NHC-Catalyzed Chemo- and Enantioselective Reaction between Aldehydes and Enals for Access to Axially Chiral Arylaldehydes

Abstract

A chiral carbene-catalyzed chemo-and enantioselective reaction with racemic biaryl aldehydes and α-bromoenals is developed for access to axially chiral 2-arylbenzaldehydes through atroposelective dynamic kinetic resolution (DKR) processes. This atroposelective DKR strategy can tolerate a broad scope of substrates with diverse functionalities. The axially chiral 2-aryl benzaldehyde products generally afford moderate to good yields and enantioselectivities. The axially chiral molecules afforded from the current approach are variable through simple transformations to afford axially chiral functional molecules with excellent optical purities.

Development of Configurationally Labile Biaryl Reagents for Atropisomer Synthesis

“…Wu, Jin, and co-workers also reported a N-heterocyclic carbene-catalyzed atroposelective acylation using racemic biaryl aldehydes and α-bromoenals to access axially chiral tetra-ortho-substituted aldehydes through dynamic kinetic resolution process (Scheme 22d). [80] Inspired by the atroposelective ring-opening reactions of bridged biaryl hemiacetals and hemiaminals, similar strategies were applied to aryl-alkenyl hemiacetals to construct axially chiral styrenes. Cheng, Shao, and co-workers developed a chiral phosphoric acid-catalyzed asymmetric reductive amination, affording axially chiral tetra-ortho-substituted styrene-type allylamines with good yields and enantioselectivities (Scheme 23a).…”