Affiliation:
1. Department of Chemistry Northwestern University Silverman Hall Evanston IL 60208 USA
2. Department of Chemistry Oregon State University 153 Gilbert Hall Corvallis OR 97331 USA
Abstract
AbstractAn enantioselective carbene‐catalyzed radical‐radical coupling of acyl imidazoles and racemic Hantzsch esters is disclosed. This method involves the coupling of an N‐heterocyclic carbene‐derived ketyl radical and a secondary sp3‐carbon radical and allows access to chiral α‐aryl aliphatic ketones in moderate‐to‐good yields and enantioselectivities without any competitive epimerization. The utility of this protocol is highlighted by the late‐stage functionalization of various pharmaceutical compounds and is further demonstrated by the transformation of the enantioenriched products to biologically relevant molecules. Computational investigations reveal the N‐heterocyclic carbene controls the double‐facial selectivity of the ketyl radical and the alkyl radicals, respectively.
Funder
National Institute of General Medical Sciences
Directorate for Mathematical and Physical Sciences
Subject
General Chemistry,Catalysis