| Abstract: | The stereochemical outcome of the base-catalyzed cyclization of diketones 5 – 8 has been investigated under protic conditions (Scheme 3). The more stable trans-fused ketols are preferentially formed in kinetically controlled aldol reactions, when the incipient angular substituent R = H (6 → 10a ) or CN ( 7 → 11a , 8a → 12a ). For R = Me (as in 5 ), axial attack of the side-chain enolate double bond on the ring C?O group results in the rather selective formation of cis- 9b. It is assumed that these cyclizations are controlled by relative product stabilities (product-like transition state) and steric effects. The competition between fused (e.g. 9 ) and bridged ketol (e.g. 13 ) formation in these cyclizations is discussed. The cis-fused (‘steroid’) ketols were readily equilibrated with their trans-counterparts (9b ? 9a, 10b ? 10a, 11b ? 11a) under aprotic conditions (5 mol-% of LDA, THF, 0°), thus, allowing assessments of relative stabilities. |
