trans-3,4-disubstituted pyrrolidines by 1,3-dipolar cycloaddition:: enantioselective approaches and their limitations

In the presence of a chiral Lewis acid as co-catalyst, the acid-catalysed 1,3-dipolar cycloaddition reaction yielding trans-3,4-disubstituted pyrrolidines from an azomethine ylide and achiral alpha,beta-unsaturated dipolarophiles proceeded with low enantioselectivity. Therefore a number of alpha,beta-unsaturated dipolarophiles linked to chiral auxiliaries were examined as substrates. Camphorsultam was the best auxiliary and gave good diastereoselectivity (dr=74:26). When combining chiral Lewis acids with a dipolarophile linked to a chiral auxiliary, the enantioselectivity could be slightly increased. As judged by C-13 NMR, the small effect of the chiral Lewis acids on selectivity was probably due to breakdown of the initially formed complex with the dipolarophile caused by the dipole precursor. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.