Application of selenocarboxylate/azide amidation to amino acids and peptides

ORGN 470

Xinghua Wu, wxhyhf1995@yahoo.com and Longqin Hu. Department of Pharmaceutical Chemistry, School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854
ABSTRACT: Selenocarboxylates smoothly react with a variety of azides to form amides via a selenotriazoline intermediate followed by a retro-[3+2] cycloaddition with the release of nitrogen and the precipitation of selenium. The reaction yield primarily depends upon the electronic properties of the azides whereas electron-deficient azides are more reactive and provide much faster reaction rates and better yields than electron-rich azides. Selenocarboxylate/azide amidation is found to be highly chemoselective and clean. This reaction can be carried out directly from carboxylic acids through our one-pot procedure: A carboxylic acid was firstly activated to form the mixed anhydride; Upon the following treatment with LiAlHSeH, the corresponding selenocarboxylate was formed in situ and directly used to react with azides. This one-pot procedure has been successfully applied to the coupling of amino acids and peptides with azides without apparent racemization in our present work. Selenocarboxylate/azide amidation reaction provides an attractive alternative method to the conventional acylation of amines when an amide bond needs to be formed without going through an amine intermediate.