Issue 15, 2024

Enantioselective synthesis of unsymmetrical α,α-diarylacetates via organocatalyzed formal C–H insertion reactions of sulfoxonium ylides with indoles and pyrroles

Abstract

The chiral unsymmetrical α,α-diarylmethine skeleton is widely found in natural products and synthetic pharmaceuticals. The catalytic asymmetric C–H insertion reaction of simple, unprotected indoles and pyrroles with α-aryl sulfur ylides provides a direct route to their stereoselective preparation. Nevertheless, controlling the reactivity and stereoselectivity of this reaction has presented a significant challenge. In this study, we present the highly enantioselective asymmetric formal C–H insertion reactions of N–H free indoles and pyrroles with sulfoxonium ylides, yielding chiral gem-heterodiarylmethine frameworks with good to excellent yields and enantioselectivities. Importantly, experimental mechanistic studies and DFT calculations indicate that the stereoselectivity originates from dynamic kinetic resolution, where multiple noncovalent interactions play a pivotal role, with C–C bond formation as the rate-determining step. The findings in this study may pave the way for the development of catalytic asymmetric C–H insertion reactions of sulfur ylides with other carbon nucleophiles.

Graphical abstract: Enantioselective synthesis of unsymmetrical α,α-diarylacetates via organocatalyzed formal C–H insertion reactions of sulfoxonium ylides with indoles and pyrroles

Supplementary files

Article information

Article type
Research Article
Submitted
26 Apr 2024
Accepted
11 Jun 2024
First published
11 Jun 2024

Org. Chem. Front., 2024,11, 4084-4093

Enantioselective synthesis of unsymmetrical α,α-diarylacetates via organocatalyzed formal C–H insertion reactions of sulfoxonium ylides with indoles and pyrroles

X. Yue, S. Li, T. Ou, Z. Xiong, F. Jiang, Y. Zhou, L. Song, Y. Zhao and W. Guo, Org. Chem. Front., 2024, 11, 4084 DOI: 10.1039/D4QO00753K

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