Stereochemistry of the Robinson Anellation: Studies on the Mode of Formation of the Intermediate Hydroxy Ketones

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 CO 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.