Configurationally labile α-bromoacid derivatives for asymmetric preparation of heterocycles

Abstract

α-Bromoacid derivatives are configurationally labile under various conditions, and the dynamic resolution of them has been recognized as an effective strategy in asymmetric synthesis. This article is a concise review of our efforts on the heteroannulation of α-bromoacid derivatives through nucleophilic substitution and subsequent ring formation with diverse carbon, nitrogen, oxygen, and sulfur nucleophiles. Chiral auxiliary (Xc)-bound α-bromoacid derivatives serve as versatile chiral building blocks for the direct incorporation of a two-carbon unit in cyclization reactions. Eight readily available chiral auxiliaries are investigated and identified to be suitable for the dynamic resolution of α-bromoacid derivatives. We have presented selected results about three distinct dynamic resolutions such as dynamic kinetic resolution (DKR), dynamic thermodynamic resolution (DTR) and crystallization induced dynamic resolution (CIDR) that have been successfully employed in the asymmetric synthesis of fourteen different scaffolds of six- or five-membered heterocycles.