Synthesis of Sulfonylated Cinchona Alkaloids via Zinc-Mediated Sulfonylation of the N-Oxides of the Quinoline Groups

Abstract

A general and practical method for the synthesis of sulfonylated cinchona alkaloids is presented. The reactions are carried out via Zn-mediated nucleophilic aromatic substitution of the N-oxides of the quinoline core in cinchona alkaloids with a range of sulfonyl chlorides. By careful optimization of the reaction parameters and the procedure, both aromatic and aliphatic sulfonyl chlorides react efficiently with the N-oxides to afford the corresponding sulfonylated products in high yields. In addition, the reaction can be reliably scaled up to gram level. As a result, this method provides a practical route for the synthesis of new cinchona alkaloid derivatives that might be potentially useful compounds, particularly in asymmetric catalysis.

Key words

cinchona alkaloids - quinoline N-oxides - quinolines - sulfonylation - nucleophilic aromatic substitution

Publication History

Received: 23 June 2022

Accepted after revision: 14 July 2022

Accepted Manuscript online:
14 July 2022

Article published online:
16 August 2022

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