Practical Synthesis of α-CF3 Amine Derivatives via Photochemical Hydroalkylation of Unactivated Alkenes Promoted by Nucleophilic Catalysis

IF 13.1 1区化学 Q1 CHEMISTRY, PHYSICAL

ACS Catalysis Pub Date : 2025-06-26 DOI:10.1021/acscatal.5c02885

Shuli Li, Tianhao Chen, Yonghao Xi, Xinjie Li, Weichen Huang

引用次数: 0

Abstract

α-Trifluoromethyl amines, serving as amide bond bioisosteres, are of great interest in pharmaceutical research, although their practical synthesis still poses significant challenges. To overcome this limitation, we developed an integrated nucleophilic organocatalysis/hydrogen atom transfer (HAT) system for the direct α-trifluoromethylamination of unactivated alkenes. Mechanistic studies reveal that thiophenol serves not only as an organonucleophilic catalyst but also as a hydrogen atom transfer (HAT) reagent, exhibiting dual catalytic roles. Control experiments revealed that α-CF₃/α-amino carbon radicals display ambiphilic reactivity, undergoing addition to alkenes regardless of electronic nature (electron-deficient, neutral, or electron-rich). Besides, the system demonstrates remarkable tolerance to sensitive functional groups and can be further extended to the synthesis of diverse fluorinated amine (α-R_f amines) derivatives.

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亲核催化下未活化烯烃光化学氢烷基化合成α-CF3胺衍生物

α-三氟甲基胺作为酰胺键生物异构体，在药学研究中备受关注，但其实际合成仍面临重大挑战。为了克服这一限制，我们开发了一种集成的亲核有机催化/氢原子转移（HAT）系统，用于直接α-三氟甲基化非活化烯烃。机理研究表明，噻吩酚不仅作为有机亲核催化剂，而且作为氢原子转移（HAT）试剂，具有双重催化作用。对照实验表明，α-CF3/α-氨基碳自由基表现出亲和性，无论电子性质（缺电子、中性或富电子）如何，都能加成烯烃。此外，该体系对敏感官能团具有良好的耐受性，可进一步扩展到合成多种氟化胺（α-Rf胺）衍生物。

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来源期刊

ACS Catalysis CHEMISTRY, PHYSICAL-

CiteScore

20.80

自引率

6.20%

发文量

1253

审稿时长

1.5 months

期刊介绍： ACS Catalysis is an esteemed journal that publishes original research in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. It offers broad coverage across diverse areas such as life sciences, organometallics and synthesis, photochemistry and electrochemistry, drug discovery and synthesis, materials science, environmental protection, polymer discovery and synthesis, and energy and fuels. The scope of the journal is to showcase innovative work in various aspects of catalysis. This includes new reactions and novel synthetic approaches utilizing known catalysts, the discovery or modification of new catalysts, elucidation of catalytic mechanisms through cutting-edge investigations, practical enhancements of existing processes, as well as conceptual advances in the field. Contributions to ACS Catalysis can encompass both experimental and theoretical research focused on catalytic molecules, macromolecules, and materials that exhibit catalytic turnover.