Non-catalytic low-cost and sustainable amidation using a twisted amide

Abstract

Cost reductions and environmental friendliness have been strongly desired in amide synthesis. In this study, carboxylic acid was converted to a twisted amide using inexpensive tosyl isocyanate and bromoacetate. The twisted amide was then reacted with an amine to give the desired amide and commercially valuable tosylglycine esters. Epimerization-suppressed amidation, application to peptide synthesis, column chromatography-free amide synthesis, and solid-phase amide synthesis were established. Moreover, the effective use of the co-product tosylglycine ester was demonstrated by sustainable peptoid synthesis. The established method can become a practical amidation approach that solves the cost and sustainability issues in amide synthesis.