Selective synthesis of gem-dihalopiperidines and 4-halo-1,2,3,6-tetrahydropyridines from halogen substituted homoallylic benzenesulfonamides and aldehydes

TL;DR

This paper presents a selective and efficient method to synthesize gem-dihalopiperidines and related compounds, which can be further modified into valuable chemical products.

Contribution

The paper introduces a novel aza-Prins cyclization method for selective synthesis of gem-dihalopiperidines and tetrahydropyridines.

Findings

The method achieves moderate to good yields with high diastereo- and regioselectivity.

Gem-dihalopiperidines can be converted into piperidin-4-ones and pyridines in good yields.

4-halo-1,2,3,6-tetrahydropyridines yield Sonogashira coupling products efficiently.

Abstract

An efficient synthesis of gem-dihalopiperidines and 4-halo-1,2,3,6-tetrahydropyridines via aza-Prins cyclization reaction of homoallylic benzenesulfonamides and aldehydes has been described. The reaction proceeds via aza-Prins followed by base-mediated elimination reaction, giving moderate to good yields. The reaction is highly diastereo- and regio-selective. Furthermore, the gem-dihalopiperidines can be easily converted to 2-substituted-1-tosylpiperidin-4-one and pyridine in good yields. Additionally, 4-halo-1,2,3,6-tetrahydropyridines can be employed to afford their corresponding Sonogashira coupling products in good yield.

A diastereo- and regioselective synthesis of gem-dihalopiperidines and 4-halo-1,2,3,6-tetrahydropyridines has been unveiled. Post synthetic modifications of these compounds provide piperidin-4-ones, pyridines, and Sonogashira coupling products.

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