Palladium-catalyzed transprotection of allyloxycarbonyl-protected amines: Efficient one-pot formation of amides and dipeptides

Article abstract of DOI:10.1021/jo00111a035

The synthetic utility of the N-(allyloxycarbonyl) (Alloc) substituent in α-amino acid derivatives is substantially extended beyond its well-known function as an amine protecting group. When the palladium-catalyzed deprotection is carried out by using tributyltin hydride as nucleophile (the Guibe method) in the presence of an active acylating agent a new acyl group is introduced on nitrogen. Successful acylating agents include carboxylic acid anhydrides, acid chlorides, and activated esters. A useful example of this methodology is the removal of the Alloc group in the presence of tert-butyl dicarbonate, which in essence amounts to a 'transprotection' to a Boc-protected α-amino acid derivative. More importantly, the use of activated N-protected α-amino ester derivatives (e.g., pentafluorophenyl esters) leads to dipeptides. This new method for peptide coupling proceeds very fast under mild conditions, in good to excellent yields, and without noticeable racemization.