钐离子促进的交叉羟醛缩合反应及串联羟醛缩合/埃文斯-蒂申科反应

Lu Ling, Chang Hung-Yu, Fang Jim-Min

Department of Chemistry, National Taiwan University, Taipei, Taiwan 106, Republic of China.

J Org Chem. 1999 Feb 5;64(3):843-853. doi: 10.1021/jo981675b.

Cross-aldol reactions of carbonyl compounds were achieved by the catalysis of SmI(2) or SmI(3), together with molecular sieves, at ambient temperature. 1,3-Dichloroacetone and 1-chloroacetone can be used as acceptor substrates in the cross-aldol reactions with donor substrates such as acetone, cyclopentanone, and cyclohexanone. The cross-aldol reactions with (R)-glyceraldehyde acetonide gave optically pure compounds 25-32, the stereochemistry of which was in agreement with a chairlike chelate transition state of dipolar mode. SmI(2)-molecular sieves or SmI(3)-molecular sieves also functioned as effective Lewis acids to catalyze tandem aldol/Evans-Tishchenko reactions. The aldol/Evans-Tishchenko reactions of methyl ketones with aldehydes occurred at 0 degrees C to give alpha,gamma-anti diol monoesters 53a-59a. When the reactions were conducted at room temperature, a certain degree of transesterification took place. The aldol/Evans-Tishchenko reactions of ethyl or benzyl ketones with aldehydes yielded alpha,beta-anti-alpha,gamma-anti diol monoesters 60a-65a. However, the aldol/Evans-Tishchenko reactions of cyclic ketones with benzaldehyde occurred with a different stereoselectivity to give alpha,beta-syn-alpha,gamma-anti diol monoesters 66a-76a. The structures of products were determined by chemical and spectroscopic methods including an X-ray diffraction analysis of 72a derived from the reaction of 4-tert-butylcyclohexanone and benzaldehyde. A reaction mechanism involving dissociation-recombination of aldols followed by intramolecular stereoselective hydride shift is proposed, based on some experimental evidence, to explain the dichotomous stereoselectivity using acyclic or cyclic ketones as the reaction substrates.

在室温下，通过二碘化钐（SmI₂）或三碘化钐（SmI₃）与分子筛的催化作用，实现了羰基化合物的交叉羟醛缩合反应。1,3 - 二氯丙酮和1 - 氯丙酮可作为受体底物，与供体底物如丙酮、环戊酮和环己酮发生交叉羟醛缩合反应。与（R）-甘油醛丙酮化物的交叉羟醛缩合反应得到了光学纯的化合物25 - 32，其立体化学与偶极模式的椅状螯合过渡态一致。SmI₂ - 分子筛或SmI₃ - 分子筛也可作为有效的路易斯酸，催化串联羟醛缩合/埃文斯 - 蒂申科反应。甲基酮与醛的羟醛缩合/埃文斯 - 蒂申科反应在0℃下进行，生成α,γ - 反式二醇单酯53a - 59a。当反应在室温下进行时，会发生一定程度的酯交换反应。乙基或苄基酮与醛的羟醛缩合/埃文斯 - 蒂申科反应生成α,β - 反式 - α,γ - 反式二醇单酯60a - 65a。然而，环酮与苯甲醛的羟醛缩合/埃文斯 - 蒂申科反应具有不同的立体选择性，生成α,β - 顺式 - α,γ - 反式二醇单酯66a - 76a。通过化学和光谱方法确定了产物的结构，包括对由4 - 叔丁基环己酮与苯甲醛反应得到的72a进行X射线衍射分析。基于一些实验证据，提出了一种反应机理，即羟醛缩合物发生解离 - 重组，随后进行分子内立体选择性氢化物转移，以解释以无环或环酮作为反应底物时的二分立体选择性。