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.
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.
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DOI：
10.1002/1521-3765(20010803)7:15
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发表时间：
2001-08
期刊：
影响因子：
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通讯作者：
Björn Bredenkötter;U. Flörke;D. Kuck
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文献类型：
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作者：
Björn Bredenkötter;U. Flörke;D. Kuck
由顺式-2,6-二苯基螺[环己烷-1,2'-茚烷]-1',3'-二醇经二次环脱水合成了具有顺式，顺式，顺式，顺式，反式-[5.5.5.6]-戊烯烷骨架的三苯并烯烷，这与先前由相应的反式二苯基螺醇合成立体异构体全顺式三苯并[5.5.5.6]戊烯烷的策略非常相似。通过这种方法，两个母体烃，全顺式三苯并[5.5.5.6]fenestrane 3和顺式，顺式，顺式，反式三苯并[5.5.5.6]fenestrane 4，分别可由螺二酮5和6得到。以顺式二苯基螺三醇8和顺式二苯基双螺乙二醇11为原料，采用相同的方法制备了4-顺、顺、顺、顺、反式雌甾烷醇9和顺、顺、顺、顺、反式雌甾烷酮12的c6功能化衍生物。顺式、顺式、顺式、反式-[5.5.5.6]芬内酯骨架在碱性条件下容易异构成更稳定的全顺式异构体，但在中性或酸性条件下稳定。例如，顺式、顺式、顺式、反式窗烷酮12在Wolff-Kishner条件下生成全顺式窗烷3，而在Clemmensen条件下生成顺式、顺式、顺式、反式异构体4。用nBu3SnH/AIBN对芬甾烷二硫代烷15进行自由基诱导脱硫，也避免了外异构化，产率很高。4的单晶x射线结构分析显示，根据力场和半经验MO计算，苯并合的cis，cis,cis,trans-[5.5.5.6]窗口三烯骨架[Estrain(4)-Estrain(3)=46 kJmol(-1)]的额外应变是由于六元环几乎完美的船形构象和中央非桥接的C4b-C15d-C11b单元的键角显着扩大（121度）。与顺、顺、顺、反式烃4在碱性条件下进行的H/D交换实验表明，菌株诱导的3的外映异构化是通过“外映体”苯基桥头C7a-H键的直接去质子化发生的，其酸性比苯基桥头的两个C-H键更强。
Tribenzofenestranes possessing the strained cis,cis,cis,trans-[5.5.5.6]-fenestrane skeleton have been synthesized from cis-2,6-diphenylspiro[cyclohexane-1,2'-indane]-1',3'-diols by two-fold cyclodehydration, in striking analogy to the strategy used previously to construct the stereoisomeric all-cis-tribenzo[5.5.5.6]fenestranes from the corresponding trans-diphenylspirodiols. 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, have been made accessible from the spirodiketones 5 and 6, respectively. 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 conditions, but cis,cis,cis,trans-isomer 4 under Clemmensen conditions. Epimerization was also circumvented by radical-induced desulfurization of fenestrane dithiolane 15 with nBu3SnH/AIBN, producing 4 in excellent yields. A single-crystal X-ray structure analysis of 4 revealed that, in accordance with force field and semi-empirical MO calculations, the extra strain of the benzoannelated cis,cis,cis,trans-[5.5.5.6]fenestratriene framework [Estrain(4)-Estrain(3)=46 kJmol(-1)] is due both to the almost perfect boat conformation of the six-membered ring and to considerable bond angle widening at the central, non-bridged C4b-C15d-C11b unit (121 degrees). H/D exchange experiments with the cis,cis,cis,trans hydrocarbon 4 under basic conditions demonstrated that the strain-induced 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.