The carbenoid approach to peptide synthesis

A different approach to the synthesis of dipeptides is described based on t he formation of the (NHCHRCONH)-C-1-(CHRCO)-C-2 bond by carbenoid N-H inser tion, rather than the formation of the peptide bond itself. Thus decomposit ion of triethyl diazophosphonoacetate catalysed by rhodium(Ii) acetate in t he presence of N-protected amino acid amides 8 gives the phosphonates 9, Su bsequent Wadsworth-Emmons reaction of 9 with aldehydes in the presence of D BU gives dehydro dipeptides 10. The reaction has been extended to a simple two-step procedure, without the isolation of the intermediate phosphonate. for conversion of a range of amino acid amides 11 into dehydro dipepides 12 and to an N-methylamide 11h, and for conversion of a dipeptide: to tripept ide (13-14). Direct conversion, by using methyl diazophenylacetate, of amin o acid amides to phenylglycine-containing dipeptides 19 proceeds in good ch emical yield, but with poor diastereoselectivity.