Back to Search
Start Over
A Convergent, Modular Approach to Trifluoromethyl‐Bearing 5‐Membered Rings via Catalytic C(sp 3 )−H Activation
- Source :
- Angewandte Chemie International Edition. 62
- Publication Year :
- 2023
- Publisher :
- Wiley, 2023.
-
Abstract
- Trifluoromethyl-bearing 5-membered ring structures are prevalent in bioactive molecules, but modular approaches to these compounds by functionalization of robust sp3 hybridized C-H bonds in a direct and selective manner are extremely challenging. Herein we report the rhodium-catalyzed α-CF3-α-alkyl carbene insertion into a broad range of C(sp3)-H bonds to access 7 types of CF3-bearing saturated 5-membered carbo- and heterocycles. The reaction is particularly effective for benzylic C-H insertion exerting good site-, diastereo- and enantiocontrol, and applicable to access chiral CF3 analogues of bioactive molecules. Ruthenium-α-CF3-α-alkyl carbene complexes underwent stoichiometric reactions to give C-H insertion products, lending evidence for the involvement of metal-α-CF3-α-alkyl carbene species in the catalytic cycle. DFT calculations revealed that the π…π attraction and intra-carbene C-H…F hydrogen bond elucidate the origin of selectivity of the benzylic C-H insertion reactions.
- Subjects :
- General Medicine
General Chemistry
Catalysis
Subjects
Details
- ISSN :
- 15213773 and 14337851
- Volume :
- 62
- Database :
- OpenAIRE
- Journal :
- Angewandte Chemie International Edition
- Accession number :
- edsair.doi.dedup.....7ceeed3405067a8e7313d708622f4b05