ASAP (As Soon As Publishable)

We report the intermolecular (4 + 3) cycloadditions of oxetanyl and azetidinyl enolsilanes with different dienes by silylium catalysis to generate bicyclic scaffolds. These enolsilanes were competent to react with furans, cyclopentadiene, and 1,3-cyclohexadiene to deliver cycloadducts in up to 96% yields.

The synthesis of coumarin– and flavonoid–chalcone hybrids via Pd-catalyzed Heck-type coupling of arene diazonium salts and 8-allylcoumarins and −flavonoids is reported. The β-hydride elimination step proceeds with high regioselectivity if an OMOM-substituent is present at the position C7, adjacent to the allyl group. A selective allylic oxidation of the coupling products was accomplished using DDQ in the presence of silica to furnish the chalcones.

The Cu(MeCN)₄PF₆-catalyzed reaction of 1-(2-hydroxyphenyl)-propargyl alcohols with aryl/alkyl mercaptan and subsequent treatment with K₂CO₃ only offered 3-(alkylthio)benzofurans, whereas the stoichiometric-exceeding CuI-mediated reaction and subsequent treatment with DIPEA furnished 2-(alkylthiomethyl)benzofurans with high selectivity. The amount of Cu(I) salts plays a key role in selective formation. This unique protocol for the selective construction of the two series of benzofurans containing alkylthio group proved to be suitable for broad substrates 1 and 2 except for aliphatic alkynyl alcohols.

Silyl-phenanthroline (NN′Si) ligand ancillary iridium-catalyzed C(sp³)–H borylation is investigated theoretically. Density functional theory calculations clearly disclose that the (NN′Si)Ir^V(H)(Bpin)₃ (NN′Si = 6-[(di-tert-butylsilyl)methyl]-1,10-phenanthroline) complex is a resting state, and the (NN′Si)Ir^III(Bpin)₂ complex serves as an active species in the catalytic cycle. The remarkably high activity of this type of a catalyst arises from the rapid reductive elimination of HBpin from (NN′Si)Ir^V(H)(Bpin)₃ to generate the active species (NN′Si)Ir^III(Bpin)₂. The silyl group plays a crucial role in accelerating the crucial hydride-migration elementary step, which allows the isomerization of the (NN′Si)Ir^V(R)(H)(Bpin)₂ intermediate to achieve the C(sp³)–B reductive elimination and afford the borylated product. Although C(sp³)–H borylation with HBpin is thermodynamically unfavorable, the Ir-dihydride intermediate (NN′Si)Ir^V(H)₂(Bpin)₂ generated after product formation is slightly more stable than resting-state (NN′Si)Ir^V(H)(Bpin)₃ in this catalytic cycle, which is an important driving force for the HBpin reaction. Such success was not attained by many other traditional bidentate ligands. The unique regioselectivity of n-butyl ethyl ether and 2-methylheptane, induced by the NN′Si-pincer ligand, is well reproduced and the underlying reason for the selectivity is clearly elucidated.

A 3-step modular procedure combining carboxylic acids with acyl hydrazines provides access to medicinally relevant [1,2,4]-fused triazoles. Good to excellent yields are achieved with tolerance of aliphatic and aryl substituents as well as 5-, 6-, and 7-membered rings for the fused ring. Conditions that can avoid column chromatography and be applicable for both small scale discovery efforts as well as large scale development processes are demonstrated within.

A series of sulfonamido-substituted oxime-ethers have been synthesized by the reaction of donor–acceptor aziridines with aldo- and keto-oximes through C–C bond cleavage. Nucleophilic attack by an oxime hydroxyl group on the in situ-generated azomethine ylide rather than the routine cycloaddition reaction draws the novelty of the developed methodology. Selective protection of the oxime hydroxyl group is observed in the presence of phenolic −OH, which made the protocol enriched. In terms of a synthetic point of view, the uniqueness had been drawn further as it occurred at room temperature and within 30 min. Participation of a wide range of aziridines with a series of aldo- and keto-oximes made the developed methodology generalized by creating a novel library of substituted oxime-ethers.

The synthesis of photocaged substrates of the biologically important enzyme HMG-CoA reductase is reported. HMG-CoA bearing a p-hydroxyphenacyl (pHP) photocage moiety was synthesized in an overall yield of 14% over seven steps in addition to caged forms of mevalonate and mevaldehyde. The absorption maximum and quantum yield for the decaging of the photocaged compounds are dependent on pH with a λ_max of 330 nm and a ϕ of 5%, respectively, at pH 9.1 but a λ_max of 290 nm and a ϕ of 16%, respectively, at pH 6.7.

A method to access highly substituted dihydrothiophenes and the corresponding thiophenes is reported. This strategy complements traditional stepwise synthesis by coupling readily accessible bicyclic 1,2,3 thiadiazoles with alkenes in a modular, Rh-catalyzed formal (3 + 2) cycloaddition. Application of this method to an array of novel thiadiazoles generates densely functionalized dihydrothiophenes that can be subsequently oxidized to the corresponding thiophene products.

We report, for the first time, a visible-light-promoted Markovnikov hydroalkoxylation of α-trifluoromethyl alkenes with 1,2-diketones. This transformation proceeded smoothly in the presence of a tertiary amine (Et₃N), providing a series of enol ethers containing the trifluoromethylated tetrasubstituted center in moderate to excellent yields. In this protocol, hydrogen atom transfer between this amine and 1,2-diketone substrate affords a ketyl radical and an α-aminoalkyl radical, which engages in the formation of a radical anion of the α-CF₃ alkene via a single electron transfer. Notably, this protocol features several advantages including metal- and external photocatalyst-free, mild conditions, easy operation, a broad substrate scope, and good functional group tolerance. Moreover, by applying this new method, a great number of important deuterium-labeled organofluorine compounds can be readily prepared using CD₃OD as a deuterium source.

Distinctive, green, innovative, and well-organized photoinduced (metal- or photocatalyst-free) regioselective decarbonylative and decarboxylative C–O bond functionalization protocols to access aryl 2-aminobenzoates and 2-substituted benzoxazinone derivatives in excellent yields have been devised. These are achieved through the chemoselective scission of isatoic anhydride with ketones, diaryliodonium triflate, nitroalkene, phthalazinone, and phenol derivatives, which, in turn, served as the representative “electrophilic and nucleophilic” coupling partners. Control experiments and DFT calculations reveal that electrophilic radical-bearing coupling partners specifically follow the decarbonylation pathway, while nucleophilic radical-bearing conjugates facilitate the decarboxylation process. Thus, the devised methods represent the chemoselective fragmentation of isatoic anhydride, which occurs due to the electronic nature of the coupling partners. Again, the regioselective C–O/O–C bond formation is also a novel outcome of this methodology. We have also devised a green method for synthesizing 2-aminobenzoate-subtituted paracetamol through a decarboxylation route. A fluorescence quenching study indicates that phenyl 2-aminobenzoate specifically detects Fe(II) ions, exhibiting no reactivity toward various other metal ions. Additionally, transition-metal-catalyzed C–H bond functionalization of 2-substituted benzoxazinone with phenyl vinyl sulfone was performed at ease with significant yields, which appreciated the strategy developed by us.

The development of novel directing groups is a valuable strategy to secure the advancement of catalytic C–H functionalization. To illustrate the feasibility of urazoles as heterocyclic directing groups, we herein present the ruthenium(II)-catalyzed annulation of N–H/C–H bonds on N-aryl urazoles with vinylene carbonate. This transformation provides the rapid construction of triazolocinnoline derivatives as hemiaminal and dehydrated forms. A series of mechanistic investigations and post-transformations highlighted the amenability of the developed method.

A comprehensive theoretical investigation into the gold-catalyzed synthesis of polysubstituted pyrazolines and dihydropyridines from imines and methyl phenylpropiolate was conducted in this study. Three imines with distinct substituents were selected as model reactants. The computational outcomes reveal that four-membered intermediates generated from aza-enyne metathesis significantly affect the reaction selectivity. For nitrogen-centered NHCO₂Me substituents (series A), an outward ring opening occurs during the metathesis of the aza-alkyne. This leads to the formation of Z-butadiene intermediates and ultimately to pyrazoline products. Conversely, with an aromatic substituent at the nitrogen site (series B and C), an inward ring opening takes place. This results in E-butadiene intermediates and the synthesis of dihydropyridine derivatives. The dihydropyridine product’s configuration is determined by the aromatic ring’s substituent. Electron-donating groups tend to directly form 1,4-dihydropyridine through a 6π electrocyclization (series B). In contrast, strong electron-withdrawing substituents initially undergo azayne metathesis, followed by 6π electrocyclization to produce 1,2-dihydropyridine products (series C). Furthermore, the distinctive selectivities were investigated in depth using global reactivity index and distortion/interaction methods. This research may contribute to the design of more effective and selective protocols to access pyrazolines, dihydropyridines, and related compounds.

Herein, an approach for synthesizing 2-amino-3-substituted quinoline-4(3H)-ones and N-phenylbenzamide derivatives was developed. A series of quinoline-4(3H)-ones were synthesized through Ullmann cross-coupling under air conditions using inexpensive, readily available cyanamide with 2-bromo-N-phenylbenzamide as the starting material, copper iodide as the catalyst, and potassium tert-butoxide as the base in dimethyl sulfoxide. Noteworthy aspects of this method include its cost-effectiveness, the accessibility of raw materials, wide substrate applicability, ligand-free, open-air conditions, and simple operating procedures. Furthermore, investigations under similar reaction conditions further show that substituting water, alcohols, phenols, amines, or mercaptans for cyanamide as the nucleophilic reagent can be used to prepare 2-functionalized N-phenylbenzamides.

A direct electrochemical sulfonylation between indoles, inorganic sulfites, and alcohols was developed, in which various indoyl sulfonate esters were prepared efficiently. In this transformation, the easy-handle and cost-effective inorganic sulfite was disclosed to engage in a Csp²–H sulfonylation as the SO₂ source in an undivided electrolysis cell under mild conditions. In addition, the unexpected paired electrosynthesis has been achieved, owing to the dual role of inorganic sulfites, and led to a sulfonylation/reduction sequence to rapidly deliver hydroxyl substituted indole sulfonate esters.

Efficient synthesis of highly functionalized cyclopentenols with an exocyclic Z double bond was investigated via a (3 + 2) annulation reaction of 2-aroyl-D–A (donor–acceptor) cyclopropanes with alkynoates in the presence of DABCO. This synthetic approach featured a wide range of readily available 2-aroyl-substituted D–A cyclopropanes with diverse functional groups, densely substituted cyclopentenols with two stereogenic centers and an exocyclic double bond in a highly stereocontrolled manner and had operationally simple and mild reaction conditions.

We successfully reported selective C–H alkynylation of 2-pyridones with bromoalkynes under the catalysis of Co(III) or Ru(II). The alkynylation reaction used easily accessible bromoalkynes instead of high-valent iodine alkynes. There is a broad substrate scope of 2-pyridones with good yields. In addition, 2-pyridone can be used as a weakly directing group for C–H alkynylation of the proximal aryl C–H bond. This method offers an efficient approach for synthesizing diverse 2-pyridone derivatives, yielding alkynylated products up to 95% yield (>40 examples).

The functionalization of pyrazole-based compounds with dinitromethyl and N-hydroxytetrazole groups resulted in enhanced energetic properties. Two key compounds, 5-(dinitromethyl)-3,4-dinitro-1H-pyrazole (5) and 5-(3,4-dinitro-1H-pyrazol-5-yl)-1H-tetrazol-1-ol (7), along with their salts, were synthesized and evaluated for their energetic properties. Notably, the bishydroxylammonium salts 5b (D_v: 8778 m·s^–1; P: 33.1 GPa) and 7b (D_v: 8988 m·s^–1; P: 34.6 GPa) demonstrated an optimal balance between high detonation performance, good thermal stability, and low sensitivity, outperforming RDX, and positioning them as promising candidates for advanced secondary energetic materials.

Herein, is the reported synthesis and utilization of redox-active arylazoformamide (AAF) ligands in palladium(II) precatalysts for the Suzuki–Miyaura cross-coupling reaction. Complexes were formed from 2 equiv of an AAF ligand with Pd(II)Cl₂ in an appropriate solvent to create the square planar (AAF)₂PdCl₂ precatalyst. A thorough investigation of aryl bromides and arylboronic acids found that 1.0 mol % precatalyst with cesium carbonate (Cs₂CO₃) as base, 1,4-dioxane as solvent at 90 °C for 24 h allowed for excellent conversions to the biphenyl products (over 20 examples). To highlight the AAF ligand class, a set of comparison reactions were performed with redox-active arylazothioformamide ligands, i.e., an (ATF)₂PdCl₂ complex, other commercial palladium(II) complexes, and a Ni(II)Cl₂ arylazoformamide coordination complex₂. The (AAF)₂PdCl₂ complexes outperformed all of others tested. Mechanistically, it is proposed that the AAF ligand singly reduces to antiferromagnetically couple to the palladium(I) complex as a transmetalation intermediate. Ni-based precatalysts were found to be inactive for the studied Suzuki–Miyaura reaction. Overall, these ligand systems offer a unique look into redox-active palladium cross-coupling reactions as well as being phosphine-free and high yielding.

l-Guluronic acid is integral to the structures of alginates and to the pathogenesis of Pseudomonas aeruginosa. The exploitation of this hexose in both existing and new contexts is, however, limited by its prohibitively high commercial cost. We report on a short and efficient synthetic route to an l-GulA building block from a simple d-mannose thioglycoside. In this synthesis, the fluorine-directing effect is exploited to achieve a stereoselective C-5 epimerization. DFT calculations illuminate the substituent effects, which operate to confer this selectivity.

This study presents the application of a novel Fe-iminopyridine catalyst for the regioselective synthesis of oxazolidinones from carbon dioxide and aziridines. Our findings demonstrate that the Fe-iminopyridine catalyst containing imidazole functional group offers promising efficiency and facilitates a sustainable approach to green chemical synthesis at 50 °C and 10 bar CO₂ pressure in a single-component Fe catalyst system. Various aziridines with carboxylic acid-derived substituents were transformed into 5-carbonyl substituted oxazolidinone products. The regioselective synthesis of oxazolidinones followed by the reduction enhances their utility for the pharmaceutically valuable compounds.

Rongalite-mediated one-pot aminomethylation of heteroarenes using secondary amines/anilines has been developed. This transition-metal-free and mild reaction offers an efficient way to synthesize aminomethylated heteroaromatic compounds with high yields and broad functional group tolerance. Here, Rongalite plays a key role in generating the C1 unit source in situ, which triggers the aminomethylation process. This approach provides a library of aminomethylated imidazo[1,2-a]pyridines and imidazo[2,1-b]thiazoles.

Here we report a strategy that eliminates the need for photocatalysts and external additives, which provides an operable and mild method for halogen radical-enabled dearomatization of N-arylpropiolamides under an oxygen atmosphere at room temperature. The method is applicable to a wide range of substrates, extending beyond the limited scope of p-methoxyl N-phenylpropynamides. Furthermore, several functional synthetic intermediates and anticancer bioactive molecules were successfully derived from 3-halogenated azaspiro[4.5]trienones.

A visible-light-induced cascade radical trifluoromethylation/cyclization/dearomatization reaction between isocyanide-containing indoles and CF₃Br has been developed to afford trifluoromethylated spiro[indole-3,3-quinoline] and spiro [indole-3,3-pyrrole] derivatives in good yields. The utility of the process is demonstrated by a scale-up experiment. The mechanism was proposed based on the control experiments. The protocol constitutes a novel and efficient route for the synthesis of trifluoromethylated 3-spiroindolenines with advantages of good generality and practical applicability, broad substrate scope, and green energy source.

In this study, 5-(2-bromoaryl)tetrazoles were reacted with 1,3-diketones in DMF in the presence of a catalytic amount of magnetic Cu-MOF-74 (Fe₃O₄@SiO₂@Cu-MOF-74) and a base under microwave irradiation to yield the corresponding 1-aminoisoquinolines. The Fe₃O₄@SiO₂@Cu-MOF-74 catalyst could be easily recovered from the reaction mixture and reused four times without any significant loss of catalytic activity. An initial copper-catalyzed C(sp²)–C(sp³) bond formation accompanied by retro-Claisen deacylative cyclocondensation (for acyclic 1,3-diketones) and direct cyclocondensation (for cyclohexane-1,3-diones) is proposed as a key reaction pathway for this process. Cyclohexanone-fused 1-aminoisoquinolines produced from the reaction between 5-(2-bromoaryl)tetrazoles and cyclohexane-1,3-diones could be aromatized into 6-aminophenanthridines via a one-pot sequential process involving reduction, dehydration, and oxidation.

Herein we report two processes facilitated by diisopropylethylamine (DIPEA) for the synthesis of novel bridged polycyclic molecule analogues to natural products. The use of 4-bromoisochroman-3-one initiated an autoxidation reaction, followed by a Diels–Alder cycloaddition in the presence of electron-deficient dienophiles. Mechanistic studies revealed isochromane-3,4-dione as a key intermediate, which undergoes in situ dienolization/dearomatization followed by a [4 + 2] cycloaddition. Subsequently, the synthesis and direct application of isochromane-3,4-diones in the Diels–Alder reaction enabled the development of an alternative method with an enhanced efficiency and improved atom economy. In addition to chalcones, other enones and common electron-poor alkenes, bearing ester, nitro and cyano electron-withdrawing groups (including both terminal, cis acyclic and cyclic alkenes), were successfully reacted. The mechanism was also investigated, and a subsequent reductive ring opening was successfully carried out.

A highly convergent and scalable second-generation synthesis of the fully functionalized HIJKLMN-ring segment of Caribbean ciguatoxin C-CTX-1, the primary toxin responsible for ciguatera fish poisoning in the Caribbean Sea and the Northeast Atlantic regions, has been accomplished. Key aspects of the synthetic approach include the efficient syntheses of the HI- and KLM-ring fragments on gram scales, a convergent fragment coupling toward the HIJKLM-ring skeleton based on the Suzuki–Miyaura coupling strategy, and optimized iron hydride-catalyzed hydrogen atom transfer-mediated olefin coupling conditions for constructing the N-ring.

The site-selective functionalization of aromatic compounds via C–H activation has emerged as a popular tool in organic synthesis. In this study, we report a regioselective coupling of maleimide to 2-arylbenzo[d]thiazoles in the presence of a rhodium(III) catalyst. Depending upon the nature of the substituent (R²-group) present in the maleimide substrate, either mono- or bis-1,4-addition products were observed in this methodology. In the case of R² = aryl, cyclohexyl, and tert-butyl, mono coupling was observed, whereas substituents, such as methyl, ethyl, benzyl, and methyl thiophene, provided bis coupling as the major products. Similar selectivity was also observed in the case of 2-arylbenzo[d]oxazoles.

We report an unexpected gold-catalyzed 5C reaction of type II diene-ynenes to synthesize dihydrosemibullvalenes, which are potential bioisosteres for drug discovery. This 5C reaction occurs through a sequence of elementary reactions of cyclopropanation/Cope rearrangement/carbon shift/cyclopropanation/C–H insertion (shortened here as the 5C reaction), supported by quantum chemistry calculations. Mechanistic studies have also been applied to answer why type-II diene-ynenes cannot access seven-membered carbocycles-embedded bridged molecules under the gold catalysis, finding that the chair-like Cope rearrangement transition state (not the traditional boat-like transition state) is the key to the change of regiochemistry.

A triazinyluronium-based dehydrative condensing reagent, 2-(4,6-dimethoxy-1,3,5-triazin-2-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (DMT-TU), has been developed. Unlike commonly used guanidinium- and uronium-based reagents, DMT-TU does not contain high-energy N–N and N–O bonds, reducing its explosivity, as suggested by differential scanning calorimetry. Using DMT-TU in the presence of ⁱPr₂EtN at room temperature, carboxylic acids and amines were effectively converted to their corresponding amides. Additionally, peptide bond formation with DMT-TU exhibited suppressed racemization ratios.

This study presents a greener approach to the visible-light-induced micellar-catalyzed diastereoselective iodosulfonylation of cyclopropenes in a water medium. Remarkably, this process operates without a photocatalyst. Instead, it utilizes an electron-donor–acceptor complex formed between sulfonyl chloride and sodium iodide. This method is highly efficient and broadly applicable for both aromatic and aliphatic sulfonyl chlorides. Furthermore, this protocol enables the transformation of iodosulfonated cyclopropanes into sulfonated cyclopropenes, highlighting its substantial value as a versatile and powerful tool in synthetic chemistry.

In anodic electrosynthesis, cation radicals are often key intermediates that can be highly susceptible to nucleophilic attack and/or deprotonation, with the selectivity of competing pathways dictating product yield. In this work, we computationally investigate the role of methanol in alcohol trapping of enol ether cation radicals for which substantial modulation of the reaction yield by the solvent environment was previously observed. Reaction free energies computed for intramolecular coupling unequivocally demonstrate that the key intramolecular alcohol attack on the oxidized enol ether group is catalyzed by methanol, proceeding through overall second-order kinetics. Methanol complexation with the formed oxonium ion group gives rise to a “Zundel-like”, shared proton conformation, providing a critical driving force for the intramolecular alcohol attack. Free energies computed for methanol solvent attack of enol ether cation radicals demonstrate an analogous mechanism and overall third-order kinetics, due to similar complexation from a secondary methanol molecule to form the “Zundel-like”, shared proton conformation. As catalyzed by methanol, both intramolecular alcohol attack and methanol attack on the oxidized enol ether group are barrierless or low-barrier reactions, with kinetic competition dictated by the conformational free energy profile of the cation radical substrate and the difference in reaction rate orders.

A practical nickel-catalyzed decarboxylative cross-coupling of N-hydroxyphthalimide esters with 1,4-diiodobenzene analogues has been developed. Under mild reaction conditions, a series of structurally interesting 1,4-dialkylbenzene analogues have been accessed with good functional group tolerance, which are versatile precursors for organic synthesis and a kind of important unit for bioactive molecules, polymers, and other materials. The synthetic application of this methodology was demonstrated by the synthesis of 3-6-dialkylcarbazole derivatives.

The umpolung of N-tosylhydrazones was reported for the first time. Synthesis of N-cyano tosylhydrazones was developed, and various N-cyano tosylhydrazones were prepared in good yields. An umpolung N-tosylhydrazones mechanism was proposed. Meanwhile, the [3,3]-sigmatropic rearrangement of N-cyano tosylhydrazones was examined, and the corresponding 2-aminoimidazoles were given.

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).

An efficient method for the synthesis of heterodiarylmethanes through the coupling of imidazo[1,2-a]pyridines and heteroarenes using indoles employing rongalite as a methylenating reagent has been developed. This regioselective C–H functionalization provides a wide range of heterodiarylmethanes of imidazo[1,2-a]pyridines and imidazo[2,1-b]thiazole. Here, rongalite plays a crucial role in generating a C1 unit in situ, which triggers the heterodiarylmethylation process. The use of inexpensive rongalite (ca. $0.03/1 g), mild reaction conditions, and gram-scale synthesis are some of the key features of this methodology.

An innovative solution that overcomes the long-standing inherently low efficiency in N-heterocyclic carbene-catalyzed aerobic oxidation of aldehydes is reported. This solution included the design and synthesis of a novel polymerized catalyst and the utilization of a flow reactor. The unprecedentedly high efficiency achieved via this protocol makes it synthetically applicable. A total turnover number (TON) of 26,300 was achieved based on recycling experiments (runs). The highest TON in a single run could be up to 2475 with a turnover frequency (TOF) of 208 h^–1, far superior to its traditional counterpart, in which a typical TON ranges from 20 to 100 with a TOF of less than 10 h^–1. The catalyst has been recycled over 50 times and is still fully active. The success was attributed to the discovery of hidden reactivity, which was observed for the first time as an autoacceleration in the reaction rate during kinetic investigations. The research also provided concrete evidence supporting the conclusion that radical intermediates played crucial roles in the catalytic cycle by having a determinative impact on the overall reaction rate.

Visible light-promoted α-aminoalkyl radical-triggered α-aminoalkylation and α-diaminoalkylation of Morita-Baylis–Hillman acetates with N-methyl arylamines to synthesize N-containing alkyl acrylates and γ,γ-diaminobutyl esters was reported. Photoinduced α-aminoalkylation is carried out with Na₂-eosin Y as an organophotocatalyst at room temperature under metal- and oxidant-free conditions. In particular, the α-diaminoalkylation is performed via α-aminoalkyl radical addition/elimination followed by a catalyst-controlled selective α-aminoalkyl radical addition strategy in one step under the [Ir(dtbbpy)(bpy)₂)]PF₆/KF catalytic system. The reaction is highly atom- and step-economic, with high selectivity, furnishing N-containing alkyl acrylates and butyl esters in moderate to good yields with wide substrate scope.

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.

Chiral diphosphines with a biphenyl bridge and the chirality borne by the phosphorus atoms and not due to the atropoisomery of the biaryl backbone have been scarcely studied. Herein, we report the asymmetric synthesis of the (S,S)-2,2′-bis(ferrocenylphenylphosphino)biphenyl (BipheP_Fc*) ligand and its application in Rh-catalyzed hydrogenation. The synthesis was based on the enantioselective preparation of P-chirogenic ferrocenyl(o-bromophenyl)phenylphosphine by the reaction of sec-phosphine-borane with 1,2-dibromobenzene and its homocoupling into BipheP_Fc*. Hydrogenations catalyzed by the Rh/BipheP_Fc* complex led to enantioselectivities of ≤96%.

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 S_N2′ 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.

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.

Electrooxidative transformations frequently rely on proton reduction as the terminal electron sink. However, this cathodic counterreaction can be slow in organic solvents and can operate at reducing potentials that are incompatible with catalysts and reagents needed for oxidative reactions. We report aminoborate adducts as redox mediators for proton reduction that operate at mild reducing potentials. This reliable cathodic couple ultimately enables successful oxidative organic transformations, including chlorodeborylation, developed herein, and Cu-catalyzed Chan–Lam coupling, reported previously by our group. Pyridinium borate adducts formed during electrooxidative chlorination of aryl trifluoroborates serve as easily reduced complexes (−1.1 V vs Fc/Fc⁺) to catalyze proton reduction. Reactions that promote the formation of borate adducts result in high yields, operate at low cell potentials, suppress aryl trifluoroborate decomposition, and mitigate electrode passivation. These studies illustrate the utility of Lewis acid–base complexes in cathodic counterreactions and underscore the importance of developing both anodic and cathodic reactions in electrosynthesis.

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 pK_a 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 pK_a modulation amplitudes were accomplished that surpass those previously reported.

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.

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.

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.

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.

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.

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.

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.

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 KO^tBu and 1.

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.

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.

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.

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.

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.

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.

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.

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.

Nucleophilic aromatic substitutions (S_NAr) 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 S_NAr 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.

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.

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.

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.

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.

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.

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 ≤ λ_em ≤ 513 nm, MeCN), which shift to the red side when converted to their water-soluble salts by alkylation with MeI (478 ≤ λ_em ≤ 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.

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.

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.

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 (pK_a) and lipophilicity (Log P) measurements, X-ray diffraction studies, and exit vector plot (EVP) analysis.

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.

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.

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.

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.