BIBOP‐Catalyzed Asymmetric Staudinger/aza‐Wittig Reaction: Unified Syntheses of (–)‐Minfiensine and (+)‐Aspidophylline A

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.