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

Autor: Rozsar D; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, OX1 3TA, Oxford, UK., Farley AJM; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, OX1 3TA, Oxford, UK., McLauchlan I; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, OX1 3TA, Oxford, UK., Shennan BDA; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, OX1 3TA, Oxford, UK., Yamazaki K; Division of Applied Chemistry, Okayama University, 700-8530, Tsushimanaka, Okayama, Japan., Dixon DJ; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, OX1 3TA, Oxford, UK.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2023 May 15; Vol. 62 (21), pp. e202303391. Date of Electronic Publication: 2023 Apr 13.
DOI: 10.1002/anie.202303391
Abstrakt: 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.)
Databáze: MEDLINE
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