Bifunctional Iminophosphorane-Catalyzed Enantioselective Nitroalkane Addition to Unactivated α,β-Unsaturated Esters

Herein we describe the enantioselective conjugate addition of nitroalkanes to unactivated α,β-un-saturated esters, catalyzed by a bifunctional iminophosphorane (BIMP) superbase. The transformation provides the most direct access to pharmaceutically relevant enantioenriched γ-nitroesters, utilizing feedstock chemicals, via unprecedented, yet fundamental reactivity. The methodology exhibits a broad substrate scope, including alkyl, aryl and heteroaryl electrophiles substituted in the β-position, and represents the most general entry to enantioenriched γ-nitroesters. The methodology was successfully applied on a gram scale with reduced catalyst loading, and additionally catalyst recovery was carried out, furthermore, the formal synthesis of a range of drugs, and the enantioselective synthesis of (S)-rolipram were achieved.