Chiral substituted bicyclic lactam templates through cyclocondensation reactions of gamma-oxo-acids and aminoalcohols: The affect of substituents on enantiomeric ratio due to dynamic kinetic resolution.

摘要

Chiral beta-substituted [3.3.0] bicyclic lactams can be synthesized with stereocontrol by cyclocondensation of substituted ketoacids and chiral amino alcohols. During synthesis, the beta-position of the lactam is racemized due to dynamic kinetic resolution (DKR). Based on the proposed mechanism, this in situ epimerization occurs during equilibration of the acyliminium ion and enamine intermediates resulting in a predominantly endo selectivity in the final beta-substituted lactam product. Data reported in this thesis from experimental studies reveal that an increase in the size of the amino alcohol substituent led to an increase in the observed endo selectivity at the beta-position of the bicyclic lactam. A similar increase in endo selectivity was shown to be dependent on the bridgehead substituent of the bicyclic lactam also. Both of these observed trends can be explained by the steric interactions on the exo face of the [3.3.0] bicyclic lactam and be attributed to dynamic kinetic resolution (DKR).