Chemoenzymatic synthesis of novel 1,4-disubstituted 1,2,3-triazole derivatives from 2-heteroaryl substituted homopropargyl alcohols

Abstract

The one-pot synthesis of novel 1,4-disubstituted 1,2,3-triazoles from homopropargyl alcohol backbones is described. The key intermediates 2-benzothiophenyl 1a and 2-benzofuranyl 1b substituted homopropargyl alcohols were synthesized starting from their corresponding carboxyaldehyde derivatives. The racemic heteroaryl-substituted homopropargyl alcohol derivatives are successfully resolved to give the corresponding enantiopure acetates and the alcohols with 84–99% ee by applying chemoenzymatic methods using various lipases. Enantiomerically enriched homopropargyl alcohol derivatives were reacted with various aromatic and aliphatic halides and sodium azide via a one-pot synthesis method and novel chiral benzothiophenyltriazoles 3a–9a and benzofuranyltriazoles 3b–9b were constructed without the isolation of potentially unstable organic azide intermediates.