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The organocatalytic enolization of 2‐arylacetamides, followed by an enantioselective intramolecular conjugate addition to tethered 2,5‐cyclohexadienones, yielding 3D fused N‐heterocycles, is described. The transformation represents the first strong activating group‐free activation of carboxamides via α‐C−H deprotonation in a metal‐free, catalytic, and enantioselective reaction, and is achieved by employing a bifunctional iminophosphorane (BIMP) superbase. [ABSTRACT FROM AUTHOR]

Herein 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., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)