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

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 P V �O/P III 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.

Palladium-Catalyzed Asymmetric Desymmetrization for the Simultaneous Construction of Chiral Phosphorus and Quaternary Carbon Stereocenters

“…P-Chiral phosphorus compounds represent a distinctive class of frameworks that are prevalent in natural products, pharmaceuticals, and biologically active molecules (Scheme a, left) . Moreover, P-stereocenter chiral ligands and organocatalysts have demonstrated remarkable significance in asymmetric organic synthesis (Scheme a, right). Therefore, the development of efficient methods for synthesizing P-chiral phosphorus compounds has garnered considerable interest among chemists .…”