Asymmetric Divergent Synthesis of ent -Kaurane-, ent -Atisane-, ent -Beyerane-, ent -Trachylobane-, and ent -Gibberellane-type Diterpenoids.

A unified strategy toward asymmetric divergent syntheses of nine C8-ethano-bridged diterpenoids A1-A9 (candol A, powerol, sicanadiol, epi -candol A, atisirene, ent -atisan-16α-ol, 4-decarboxy-4-methyl-GA 12 , trachinol, and ent -beyerane) has been developed based on late-stage transformations of common synthons having ent -kaurane and ent -trachylobane cores. The expeditious assembly of crucial advanced ent -kaurane- and ent -trachylobane-type building blocks is strategically explored through a regioselective and diastereoselective Fe-mediated hydrogen atom transfer (HAT) 6- exo -trig cyclization of the alkene/enone and 3- exo -trig cyclization of the alkene/ketone, showing the multi-reactivity of densely functionalized polycyclic substrates with π C═C and π C═O systems in HAT-initiated reactions. Following the rapid construction of five major structural skeletons ( ent -kaurane-, ent -atisane-, ent -beyerane-, ent -trachylobane-, and ent -gibberellane-type), nine C8-ethano-bridged diterpenoids A1-A9 could be accessed in the longest linear 8 to 11 steps starting from readily available chiral γ-cyclogeraniol 1 and known chiral γ-substituted cyclohexenone 2 , in which enantioselective total syntheses of candol A ( A1 , 8 steps), powerol ( A2 , 9 steps), sicanadiol ( A3 , 10 steps), epi -candol A ( A4 , 8 steps), ent -atisan-16α-ol ( A6 , 11 steps), and trachinol ( A8 , 10 steps) are achieved for the first time.