Radical-initiated polyolefinic cyclizations in linear triquinane synthesis. Model studies and total synthesis of (±)-hirsutene

Article abstract of DOI:10.1016/S0040-4020(01)97175-3

Details of a novel radical-initiated polyolefinic cyclization approach to linear condensed cyclopentanoids are reported. The strategy is executed in three stages: (1) S(n)2'-anti opening of a vinyl lactone to produce a trans-3,5-disubstituted cyclopentene, (2) rapid elaboration to a cyclization precursor, and (3) single step tandem radical cyclization to produce a cis-anti-cis tricyclo[3.3.0]undecane. Model substrates 16a and 16b give high yields of tricyclic products 17 and 18, respectively. An effort to rationalize the interesting endo selectivity via the Beckwith transition state model is proposed. Cyclizations of 28 and 29 to 30 and 31 demonstrate the viability of a tandem hexenyl-hexynyl cyclization. The work culminates with a total synthesis of (±)-hirsutene. A selective approach to methyl substituted vinyl lactones by Claisen rearrangement-phenylselenolactonization-elimination of acetoxy cyclopentenols is exemplified by the synthesis of 12. Tandem cyclization of 38 produces hirsutene (1) in a single step. Alternatively, cyclization of 37 yields trimethylsilyl hirsutene.