Chromium Catalyzed Asymmetric Reformatsky Reaction

• Published in: Angewandte Chemie International Edition Vol. 63; no. 33; pp. e202406109 - n/a
• Main Authors: Lv, Yong‐Feng, Liu, Gang, Shi, Zhaoxin, Wang, Zhaobin
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 12.08.2024
• Edition: International ed. in English
• Subjects: Aldehydes; Amides; asymmetric Reformatsky reaction; Asymmetry; Bromination; Carbonyl compounds; Carbonyls; Catalysts; Chemical synthesis; chiral alcohol; Chromium; chromium catalysis; Chromium compounds; Esters; Functional groups; photoredox catalysis; radical-polar crossover; radical-polar crossover; photoredox catalysis; asymmetric Reformatsky reaction; chiral alcohol; chromium catalysis
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202406109

This study describes an unprecedented chromium‐catalyzed asymmetric Reformatsky reaction, enabling the synthesis of chiral β‐hydroxy carbonyl compounds from α‐chlorinated or α‐brominated esters and amides. By employing a chiral chromium/diarylamine bis(oxazoline) catalyst, we achieved relatively broad functional group tolerance. Distinct from known reports, the protocol operates under both classical and photoredox conditions, facilitated by the in situ formation of a nucleophilic chiral chromium intermediate through a radical‐polar crossover mechanism. Preliminary mechanistic insights, supported by DFT calculations, identify the nucleophilic aldehyde addition as the key stereo‐determining step. This approach not only overcomes the limitations of existing Reformatsky reactions but also provides a versatile strategy for accessing complex chiral molecules. An unprecedented Cr‐catalyzed asymmetric Reformatsky reaction of aldehydes with α‐chlorinated esters and amides has been developed, providing modular access to valuable chiral β‐hydroxy carbonyl compounds.