Journal of the American Chemical Society, Vol.123, No.9, 1856-1861, 2001
Remarkable control of radical cyclization processes of cyclic enyne: Total syntheses of (+/-)-methyl gummiferolate, (+/-)-methyl 7 beta-hydroxykaurenoate, and (+/-)-methyl 7-oxokaurenoate and formal synthesis of (+/-)-gibberellin A(12) from a common synthetic precursor
Total syntheses of (+/-)-methyl gummiferolate (13b), (+/-)-methyl 7 beta -hydroxykaurenoate (14b), and (+/-)-methyl 7-oxokaurenoate (14d) and a formal synthesis of (+/-)-gibberellin A(12) (15) have been accomplished through the common synthetic precursor, (3aR*,7aR*)-3,3-dimethyl-7a-(2-propynyl )-3a,4,7,7a-tetrahydroisobenzofuranone (16). The homoallyl-homoallyl radical rearrangement reaction of the monocyclic enyne 25, derived from 16 in two steps, afforded the bicyclo[2.2.2]octane compound 26, which was converted to (+/-)-methyl gummiferolate (13b). In contrast, the radical cyclization of the bicyclic enyne 16 gave the tricyclic lactone 19, leading to (+/-)-methyl 7 beta -hydroxykaurenoate (14b) and (+/-)-methyl 7-oxokaurenoate (14d). Transformation of 14d into lactone 20 was carried out in a single step under bromination conditions. This constitutes a formal total synthesis of gibberellin A(12) (15).