二氟烷基化的研究进展
Research Progress on Difluoroalkylation
DOI: 10.12677/JOCR.2023.114018, PDF,   
作者: 王欢欢*, 郑丁铭:浙江师范大学,化学与生命科学学院,浙江 金华
关键词: 有机氟化合物二氟烷基化Organofluorine Chemistry Difluoroalkylation
摘要: 有机氟化合物广泛存在于药物、农用化学品、材料和PET成像应用中。将氟原子或含氟基团掺入药物分子中通常可以改善其生物和物理性质,包括生物利用度、代谢稳定性、亲脂性和结合选择性等。据统计,超过20%的药物分子中含有氟原子,包括最畅销的药物,如立普妥、百忧解和西普贝等。二氟甲基作为含氟基团能使药物分子具有更好的代谢稳定性,因此对化合物二氟烷基化的研究具有重要意义。文献调研后,本文对近年来二氟烷基化的研究进行总结和探讨,尤其对烯烃和炔烃的二氟烷基化进行了详细的介绍。
Abstract: Organofluorine compounds play a central role in a wide range of pharmaceutical, agrochemical, material, and PET imaging applications. The incorporation of fluorine atoms or fluorine-containing groups into organic compounds can often significantly improve biological and physical properties, including bioavailability, metabolic stability, lipophilicity, and binding selectivity. It is estimated that more than 20% of drugs contain at least one fluorine atom, including best-selling drugs such as Lipitor, Prozac, and Cipbe. Difluoromethyl as a fluorinated group can endow drug molecules with better metabolic stability, making the study of the difluoromethylation of compounds significantly important. After a careful literature review, this paper provides a summary and discussion of research on difluoromethylation in recent years, particularly providing a detailed introduction to the difluoromethylation of alkenes and alkynes.
文章引用:王欢欢, 郑丁铭. 二氟烷基化的研究进展[J]. 有机化学研究, 2023, 11(4): 182-192. https://doi.org/10.12677/JOCR.2023.114018

参考文献

[1] Kirsch, P. (2013) Modern Fluoroorganic Chemistry: Synthesis, Reactivity and Applications. 2nd Edition, Wiley-VCH, Weinheim. [Google Scholar] [CrossRef
[2] Hiyama, T. (2000) Organofluorine Compounds, Chemistry and Applications. Springer-Verlag, Berlin. [Google Scholar] [CrossRef
[3] Meanwell, N.A. (2011) Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design. Journal of Medicinal Chemistry, 54, 2529-2591. [Google Scholar] [CrossRef] [PubMed]
[4] Hagmann, W.K. (2008) The Many Roles for Fluorine in Medicinal Chemistry. Journal of Medicinal Chemistry, 51, 4359-4369. [Google Scholar] [CrossRef] [PubMed]
[5] Harper, D.B. and O’Hagan, D. (1994) The Fluorinated Natural Products. Natural Product Reports, 11, 123-133. [Google Scholar] [CrossRef] [PubMed]
[6] O’Hagan, D. and Harper, D.B. (1999) Fluorine-Containing Natural Products. Journal of Fluorine Chemistry, 100, 127-133. [Google Scholar] [CrossRef
[7] Itoh, T., Hayase, S. and Nokami, T. (2023) Synthesis of Selectively gem-Difluorinated Molecules; Chiral gem-Difluorocyclopropanes via Chemo-Enzymatic Reaction and gem-Difluorinated Compounds via Radical Reaction. The Chemical Record, 23, e202300028. [Google Scholar] [CrossRef] [PubMed]
[8] 潘军, 吴晶晶, 吴范宏. 多组分参与的氟烷基化反应研究进展[J]. 有机化学, 2021, 41(3): 983-1001. [Google Scholar] [CrossRef
[9] O’Hagan, D. (2008) Understanding Organofluorine Chemistry. An Introduction to the C-F Bond. Chemical Society Reviews, 37, 308-319. [Google Scholar] [CrossRef
[10] 倪传法, 朱林桂, 胡金波. 过渡金属促进的二氟烷基化和一氟烷基化反应研究进展[J]. 化学学报, 2015, 73(2): 90-115. [Google Scholar] [CrossRef
[11] Surapanich, N., Kuhakarn, C., Pohmakotr, M. and Reutrakul, V. (2012) Palladium-Mediated Heck-Type Reactions of [(Bromodifluoromethyl)-sulfonyl]benzene: Synthesis of α-Alkenyl- and α-Heteroaryl-Substituted α,α-Difluoromethyl Phenyl Sulfones. European Journal of Organic Chemistry, 2012, 5943-5952. [Google Scholar] [CrossRef
[12] Feng, Z., Min, Q.-Q., Zhao, H.-Y., Gu, J.-W. and Zhang, X.-G. (2015) A General Synthesis of Fluoroalkylated Alkenes by Palladium-Catalyzed Heck-Type Reaction of Fluoroalkyl Bromides. Angewandte Chemie International Edition, 19, 1270-1274. [Google Scholar] [CrossRef] [PubMed]
[13] Belhomme, M.-C., Poissan, T. and Pannecoucke, X. (2013) Copper Catalyzed β-Difluoroacetylation of Dihydropyrans and Glycals by Means of Direct C-H Functionalization. Organic Letters, 15, 3428-3431. [Google Scholar] [CrossRef] [PubMed]
[14] Caillot, G., Dufour, J., Belhomme, M.-C., Poisson, T., Grimaud, L., Pannecoucke, X. and Gillaizeau, I. (2014) Copper-Catalyzed Olefinic C-H Difluoroacetylation of Enamides. Chemical Communications, 50, 5887-5890. [Google Scholar] [CrossRef
[15] Feng, Z., Xiao, Y.-L. and Zhang, X.-G. (2018) Transition-Metal (Cu, Pd, Ni)-Catalyzed Difluoroalkylation via Cross-Coupling with Difluoroalkyl Halides. Accounts of Chemical Research, 51, 2264-2278. [Google Scholar] [CrossRef] [PubMed]
[16] Zhao, Y.-N., Luo, Y.-C., Wang, Z.-Y. and Xu, P. (2018) A New Approach to Access Difluoroalkylated Diarylmethanes via Visible-Light Photocatalytic Cross-Coupling Reactions. Chemical Communications, 54, 3993-3996. [Google Scholar] [CrossRef
[17] Laishram, R.D., Chen, J.C. and Fan, B.M. (2020) Progress in Visible Light-Induced Difluroalkylation of Olefins. The Chemical Record, 21, 69-86. [Google Scholar] [CrossRef] [PubMed]
[18] Jiang, H., Huang, C.M., Guo, J.J., Zeng, C.Q., Zhang, Y. and Yu, S.Y. (2012) Direct C-H Functionalization of Enamides and Enecarbamates by Using Visible-Light Photoredox Catalysis. Chemistry—A European Journal, 18, 15158-15166.
[19] Yu, C., Iqbal, N., Park, S. and Cho, E.J. (2014) Selective Difluoroalkylation of Alkenes by Using Visible Light Photoredox Catalysis. Chemical Communications, 50, 12884-12887. [Google Scholar] [CrossRef
[20] Tang, X.-J., Zhang, Z.-X. and Dolbier Jr., W.R. (2015) Direct Photoredox-Catalyzed Reductive Difluoromethylation of Electron-Deficient Alkenes. Chemistry—A European Journal, 21, 18961-18965. [Google Scholar] [CrossRef] [PubMed]
[21] Arai, Y., Tomita, R., Ando, G., Koike, T. and Akita, M. (2016) Oxydifluoromethylation of Alkenes by Photoredox Catalysis: Simple Synthesis of CF2H-Containing Alcohols. Chemistry—A European Journal, 22, 1262-1265. [Google Scholar] [CrossRef] [PubMed]
[22] Sumino, S., Uno, M., Fukuyama, T., Ryu, I., Matsuura, M., Yamamoto, A. and Kishikaw, Y. (2017) Photoredox Catalyzed Hydrodifluoroalkylation of Alkenes Using Difluorohaloalkyl Compounds and a Hantzsch Ester. The Journal of Organic Chemistry, 82, 5469-5474. [Google Scholar] [CrossRef] [PubMed]
[23] Shu, W., Merino, E. and Nevado, C. (2018) Visible Light Mediated, Redox Neutral Remote 1,6-Difunctionalizations of Alkenes. ACS Catalysis, 8, 6401-6406. [Google Scholar] [CrossRef
[24] Lv, X.L., Wang, C., Wang, Q.L. and Shu, W. (2019) Rapid Synthesis of γ-Arylated Carbonyls Enabled by the Merge of Copper- and Photocatalytic Radical Relay Alkylarylation of Alkenes. Organic Letters, 21, 56-59. [Google Scholar] [CrossRef] [PubMed]
[25] Zhang, M., Lin, J.H. and Xiao, J.C. (2019) Photocatalyzed Cyanodifluoromethylation of Alkenes. Angewandte Chemie International Edition, 58, 6079-6083. [Google Scholar] [CrossRef] [PubMed]
[26] He, Y.T., Wang, Q., Li, L.H., Liu, X.Y., Xu, P.F. and Liang, Y.M. (2015) Palladium-Catalyzed Intermolecular Aryldifluoroalkylation of Alkynes. Organic Letters, 17, 5188-5191. [Google Scholar] [CrossRef] [PubMed]
[27] Wang, Q., He, Y.T., Zhao, J.H., Qiu, Y.F., Zheng, L., Hu, J.Y., Yang, Y.C., Liu, X.Y. and Liang, Y.M. (2016) Palladium-Catalyzed Regioselective Difluoroalkylation and Carbonylation of Alkynes. Organic Letters, 18, 2664-2667. [Google Scholar] [CrossRef] [PubMed]
[28] He, Y.T., Li, L.H., Wang, Q., Wu, W. and Liang, Y.M. (2016) Synthesis of β-Difluoroalkylated Acrylonitriles in the Presence of Copper Powder. Organic Letters, 18, 5158-5161. [Google Scholar] [CrossRef] [PubMed]
[29] Zhang, P.B., Ying, J.X., Tang, G. and Zhao, Y.F. (2017) Phosphinodifluoroalkylation of Alkynes Using P(O)H Compounds and Ethyl Difluoroiodoacetate. Organic Chemistry Frontiers, 4, 2054-2057. [Google Scholar] [CrossRef
[30] Wang, Q., Zheng, L., He, Y.T. and Liang, Y.M. (2017) Regioselective Synthesis of Difluoroalkyl/Perfluoroalkyl Enones via Pd-Catalyzed Four-Component Carbonylative Coupling Reactions. Chemical Communications, 53, 2814-2817. [Google Scholar] [CrossRef
[31] Liang, J.Q., Huang, G.Z., Peng, P., Zhang, T., Wu, J. and Wu, F. (2018) Palladium-Catalyzed Benzodifluoroalkylation of Alkynes: A Route to Fluorine-Containing 1,1-Diarylethylenes. Advanced Synthesis & Catalysis, 360, 2221-2227. [Google Scholar] [CrossRef
[32] Suginome, M., Yamamoto, A. and Murakami, M. (2003) Palladium- and Nickel-Catalyzed Intramolecular Cyanoboration of Alkynes. Journal of the American Chemical Society, 125, 6358-6359. [Google Scholar] [CrossRef] [PubMed]
[33] Suginome, M., Yamamoto, A. and Murakami, M. (2005) Palladium-Catalyzed Addition of Cyanoboranes to Alkynes: Regio- and Stereoselective Synthesis of α,β-Unsaturated β-Boryl Nitriles. Angewandte Chemie International Edition, 44, 2380-2382. [Google Scholar] [CrossRef] [PubMed]
[34] Suginome, M., Shirakura, M. and Yamamoto, A. (2006) Nickel-Catalyzed Addition of Alkynylboranes to Alkynes. Journal of the American Chemical Society, 128, 14438-14439. [Google Scholar] [CrossRef] [PubMed]
[35] Kubota, K., Iwamoto, H., Yamamoto, E. and Ito, H. (2015) Silicon-Tethered Strategy for Copper(I)-Catalyzed Stereo- and Regioselective Alkylboration of Alkynes. Organic Letters, 17, 620-623. [Google Scholar] [CrossRef] [PubMed]
[36] Su, W., Gong, T.J., Zhang, Q., Zhang, Q., Xiao, B. and Fu, Y. (2016) Ligand-Controlled Regiodivergent Copper-Catalyzed Alkylboration of Unactivated Terminal Alkynes. ACS Catalysis, 6, 6417-6421. [Google Scholar] [CrossRef
[37] Itoh, T., Shimizu, Y. and Kanai, M. (2016) Ligand-Enabled, Copper-Catalyzed Regio- and Stereoselective Synthesis of Trialkylsubstituted Alkenylboronates from Unactivated Internal Alkynes. Journal of the American Chemical Society, 138, 7528-7531. [Google Scholar] [CrossRef] [PubMed]
[38] Mateos, J., Rivera-Chao, E. and Fañanás-Mastral, M. (2017) Synergistic Copper/Palladium Catalysis for the Regio- and Stereoselective Synthesis of Borylated Skipped Dienes. ACS Catalysis, 7, 5340-5344. [Google Scholar] [CrossRef
[39] Uno, Y., Yamashita, M. and Nozaki, K. (2011) Borylcyanocuprate in a One-Pot Carboboration by a Sequential Reaction with an Electron-Deficient Alkyne and an Organic Carbon Electrophile. Angewandte Chemie International Edition, 50, 920-923. [Google Scholar] [CrossRef] [PubMed]
[40] Nagao, K., Ohmiya, H. and Sawamura, M. (2014) Phosphine-Catalyzed Anti-Carboboration of Alkynoates with Alkyl-, Alkenyl-, and Arylboranes. Journal of the American Chemical Society, 136, 10605-10608. [Google Scholar] [CrossRef] [PubMed]
[41] Yamazaki, A., Nagao, K., Lwai, T., Ohmiya, H. and Sawamura, M. (2018) Phosphine-Catalyzed Anti-Carboboration of Alkynoates with 9-BBN-Based 1,1-Diborylalkanes: Synthesis and Use of Multisubstituted γ-Borylallylboranes. Angewandte Chemie International Edition, 57, 3196-3199. [Google Scholar] [CrossRef] [PubMed]
[42] Roscales, S. and Csákÿ, A.G. (2015) Transition-Metal-Free Direct Anti-Carboboration of Alkynes with Boronic Acids to Produce Alkenylheteroarenes. Organic Letters, 17, 1605-1608. [Google Scholar] [CrossRef] [PubMed]
[43] Nogami, M., Hirano, K., Kanai, M., Wang, C., Saito, T., Miyamoto, K., Muranaka, A. and Uchiyama, M. (2017) Transition Metal-Free trans-Selective Alkynylboration of Alkynes. Journal of the American Chemical Society, 139, 12358-12361. [Google Scholar] [CrossRef] [PubMed]
[44] Wang, S.F., Zhang, J., Kong, L.C., Tan, Z., Bai, Y.H., Zhu, G.G. Wang, S.F., Zhang, J., Kong, L.C., Tan, Z., Bai, Y.H. and Zhu, G.G. (2018) Palladium-Catalyzed Anti-Selective Fluoroalkylboration of Internal and Terminal Alkynes. Organic Letters, 20, 5631-5635. [Google Scholar] [CrossRef] [PubMed]
[45] Li, K.K., Zhang, X.X., Chen, J.C., Gao, Y., Yang, C.H., Zhang, K.Y., Zhou, Y.Y. and Fan, B.M. (2019) Blue Light Induced Difluoroalkylation of Alkynes and Alkenes. Organic Letters, 21, 9914-9918. [Google Scholar] [CrossRef] [PubMed]