BIBOP‐Catalyzed Asymmetric Staudinger/aza‐Wittig Reaction: Unified Syntheses of (–)‐Minfiensine and (+)‐Aspidophylline A
Abstract
ABSTRACT A unified approach has been developed to construct the characteristic 4a,9a‐heterocycle‐fused tetrahydrocarbazole skeleton present in various monoterpene indole alkaloids. This method hinges on a unique chiral bisphosphine BIBOP‐catalyzed asymmetric Staudinger/aza‐Wittig reaction followed by imine cyclization. Compared to conventional mono‐ and bisphosphines, BIBOP exhibits more robust performance across diverse reaction settings. Mechanistic studies revealed that BIBOP(O), the mono‐oxidized derivative of BIBOP, could also promote the asymmetric transformation with excellent enantioselectivity. Leveraging the developed method, we have accomplished a concise total synthesis of (–)‐minfiensine and a formal synthesis of (+)‐aspidophylline A. This work not only establishes a versatile platform for the synthesis of diverse monoterpene indole alkaloids but also offers a new class of organophosphine catalysts applicable to asymmetric Staudinger/aza‐Wittig reaction as well as related transformations.
Article Details
Authors (7)
Zhen Dong
Zhengwen Xue
School of Pharmaceutical Sciences MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology Beijing Frontier Research Center for Biological Structure Tsinghua University Beijing China
Zhuoping Deng
School of Pharmaceutical Sciences MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology Beijing Frontier Research Center for Biological Structure Tsinghua University Beijing China
Jingyang Zhang
Key Laboratory for Green Chemical Technology of Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering, School of Chemical Engineering and Technology
Shuang Xi
School of Pharmaceutical Sciences MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology Beijing Frontier Research Center for Biological Structure Tsinghua University Beijing China
Zinan Gong
School of Pharmaceutical Sciences MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology Beijing Frontier Research Center for Biological Structure Tsinghua University Beijing China
Yefeng Tang