Enantiopure Triazolium Salts: Chemoenzymatic Synthesis and Applications in Organocatalysis

Abstract

A novel family of triazolium salt enantiomers has been efficiently synthesized by combining chemical and biocatalytic methods. The stereoselective action shown by hydrolytic enzymes led to the design of simple and general chemoenzymatic routes in which tunable vectors, such as ring size, substituent stereochemistry, oxygen substitution, anion nature, or N4-triazole alkylating chain, were considered to produce 30 enantiopure triazolium salts in very high overall yields. Finally, selected triazolium salts were tested as phase-transfer catalysts in the asymmetric Michael addition of diethyl malonate to trans-chalcone to rationalize their activity and stereopreference. Low to complete conversion values were achieved in the formation of the Michael addition adduct, which mainly gave low levels of stereoselectivity depending on the different structural patterns considered in this systematic study.