Several related techniques to effect the synthesis of optically active heterocycles are proposed. These methods, which involve the use of diastereotopic group selectivity, can be separated into two general classes. A scheme for the synthesis of optically active lactones is based on a synthetic equivalent of an asymmetric Beckmann rearrangement. In this plan, a prochiral ketone (such as a 4- substituted cyclohexanone or a meso-bicyclic structure) is converted into a imine bearing a chiral substituent on nitrogen, which is then stereospecifically oxidized to an oxaziridine. These materials then undergo a stereospecific rearrangement reaction upon photolysis, affording (after removal of the chiral substituent on nitrogen) enantiomerically enriched lactams. In addition, enantiospecific deprotonations and enamine reactions are proposed in order to effect stereocontrol at distal stereocenters in the proposed substrates. This technology can then intersect with standard insertion (Beckmann, Baeyer- Villager) chemistry to yield heterocycles with substituent patterns that are complementary to those achieved in the scheme above. The chemistry proposed will be applied to three classes of organic medicinal agents, each of which has been shown to be biologically active or inactive depending on absolute configuration: carnitine and other gamma-amino acids, the benzomorphinan analgesics, and the yohimbine alkaloids. Finally, a novel scheme to control regioselectivity on nearly- symmetrical double bonds or epoxides will be presented.
