Development of a mild and versatile directed cycloaddition approach to pyridines

Sylvestre P J T Bachollet; Jérôme F Vivat; Dean C Cocker; Harry Adams; Joseph P A Harrity

doi:10.1002/chem.201403916

Development of a mild and versatile directed cycloaddition approach to pyridines

Chemistry. 2014 Sep 26;20(40):12889-93. doi: 10.1002/chem.201403916. Epub 2014 Aug 21.

Authors

Sylvestre P J T Bachollet¹, Jérôme F Vivat, Dean C Cocker, Harry Adams, Joseph P A Harrity

Affiliation

¹ Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, S3 7HF (UK).

Abstract

The aza-Diels-Alder cycloaddition of 1,2,4-triazines with alkynes offers a rapid and convenient method for the synthesis of highly substituted pyridines, but often requires harsh conditions and long reaction times. The present study offers a solution to these limitations by use of a temporary tether established by a Lewis acid-base complexation of in situ generated alkynylboranes and triazines bearing a Lewis basic donor. The cycloaddition reactions take place within 20 min at 40 °C and provide direct access to a broad range of pyridines with complete and predictable regiocontrol. The carbonboron bond can be further functionalised by cross-coupling allowing further functionality to be introduced after cycloaddition.

Keywords: boranes; cycloadditions; pyridines; regioselectivity; triazines.