Synthesis of Axially Chiral Aldehydes by N‐Heterocyclic‐Carbene‐Catalyzed Desymmetrization Followed by Kinetic Resolution

• Published in: Angewandte Chemie International Edition Vol. 61; no. 14; pp. e202117340 - n/a
• Main Authors: Wu, Yingtao, Li, Mingrui, Sun, Jiaqiong, Zheng, Guangfan, Zhang, Qian
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 28-03-2022
• Edition: International ed. in English
• Subjects: Aldehydes; Axially Chiral Aldehydes; Catalysis; Desymmetrization; Enantiomers; Esterification; Kinetic Resolution; N-Heterocyclic Carbenes; Kinetic Resolution; Axially Chiral Aldehydes; N-Heterocyclic Carbenes; Esterification; Desymmetrization
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202117340

Axially chiral aldehydes have received increasing attention in enantioselective catalysis. However, only very few catalytic methods have been developed to construct structurally diverse axially chiral aldehydes. We herein describe an NHC‐catalyzed atroposelective esterification of biaryl dialdehydes as a general and practical strategy for the construction of axially chiral aldehydes. Mechanistic studies indicate that coupling proceeds through a novel combination of NHC‐catalyzed desymmetrization of the dialdehydes and kinetic resolution. This protocol features excellent enantioselectivity, mild conditions, good functional‐group tolerance, and applicability to late‐stage functionalization and provides a modular platform for the synthesis of axially chiral aldehydes and their derivatives.
N‐Heterocyclic carbene (NHC)‐catalyzed atroposelective esterification of dialdehydes led to structurally diverse axially chiral aldehydes in good yields, with high enantioselectivity enabled by unprecedented NHC‐catalyzed desymmetrization of the dialdehydes followed by kinetic resolution. This protocol, which features mild reaction conditions and broad functional‐group tolerance, provides modular access to value‐added axially chiral aldehydes and their derivatives.