ACS Publications. Most Trusted. Most Cited. Most Read
Radical-Based Regioselective C–H Functionalization of Electron-Deficient Heteroarenes: Scope, Tunability, and Predictability

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Am. Chem. Soc. 2013, 135, 32, 12122-12134
    Article

    Radical-Based Regioselective C–H Functionalization of Electron-Deficient Heteroarenes: Scope, Tunability, and Predictability
    Click to copy article linkArticle link copied!

    View Author Information
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States
    [email protected]; [email protected]
    Other Access OptionsSupporting Information (2)

    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2013, 135, 32, 12122–12134
    Click to copy citationCitation copied!
    https://doi.org/10.1021/ja406223k
    Published July 17, 2013
    Copyright © 2013 American Chemical Society
    Request reuse permissions

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    Radical addition processes can be ideally suited for the direct functionalization of heteroaromatic bases, yet these processes are only sparsely used due to the perception of poor or unreliable control of regiochemistry. A systematic investigation of factors affecting the regiochemistry of radical functionalization of heterocycles using alkylsulfinate salts revealed that certain types of substituents exert consistent and additive effects on the regioselectivity of substitution. This allowed us to establish guidelines for predicting regioselectivity on complex π-deficient heteroarenes, including pyridines, pyrimidines, pyridazines, and pyrazines. Since the relative contribution from opposing directing factors was dependent on solvent and pH, it was sometimes possible to tune the regiochemistry to a desired result by modifying reaction conditions. This methodology was applied to the direct, regioselective introduction of isopropyl groups into complex, biologically active molecules, such as diflufenican (44) and nevirapine (45).

    Copyright © 2013 American Chemical Society

    Subjects

    what are subjects

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Supporting Information

    Click to copy section linkSection link copied!

    Experimental procedures and analytical data for all new compounds, including 1H, 13C, and 19F NMR files. This material is available free of charge via the Internet at http://pubs.acs.org.

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    Click to copy section linkSection link copied!
    Citation Statements
    Explore this article's citation statements on scite.ai
    powered by  Scite

    This article is cited by 295 publications.

    1. Jiatian Zhuo, Jinshan Liu, Min Zhou, Lin Ma, Min Zhang. Visible-Light-Induced C(sp3)-H Activation for Minisci Alkylation of Pyrimidines Using CHCl3 as Radical Source and Oxidant. The Journal of Organic Chemistry 2025, 90 (3) , 1400-1410. https://doi.org/10.1021/acs.joc.4c02855
    2. Daniel C. Schultz, Upendra Rathnayake, Renn A. Duncan, Alexa E. Richardson, Aaron M. Bender. Synthesis of the Dimeric Diarylheptanoids Alpinidinoid C and Officinine B Enabled by Blue-Light-Mediated Triple-Minisci-Type Alkylation. Organic Letters 2024, 26 (42) , 9028-9033. https://doi.org/10.1021/acs.orglett.4c03227
    3. Zhan-Jie Wang, Jun-Jie Chen, Huan-Ming Huang. Site-Selective Pyridine Carbamoylation Enabled by Consecutive Photoinduced Electron Transfer. ACS Catalysis 2024, 14 (20) , 15521-15527. https://doi.org/10.1021/acscatal.4c04032
    4. Serhii Holovach, Illia Poroshyn, Kostiantyn P. Melnykov, Oleksandr S. Liashuk, Olena O. Pariiska, Sergey V. Kolotilov, Alexander B. Rozhenko, Dmytro M. Volochnyuk, Oleksandr O. Grygorenko. Parallel Minisci Reaction of gem-Difluorocycloalkyl Building Blocks. ACS Organic & Inorganic Au 2024, 4 (4) , 424-431. https://doi.org/10.1021/acsorginorgau.4c00028
    5. Xingyu Lei, Yihan Wang, Shanshan Ma, Peng Jiao. Purple Light-Promoted Coupling of Bromopyridines with Grignard Reagents via SET. The Journal of Organic Chemistry 2024, 89 (10) , 7148-7155. https://doi.org/10.1021/acs.joc.4c00525
    6. Jeff Shen, Nicholas A. White, Qingping Tian, Lauren E. Sirois, Haiming Zhang, Francis Gosselin. Manufacturing Process for 6-Bromo-N,N-bis(4-methoxybenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine, a Key Intermediate in the Synthesis of KRAS G12C Inhibitor Divarasib. Organic Process Research & Development 2024, 28 (1) , 92-101. https://doi.org/10.1021/acs.oprd.3c00366
    7. Li-Chen Xu, Xiao-Di Ma, Kun-Ming Liu, Xin-Fang Duan. Chemo- and Regioselective Alkylation of Pyridine N-Oxides with Titanacyclopropanes. Organic Letters 2023, 25 (48) , 8640-8644. https://doi.org/10.1021/acs.orglett.3c03469
    8. Fang Fang, Jie Xia, Siying Quan, Shanping Chen, Guo-Jun Deng. Metal- and Solvent-Free Synthesis of Substituted Pyrimidines via an NH4I-Promoted Three-Component Tandem Reaction. The Journal of Organic Chemistry 2023, 88 (20) , 14697-14707. https://doi.org/10.1021/acs.joc.3c01700
    9. P. David Bacoş, Antti S. K. Lahdenperä, Robert J. Phipps. Discovery and Development of the Enantioselective Minisci Reaction. Accounts of Chemical Research 2023, 56 (14) , 2037-2049. https://doi.org/10.1021/acs.accounts.3c00247
    10. Ashley Dang-Nguyen, Kristine C. Legaspi, Connor T. McCarty, Diane K. Smith, Jeffrey Gustafson. A Light-Promoted Innate Trifluoromethylation of Pyridones and Related N-Heteroarenes. Organic Letters 2023, 25 (26) , 4898-4902. https://doi.org/10.1021/acs.orglett.3c01710
    11. Celena M. Josephitis, Hillary M. H. Nguyen, Andrew McNally. Late-Stage C–H Functionalization of Azines. Chemical Reviews 2023, 123 (12) , 7655-7691. https://doi.org/10.1021/acs.chemrev.2c00881
    12. Claire G. Page, Jingzhe Cao, Daniel G. Oblinsky, Samantha N. MacMillan, Shiva Dahagam, Ruth M. Lloyd, Simon J. Charnock, Gregory D. Scholes, Todd K. Hyster. Regioselective Radical Alkylation of Arenes Using Evolved Photoenzymes. Journal of the American Chemical Society 2023, 145 (21) , 11866-11874. https://doi.org/10.1021/jacs.3c03607
    13. Emilien Le Saux, Eleni Georgiou, Igor A. Dmitriev, Will C. Hartley, Paolo Melchiorre. Photochemical Organocatalytic Functionalization of Pyridines via Pyridinyl Radicals. Journal of the American Chemical Society 2023, 145 (1) , 47-52. https://doi.org/10.1021/jacs.2c12466
    14. Myojeong Kim, Yejin Koo, Sungwoo Hong. N-Functionalized Pyridinium Salts: A New Chapter for Site-Selective Pyridine C–H Functionalization via Radical-Based Processes under Visible Light Irradiation. Accounts of Chemical Research 2022, 55 (20) , 3043-3056. https://doi.org/10.1021/acs.accounts.2c00530
    15. Ramkrishna Laha, Twinkle I. Patel, Matthew J. Moschitto. Desulfinative Alkylation of Heteroarenes via an Electrostatic Electron Donor–Acceptor Complex. Organic Letters 2022, 24 (40) , 7394-7399. https://doi.org/10.1021/acs.orglett.2c02932
    16. Jacob O. Rothbaum, Alessandro Motta, Yosi Kratish, Tobin J. Marks. Chemodivergent Organolanthanide-Catalyzed C–H α-Mono-Borylation of Pyridines. Journal of the American Chemical Society 2022, 144 (37) , 17086-17096. https://doi.org/10.1021/jacs.2c06844
    17. Xin-Yue Zhou, Ming Zhang, Zhong Liu, Jia-Hao He, Xiao-Chen Wang. C3-Selective Trifluoromethylthiolation and Difluoromethylthiolation of Pyridines and Pyridine Drugs via Dihydropyridine Intermediates. Journal of the American Chemical Society 2022, 144 (32) , 14463-14470. https://doi.org/10.1021/jacs.2c06776
    18. Liuzhou Gao, Xueting Liu, Guoao Li, Shengda Chen, Jia Cao, Guoqiang Wang, Shuhua Li. 1,2-Silylpyridylation Reaction of Aryl Alkenes with Silylboronate. Organic Letters 2022, 24 (31) , 5698-5703. https://doi.org/10.1021/acs.orglett.2c02074
    19. Jun-Bao Ma, Xia Zhao, Dongju Zhang, Shi-Liang Shi. Enantio- and Regioselective Ni-Catalyzed para-C–H Alkylation of Pyridines with Styrenes via Intermolecular Hydroarylation. Journal of the American Chemical Society 2022, 144 (30) , 13643-13651. https://doi.org/10.1021/jacs.2c04043
    20. Zhong Liu, Jia-Hao He, Ming Zhang, Zhu-Jun Shi, Han Tang, Xin-Yue Zhou, Jun-Jie Tian, Xiao-Chen Wang. Borane-Catalyzed C3-Alkylation of Pyridines with Imines, Aldehydes, or Ketones as Electrophiles. Journal of the American Chemical Society 2022, 144 (11) , 4810-4818. https://doi.org/10.1021/jacs.2c00962
    21. Jianbin Li, Chia-Yu Huang, Jing-Tan Han, Chao-Jun Li. Development of a Quinolinium/Cobaloxime Dual Photocatalytic System for Oxidative C–C Cross-Couplings via H2 Release. ACS Catalysis 2021, 11 (22) , 14148-14158. https://doi.org/10.1021/acscatal.1c04073
    22. Xue-Qiang Chu, Danhua Ge, Yan-Ying Cui, Zhi-Liang Shen, Chao-Jun Li. Desulfonylation via Radical Process: Recent Developments in Organic Synthesis. Chemical Reviews 2021, 121 (20) , 12548-12680. https://doi.org/10.1021/acs.chemrev.1c00084
    23. Jin Choi, Gabriele Laudadio, Edouard Godineau, Phil S. Baran. Practical and Regioselective Synthesis of C-4-Alkylated Pyridines. Journal of the American Chemical Society 2021, 143 (31) , 11927-11933. https://doi.org/10.1021/jacs.1c05278
    24. Eduardo de Pedro Beato, Davide Spinnato, Wei Zhou, Paolo Melchiorre. A General Organocatalytic System for Electron Donor–Acceptor Complex Photoactivation and Its Use in Radical Processes. Journal of the American Chemical Society 2021, 143 (31) , 12304-12314. https://doi.org/10.1021/jacs.1c05607
    25. Edwin Alfonzo, Sudhir M. Hande. α-Heteroarylation of Thioethers via Photoredox and Weak Brønsted Base Catalysis. Organic Letters 2021, 23 (15) , 6115-6120. https://doi.org/10.1021/acs.orglett.1c02151
    26. Kevin D. Freeman-Cook, Robert L. Hoffman, Douglas C. Behenna, Britton Boras, Jordan Carelli, Wade Diehl, Rose Ann Ferre, You-Ai He, Andrea Hui, Buwen Huang, Nanni Huser, Rhys Jones, Susan E. Kephart, John Lapek, Michele McTigue, Nichol Miller, Brion W. Murray, Asako Nagata, Lisa Nguyen, Sherry Niessen, Sacha Ninkovic, Inish O’Doherty, Martha A. Ornelas, James Solowiej, Scott C. Sutton, Khanh Tran, Elaine Tseng, Ravi Visswanathan, Meirong Xu, Luke Zehnder, Qin Zhang, Cathy Zhang, Stephen Dann. Discovery of PF-06873600, a CDK2/4/6 Inhibitor for the Treatment of Cancer. Journal of Medicinal Chemistry 2021, 64 (13) , 9056-9077. https://doi.org/10.1021/acs.jmedchem.1c00159
    27. Rupert S. J. Proctor, Padon Chuentragool, Avene C. Colgan, Robert J. Phipps. Hydrogen Atom Transfer-Driven Enantioselective Minisci Reaction of Amides. Journal of the American Chemical Society 2021, 143 (13) , 4928-4934. https://doi.org/10.1021/jacs.1c01556
    28. Lawrence Barrett, Fatoumata Ide Seyni, Mallikharjuna Rao Komarneni, John A. Zapata-Hincapie, Daniel T. Glatzhofer, Brian P. Grady, Steven Crossley. Anisotropically Functionalized Nanotube Anchors for Improving the Mechanical Strength of Immiscible Polymer Composites. ACS Applied Nano Materials 2021, 4 (1) , 580-589. https://doi.org/10.1021/acsanm.0c02886
    29. Savio Cardoza, Manoj Kumar Shrivash, Parthasarathi Das, Vibha Tandon. Strategic Advances in Sequential C-Arylations of Heteroarenes. The Journal of Organic Chemistry 2021, 86 (2) , 1330-1356. https://doi.org/10.1021/acs.joc.0c02151
    30. Kristaps Ermanis, Avene C. Colgan, Rupert S. J. Proctor, Barbara W. Hadrys, Robert J. Phipps, Jonathan M. Goodman. A Computational and Experimental Investigation of the Origin of Selectivity in the Chiral Phosphoric Acid Catalyzed Enantioselective Minisci Reaction. Journal of the American Chemical Society 2020, 142 (50) , 21091-21101. https://doi.org/10.1021/jacs.0c09668
    31. Nikolaos Papaioannou, M. Jonathan Fray, Andreas Rennhack, Thomas J. Sanderson, Jamie E. Stokes. Regioselective Amidomethylation of 4-Chloro-3-fluoropyridine by Metalation and Minisci-Type Reactions. The Journal of Organic Chemistry 2020, 85 (19) , 12067-12079. https://doi.org/10.1021/acs.joc.0c01168
    32. Woohyun Jo, Seung-yeol Baek, Chiwon Hwang, Joon Heo, Mu-Hyun Baik, Seung Hwan Cho. ZnMe2-Mediated, Direct Alkylation of Electron-Deficient N-Heteroarenes with 1,1-Diborylalkanes: Scope and Mechanism. Journal of the American Chemical Society 2020, 142 (30) , 13235-13245. https://doi.org/10.1021/jacs.0c06827
    33. Wenkun Luo, Yongjie Yang, Bo Liu, Biaolin Yin. Iron-Catalyzed Oxidative Decarbonylative α-Alkylation of Acyl-Substituted Furans with Aliphatic Aldehydes as the Alkylating Agents. The Journal of Organic Chemistry 2020, 85 (14) , 9396-9404. https://doi.org/10.1021/acs.joc.0c01002
    34. Yonghoon Moon, Wooseok Lee, Sungwoo Hong. Visible-Light-Enabled Ortho-Selective Aminopyridylation of Alkenes with N-Aminopyridinium Ylides. Journal of the American Chemical Society 2020, 142 (28) , 12420-12429. https://doi.org/10.1021/jacs.0c05025
    35. Sungwoo Jung, Sanghoon Shin, Seongjin Park, Sungwoo Hong. Visible-Light-Driven C4-Selective Alkylation of Pyridinium Derivatives with Alkyl Bromides. Journal of the American Chemical Society 2020, 142 (26) , 11370-11375. https://doi.org/10.1021/jacs.0c04499
    36. Aili Feng, Yiying Yang, Yanhong Liu, Cuihuan Geng, Rongxiu Zhu, Dongju Zhang. Mechanism and Origins of Enantio- and Regioselectivities in Catalytic Asymmetric Minisci-Type Addition to Heteroarenes. The Journal of Organic Chemistry 2020, 85 (11) , 7207-7217. https://doi.org/10.1021/acs.joc.0c00597
    37. Sheng Zhang, Lijun Li, Xinru Li, Junqi Zhang, Kun Xu, Guigen Li, Michael Findlater. Electroreductive 4-Pyridylation of Electron-deficient Alkenes with Assistance of Ni(acac)2. Organic Letters 2020, 22 (9) , 3570-3575. https://doi.org/10.1021/acs.orglett.0c01014
    38. Harrison A. Mills, Joshua L. Martin, Arnold L. Rheingold, Alexander M. Spokoyny. Oxidative Generation of Boron-Centered Radicals in Carboranes. Journal of the American Chemical Society 2020, 142 (10) , 4586-4591. https://doi.org/10.1021/jacs.0c00300
    39. Nenad Manevski, Lloyd King, William R. Pitt, Fabien Lecomte, Francesca Toselli. Metabolism by Aldehyde Oxidase: Drug Design and Complementary Approaches to Challenges in Drug Discovery. Journal of Medicinal Chemistry 2019, 62 (24) , 10955-10994. https://doi.org/10.1021/acs.jmedchem.9b00875
    40. Zhen Wang, Jianyang Dong, Yanan Hao, Yongqiang Li, Yuxiu Liu, Hongjian Song, Qingmin Wang. Photoredox-Mediated Minisci C–H Alkylation Reactions between N-Heteroarenes and Alkyl Iodides with Peroxyacetate as a Radical Relay Initiator. The Journal of Organic Chemistry 2019, 84 (24) , 16245-16253. https://doi.org/10.1021/acs.joc.9b02848
    41. Jolene P. Reid, Rupert S. J. Proctor, Matthew S. Sigman, Robert J. Phipps. Predictive Multivariate Linear Regression Analysis Guides Successful Catalytic Enantioselective Minisci Reactions of Diazines. Journal of the American Chemical Society 2019, 141 (48) , 19178-19185. https://doi.org/10.1021/jacs.9b11658
    42. Sungwoo Jung, Hyeonyeong Lee, Yonghoon Moon, Hoi-Yun Jung, Sungwoo Hong. Site-Selective C–H Acylation of Pyridinium Derivatives by Photoredox Catalysis. ACS Catalysis 2019, 9 (11) , 9891-9896. https://doi.org/10.1021/acscatal.9b03367
    43. Liuzhou Gao, Guoqiang Wang, Jia Cao, Hui Chen, Yuming Gu, Xueting Liu, Xu Cheng, Jing Ma, Shuhua Li. Lewis Acid-Catalyzed Selective Reductive Decarboxylative Pyridylation of N-Hydroxyphthalimide Esters: Synthesis of Congested Pyridine-Substituted Quaternary Carbons. ACS Catalysis 2019, 9 (11) , 10142-10151. https://doi.org/10.1021/acscatal.9b03798
    44. Inwon Kim, Gyumin Kang, Kangjae Lee, Bohyun Park, Dahye Kang, Hoimin Jung, Yu-Tao He, Mu-Hyun Baik, Sungwoo Hong. Site-Selective Functionalization of Pyridinium Derivatives via Visible-Light-Driven Photocatalysis with Quinolinone. Journal of the American Chemical Society 2019, 141 (23) , 9239-9248. https://doi.org/10.1021/jacs.9b02013
    45. Gabriel dos Passos Gomes, Alexander Wimmer, Joel M. Smith, Burkhard König, Igor V. Alabugin. CO2 or SO2: Should It Stay, or Should It Go?. The Journal of Organic Chemistry 2019, 84 (10) , 6232-6243. https://doi.org/10.1021/acs.joc.9b00503
    46. Sadhanendu Samanta, Alakananda Hajra. Mn(II)-Catalyzed C–H Alkylation of Imidazopyridines and N-Heteroarenes via Decarbonylative and Cross-Dehydrogenative Coupling. The Journal of Organic Chemistry 2019, 84 (7) , 4363-4371. https://doi.org/10.1021/acs.joc.9b00366
    47. Joel M. Smith, Janice A. Dixon, Justine N. deGruyter, Phil S. Baran. Alkyl Sulfinates: Radical Precursors Enabling Drug Discovery. Journal of Medicinal Chemistry 2019, 62 (5) , 2256-2264. https://doi.org/10.1021/acs.jmedchem.8b01303
    48. Noah B. Bissonnette, Michael J. Boyd, Gregory D. May, Simon Giroux, Philippe Nuhant. C–H Functionalization of Heteroarenes Using Unactivated Alkyl Halides through Visible-Light Photoredox Catalysis under Basic Conditions. The Journal of Organic Chemistry 2018, 83 (18) , 10933-10940. https://doi.org/10.1021/acs.joc.8b01589
    49. Xiao-Jing Wei, Timothy Noël. Visible-Light Photocatalytic Difluoroalkylation-Induced 1, 2-Heteroarene Migration of Allylic Alcohols in Batch and Flow. The Journal of Organic Chemistry 2018, 83 (18) , 11377-11384. https://doi.org/10.1021/acs.joc.8b01624
    50. Jacob M. Ganley, Melodie Christensen, Yu-hong Lam, Zhengwei Peng, Angie R. Angeles, Charles S. Yeung. Metal- and Acid-Free C–H Formylation of Nitrogen Heterocycles: Using Trioxane as an Aldehyde Equivalent Enabled by an Organic-Soluble Oxidant. Organic Letters 2018, 20 (18) , 5752-5756. https://doi.org/10.1021/acs.orglett.8b02453
    51. Joel M. Smith, Stephen J. Harwood, Phil S. Baran. Radical Retrosynthesis. Accounts of Chemical Research 2018, 51 (8) , 1807-1817. https://doi.org/10.1021/acs.accounts.8b00209
    52. Rongkang Wang, Lvqi Jiang, Wenbin Yi. Metal-Free Electrophilic Trifluoroethylthiolation with NaSO2CH2CF3. The Journal of Organic Chemistry 2018, 83 (15) , 7789-7798. https://doi.org/10.1021/acs.joc.8b00676
    53. Rory C. McAtee, Joel W. Beatty, Christopher C. McAtee, Corey R. J. Stephenson. Radical Chlorodifluoromethylation: Providing a Motif for (Hetero)arene Diversification. Organic Letters 2018, 20 (12) , 3491-3495. https://doi.org/10.1021/acs.orglett.8b01249
    54. Vincent L. Revil-Baudard, Jean-Pierre Vors, Samir Z. Zard. Xanthate-Mediated Incorporation of Quaternary Centers into Heteroarenes. Organic Letters 2018, 20 (12) , 3531-3535. https://doi.org/10.1021/acs.orglett.8b01299
    55. Ryu Sakamoto, Tomomi Yoshii, Hiroyuki Takada, Keiji Maruoka. A Synthetic Route to Sodium α-Aminoalkanesulfinates and Their Application in the Generation of α-Aminoalkyl Radicals for Radical Addition Reactions. Organic Letters 2018, 20 (7) , 2080-2083. https://doi.org/10.1021/acs.orglett.8b00621
    56. Takahiro Shirai, Motomu Kanai, Yoichiro Kuninobu. 2-Position-Selective C–H Perfluoroalkylation of Quinoline Derivatives. Organic Letters 2018, 20 (6) , 1593-1596. https://doi.org/10.1021/acs.orglett.8b00339
    57. Trevor C. Sherwood, Ning Li, Aliza N. Yazdani, and T. G. Murali Dhar . Organocatalyzed, Visible-Light Photoredox-Mediated, One-Pot Minisci Reaction Using Carboxylic Acids via N-(Acyloxy)phthalimides. The Journal of Organic Chemistry 2018, 83 (5) , 3000-3012. https://doi.org/10.1021/acs.joc.8b00205
    58. Mateusz Imiołek, Gogulan Karunanithy, Wai-Lung Ng, Andrew J. Baldwin, Véronique Gouverneur, and Benjamin G. Davis . Selective Radical Trifluoromethylation of Native Residues in Proteins. Journal of the American Chemical Society 2018, 140 (5) , 1568-1571. https://doi.org/10.1021/jacs.7b10230
    59. Andrei Nikolaev, Claude Y. Legault, Minhao Zhang, and Arturo Orellana . The Acid-Free Cyclopropanol-Minisci Reaction Reveals the Catalytic Role of Silver–Pyridine Complexes. Organic Letters 2018, 20 (3) , 796-799. https://doi.org/10.1021/acs.orglett.7b03938
    60. Hengbin Wang and Nathan T. Jui . Catalytic Defluoroalkylation of Trifluoromethylaromatics with Unactivated Alkenes. Journal of the American Chemical Society 2018, 140 (1) , 163-166. https://doi.org/10.1021/jacs.7b12590
    61. Gagan N. Kangovi and Sangwoo Lee . Phase Behavior of Pyrene and Vinyl Polymers with Aromatic Side Groups. Macromolecules 2017, 50 (21) , 8678-8687. https://doi.org/10.1021/acs.macromol.7b01893
    62. Peng Liu, Wenbo Liu, and Chao-Jun Li . Catalyst-Free and Redox-Neutral Innate Trifluoromethylation and Alkylation of Aromatics Enabled by Light. Journal of the American Chemical Society 2017, 139 (40) , 14315-14321. https://doi.org/10.1021/jacs.7b08685
    63. Álvaro Gutiérrez-Bonet, Camille Remeur, Jennifer K. Matsui, and Gary A. Molander . Late-Stage C–H Alkylation of Heterocycles and 1,4-Quinones via Oxidative Homolysis of 1,4-Dihydropyridines. Journal of the American Chemical Society 2017, 139 (35) , 12251-12258. https://doi.org/10.1021/jacs.7b05899
    64. Kaila A. Margrey, Joshua B. McManus, Simone Bonazzi, Frederic Zecri, and David A. Nicewicz . Predictive Model for Site-Selective Aryl and Heteroaryl C–H Functionalization via Organic Photoredox Catalysis. Journal of the American Chemical Society 2017, 139 (32) , 11288-11299. https://doi.org/10.1021/jacs.7b06715
    65. Andrea Gualandi, Daniele Mazzarella, Aitor Ortega-Martínez, Luca Mengozzi, Fabio Calcinelli, Elia Matteucci, Filippo Monti, Nicola Armaroli, Letizia Sambri, and Pier Giorgio Cozzi . Photocatalytic Radical Alkylation of Electrophilic Olefins by Benzylic and Alkylic Zinc-Sulfinates. ACS Catalysis 2017, 7 (8) , 5357-5362. https://doi.org/10.1021/acscatal.7b01669
    66. Eric C. Hansen, Changfeng Li, Sihang Yang, Dylan Pedro, Daniel J. Weix. Coupling of Challenging Heteroaryl Halides with Alkyl Halides via Nickel-Catalyzed Cross-Electrophile Coupling. The Journal of Organic Chemistry 2017, 82 (14) , 7085-7092. https://doi.org/10.1021/acs.joc.7b01334
    67. Qi Huang and Samir Z. Zard . Modular Route to Azaindanes. Organic Letters 2017, 19 (14) , 3895-3898. https://doi.org/10.1021/acs.orglett.7b01772
    68. Kei Murakami, Shuya Yamada, Takeshi Kaneda, and Kenichiro Itami . C–H Functionalization of Azines. Chemical Reviews 2017, 117 (13) , 9302-9332. https://doi.org/10.1021/acs.chemrev.7b00021
    69. Feng Xie, Rong Xie, Jia-Xi Zhang, Huan-Feng Jiang, Li Du, and Min Zhang . Direct Reductive Quinolyl β-C–H Alkylation by Multispherical Cavity Carbon-Supported Cobalt Oxide Nanocatalysts. ACS Catalysis 2017, 7 (7) , 4780-4785. https://doi.org/10.1021/acscatal.7b01337
    70. Wen-Bo Liu, David P. Schuman, Yun-Fang Yang, Anton A. Toutov, Yong Liang, Hendrik F. T. Klare, Nasri Nesnas, Martin Oestreich, Donna G. Blackmond, Scott C. Virgil, Shibdas Banerjee, Richard N. Zare, Robert H. Grubbs, K. N. Houk, and Brian M. Stoltz . Potassium tert-Butoxide-Catalyzed Dehydrogenative C–H Silylation of Heteroaromatics: A Combined Experimental and Computational Mechanistic Study. Journal of the American Chemical Society 2017, 139 (20) , 6867-6879. https://doi.org/10.1021/jacs.6b13031
    71. Guoqiang Wang, Jia Cao, Liuzhou Gao, Wenxin Chen, Wenhao Huang, Xu Cheng, and Shuhua Li . Metal-Free Synthesis of C-4 Substituted Pyridine Derivatives Using Pyridine-boryl Radicals via a Radical Addition/Coupling Mechanism: A Combined Computational and Experimental Study. Journal of the American Chemical Society 2017, 139 (10) , 3904-3910. https://doi.org/10.1021/jacs.7b00823
    72. Jennifer K. Matsui and Gary A. Molander . Organocatalyzed, Photoredox Heteroarylation of 2-Trifluoroboratochromanones via C–H Functionalization. Organic Letters 2017, 19 (4) , 950-953. https://doi.org/10.1021/acs.orglett.7b00196
    73. Luca Legnani, Gabriele Prina Cerai, and Bill Morandi . Direct and Practical Synthesis of Primary Anilines through Iron-Catalyzed C–H Bond Amination. ACS Catalysis 2016, 6 (12) , 8162-8165. https://doi.org/10.1021/acscatal.6b02576
    74. Ming Yan, Julian C. Lo, Jacob T. Edwards, and Phil S. Baran . Radicals: Reactive Intermediates with Translational Potential. Journal of the American Chemical Society 2016, 138 (39) , 12692-12714. https://doi.org/10.1021/jacs.6b08856
    75. Sébastien Laulhé, J. Miles Blackburn, and Jennifer L. Roizen . Selective and Serial Suzuki–Miyaura Reactions of Polychlorinated Aromatics with Alkyl Pinacol Boronic Esters. Organic Letters 2016, 18 (17) , 4440-4443. https://doi.org/10.1021/acs.orglett.6b02323
    76. Taye B. Demissie and Jørn H. Hansen . Mechanism and Site Selectivity in Visible-Light Photocatalyzed C–H Functionalization: Insights from DFT Calculations. The Journal of Organic Chemistry 2016, 81 (16) , 7110-7120. https://doi.org/10.1021/acs.joc.6b00977
    77. Sandeep R. Vemula, Dinesh Kumar, and Gregory R. Cook . Palladium-Catalyzed Allylic Amidation with N-Heterocycles via sp3 C–H Oxidation. ACS Catalysis 2016, 6 (8) , 5295-5301. https://doi.org/10.1021/acscatal.6b01818
    78. Huimin Dai, Chao Yu, Zihao Wang, Hong Yan, and Changsheng Lu . Solvent-Controlled, Tunable β-OAc and β-H Elimination in Rh(III)-Catalyzed Allyl Acetate and Aryl Amide Coupling via C–H Activation. Organic Letters 2016, 18 (14) , 3410-3413. https://doi.org/10.1021/acs.orglett.6b01566
    79. Zhenda Tan, Huanfeng Jiang, and Min Zhang . Ruthenium-Catalyzed Dehydrogenative β-Benzylation of 1,2,3,4-Tetrahydroquinolines with Aryl Aldehydes: Access to Functionalized Quinolines. Organic Letters 2016, 18 (13) , 3174-3177. https://doi.org/10.1021/acs.orglett.6b01390
    80. Evan J. Horn, Brandon R. Rosen, and Phil S. Baran . Synthetic Organic Electrochemistry: An Enabling and Innately Sustainable Method. ACS Central Science 2016, 2 (5) , 302-308. https://doi.org/10.1021/acscentsci.6b00091
    81. Shuya Yamada, Kei Murakami, and Kenichiro Itami . Regiodivergent Cross-Dehydrogenative Coupling of Pyridines and Benzoxazoles: Discovery of Organic Halides as Regio-Switching Oxidants. Organic Letters 2016, 18 (10) , 2415-2418. https://doi.org/10.1021/acs.orglett.6b00932
    82. Landon J. Durak, James T. Payne, and Jared C. Lewis . Late-Stage Diversification of Biologically Active Molecules via Chemoenzymatic C–H Functionalization. ACS Catalysis 2016, 6 (3) , 1451-1454. https://doi.org/10.1021/acscatal.5b02558
    83. Biao Xiong, Shudi Zhang, Huanfeng Jiang, and Min Zhang . Hydrogen-Transfer-Mediated Direct β-Alkylation of Aryl-1,8-naphthyridines with Alcohols under Transition Metal Catalyst Free Conditions. Organic Letters 2016, 18 (4) , 724-727. https://doi.org/10.1021/acs.orglett.5b03699
    84. Tomohiro Iwai and Masaya Sawamura . Transition-Metal-Catalyzed Site-Selective C–H Functionalization of Quinolines beyond C2 Selectivity. ACS Catalysis 2015, 5 (9) , 5031-5040. https://doi.org/10.1021/acscatal.5b01143
    85. Tongtong Wang, Michael Schrempp, Andreas Berndhäuser, Olav Schiemann, and Dirk Menche . Efficient and General Aerobic Oxidative Cross-Coupling of THIQs with Organozinc Reagents Catalyzed by CuCl2: Proof of a Radical Intermediate. Organic Letters 2015, 17 (16) , 3982-3985. https://doi.org/10.1021/acs.orglett.5b01845
    86. Wei Guo, Tao Zhou, and Yuanzhi Xia . Mechanistic Understanding of the Aryl-Dependent Ring Formations in Rh(III)-Catalyzed C–H Activation/Cycloaddition of Benzamides and Methylenecyclopropanes by DFT Calculations. Organometallics 2015, 34 (12) , 3012-3020. https://doi.org/10.1021/acs.organomet.5b00317
    87. Timothy D. Neubert, Yvonne Schmidt, Erica Conroy, and Dean Stamos . Radical Mediated C–H Functionalization of 3,6-Dichloropyridazine: Efficient Access to Novel Tetrahydropyridopyridazines. Organic Letters 2015, 17 (10) , 2362-2365. https://doi.org/10.1021/acs.orglett.5b00861
    88. Chuanfa Ni, Mingyou Hu, and Jinbo Hu . Good Partnership between Sulfur and Fluorine: Sulfur-Based Fluorination and Fluoroalkylation Reagents for Organic Synthesis. Chemical Reviews 2015, 115 (2) , 765-825. https://doi.org/10.1021/cr5002386
    89. Jian-Jun Dai, Wen-Tao Xu, Ya-Dong Wu, Wen-Man Zhang, Ying Gong, Xia-Ping He, Xin-Qing Zhang, and Hua-Jian Xu . Silver-Catalyzed C(sp2)–H Functionalization/C–O Cyclization Reaction at Room Temperature. The Journal of Organic Chemistry 2015, 80 (2) , 911-919. https://doi.org/10.1021/jo5024238
    90. Charles S. Thomoson, Xiao-Jun Tang, and William R. Dolbier, Jr. . Chloro, Difluoromethylation and Chloro, Carbomethoxydifluoromethylation: Reaction of Radicals Derived from RfSO2Cl with Unactivated Alkenes under Metal-Free Conditions. The Journal of Organic Chemistry 2015, 80 (2) , 1264-1268. https://doi.org/10.1021/jo502595g
    91. Alexander Gontcharov and Joshua R. Dunetz . Rapid Enabling of Negishi Couplings for a Pair of mGluR5 Negative Allosteric Modulators. Organic Process Research & Development 2014, 18 (9) , 1145-1152. https://doi.org/10.1021/op500174m
    92. Lizhi Zhang, Zejiang Li, and Zhong-Quan Liu . A Free-Radical Cascade Trifluoromethylation/Cyclization of N-Arylmethacrylamides and Enynes with Sodium Trifluoromethanesulfinate and Iodine Pentoxide. Organic Letters 2014, 16 (14) , 3688-3691. https://doi.org/10.1021/ol5014747
    93. Patrick S. Fier and John F. Hartwig . Synthesis and Late-Stage Functionalization of Complex Molecules through C–H Fluorination and Nucleophilic Aromatic Substitution. Journal of the American Chemical Society 2014, 136 (28) , 10139-10147. https://doi.org/10.1021/ja5049303
    94. Matthew A. Larsen and John F. Hartwig . Iridium-Catalyzed C–H Borylation of Heteroarenes: Scope, Regioselectivity, Application to Late-Stage Functionalization, and Mechanism. Journal of the American Chemical Society 2014, 136 (11) , 4287-4299. https://doi.org/10.1021/ja412563e
    95. Fionn O’Hara, Aaron C. Burns, Michael R. Collins, Deepak Dalvie, Martha A. Ornelas, Alfin D. N. Vaz, Yuta Fujiwara, and Phil S. Baran . A Simple Litmus Test for Aldehyde Oxidase Metabolism of Heteroarenes. Journal of Medicinal Chemistry 2014, 57 (4) , 1616-1620. https://doi.org/10.1021/jm4017976
    96. Sunggi Lee, Hyelee Lee, and Kian L. Tan . Meta-Selective C–H Functionalization Using a Nitrile-Based Directing Group and Cleavable Si-Tether. Journal of the American Chemical Society 2013, 135 (50) , 18778-18781. https://doi.org/10.1021/ja4107034
    97. Goutam Brahmachari. Visible light–driven organic synthesis under iridium (IrIII)-complex photocatalysis. 2025, 221-300. https://doi.org/10.1016/B978-0-323-95893-6.00004-9
    98. Joneswar Basumatary, Kimron Protim Phukan, Samuzal Bhuyan, Biswajit Gopal Roy. A Direct Visible‐Light Mediated Coupling Of Azaarenes with Diversely Functionalized Alkyl Carbons via Organophotocatalytic Sp 3 C−H Bond Activation. European Journal of Organic Chemistry 2024, 27 (48) https://doi.org/10.1002/ejoc.202400819
    99. Serena Pillitteri, Erik V. Van der Eycken, Upendra K. Sharma. Recent developments in the photoredox catalyzed Minisci-type reactions under continuous flow. Chemical Communications 2024, 61 (1) , 13-22. https://doi.org/10.1039/D4CC04801F
    100. Margaret A. P. Ball, Preston J. Myers, Grayson D. Ritch, Jamey K. Bower, Curtis E. Moore, Nathaniel K. Szymczak, Shiyu Zhang. The Role of Electron Transfer in Copper‐Mediated C(sp 2 )−H Trifluoromethylation. Angewandte Chemie International Edition 2024, https://doi.org/10.1002/anie.202420677
    Load more citations
    Download PDF
    Go to Journal of the American Chemical Society
    Get e-Alerts
    Get e-Alerts

    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2013, 135, 32, 12122–12134
    Click to copy citationCitation copied!
    https://doi.org/10.1021/ja406223k
    Published July 17, 2013
    Copyright © 2013 American Chemical Society
    Request reuse permissions

    Article Views

    24k

    Altmetric

    -

    Citations

    295
    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.