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

Hongzhi Yang; Truc Quynh Nguyen; Yefeng Tang

doi:10.1055/s-0043-1775038

Synlett, Inhaltsverzeichnis

Synlett 2025; 36(04): 299-306
DOI: 10.1055/s-0043-1775038

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

Hongzhi Yang

^aSchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, P. R. of China

,

Truc Quynh Nguyen

^bInstitute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany

,

Yefeng Tang ∗

^aSchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, P. R. of China

^cBeijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing 100084, P. R. of China

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Abstract

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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

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