Racemization-free synthesis of dipeptide, amide and ester by oxalyl chloride and catalytic triphenylphosphine oxide

Abstract

An efficient triphenylphosphine oxide (Ph3PO) catalyzed amidation and esterification reaction for rapid synthesis of a series of dipeptides, amides and esters under mild condition is described. This reaction is applicable to challenging couplings of hindered carboxylic acid with low nucleophilic amine or alcohol, giving products in good yields (67-90%) without any racemization. This system employs highly reactive intermediate Ph3PCl2 as activator of carboxylate, in a catalytic manner, and drive the reaction to complete in short reaction time (less than 10 min). It has the advantages of good functional group tolerance, broad substrate scope and good atom-economy. A 100 mmol scale reaction with good yield shed light on its potential for industrial application. A plausible mechanism is proposed based on 31 P NMR monitor of reaction process. Supporting InformationComplete experimental procedures and characterization of new products; NMR spectra and HPLC chromatograms (PDF)