Benzoannelated cis,cis cis,trans-[5.5.5.6]Fenestranes:Syntheses,Base Lability,and Flattened Molecular Structure of Strained Epimers of the all-cis Series

摘要

Tribenzofenestranes possess-ing the strained cis,cis,cis,trans-[5.5.5.6]-fenestrane skeleton have been synthe-sized from cis-2,6-diphenylspiro-[cyclo-hexane-1,2'-indane]-1,3'-diols by two-fold cyclodehydration,in striking anal-ogy to the strategy used previously to construct the stereoisomeric all-cis-tri-benzo[5.5.5.6]fenestranes from the cor-responding trans-diphenylspirodiols.In this manner,both of the parent hydro-carbons,all-cis-tribenzo[5.5.5.6]fenestrane 4,have been made accessible from the spirodiketones 5 and 6,respec-tively.The C6-functionalized derivatives of 4-cis,cis,cis,trans-fenestranol 9 and cis,cis,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 yielded all-cis fenestrane 3 under Wolff-Kishner condi-tions,but cis,cis,cis,trans-isomer 4under Clemmensen conditions.Epimerization was also circumvented by radical-in-duced desulfurization of fenestrane di-thiolane 15 with nBu_3SnH/AIBN,pro-ducing 4 in excellent yields.A single-crystal X-ray structrue analysis of 4 revealed that,in accordance with force field and semi-empirical MO calcula-tions,the extra strain of the benzoanne-lated cis,cis,cis,trans-[5.5.5.6]fenestra-triene framework [E_(strain(4)-E_(strain)(3)=46KJmol~(-1)] is due both to the almost perfect boat conformation of the six- membered ring and to consider-able bond angle widening at the central,non-bridged C4b-C15d-C11b unit(121 deg).H/D exchange experiments with the cis,cis,cis,trans hydrocarbon 4 under basic conditions demonstrated that the strain-induced epimerization of the "epimeric"benzylic bridgehead C7a-Hbond,which was found to9 be more acidic than the two C-H bonds at the benzhy-drylic bridgeheads.