One-pot four-component sequential synthesis of S-alkyl dithiocarbamates using lipase as a biocatalyst.

Dithiocarbamates are widely recognized for their versatile applications in both agriculture as effective pesticides and medicine, where they serve as antifungal and anticancer agents. As a result, their synthesis has garnered significant attention in recent years. In this study, we present an efficient one-pot four-component approach for the synthesis of these scaffolds, utilizing aldehydes, ethyl acetoacetate, carbon disulfide (CS2), and amines. Initially, α,β-unsaturated carbonyl compounds, serving as Michael acceptors, were generated from aldehydes and ethyl acetoacetate through a decarboxylative Knoevenagel reaction under mild conditions, using lipase as a biocatalyst. These intermediates then sequentially undergo a nucleophilic addition reaction with dithiocarbamate anions, which are generated in situ by reacting CS2 with amines. This sequence successfully yields 15 derivatives of S-alkylated dithiocarbamates with high to excellent yields ranging from 69% to 96%.