Benzoannelated cis,cis,cis,trans-[5.5.5.6]fenestranes: Syntheses, base lability, and flattened molecular structure of strained epimers of the all-cisseries

Tribenzofenestranes possessing the strained cis,cis,cis.trans[5.5.5.6]-fene strane skeleton have been synthesized from cis-2.6-diphenylspiro[cyclohexan e-1.2 ' -indane]-1 ' .3 ' -diols by twofold cyclodehydration, in striking a nalogy to the strategy used previously to construct the stereoisomeric all- cis-tribenzo[5.5.5.6]fenestranes from the corresponding trans-diphenylspiro diols. In this manner, both of the parent hydrocarbons, all-cis-tribenzo[5. 5.5.6]fenestrane 3 and cis.cis.cis.trans-tribenzo[5.5.5.6]fenestrane 4, hav e been made accessible from the spirodiketones 5 and 6, respectively. The C 6-functionalized derivatives of 4-cis.cis.cis.trans-fenestranol 9 and cis.c is.cis.trans-fenestranone 12-were prepared through cis-diphenylspirotriol 8 and cis-diphenyldispiroacetaldiol 11. by using the same strategy. The cis, cis, cis.trans-[5.5.5.6]fenestrane framework readily epimerizes to the more stable all-cis isomers under basic conditions, but is stable under neutral or acidic conditions. For example, cis,cis.cis.trans-fenestranone 12 yield ed all-cis fenestrane 3 under Wolff-Kishner conditions, but cis,cis,cis,tra ns-isomer 4 under Clemmensen conditions. Epimerization was also circumvente d by radical-induced desulfurization of fenestrane dithiolane 15 with nBu(3 )SnH/AIBN. producing 4 in excellent yields. A single-crystal X-ray structur e analysis of 4 revealed that, in accordance with force field and semi-empi rical MO calculations. the extra strain of the benzoannelated cis,cis,cis,t rans-[5.5.5.6]fenestratriene framework [E-strain(4)- E-strain(3) = 46 kJ mo l(-1)] is due both to the almost perfect boat conformation of the six-membe red ring and to considerable bond angle widening at the central non-bridged C4b-Cl5d-C11b unit (121). H/D exchange experiments with the cis cis,cis,tr ans hydrocarbon 4 under basic conditions demonstrated that the strain-induc ed epimerization to 3 occurs through direct deprotonation of the "epimeric" benzylic bridgehead C7a-H bond, which was found to be more acidic than the two C-H bonds at the benzhydrylic bridgeheads.