清华大学唐叶峰团队报道了手性双膦催化不对称Staudinger/aza-Wittig反应——Crinine型石蒜科生物碱的对映选择性不对称合成方法。相研究成果于2024年4月20日发表在国际顶尖学术期刊《美国化学会杂志》。

研究人员报道了一种前所未有的，手性双膦催化的2,2-二取代环己烷-1,3-二酮的不对称Staudinger/aza-Wittig反应，使其能够以优异的对映选择性以高产率获得广泛的顺式-3a-芳基氢吲哚。该项工作成功的关键在于手性双膦DuanPhos，首次应用于不对称Staudinger/aza-Wittig反应。

研究人员建立了一个有效的还原系统来解决，具有挑战性的PV═O/PIII与手性双膦催化剂相关的氧化还原循环。此外，研究人员还进行了全面的实验和计算研究，以阐明不对称反应的机理。利用新开发的化学方法，高效地完成了几种Crinine型石蒜科生物碱的对映选择性全合成，包括（+）-鲍威文殊兰碱、（+）-布蕃胺、（+）-条纹(小星蒜)碱以及(+)-crinane。

附：英文原文

Title: Chiral Bisphosphine-Catalyzed Asymmetric Staudinger/aza-Wittig Reaction: An Enantioselective Desymmetrizing Approach to Crinine-Type Amaryllidaceae Alkaloids

Author: Hongzhi Yang, Jingyang Zhang, Sen Zhang, Zhengwen Xue, Shengkun Hu, Yi Chen, Yefeng Tang

Issue&Volume: April 20, 2024

Abstract: An unprecedented chiral bisphosphine-catalyzed asymmetric Staudinger/aza-Wittig reaction of 2,2-disubstituted cyclohexane-1,3-diones is reported, enabling the facile access of a broad range of cis-3a-arylhydroindoles in high yields with excellent enantioselectivities. The key to the success of this work relies on the first application of chiral bisphosphine DuanPhos to the asymmetric Staudinger/aza-Wittig reaction. An effective reductive system has been established to address the challenging PV═O/PIII redox cycle associated with the chiral bisphosphine catalyst. In addition, comprehensive experimental and computational investigations were carried out to elucidate the mechanism of the asymmetric reaction. Leveraging the newly developed chemistry, the enantioselective total syntheses of several crinine-type Amaryllidaceae alkaloids, including (+)-powelline, (+)-buphanamine, (+)-vittatine, and (+)-crinane, have been accomplished with remarkable conciseness and efficiency.

DOI: 10.1021/jacs.4c02755

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c02755