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.
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.
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.
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