Recyclable Hypervalent Iodine(Ⅲ) Reagent Iodosodilactone As An Efficient Coupling Reagent For Esterification,Macrolactonization, Amidation, And Peptide Coupling

For the first time, a hypervalent iodine(III) reagent iodosodilactone plays a novel role as an efficient coupling reagent in combination with PPh3and DMAP to promote the direct condensation between carboxylic acids and alcohols or amines to provide esters, macrocyclic lactones, amides, as well as peptides without racemization, which is also the first application of iodosodilactone. The single crystal of iodosodilactone is first obtained from DMSO/Et2O, and its X-ray crystallographic analysis showed a structure of overall planar shape unlike other usually employed aryl-A3-iodanes with a typical T-shape structure. Iodosodilactone is ready availability, stability, and can be easily regenerated from the reaction mixture. By the study of the mechanism, it was believed that the key intermediate acyloxyphosphonium ion from the activation of a carboxylic acid was involved in the present esterification reaction.Furthermore, an upgraded version of iodosodilactone/PPh3/DMAP system is developed for the efficient synthesis of peptide chains. When (4-MeOPh)3P, a commercially available phosphine reagent with stronger nucleophilicity, is employed in place of PPh3, the peptide coupling reaction is accomplished at room temperature within3-4hours even in the absence of DMAP. In addition, a new kind of water-soluble phosphine reagent (4-Et2NCH2CH2OPh)3P·3HCl is designed and prepared in present work for improving the efficiency of product isolation and purification.