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

Abstract

Details of a novel radical-initiated polyolefinic cyclization approach to linear condensed cyclopentanoids are reported. The strategy is executed in three stages: (1) Sn2′-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-anticis 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.