New Methodologies for Construction of Medium- and Large-sized Carbocycles

(1)3-(烷硫基)-2-(硅氧基)-和3-(烷硫基)-2-(硅甲基)烯丙基乙酸酯是[3+2]环戊酮和亚甲基环戊烷与富电子烯烃反应中有用的三个碳单元。还提出了高的区域选择性是由于该反应的热力学控制，而在与乙烯基硫化物的反应中观察到的良好的立体选择性可能是由于具有最大HOMO系数的硫的显著作用。根据3-(烷硫基)烯丙基乙酸酯的显著特点，采用具有合适烯烃基团的底物，考察了中碳环或大碳环的结构。在合适的Lewis酸的影响下，反应干净地进行，得到了几乎完全具有区域选择性的大尺寸碳环。(3)为了构建一种独特的吲哚碳环，设计并考察了环化和碳骨架重排的一步反应过程。通过使用合适的铝试剂，预期的反应可以很好地进行，得到含有金刚烷ABC-三碳环的产物。通过利用目前的方法学，正在进行对吲哚酚的合成研究。

The following synthetically useful methodologies have been developed by this research project.(1) The substrates such as 3- (alkylthio) -2- (siloxy) - and 3- (alkylthio) -2- (silylmethyl) allyl acetates have been shown as useful three carbon units for [3 + 2] cylopentanone and methylene cyclopentane annulation in the reactions with electron-rich olefins. It has also been proposed the high observed regioselectivity is due to thermodynamic control of this reaction, and excellent stereoselectivity observed in the reaction with vinylsulfides may be due to remarkable effect of sulfur having a largest HOMO coefficient. Based on this methodology, enantioselective total synthesis of coriolin has also been achieved.(2) Based on the remarkable feature of 3- (alkylthio) allylic acetates, construction of medium or large carbocycles has been examined by using substrates having appropriate olefinic moieties. Under the influence of appropriate Lewis acid, the reaction took place cleanly to afford the corresponding larger-sized carbocycles with almost complete regioselectivity.(3) For construction of a unique carbocycle of ingenol, a one step process involving cyclization followed by carbon skeleton rearrangement has been designed and examine. By using an appropriate Al reagent, the expected reaction proceeded nicely to give the product containing ingenane ABC-tricarbocycles. By utilizing the present methodology, synthetic studies on ingenol is in progress.