes an atom-economical strategy to access substituted tropones that exist in some bioactive compounds. Herein, we report a convenient method for the preparation of 2-hydrazinotropones via C(sp2)–H bond functionalization. A variety of tropones participated in the dehydrogenative hydrazination reaction with hydrazine, delivering structurally diverse 2-hydrazinotropones in moderate to good yields with extremely high regioselectivity. This method is featured by operational simplicity and metal-free reaction conditions, thereby tolerating various functional groups.
Diarenofuran[b]-fused BODIPYs: One-Pot SNAr-Suzuki Synthesis and Properties
Limin He - ,
Na Li - ,
Yanqing Li - ,
Yunxia Zhao - ,
Shulin Gao - ,
Zhaohui Wang - ,
Xiangguang Li *- ,
Yanhua Yang *- , and
Wei Jiang *
We present a streamlined methodology that integrates regioselective tetrahalogen-BODIPY and o-hydroxyphenylboronic acid in a one-pot process, leveraging SNAr nucleophilic substitution in conjunction with Suzuki coupling to afford diarenofuran [b]-fused BODIPYs (DBFB1–9) with commendable yields (85–95%) and short reaction times (0.5–1.0 h). X-ray structure analyses of DBFB5,7–9 elucidate that these diarenofuran[b]-fused BODIPYs adopt a “butterfly” conformation, maintaining a highly rigid planarity. A comprehensive examination of the spectroscopic and electrochemical properties of these diarenofuran[b]-fused BODIPY derivatives, incorporating various substituents, reveals intriguing characteristics, including pronounced absorption and emission in the near-infrared region (NIR), elevated fluorescence quantum yields (ΦF = 75–89% in dichloromethane), and tunable HOMO–LUMO levels. Remarkably, compared to DBFB1–8, DBFB9 possesses a large extended π-conjugated system, resulting in significant red shifts in its absorption and emission maxima, reaching 623 and 635 nm, respectively, and a reduced HOMO–LUMO gap. Despite this substantial structural expansion, DBFB9 maintains a surprisingly high fluorescence quantum yield (ΦF = 80%), underscoring its exceptional photophysical performance and strong potential for applications requiring efficient NIR emission and robust fluorescence retention.
Expedited Aminoglutarimide C–N Cross-Coupling Enabled by High-Throughput Experimentation
Jacqueline W. Gu - ,
Martins S. Oderinde - ,
Hui Li - ,
Frederick Roberts - ,
Jacob M. Ganley *- , and
Maximilian D. Palkowitz *
A simple protocol for the Buchwald–Hartwig cross-coupling of (hetero)aryl halides with unprotected aminoglutarimide to afford diverse cereblon binding motifs is disclosed. The development of this C–N cross-coupling method was enabled by high-throughput combinatory screening of solvents, bases, temperatures, and ligands. Scope studies revealed generality across various heteroaryl and aryl halides with the reaction proceeding under mild conditions. In comparison, this method demonstrated strategic superiority over previously reported approaches, as evidenced by a significant decrease in step count from known syntheses in the patent literature.
November 14, 2024
Cu-Catalyzed Multicomponent Reaction of Arylhydrazines with β-Ketoesters and TBN: One-Pot Access to N2-Aryl 1,2,3-Triazole-1-Oxides
Mohammad Mujahid - ,
Vijay Vara - ,
Usman Arshad - ,
Rama Krishna Gamidi - , and
M. Muthukrishnan *
We report a copper-catalyzed one-pot, multicomponent strategy for the convenient synthesis of N2-aryl 1,2,3-triazole-1-oxides using arylhydrazines, β-ketoesters, and tert-butyl nitrite. This mild and simple reaction proceeds in an atom-economic manner with broad substrate scope, affording a variety of N2-aryl 1,2,3-triazole-1-oxide derivatives. Other salient features of the reaction are good functional group tolerance, scalability, and product diversification.
Gold(I)-Catalyzed Synthesis of 2,2′-Biindoles via One-Pot Double Cycloisomerization Strategy
Jaime G. Ibarra-Gutiérrez - ,
César R. Solorio-Alvarado *- ,
Luis Chacón-García *- ,
Jesús Adrián López *- ,
B. Yoaly Delgado-Piedra - ,
Luis A. Segura-Quezada - ,
Edson D. Hernández-Velázquez - , and
Ana K. García-Dueñas
The first systematic, concise and target-directed gold(I)-catalyzed synthesis of a family of 2,2′-biindoles containing different substitution patterns is described. The developed protocol involves the synthesis of 1,3-diyne-anilines followed by a one-pot gold(I)-catalyzed double cycloisomerization, giving rise to an efficient, broad and general protocol to get different 2,2′-biindoles under mild reaction conditions. Due to the methodological restriction of present methods for accessing this class of compounds, herein we present our synthetic proposal which allowed the preparation of several examples of 2,2′-biindoles. Their functionalization-guided us to the discovery that the chemical stability, is substitution structure-dependent.
C1 Functionalization of β-Carboline via Knochel–Hauser Base-Directed Metalation and Negishi Coupling
Jin Tan - ,
Kyle Clagg *- , and
Haiming Zhang *
The synthesis of C1-functionalized β-carbolines from N-Boc norharman is described. Substitution is realized by employing the Knochel–Hauser base (TMPMgCl·LiCl) followed by transmetalation with ZnCl2 and subsequent Negishi cross-coupling of the resulting organozinc species. A variety of aryl or heteroaryl bromides participated in this one-pot reaction sequence, allowing for rapid diversification of the β-carboline scaffold in moderate to excellent yields. The reaction protocol has been applied to the synthesis of natural alkaloids nitramarine, nitraridine, eudistomin U, and perlolyrine.
Solvent-Controlled Rh(III)-Catalyzed Mono- and Dual Functionalization of Quinolyl Aldoximes with Diazo Compounds
Peng Zhang - ,
Shan Xu - ,
ShihaoZhi Wang - ,
Xue-jing Zhang - , and
Ming Yan *
A solvent-controlled Rh(III)-catalyzed mono- and dual-C–H bond activation/carbene migratory insertion with diazo compounds as a single coupling partner was demonstrated. The reaction proceeded under mild conditions, yielding products in good to excellent yields. These results are significant for the development of the domino multiple functionalization of C(sp2)–H bonds via a carbenoid insertion approach.
Synthesis of Pyrrolidine-2-ylidenes from Isoxazolines and Allenes
Dylan C. Keane - ,
Guanqun Zhang - ,
Abdullah S. Alshreimi - ,
Donald J. Wink - , and
Laura L. Anderson *
A diastereoselective addition and rearrangement reaction has been developed for the synthesis of pyrrolidine-2-ylidenes from NH-isoxazolines and electron-deficient allenes. This method proceeds via the rearrangement of a proposed N-alkenylisoxazoline intermediate to generate densely functionalized pyrrolidine-2-ylidenes under simple catalyst-free conditions that tolerate ketone substituents and install relative stereochemistry at positions 3 and 4 of the heterocycle. Reaction optimization and the substrate scope are described in addition to studies evaluating the reactivity of the gem-dione and enaminone groups of the products.
Visible-Light-Mediated Three-Component Decarboxylative Coupling Reactions for the Synthesis of 4-Alkylpyridines
Ai Wang - ,
Yijian Ma - ,
Jia-Hui Jin - ,
Le-Quan Wang - ,
Dan-Dan Li - ,
Zi-Wei Xi *- ,
Chengshuo Shen *- , and
Yong-Miao Shen *
4-Alkylation of pyridines has been achieved by a photocatalyzed three-component reaction of an olefin, an aryloxyacetic acid, and cyanopyridine using Ir[dF(CF3)ppy]2(dtbbpy)PF6 as a photocatalyst. In this way, a new type of 4-alkylpyridines bearing aryl and aryloxy substituents on the phenyl was accessed with potential pharmaceutical value. In addition to mild reaction conditions, the method has several other advantages, including a multicomponent one-pot protocol, good functional group tolerance, and easy amplification of the reaction scale. The reaction mechanism has been clarified by control experiments and computation of the reaction energy profile.
Access to Functionalized Amines and Medium N-Heterocycles via Amine-Enabled Remote C–H Alkynylation
Xiaojian Chen - ,
Yang Gao - ,
Jiye Luo - ,
Yuan Liu - ,
Qian Chen - ,
Yanping Huo - , and
Xianwei Li *
By using weakly coordinating amines, we developed remote C–H alkynylation with precise control of reactivity and regioselectivity, enabling modification of complex drugs, natural products, and materials. The readily transformable alkyne-containing amine products would facilitate expedient delivery of molecular libraries of functionalized amines and medium N-heterocycles, which are previously elusive to access. Moreover, the introduced alkyne functionality could serve as a versatile handle to expand the diversity and synthetic application of this remote C–H functionalization.
Masterpenoids A–D, Four Unprecedented Nortriterpenoids from the Mastic (Pistacia lentiscus) and Their Anti-inflammatory Activity
Xuerui An - ,
Wei Liu *- ,
Hengwei Zhou - ,
Jiaxu Zhang - ,
Yuwei Sun - ,
Tianzhi Li - ,
Wentian Xiang - , and
Tao Yuan *
Four unprecedented nortriterpenoids, masterpenoids A–D, were isolated and fully elucidated from the resin of the mastic tree (Pistacia lentiscus). Masterpenoids A–C are the first norterpenoids featuring an unprecedented 6/6/6/10 ring system, while masterpenoid D possesses a novel 6/6/6/7/5 ring system. The anti-inflammatory potential of the compounds was meticulously assessed through the establishment of an in vitro model of lipopolysaccharide-induced inflammation in RAW264.7 macrophage cells. Among them, Masterpenoids A and D showed potent inhibition of NO production, with IC50 values of 10.6 ± 0.8 and 8.2 ± 0.9 μM, respectively, compared to positive control dexamethasone (IC50 = 23.2 ± 1.2 μM).
A Tale of Two Cities in Fluorescent Sensing of Carbon Monoxide: Probes That Detect CO and Those That Detect Only Chemically Reactive CO Donors (CORMs), but Not CO
Dongning Liu - ,
Xiaoxiao Yang - , and
Binghe Wang *
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Carbon monoxide (CO) is endogenously produced with a range of pharmacological activities. Sensitive and selective detection of CO is critical to studying its biology. Since the first report of a CO fluorescent probe in 2012, more than 100 papers on this topic have appeared. Noteworthy in such work is the widespread use of two commercially available ruthenium–carbonyl complexes (CORM-2 and CORM-3) as CO surrogates. Unfortunately, these two CORMs are chemically very reactive and preferentially release CO2 but not CO, unless in the presence of a nucleophile. As a result, there are “two tales” of the reported CO probes: those that detect CO and those that detect only the CORM used but not CO. In addition, because of their lack of reliable CO production and fast degradation in an aqueous solution, there is the question of what “detecting CORM-2 or CORM-3” really means in the context of CO research. Additionally, for applying fluorescent CO probes in detecting low levels (often nanomolar) of CO in vivo, fast reaction kinetics is a prerequisite for meaningful results. In this Perspective, we discuss in detail these issues with the understanding of the evolutionary nature of scientific discoveries and the aim of preventing further confusion.
November 13, 2024
Oxidative Coupling of Primary Benzamide with Alkenes via o-CH Activation Mediated by Cu(II)/Ru(II)
Aditi Soni - ,
Lalit Negi - ,
Charu Sharma - ,
Avinash K. Srivastava - , and
Raj K. Joshi *
A selective ortho-olefination of primary amides yields valuable motifs for pharmaceuticals. Primary amide-directed ortho-olefination of benzamide using unactivated alkenes was successfully conducted with a ruthenium(II) catalyst. The established protocol demonstrates efficacy across various benzamides, achieving moderate to good yields with high functional group tolerance. Furthermore, the transformation of ortho-olefinated amides into five-membered lactams highlights their synthetic applicability in the pharmaceutical sector.
Regio- and Stereoselective Construction of 1,3,5-Triaroylcyclohexanes via KOtBu-Mediated Cyclotrimerization of Aryl Vinyl Ketones
Sachin D. Mahale - ,
Vinita Yadav - ,
Rajesh G. Gonnade - , and
Santosh B. Mhaske *
Herein, we disclose a simple one-pot method for an efficient regio- and stereoselective synthesis of 1,3,5-triaroylcyclohexanes from aryl vinyl ketones using potassium tert-butoxide. The developed protocol allows the construction of various symmetrically substituted cyclohexanes in good to excellent yields. The major product 2 also can be converted to the product 3 (all equatorial) conveniently by acid catalysis. This protocol features a good substrate scope and functional group compatibility.
Ynone Promoted Deaminative Coupling of Gramines with C- and N-Nucleophiles
Iker Hernández - ,
Guillermo Domínguez - ,
Vadim A. Soloshonok - ,
Aitor Landa *- , and
Mikel Oiarbide *
The deaminative coupling of gramines with nucleophiles represents a versatile approach for structure diversification, but often involves non innocent conditions and/or reagents. Here a new acetylenic reagent 2 is developed for the C–N bond activation of gramines and their in situ coupling with C- and N-centered nucleophiles. Using the new acid/base- and redox-neutral ynone reagent 2 the coupling reactions proceed exceedingly as exemplified by the synthesis of several indol-3-ylmethyl derivatives, including new indole-benzodiazepine and indole-hydrazone conjugates.
Construction of Naphtho[2,1-d]oxazoles and 1,4-Epoxyisoquinolines via Regioselectivity-Switchable Diels–Alder Reaction of 4-Alkenyloxazoles with Arynes
Ying-Yi Wang - ,
Feng Sha *- ,
Yu-Hui Zheng - , and
Xin-Yan Wu *
A Regioselectivity-switchable Diels–Alder reaction of arynes and 4-alkenyloxazoles was explored. By regulating the reaction temperature and the polarity of the solvent, the reaction activity of aryne was controlled to selectively react with different favorable reaction sites of 4-alkenyloxazoles, providing naphtho[2,1-d]oxazoles and 1,4-epoxyisoquinolines. Density functional theory (DFT) calculations demonstrated that the Diels–Alder reaction on acyclic dienes site needs more energy than the reaction on cyclic dienes to overcome the potential reaction barrier.
Construction of Spiro[pyrrolidine-azlactone] via [2 + 3] Cycloaddition of Alkylidene Azlactone with Trifluoromethylated Imine
Lesong Li - ,
Xia Wang - , and
Yang Wang *
A Ag-catalyzed [2 + 3] cycloaddition of alkylidene azlactones with trifluoromethylated imines has been documented, providing spiro[pyrrolidine-azlactones] bearing four adjacent stereogenic centers with good yields and excellent diastereoselectivities. Catalytic asymmetric cycloaddition has also been developed with good yields and excellent enantioselectivities. Further gram-scale preparation and synthetic transformation to pyrrolidine derivative showed the good practicality and applicability of this reaction.
Cascade Cyclization/Annulation of β-Enamino Diketones and o-Phenylenediamine: A Strategy to Access Pyrrole-fused 1,5-Benzodiazepines
Julia Poletto - ,
Julia C. M. Willig - ,
Jeniffer N. A. Camargo - ,
Helio G. Bonacorso - ,
Michael J. V. Silva - , and
Fernanda A. Rosa *
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Herein, we introduce an unprecedented cascade reaction for the assembly of pyrrole-fused 1,5-benzodiazepine frameworks. These diverse privileged scaffolds were controllably constructed by intramolecular cyclization of β-enamino diketone, followed by annulation with o-phenylenediamine. The protocol features efficient one-pot cascade cyclization/annulation, performed under simple and mild reaction conditions. The products are obtained in a metal-free manner, in good to excellent yields (65–91%), and represent a fused heterocyclic scaffold that is not yet found in nature.
Correction to “Dehydrogenation Coupling and [3 + 2] Cycloaddition of Indolizines with Allenes in the Presence of Piezoelectric Materials under Ball Milling Conditions”
Mingzhou Huang - ,
Lichan Deng - ,
Tianfeng Lao - ,
Ziwu Zhang - ,
Zhengquan Su - ,
Yue Yu *- , and
Hua Cao *
This publication is free to access through this site. Learn More
November 12, 2024
Photoinduced Ag-Mediated Azaspirocyclic Approach Involves Cyclization and Dearomatization
Ming Li *- ,
Dong-Yu Miao - ,
Fan Gao - ,
Guo-Qing Sun - ,
Dong-Ping Chen - ,
Yi-Feng Qiu - ,
Shun-Xi Li - ,
Zheng-Jun Quan *- ,
Xi-Cun Wang *- , and
Yong-Min Liang
A visible-light-promoted protocol for azaspirocyclic synthesis from N-benzylacrylamides and alkyl chlorooxoacetates has been established. This cascade reaction proceeds through sequential free radical addition, cyclization, and dearomatization, enabling the convenient construction of key azaspirocyclic derivatives and the introduction of valuable ester groups in a single step. In addition, this transformation demonstrates broad substrate compatibility and high tolerance toward different functional groups, showcasing remarkable efficiency in functional group insertion and bond formation.
Synthesis of 4-Hydroxyindolin-2-ones via Phosphoric Acid-Mediated Annulation of β-Nitrostyrenes with 1,3-Cyclohexanedione
Haiwen Li - ,
Wenzhe Cheng - ,
Jiaman Lv - , and
Cunde Wang *
The efficient synthesis of 4-hydroxy-3-arylindolin-2-ones via phosphoric acid-mediated annulation of various β-nitrostyrenes and 1,3-cyclohexanedione is described. This annulation reaction gives a practical method for affording a diverse set of oxindoles, having simple experimentation, readily available starting materials, and very good yields. Additionally, substituted 1,3-cyclohexanediones under the same conditions afforded tetrahydrobenzofuran oxime compounds.
Intermolecular Oxidopyrylium (5 + 2) Cycloaddition/Reductive Ring-Opening Strategy for the Synthesis of α-Methoxytropones
Orugbani S. Eli - ,
Lauren P. Bejcek - ,
Anastasiya Lyubimova - ,
Dan L. Sackett - , and
Ryan P. Murelli *
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α-Methoxytropone is a structural motif found in various natural products and other compounds of interest to the scientific community but remains a synthetic challenge. The present Note describes the synthesis of variously substituted α-methoxytropones and related compounds through an intermolecular 3-hydroxy-4-pyrone-based oxidopyrylium (5 + 2) cycloaddition followed by a samarium iodide-mediated reductive ring-opening. The strategy is highlighted in the synthesis of a novel AC-ring analogue of colchicine to compare it to existing methods.
Correction to “Synthesis of a 3′-Fluoro-3′-deoxytetrose Adenine Phosphonate”
Swarup De - ,
Steven De Jonghe - , and
Piet Herdewijn *
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Mild and Effective Method for the Nickel-Catalyzed Arylation of Glycosyl Thiols in Aqueous Surfactant Solution
Zoe Beato - ,
Sally Howard Ihle - , and
Xiangming Zhu *
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Aryl thioglycosides have broad applicability as both glycosyl donors and glycomimetic compounds. Their synthesis via the cross-coupling of glycosyl thiols with aryl halides has become a popular method for their construction because it allows better selectivity for anomeric configuration as well as a wider functional group tolerance compared to traditional methods. Herein, we report a nickel-catalyzed method for the synthesis of aryl thioglycosides which utilizes an aqueous micellar environment as the reaction medium. This alternative method allows for mild conditions while circumventing expensive palladium, leading to the successful synthesis of over 30 aryl thioglycosides, including challenging 1,2-cis thioglycoside products.
Rhodaelectro-Catalyzed Synthesis of Pyrano[3,4-b]indol-1(9H)-ones via the Double Dehydrogenative Heck Reaction between Indole-2-carboxylic Acids and Alkenes
Fengyi Xiao - ,
Xinlu Xu - ,
Jiaqi Zhang - ,
Ximan Chen - ,
Xin Ruan - ,
Qi Wei - ,
Xiaofeng Zhang *- , and
Qiufeng Huang *
A rhodaelectro-catalyzed double dehydrogenative Heck reaction of indole-2-carboxylic acids with alkenes has been developed for the synthesis of pyrano[3,4-b]indol-1(9H)-ones. The weakly coordinating carboxyl group is utilized twice as a directing group to activate the C–H bonds throughout the reaction. This reaction precedes an acceptorless dehydrogenation under exogenous oxidant-free conditions in an undivided cell with a constant current.
Polysubstituted Pyridines from 1,4-Oxazinone Precursors
L. C. Thompson - ,
Adrianne M. Kinsey - ,
Zannatul Shahla - , and
Jonathan R. Scheerer *
This publication is Open Access under the license indicated. Learn More
This study describes a general method for the preparation of 1,4-oxazin-2-one intermediates from acetylene dicarboxylate and β-amino alcohol precursors. Oxazinones prepared in this manner were employed in a tandem cycloaddition/cycloreversion reaction sequence with a model alkyne (phenyl acetylene) to give substituted pyridine products. Fundamental reactivity and selectivity studies are complemented by the synthesis of the polycyclic ergot alkaloid natural product xylanigripone A.
November 11, 2024
NaNH2 as a Nitrogen Source and Base to Synthesize Triarylamines from Aryl Halides Using Pd-Catalyzed C–N Coupling
Chinraj Sivarajan - ,
Shriya Saha - ,
Suhel Mulla - , and
Raja Mitra *
Triarylamines (TAAs) are excellent core structures for multifunctional materials. Reversible single-electron oxidation is the key to versatile applications. Synthesizing these from feedstock materials is inevitable. Here, we report the one-pot synthesis of TAAs from aryl halides and inexpensive NaNH2 as a nitrogen source and base (dual role). The Pd/Xantphos catalytic system shows excellent selectivity toward TAAs from aryl bromides without adding organic amines and an additional base. Various para substituents on the aryl ring show good functional group tolerance in the presence of NaNH2, resulting in moderate to excellent yield (20–91%). Even though the meta-substituted aryl bromides give TAA products in moderate to excellent yields (20–81%), the ortho substitution leads to only diarylamine products. TAAs from aryl chlorides can be achieved only by changing the ligand to Xphos. The mechanistic investigation suggests that three sequential C–N cross-coupling reactions give the TAA products in the presence of NaNH2. The photophysical and electrochemical properties of TAAs and corresponding radicals were tunable based on substitution patterns.
Electrochemical Synthesis of Quinazolines: N–H/C(sp3)–H Coupling of o-Carbonyl Anilines with Amino Acids and Amines
Jiwei Wu - ,
Lingxiang Yu - ,
Kaixuan Li - ,
Di Zhang - ,
Longqiang Ye *- ,
Xiaolan Xu *- ,
Jie Zhou - ,
Zirong Li *- , and
Huajian Xu *
A mild and efficient electrochemical protocol for the synthesis of quinazolines through N–H/C(sp3)–H coupling of o-carbonyl anilines with natural amino acids/amines has been developed. The products quinazolines can easily be isolated in moderate to excellent yields under external chemical oxidant-free conditions. Moreover, this reaction can be safely conducted on gram scale.
Iodine-Catalyzed Regioselective C-3 Chalcogenation of 7-Azaindoles: Access to Benzothiophene-Fused 7-Azaindole Analogs
Krishanu Mondal - ,
Siddhartha Paul - ,
Pallabi Halder - ,
Vishal Talukdar - , and
Parthasarathi Das *
An iodine-catalyzed method has been reported for efficient regioselective C-3 sulfenylation, selenylation, thiocyanation, and selenocyanation of NH-free 7-azaindoles using thiophenols, diselenides, potassium thiocyanates, and selenocyanates, respectively. This approach showcases high efficiency and remarkable versatility, facilitating the synthesis of diverse chalcogenated 7-azaindoles. Additionally, the sulfenylated derivatives have been further diversified to generate a new array of benzothiophene-fused 7-azaindole cores of pharmaceutical interest. The synthetic flexibility of this protocol has been highlighted through the gram-scale synthesis of sulfonylated 7-azaindole-based bioactive 5-HT6 receptor agonists.
Cycloaddition of Butadiene with Perfluoroethylene: Prediction of a Periselectivity Switch under Pressure
Mohammed Loukili - ,
Ivan Rivilla - ,
Fernando P. Cossio - ,
Roberto Cammi - , and
Bo Chen *
Defying the common Diels–Alder reactivity, the thermal cycloaddition between butadiene and tetrafluoroethylene (TFE) yields exclusively a [2 + 2] cycloadduct via a stepwise diradical mechanism. Here, we study the possibility of reverting to the normal [4 + 2] reactivity in this reaction under high pressure. DFT calculations using the eXtreme Pressure Polarizable Continuum Model (XP-PCM) suggest a more negative activation volume for the concerted [4 + 2] mechanism than the stepwise [2 + 2] mechanism and predict a switch in periselectivity at 1.4 gigapascal (GPa).
Iodide Ion-Promoted Highly Regioselective Triazolization of Aldehydes via Desulfonation-Associated Direct Radical Coupling
Yaqi Deng - ,
Qinghua Wei - ,
Jian Xue - ,
Xiang Wu - , and
Shunying Liu *
A highly efficient iodide ion (I–)-promoted method for direct α-C(sp2)–H triazolization of aldehydes has been developed for the regioselective synthesis of N2-substituted triazole derivatives. The developed method features the corresponding products in good yields (up to 99%) with an excellent functional group tolerance via an intermolecular oxidative radical coupling. Experimental mechanistic investigations indicate that the reaction proceeds via an I–-promoted synergistic desulfonylation process, which provides a high regioselectivity. The developed method provides a direct, metal-free, operationally simple, and highly regioselective approach to C(sp2)–H triazolization from easily accessible aldehydes in air.
Hydroxyl-Assisted and Co(III)-Catalyzed Redox-Neutral C–H Activation/Directing Group Migration of 2-Pyridones with Propargyl Alcohols: Synthesis of Tetrasubstituted Alkenes
Yue-Lu Zhu *- ,
Yan-Lin Long - ,
Ming-Yang Yang - ,
Qi Zhou - ,
Na Zhao - ,
Xue-Xiang Ma *- , and
Jiao Chen *
This study provides a practical route to synthesize tetrasubstituted alkenes that involves Co(III)-catalyzed C–H bond activation and regioselective insertion of the alkyne, followed by chelation of the substrate hydroxyl to Co and migration of the pyridine group. Density functional theory studies revealed the origin of regioselectivity and elucidated the crucial role of the hydroxyl group for the migration of pyridine. The method can be conducted on a gram scale, is compatible with a wide range of substrates, and has a high functional group tolerance. To demonstrate its significance, the method was used for the late-stage modification of Fasudil. Furthermore, the synthetic significance of the method was demonstrated by the various derivatizations of the products, many of which exhibit intriguing fluorescence characteristics.
Reactions of In Situ-Generated Difluorocarbene (:CF2) with Aromatic/Heteroaromatic Alcohols, Thiols, Olefins, and Alkynes under Environmentally Responsible Conditions
Erfan Oftadeh - ,
Madison J. Wong - ,
Julie Yu - ,
Xiaohan Li - ,
Yilin Cao - ,
Fabrice Gallou - ,
Luisa Heinz - , and
Bruce H. Lipshutz *
Environmentally respectful methods for generating and utilizing difluorocarbene (:CF2) in the synthesis of a wide array of valuable difluoromethylated compounds are disclosed. In particular, the insertion of the CF2 moiety into aromatic/heteroaromatic alcohols, thiols, olefins, and alkynes under neat or aqueous micellar catalysis conditions is demonstrated. These methods yield both satisfactory results and significantly lower E-Factors compared to traditional synthetic approaches. Key applications of these methodologies include optimization en route to a pantoprazole intermediate and development of a representative one-pot chemoenzymatic sequence. Additionally, analysis via calorimetry indicates no significant safety risk in the context of the developed solvent-free conditions.
Inhibition of Kornblum Reaction with Lithium Salts in SN2 Reactions of Sulfonates and a Nucleophile Containing a Pyridine N-Oxide Moiety: Convergent and Selective Synthesis of an MRGPRX2 Antagonist
Heng Chen *- ,
Sing R. Gurung - ,
Yexenia Nieves-Quinones - ,
Damian P. Hruszkewycz - ,
Mark G. Nilson - ,
Kavitha Jakka - ,
Kehua Yin - ,
Benjamin R. Hawkins - ,
Kevin J. Splaine - ,
Holly A. Slepian - , and
Shiping Xie
A critical step in the development of a convergent synthesis of an MRGPRX2 antagonist (1) was the SN2 reaction with a highly functionalized lactamide electrophile and a unique difluoropiperidine nucleophile containing a pyridine N-oxide moiety. Initial reactions with sulfonate leaving groups exhibited superb stereoselectivity, but yields were very low due to side reactions originated from competitive Kornblum reactions of the pyridine N-oxide and the sulfonates. Markedly improved reaction profiles were achieved by including stoichiometric lithium triflate. NMR data provided insights into how the lithium cation impacted the pyridine N-oxide through coordination and attenuating its nucleophilicity, leading to the inhibition of the undesired Kornblum reactions. Our approach is highly relevant to preservation of the N-oxide, a structural motif known to several marketed products and emerging as an important class in drug discovery in nucleophilic substitutions. Application of this method enabled the production of the target (1 and its HCl salt 1a) up to multikilogram scale with high selectivity and in much improved yield.
Visible Light-Induced Three-Component Alkoxyalkylation of Alkenes with α-Halocarbonyls and Alcohols
Soumyadeep Roy Chowdhury - ,
Hun Young Kim *- , and
Kyungsoo Oh *
A visible-light-induced three-component alkoxyalkylation of alkenes has been developed under the photocatalysis of fac-Ir(ppy)3. The alkene substrate scope included aryl and aliphatic alkenes as well as electron-rich and electron-deficient alkenes, allowing the facile coupling with a diverse array of α-halocarbonyl compounds. The redox potential-guided orchestration of radical processes with precision allows rapid access to highly functionalized products that are useful building blocks in organic synthesis.
Base-Promoted Coupling of HFIP in Cu-Catalyzed Asymmetric Ring Opening of Cyclic Diaryliodoniums
Abdur Rahim - ,
Biqiong Hong *- , and
Zhenhua Gu *
We report a Cu-catalyzed asymmetric ring-opening reaction of cyclic diaryliodoniums with 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), enabling the construction of axially chiral biaryl compounds containing HFIP ether. HFIP is highly polar and exceptionally stable; thus, it is commonly used as a solvent due to its poor nucleophilicity. However, its use as a nucleophilic reagent has been rare. In this study, we successfully employed HFIP as a nucleophilic coupling partner in a Cu-catalyzed asymmetric ring-opening experiment of cyclic diaryliodoniums.
November 10, 2024
Acid–Solvent Cluster-Promoted General and Regioselective Friedel–Crafts Acylation with Carboxylic Acids
Xi Wang - ,
Wanting Fu - ,
Yuanli Ding - ,
Yongcheng An - ,
Liyu Yuan - ,
Jing Tian - ,
Baokun Tang *- , and
Zikun Wang *
Carboxylic acids are considered to be the most ideal acylating reagents for Friedel–Crafts acylation. However, the low electrophilicity of carboxylic acids and the ability of their byproduct water to deactivate Lewis and Brønsted acids greatly limit their application in this reaction. In this work, we developed a general and regioselective Friedel–Crafts acylation with carboxylic acids, wherein unactivated/activated arenes and various aromatic and aliphatic carboxylic acids were viable starting materials. Key to this accomplishment is the use of trifluoromethanesulfonic acid–hexafluoroisopropanol clusters.
Metal-Free Synthesis of Benzisoxazolones Utilizing ortho-Ester and ortho-Cyano-Functionalized Diaryliodonium Salts with Protected Hydroxylamines
Elghareeb E. Elboray - ,
Taeho Bae - ,
Kotaro Kikushima - ,
Naoko Takenaga - ,
Yasuyuki Kita *- , and
Toshifumi Dohi *
Herein, we report the development of metal-free one/two-pot procedures for the synthesis of benzo[c]isoxazol-3(1H)-one (benzisoxazolone) heterocycles by designing diaryliodonium salts featuring ortho-ester or nitrile functional groups. These react smoothly with protected hydroxylamines under mild conditions to produce N-arylhydroxylamine intermediates, which readily cyclize to give benzisoxazolone derivatives under acidic conditions. This metal-free process maintains the weak N–O bond, tolerates a wide range of diaryliodonium salts and protected hydroxylamines with diverse functional/protecting groups, thereby overcoming the challenges associated with previous transformations. The protocol expands the reaction scope and broadens the chemical space of the fused isoxazolone backbones to include unprecedented five-membered heteroaryl-fused isoxazolones in high yields. This method is also applicable to gram-scale synthesis, and the resulting benzisoxazolones can be effectively derivatized at the N-position to afford valuable compounds.
Tandem Cyclization of o-Hydroxyphenyl Propargyl Alcohols with Thionucleophiles: A Metal-Free and Modular Access to 3-Fluoroalkylsulfonyl/Thio Benzofurans
Lele Wang - ,
Lan Bao - ,
Guili Li - ,
Jinhuan Dong *- , and
Xianxiu Xu *
Despite both fluoroalkylsulfonyl groups and benzofurans are important bioactive moieties, the construction of fluoroalkanesulfonylated benzofurans that incorporate these two fragments remains underdeveloped. Here, we report a tandem cyclization protocol to construct a wide range of 3-fluoroalkylsulfonyl benzofurans using readily accessible o-hydroxyphenyl propargyl alcohols and sodium fluoroalkanesulfinates. Furthermore, this synthetic strategy can also be adapted to prepare 3-thio benzofurans by changing the S-nucleophiles to thiols or thiophenols.
November 9, 2024
Ru-Catalyzed Ortho C–H Alkylation of 4-Aryl-pyrrolo[2,3-d]pyrimidines with Diazo Compounds: An Access to Fluorescent Fused Heteroarenes
Jiangrong Wang - ,
Chunfeng Li - ,
Chunwei Shen - ,
Zhuo Zhang - ,
Mingrui Liu - , and
Xingxian Zhang *
A Ru(II)-catalyzed migratory insertion of carbene into ortho C–H bonds of 4-aryl-pyrrolo[2,3-d]pyrimidines has been developed. This transformation endows the facile fabrication of C–C bonds with high atom economy, good regioselectivity, and wide functional group tolerance, exploiting the directing properties of pyrimidinic nitrogen. In addition, the planar polycyclic pyrrolo-pyrimido-isoindole framework has been accomplished from a cascade reaction of bromination, cyclization, and decarboxylation of synthesized products. Furthermore, the fluorescence properties of C–N annulated compounds have also been determined, which are valuable in the field of fluorescence properties of heterocycles.
November 8, 2024
PdII/CuI-Cocatalyzed Radical Arylation of gem-Difluoroalkenes Using Arylsulfonyl Chlorides
Jiahui Huang - ,
Yixiao Li - ,
Yuantao You - ,
Xingying He - ,
Xiaozhen Wang - , and
Kedong Yuan *
A PdII/CuI-cocatalyzed arylation of gem-difluoroalkenes with arylsulfonyl chlorides, affording various defluorinative arylation/1,2-difunctionalized products, was developed. The interception of aryl radicals generated from the reduction of arylsulfonyl chlorides delivers some hypervalent Pd species, which present high reactivities and chemoselectivities toward the defluorinative arylation product formation. Besides, the nature of the electron-deficient Pd metal center is more prone to reductive elimination under acidic conditions, providing an opportunity to explore new reactivates of fluorinated alkenes into more elaborate substructures.
Mechanistic Investigations of Chiral Lithium Binaphtholate Catalysis for Asymmetric Aldol–Tishchenko Reaction of α-Fluoroarylketones
Shunsuke Kotani *- ,
Toshifumi Asano - ,
Sachie Arae - ,
Masaharu Sugiura - , and
Makoto Nakajima *
In this study, we analyzed the asymmetric aldol-Tishchenko reaction of α-fluoroarylketones with aldehydes in the presence of chiral lithium binaphtholate, which was readily prepared from a chiral BINOL derivative and lithium tert-butoxide. This tandem reaction afforded enantiomerically enriched 2-fluoro-1,3-diols with three contiguous stereogenic centers in high yield and with high diastereo- and enantioselectivities. Moreover, mechanistic investigations of the lithium binaphtholate-catalyzed enantioselective aldol-Tishchenko reaction were performed based on the kinetic isotope effect and computational analyses.
Synthesis of Tetra-ortho-Methoxylated Azobenzene Photoswitches via Sequential Catalytic C–H Activation and Methoxylation
Albert Ruiz-Soriano - ,
Lara Lamelza - ,
Elena Pizzamiglio - , and
Xavier Just-Baringo *
This publication is Open Access under the license indicated. Learn More
Functionalized tetra-ortho-methoxyazobenzenes have been prepared in a two-step approach based on palladium-catalyzed C–H ortho bromination of azobenzenes, followed by copper-catalyzed methoxylation. The method has shown a broad tolerance to different functional groups that could not be incorporated by previous strategies. With this two-step transition metal-catalyzed strategy, we achieved overall yields that range from good to excellent and enable the exploitation of these highly coveted photoswitches. The superior robustness of this scaffold for solid phase peptide synthesis (SPPS) applications when compared to its chlorinated counterpart has been demonstrated after extensive treatments with piperidine while bound to a RinkAmide ChemMatrix resin, showcasing their potential for use in the synthesis of red-light-operated peptides.
Stereoselective Ring-Opening Reaction of α-Fluorinated Oxetanes: A Practical and Theoretical Investigation
David Leparfait - ,
Thibault Thierry - ,
Nicola L. da Rocha - ,
Rémi Legay - ,
Emmanuel Pfund - ,
Rodrigo A. Cormanich *- , and
Thierry Lequeux *
The ring-opening reaction of fluorinated oxetanes by halides, including alkylidene oxetanes and spirocyclic oxetanes, was highly stereoselective and directed by the presence of a fluorine atom. This reaction allowed a stereoselective preparation of tetrasubstituted alkenes and substituted pyrrolidines containing all-carbon quaternary centers. Theoretical calculations were performed to shed light on experimentally observed regioselectivity in the opening of oxetane derivatives. Transition state calculations were carried out to compare the energy of transition states responsible for forming different diastereoisomers. These calculations were performed using several DFT functionals and benchmarked to DLPNO–CCSD(T)/def2-TZVP calculations. Intrinsic reaction coordinated (IRC) calculations were run to confirm if the found transition states connect reactants and products. The IRC paths were then decomposed into the electrostatic, steric hyperconjugative contributions to reaction barriers by using the natural bond orbital (NBO) analysis. The destabilizing Fδ−···Br– electrostatic interaction directs the reaction pathway.
Dirhodium-Catalyzed [2 + 2 + 2] Cycloaddition of 1,6-Diynes and Alkynes
Xiang Gao - ,
Wendeng Li - ,
Yang Chen - ,
Rui Wu *- , and
Shifa Zhu *
A facile method for the construction of fused arenes has been developed through dirhodium-catalyzed [2 + 2 + 2] cycloaddition, which represents a new application of dirhodium complexes. This protocol is convenient to handle without the addition of extra ligands and reductants and tolerates a broad range of functional groups. Mechanistic studies revealed that the two-electron oxidation process, carboxylate ligand departure, and heteroatom coordination-promoted [2 + 2 + 2] cycloaddition were possibly involved.
Synthesis of Amide-Containing Indolo[2,1-a]isoquinoline Derivatives via Palladium-Catalyzed Cascade Reactions
Jianyi Ma - ,
Leming Wang - , and
Shufeng Chen *
A convenient palladium-catalyzed cascade cyclization reaction for the construction of amide-containing indolo[2,1-a]isoquinolines from 2-aryl-N-propenyl indoles with aromatic amines and chloroform is described. A variety of amide-containing indolo[2,1-a]isoquinoline compounds have been successfully synthesized in moderate to good yields in which chloroform is employed as the source of CO.
Boron-Mediated Selective C–H Hydroxylation of 1-Phenyl-1H-Pyrazoles
Gaorong Wu - ,
Yuxi Liu - ,
Weiming Chen - ,
Jiuzhong Huang - ,
Xiangzhao Chen - ,
Qingrong Wu *- , and
Hao Huang *
A novel strategy for boron-mediated C–H hydroxylation of 1-phenyl-1H-pyrazoles is presented. The protocol exhibits high efficiency and site exclusivity, offering the corresponding phenols in moderate to excellent yields with wide functional group tolerance under simple and metal-free conditions. Moreover, the hydroxylated products show good derivatization applications. This route provides a convenient and practical way to obtain functionalized 1-phenyl-1H-pyrazoles.
Retraction of “Mechanochemically Induced Dehydrogenation Coupling and [3+2] Cycloaddition of Indolizines with Allenes Using Piezoelectric Materials”
Mingzhou Huang - ,
Lichan Deng - ,
Tianfeng Lao - ,
Ziwu Zhang - ,
Zhengquan Su - ,
Yue Yu - , and
Hua Cao
This publication is free to access through this site. Learn More
November 7, 2024
HFIP-Mediated Synthesis of 4-Aryl-NH-1,2,3-Triazoles and 1,5-Disubstituted 1,2,3-Triazolyl Glycoconjugates
Manoj K. Jaiswal - ,
Mangal S. Yadav - ,
Shristy Maurya - ,
Danish Ansari - , and
Vinod K. Tiwari *
We herein report a multicomponent reaction for the synthesis of N-unsubstituted-1,2,3-triazoles and N-substituted-1,2,3 triazoles from the reaction of aldehydes, nitroalkanes, and sodium azides/glycosyl azides in the presence of 1,1,1,3,3,3-hexafluoroisopropanol, a hydrogen bond-donating reaction medium. This three-component reaction provides a metal-free strategy for sequentially forming one C–C and two C–N bonds in a one-pot fashion. One-pot mild reaction condition, operational simplicity, wide substrate scope, good functional group tolerance, easy purification, high reaction yields, and altogether excellent regioselectivity are the notable advantages of this 1,2,3-triazole-forming protocol. Moreover, this protocol provides practical access to the gram-scale synthesis of potent inhibitors of indoleamine 2,3-dioxygenase 1.
A Multicomponent [2+2+1] Cascade Cyclization to Synthesize Thiazol-2(3H)-one
Mingxu Wang - ,
Yuchen Gong - ,
Yaolian Shi - ,
Qihai Zhao - ,
Xiao-Jing Zhao - ,
Ganpeng Li *- , and
Yonghui He *
A multicomponent [2+2+1] tandem cyclization of alkynones with amines and water using potassium thiocyanate as electrolyte and raw material to access thiazol-2(3H)-ones has been developed. This transformation proceeded smoothly via electrocatalytic oxidative C–H bond thiolation, and nucleophilic cascade cyclization to build the (C–S/C–N) bonds to construct the C–O bond. The reaction avoided using transition metal catalysts or oxidation reagents, making it more sustainable and renewable.
Diamagnetic Precursor to Biradical by Means of a Thermal Trigger: A Head-to-Tail (N–O)2 Four-Membered Ring Formed in Naphthalene-1,8-diyl Bis(tert-butyl Nitroxide)
Rika Uesugi - ,
Rina Takano - , and
Takayuki Ishida *
The title compound was synthesized, and ESR and magnetic analysis revealed diamagnetic properties below 400 K. The crystal structure analysis clarified that the molecule possesses an approximate C2 symmetry with a head-to-tail (N–O)2 four-membered ring. The N···O distances are 2.349(4) – 2.374(4) Å, belonging to the class found in diamagnetic phases of dimerized nitroxide materials. A zero-field splitting pattern appeared in the solid-state ESR around 440 K on heating. The density functional theory (DFT) calculations supported the formation of a biradical.
Dehydrogenative Photocyclization of 3-Styryl Indoles to Fused Indole Systems
Yunus Taskesenligil - and
Nurullah Saracoglu *
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The synthesis of 5-aryl- or 5,6-diaryl-11H-benzo[a]carbazoles has been achieved from 3-styryl indoles through catalyst-free photoinitiated dehydrogenative cyclization transformation, providing a range of structurally diverse products in excellent yields under mild conditions. The protocol is also applicable to furan and thiophene samples. This Mallory-type reaction takes place in an argon atmosphere without external oxidants. Finally, detailed mechanistic studies were performed, and kinetic isotope effect experiments indicate that dehydrogenative annulation reaction involves photoinduced 6π-electrocyclic ring-closing and hydrogen evolution cascade processes.
Iron-Catalyzed One-Pot Cascade Reactions of Oximes with Inactivated Saturated Ketones: Entry to Highly Substituted Pyridines
Yan-Yun Liu *- and
Yu-Ting Zhai
An iron-catalyzed oxidative [3 + 3] annulation of oxime esters with inactivated saturated ketones is described. This cascade strategy allows one-step rapid synthesis of various structurally important pyridines through an oxidative dehydrogenation/annulation/oxidative aromatization sequence via direct α,β-dehydrogenation of simple saturated ketones followed by annulation with oximes. This method shows good functional group tolerance, readily accessible starting materials, a wide substrate scope, high chemoselectivity, and no need for extra stoichiometric oxidant and is also applicable to the late-stage functionalization of natural products.
Reductive Amination of Carbonyl C–C Bonds Enables Formal Nitrogen Insertion
Charis Amber - ,
Lucas T. Göttemann - ,
Ryan T. Steele - ,
Timothée M. Petitjean - , and
Richmond Sarpong *
Given its relevance across numerous fields, reductive amination is one of the oldest and most widely used methods for amine synthesis. As a cornerstone of synthetic chemistry, it has largely remained unchanged since its discovery over a century ago. Herein, we report the mechanistically driven development of a complementary reaction, which reductively aminates the C–C σ-bond of carbonyls, not the carbonyl C–O π-bond, generating value-added linear and cyclic 3° amines in a modular fashion. Critical to our success were mechanistic insights that enabled us to modulate the resting state of a borane catalyst, minimize deleterious disproportionation of a hydroxylamine nitrogen source, and control the migratory selectivity of a key nitrenoid reactive intermediate. Experiments support the reaction occurring through a reductive amination/reductive Stieglitz cascade, via a ketonitrone, which can be interrupted under catalyst control to generate valuable N,N-disubstituted hydroxylamines. The method reported herein enables net transformations that would otherwise require lengthy synthetic sequences using pre-existing technologies. This is highlighted by its application to a two-step protocol for the valorization of hydrocarbon feedstocks, the late-stage C–C amination of complex molecules, diversity-oriented synthesis of isomeric amines from a single precursor, and transposition of nitrogen to different positions within a heterocycle.
Palladium Catalyzed Cyanation of Diaryl Sulfoxides
Xianchao Qiu - ,
Guangcai Qu - ,
Benqiang Cui *- ,
Changsheng Cao *- , and
Yanhui Shi *
Aryl nitriles are highly versatile and useful compounds. A palladium-catalyzed cyanation of diaryl sulfoxides using bench-stable Zn(CN)2 as the cyanating reagent has been developed. The reaction proceeded well using Pd(OAc)2 as the catalyst with the inexpensive ligand PCy3 in the presence of t-BuONa. The method has a broad scope of substrates and is scalable. The regioselective cyanation of unsymmetrical diaryl sulfoxides was observed at the side of electron-deficient and more steric hindered aryl groups.
October 25, 2024
Synthesis of (Z)-Enediynes via Stereoinvertive Nucleophilic Substitution of (E)-Sulfonylethenes with Arylethynide, and Their Aggregation-Induced Optical Properties
Yuta Akagi - ,
Hikaru Watanabe - ,
Toshiki Sakami - ,
Sou Furumatsu - ,
Shunsuke Yamada - ,
Ryosuke Maki - ,
Yasuhiro Okuda - ,
Haruo Akashi - ,
Kan Wakamatsu - ,
Yoshihiro Kusano - , and
Akihiro Orita *
(Z)-Enediynes were successfully synthesized from a trio of terminal ethynes through consecutive three-step reactions: iodosulfonylation of ethyne with I2/PhSO2Na, followed by ethynylations of iodo and sulfonyl moieties of the resulting iodosulfonylethene via Sonogashira−Hagihara coupling and nucleophilic addition–elimination, respectively. The molecular structure of the obtained (Z)-enediyne was fully characterized by X-ray crystal structure analysis, revealing that the nucleophilic substitution of (E)-sulfonylethene with arylethynide underwent a selective stereoinversion. The (Z)-enediynes exhibited photoluminescence in both the solution and solid states (crystals and powders). Ph2N-substituted derivatives showed remarkable solvatofluorochromism, and upon replacing the solvent from toluene to acetonitrile, the emission color changed from blue to yellow.
October 24, 2024
Intrastrand Photo-Crosslinking of 5-Fluoro-2′-O-methyl-4-thiouridine-Modified Oligonucleotides and Its Implication for Fluorescence-Based Detection of DNA Sequences
Joanna Nowak-Karnowska *- ,
Katarzyna Taras-Goslinska - ,
Shozeb Haider - , and
Bohdan Skalski
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DNA photo-crosslinking reactions occur widely in biological systems and are often used as valuable tools in molecular biology. In this article, we demonstrate the application of an oligonucleotide 5-fluoro-2′-O-methyl-4-thiouridine (FSU)-containing probe for the fluorescent detection of specific DNA sequences. The design of the probe was predicated on studies of agents that could adversely affect its efficiency. The most important of these is the intrastrand photo-crosslinking of single-stranded oligodeoxynucleotides bearing FSU. Our research findings indicate that FSU after photoexcitation can react with nonadjacent bases; specifically, it can react with distant thymine and cytosine residues in the chain, forming fluorescent and nonfluorescent intrastrand crosslinks, respectively. In addition, partial photooxidation of the FSU residue to 5-fluorouridine was also observed. The results of the study are significant in terms of the use of FSU-labeled oligonucleotide probes in the fluorescence-based detection of specific DNA sequences because the creation of a fluorescent intrastrand crosslink could produce a false signal. To overcome this problem, replacing thymidine with deoxyuridine in the FSU-labeled oligonucleotide probe is proposed and tested.
October 23, 2024
AIE Active Imidazole-Stilbene Conjugated Fluorescent Probes: Illuminating Latent Fingerprints and Advancing Anticounterfeiting Technologies
Selin Manoj Kumar - ,
Sathishkumar Munusamy - ,
Saravanan Enbanathan - , and
Sathiyanarayanan Kulathu Iyer *
Aggregation-induced emission luminogens (AIEgens) are widely used in the realm of latent fingerprint visualization owing to their luminosity and resistance to photobleaching. However, challenges such as significant background interference and limited resolution hinder their rapid advancement. Consequently, there is a pressing need to improve the detailed visualization of latent fingerprint (LFP) imaging, particularly for analyzing level 3 details. To address this, we have designed donor–acceptor (D–A) type AIEgens named MMIMV, DMIMV, and TMIMV. These compounds exhibit robust emissions ranging from 481 to 552 nm and signify positive fluorosolvatochromism. When applied as powder dusting, these derivatives enable the fluorescence imaging of LFPs on various material substrates. The analysis of these imaged LFPs yields intricate details regarding fingerprint ridge patterns. Our results underscore the potential of highly emissive AIEgens MMIMV, DMIMV, and TMIMV as promising candidates for fingerprint visualization, thus offering significant implications for forensic investigations. Furthermore, these derivatives serve as effective fluorescent security inks for writing and drawing, presenting a novel avenue for robust anticounterfeiting applications.
October 16, 2024
Direct Synthesis of Saturated Alcohols from Conjugated Ketones Using NaBH4 and Catalytic Amount of CuCN in Ethanol: Additive Catalysis with a Lithium Salt or a Sodium Salt
Florian Berthiol - ,
Fabrice Thomas - ,
Cyrille Sabot - , and
Jean-Pierre Deprés *
A direct, efficient, and highly chemoselective synthesis of saturated alcohols through one-pot sequential 1,4- and 1,2-reduction of cyclic and acyclic conjugated ketones is reported. The saturated alcohols are obtained in very good yields using sodium borohydride (NaBH4) as a reducing agent and a catalytic amount of copper(I) cyanide (CuCN) in ethanol as a green solvent. This nontoxic solvent significantly favors full 1,4-reduction, as opposed to methanol. Selectivity is further enhanced by the combination of two additives (a lithium salt or a sodium salt, such as NaI).