Efficient, non-acidolytic method for the selective cleavage of N-Boc amino acid and peptide phenacyl esters linked to a polystyrene resin

An efficient, non-acidolytic method for the selective cleavage of phenacyl esters of N-Boc-amino acids and -peptides linked to a polystyrene resin by (CH3)3SnOH (TMTOH) or [(n-C4H9)3Sn]2O (BBTO) is described. We highly recommend the use of trimethyltin hydroxide for the selective cleavage of carboxylic esters based on its favourable properties. The method is compatible with an N-Boc/O-Bn (benzyl ether) strategy and yields enantiomerically pure N-Boc-peptides useful for further manipulation, for segment condensations or for cyclization strategies. A mechanism for the cleavage of methyl phenylacetate in solution by TMTOH is postulated.