Synthesis of Optically Active alpha, alpha-Disubstituted Cyclohexanone Derivatives and Their CD Spectra

在第一年，我们进行了（S）-（-）-苯乙胺与2-甲基环己酮和2-乙基环己酮的亚胺与丙烯酸甲酯反应的研究工作。在第二年，这扩展到2-烯丙基-，2-异丙基-，2-辛基环己酮，和二取代的环己酮，2-甲基-4-叔丁基和2-乙基-4-叔丁基环己酮。在这些反应中得到的酮酯的绝对构型建立了由X-射线晶体学。用600 MHz核磁共振谱研究了三取代酮酯的立体化学，并确定了其构象。2-甲基环己酮系列衍生物的圆二色谱符号为（+），而2-乙基系列及其它衍生物的圆二色谱符号为（-）。这种差异不是由于绝对位形的错误分配，也不是由于前八分圆。2-甲基和2-乙基环己酮的圆二色光谱符号的不同，可能是由于六元环的构象不同。具有三个取代基的化合物必须采用其中两个处于赤道位置的构象。CD谱的符号可以从这个假设中预测。用MM 2软件计算了2，3-二甲基环己酮的最稳定构象，由于3-甲基的存在，该反应存在着匹配和错配，因此该反应操作简单，产物ee值高，是合成cic-2，3-二甲基-2-取代环己酮衍生物的一个非常有用的方法。这是该反应应用于三取代环己酮的第一个例子。

In the first year, a research work on the reaction of the imine from (S)-(-)-phenylethylamine and 2-methylcyclohexanone and 2-ethylcyclohexanone with methyl acrylate has been carried out. In the second year, this extended to 2-allyl-, 2-isopropyl-, 2-octylcyclohexanone, and disubstituted cyclohexanones, 2-methyl-4-t-butyl and 2-ethyl-4-t-butylcyclohexanones. The absolute configurations of keto esters obtained in these reactions were established by X-ray crystallography. The stereochemistries of keto esters with three substituents have been examined by 600 MHz NMR spectroscopy, and the conformations were thus determined. The sign of the CD spectra for derivatives of 2-methylcyclohexanone series was (+), while those for 2-ethyl series and other derivatives examined was (-). The difference is not due to the misassignment of the absolute configuration, nor the front octant. The difference of the sign of the CD spectra between 2-methyl and 2-ethylcyclohexanones must be due to the conformation of the 6-membered ring. Compounds having three substituents must adopt the conformation that two of them are in the equatorial position. The sign of the CD spectrum is predictable from this assumption. The most stable conformations were calculated by MM2 with CONFLEX.In the case of 2, 3-dimethylcyclohexanone, matching and mismatching combinations exist due to the 3-methyl group and thus this reaction is highly useful for synthesis of cic-2, 3-dimethyl-2-substitutedcyclohexanone derivative because it is easy to operate and ee's of the products are usually high. This is the first example of the application of this reaction to the trisubstituted cyclohexanones.