Chiral-Bisphosphine-Catalyzed Asymmetric Staudinger/Aza-Wittig Reaction: Development, Mechanism Study, and Synthetic Application

Abstract

The enantioselective desymmetrization of 2,2-disubstituted cyclohexane-1,3-diones has been realized through an unprecedented chiral-bisphosphine-catalyzed asymmetric Staudinger/aza-Wittig reaction. The key to this work’s success lies in utilizing an electronically rich and sterically hindered chiral bisphosphine reagent, namely DuanPhos, as a catalyst. In addition, a unique reductive system was established to address the requisite P^III/PV = O redox cycle. The mechanism of the chiral-bisphosphine-catalyzed asymmetric Staudinger/aza-Wittig reaction has been elucidated through combined computational and experimental studies. Several crinine-type amaryllidaceae alkaloids have been synthesized concisely, hinging on the newly developed methodology.

Key words

enantioselective desymmetrization - Staudinger/aza-Wittig reaction - chiral bisphosphine - total synthesis - amaryllidaceae alkaloids

Publication History

Received: 25 June 2024

Accepted after revision: 24 July 2024

Article published online:
22 August 2024

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