Asymmetric synthesis of L-proline regio- and stereoselectively labelled wiith deuterium

A synthesis of L-proline where all of the ring methylenes me stereoselectiv eiy labelled with deuterium is described. A catalytic deuteration of protec ted 3,4-dehydro-L-proline using transition metal catalyst followed by RuO4- oxidation gave a [3,4-D-2]pyroglutamic acid derivative. A syn-selective deu teration of the aminal derived from the pyroglutamate with Et3SiD-BF3. OEt2 furnished (2S,3S,4R,5S)-[3,4,5-D-3]proline. The present procedure is also applied to the synthesis of the corresponding (2S,3S,4R,SR)-isomer. (C) 199 9 Elsevier Science Ltd. All rights reserved.