Free-Radical-5-exo-Trig Cyclization of Chiral 3-Silylhepta-1,6-dienes:  Concise Approach to the A−B−C Ring Core of Hexacyclinic Acid

Free-radical-mediated 5-exo-trig cyclization of hepta-1,6-dienes 6a − c incorporating an allylsilane moiety was shown to provide at low temperature exclusively the trans-cis cyclopentanes 7a − c in good yield. In contrast, the same reaction with the alkyl analogue 9a led to the formation of all four possible stereoisomers. Interestingly, extension of this sequence of radical processes to alkoxy analogues 12 − 14 provided the complementary cis-cis stereoisomers with modest to excellent stereoselectivity. It is noteworthy that under such conditions allylsilanes were found to be much more reactive than their alkyl and alkoxy analogues. Beckwith−Houk-type models were proposed that rationalize the stereochemical course of these 5-exo-trig cyclizations. Finally, an illustration of the value of this methodology was proposed with the synthesis of the A−B−C tricyclic unit of polyketide hexacyclinic acid 3a.