One-pot synthesis of a 3-thiazolidine through combination of an Asinger-type multi-component-condensation reaction with an enzymatic imine reduction

Abstract

Addressing the combination of heterocyclic chemistry and biocatalysis, a one-pot synthesis of a 3-thiazolidine by means of an initial Asinger-type multi-component-condensation reaction under formation of a 3-thiazoline and a subsequent enzymatic reduction of this cyclic imine is reported. The one-pot process is conducted in a sequential mode and without the need for a spatial compartmentalization of the single reaction steps. For the biocatalytic reduction an imine reductase was used in combination with a glucose dehydrogenase and D-glucose for in situ-cofactor recycling. This process has been applied successfully towards the synthesis of (S)-2,2,3-trimethyl-1-thia-4-azaspiro[4.4]nonane on a 4.5 mmol scale leading to moderate conversion and excellent enantioselectivity of 99% enantiomeric excess.

Keywords: Asinger-type multi-component-condensation reaction; Asymmetric synthesis; Biocatalysis; Cascades; Heterocycles; One-pot processes.