ASYMMETRIC FUNCTIONALIZATION OF CONFORMATIONALLY DISTINCTIVE CS-SYMMETRICAL CIS[N.3.1] BICYCLIC KETONES - DEFINITION OF THE ABSOLUTE COURSE OF ENANTIODIFFERENTIATION AND DIASTEREODIFFERENTIATION

The four C(s)-symmetric cis[n.3.1] bicyclic ketones where n = 3, 5, 7, and 9 were acetalized with (R,R)-2,4-pentanediol, and the resulting derivatives were cleaved with triisobutylaluminum (TRIBAL). The first three examples, all of which have their polymethylene chain rigidly fixed in a diaxial orientation, undergo ring opening with very high diastereoselectivity to give 5. In the fourth case (n = 9), the chain is sufficiently long to be attached in a diequatorial manner. The response of 4d to TRIBAL is to deliver a 1:1 mixture of 11 and 12. The stereochemical course of epoxidation and cyclopropanation reactions of these enol ethers has been assessed. Where 5 and 11 are concerned, these functionalization reactions are 100% pi-facially selective. Only 12 is the exception. Also examined in this study was the enantioselective deprotonation of the same ketones with the enantiomerically pure lithium amide base 27. The resulting enolates were trapped as their silyl enol ethers and transformed directly into optically active alpha-hydroxy ketones and alpha,beta-unsaturated enones by epoxidation and selenenylation-oxidative elimination, respectively. The sense of the observed enantioselectivity was the same irrespective of the diaxial or diequatorial disposition of the (CH2)n loop. However, the asymmetry induced by this means was consistently opposite to that realized by TRIBAL-promoted acetal cleavage. When these complementary processes are compared at the alpha-hydroxy ketone stage, the acetal cleavage-epoxidation option was invariably 100% enantioselective; greater variability in optical purity was seen via the deprotonation-silylation-epoxidation option. The possible mechanistic basis of these observations is explored.