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-GA12, 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 πC═C and πC═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.

Enantioselective synthesis of chiral α-alkynylated thiazolidones by tandem S-addition/acetalization of alkynyl imines.

A SPINOL-derived chiral phosphoric acid catalyzed asymmetric formal [2 + 3]-annulation of in situ generated alkynyl imines and 1,4-dithiane-2,5-diol has been developed to afford enantiopure α-alkynylated thiazolidones with up to 72% yield and 98.5 : 1.5 er. This tandem annulation involved a tandem S-addition of alkynyl imines/intramolecular acetalization, followed by PDC-mediated oxidation. The α-alkynylated thiazolidones could facilely afford the corresponding chiral α-alkynylated or α-alkenylated cyclic sulfoxides via further elaboration.