Affiliation:
1. Department of Chemistry University of Oxford Chemistry Research Laboratory OX1 3TA Oxford UK
2. Division of Applied Chemistry Okayama University 700-8530 Tsushimanaka Okayama Japan
Abstract
AbstractHerein we describe the enantioselective intermolecular conjugate addition of nitroalkanes to unactivated α,β‐unsaturated esters, catalyzed by a bifunctional iminophosphorane (BIMP) superbase. The transformation provides the most direct access to pharmaceutically relevant enantioenriched γ‐nitroesters, utilizing feedstock chemicals, with unprecedented selectivity. The methodology exhibits a broad substrate scope, including β‐(fluoro)alkyl, aryl and heteroaryl substituted electrophiles, and was successfully applied on a gram scale with reduced catalyst loading, and, additionally, catalyst recovery was carried out. The formal synthesis of a range of drug molecules, and an enantioselective synthesis of (S)‐rolipram were achieved. Additionally, computational studies revealed key reaction intermediates and transition state structures, and provided rationale for high enantioselectivities, in good agreement with experimental results.
Funder
Engineering and Physical Sciences Research Council