Enantioselective Synthesis of Quaternary Oxindoles: Desymmetrizing Staudinger-Aza-Wittig Reaction Enabled by a Bespoke HypPhos Oxide Catalyst

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2022 Nov 14

PMID 36375169

Authors

Changmin Xie

Jacob Kim

Binh Khanh Mai

Shixuan Cao

Rong Ye

Xin-Yi Wang

Peng Liu

Ohyun Kwon

Affiliations

Soon will be listed here.

Abstract

This paper describes a catalytic asymmetric Staudinger-aza-Wittig reaction of (-azidoaryl)malonates, allowing access to chiral quaternary oxindoles through phosphine oxide catalysis. We designed a novel HypPhos oxide catalyst to enable the desymmetrizing Staudinger-aza-Wittig reaction through the P/P═O redox cycle in the presence of a silane reductant and an Ir-based Lewis acid. The reaction occurs under mild conditions, with good functional group tolerance, a wide substrate scope, and excellent enantioselectivity. Density functional theory revealed that the enantioselectivity in the desymmetrizing reaction arose from the cooperative effects of the Ir species and the HypPhos catalyst. The utility of this methodology is demonstrated by the (formal) syntheses of seven alkaloid targets: (-)-gliocladin C, (-)-coerulescine, (-)-horsfiline, (+)-deoxyeseroline, (+)-esermethole, (+)-physostigmine, and (+)-physovenine.

Citing Articles

Amino Acid-Derived Ionic Chiral Catalysts Enable Desymmetrizing Cross-Coupling to Remote Acyclic Quaternary Stereocenters.

Wei J, Gandon V, Zhu Y J Am Chem Soc. 2023; 145(30):16796-16811.

PMID: 37471696 PMC: 10401725. DOI: 10.1021/jacs.3c04877.

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