Pergamon Tetrahedron Letters, Vol. 38, No. 37, pp. 6505-6508, 1997 © 1997 Published by Elsevier Science Ltd All rights reserved. Printed in Great Britain PII: S0040-4039(97)01515-3 0040-4039/97$17.00+ 0.0o Enantioselective Synthesis of Phenylglycines Using (-) Sparteine-s-BuLi Complex Normand Voyer*~, Johanne Roby, Sylvain Chrnard, and Claude Barberis Drpartement de chimie, Universit6 de Sherbrooke, Sherbrooke, QuEbec, Canada J1K 2R1 Abstract: The enantioselective synthesis of N-t-Boc protected phenylglycine derivatives is reported. The synthetic strategy involved the enantioselective deprotonation of N-t-Boc-N-TMS protected benzylamines using the (-) sparteine.s-BuLi complex. © 1997 Published by ElsevierScienceLtd. The synthesis of unnatural aminoacids, in particular phenylglycines, is of great interest for their use in medicinal chemistry) As part of our research program on the development of peptide based supramolecular devices 3, we required the preparation of N-t-Boc protected phenylglycine derivatives !. Toward that goal, we sought to synthesize I by the strategy illustrated in Scheme 1 using the versatile (-) sparteine 4_ os-BuLi complex as chiral base.4 The key steps were the enantioselective deprotonation of the N-t-Boc protected benzylamine 2 by the chiral complex and the stereoselective carboxylation of the dianionic specie 3. Although I was prepared by that route in a 50% yield, no chiral induction was observed. 5 This was attributed to the presence of the negative charge on the carbamate which decreases the comqgurational stability of the benzylic organolithium 3. Indeed, the replacement of the carbamate proton by a methyl group lead to the enantioselective synthesis of N-t-Boc protected phenylsarcosine. 6 .~I (-) 4 " _ -t-Boc - ff,'/,,..o/t 8u c°____Z_2 ~N.,.t_Boc s-~i 5o~ ~,~.j ~ _2 3 ! O%ee (-) ~! Scheme 1 6505