Issue 26, 2021

Phosphite mediated asymmetric N to C migration for the synthesis of chiral heterocycles from primary amines

Abstract

A phosphite mediated stereoretentive C–H alkylation of N-alkylpyridinium salts derived from chiral primary amines was achieved. The reaction proceeds through the activation of the N-alkylpyridinium salt substrate with a nucleophilic phosphite catalyst, followed by a base mediated [1,2] aza-Wittig rearrangement and subsequent catalyst dissociation for an overall N to C-2 alkyl migration. The scope and degree of stereoretention were studied, and both experimental and theoretical investigations were performed to support an unprecedented aza-Wittig rearrangement–rearomatization sequence. A catalytic enantioselective version starting with racemic starting material and chiral phosphite catalyst was also established following our understanding of the stereoretentive process. This method provides efficient access to tertiary and quaternary stereogenic centers in pyridine systems, which are prevalent in drugs, bioactive natural products, chiral ligands, and catalysts.

Graphical abstract: Phosphite mediated asymmetric N to C migration for the synthesis of chiral heterocycles from primary amines

Supplementary files

Article information

Article type
Edge Article
Submitted
02 mar 2021
Accepted
27 may 2021
First published
28 may 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2021,12, 8996-9003

Phosphite mediated asymmetric N to C migration for the synthesis of chiral heterocycles from primary amines

S. Rani, S. R. Dash, A. Bera, M. N. Alam, K. Vanka and P. Maity, Chem. Sci., 2021, 12, 8996 DOI: 10.1039/D1SC01217G

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