Direct Mono-N-methylation of Solid-Supported Amino Acids: A Useful Application of the Matteson Rearrangement of α-Aminoalkylboronic Esters

A novel solid-phase method for the mono-N-methylation of resin-supported amino acids was developed on the basis of Matteson's 1,2-carbon-to-nitrogen migration of boron in α-aminoalkylboronic esters. Amino acids supported on either Wang resin or the highly acid-sensitive SASRIN resin can be methylated by reaction with pinacol chloromethylboronic ester, followed by rearrangement of the resulting aminomethylboronate and subsequent cleavage of the boronate group. This direct method requires only a simple and expedient oxidative resin wash to repair overalkylated sites.