NHC-Catalyzed Enantioselective Dearomatizing Hydroacylation of Benzofurans and Benzothiophenes for the Synthesis of Spirocycles

Abstract

Benzofurans and benzothiophenes have been efficiently employed as substrates in an enantioselective intramolecular hydroacylation. Breaking aromaticity in a 5-exo-trig cyclization of easily accessible heteroarenes by NHC-catalyzed hydroacylation gives access to a simple class of mainly unexplored spirocycles with up to 99% enantiomeric excess (ee). The formed product class bears interesting three-dimensional pseudoaxial chirality and shows typical ketone reactivity. Density functional theory (DFT) calculations reveal erosion of the ee via a stepwise mechanism bearing a hetero Wheland intermediate. Theoretical data are in agreement with deuterium-labeling studies and a linear correlation between electronics (σ) and the ee.