Diastereoselective Construction of Contiguous Chilal Centers by the Aldol Reaction of Acylsilane Silyl Enol Ethers.

通过酰基硅烷甲硅烷基烯醇醚的羟醛反应非对映选择性构建连续手性中心。

基本信息

批准号：
03650694
负责人：
NAKAJIMA Tadashi
金额：
$ 1.22万
依托单位：
KANAZAWA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

There has been considerable interest in recent years in the stereoselective formation of multiple chiral centers using aldol reaction between prochiral enolates and aldehydes. We disclosed here an convenient method of diastereoselective construction of the three or four contiguous chiral centers using the Lewis acid mediated reaction of acylsilane silyl enol ethers (I) with acetals and the subsequent nucleophilic addition to the carbonyl group of the resulting acylsilanes (II).Treatment of E-or Z-acylsilane silyl enol ethers (I) derived from acylsilanes having enolizable methylene proton with a mixture of aldehyde dimethylacetals and TiCl_4 in dichloromethane gave the corresponding 2,3-anti-3-methoxy-1-silyl-1-alkanones (II) in high diastereo excess,independent of the double bond stereochemistry of I used. The similar reaction of E-I with d,1-phenylpropionealdehyde afforded 2,3-syn-3,4-syn-3-methoxy-1-silyl-1-butanal (V) in high stereoselectivity.The resulting acylsilane 2,3-anti-II and 2,3-syn-3,4-syn-V were subjected to the nucleophilic reaction with alkyl or phenyllithium to yield the corresponding 3-methoxy-1-silyl-1-alkanols with three and four contiguous asymmetric centers (III and VI, respectively) stereoselectively. The protiodesilylation of III and VI with F^- reagent to afford the corresponding 1,2-anti-al- kanols with three and four contiguous asymmetric centers, IV and VII in 95-99% diastereo excess.

近年来，使用甲醛和醛之间的醛醇反应，近年来，人们对多手性中心的立体选择性形成引起了极大的兴趣。我们在这里披露了一种方便的非对映选择构造方法，该方法使用刘易斯酸介导的乙二胺甲硅烷基烯醇乙醇（I）与乙酰基的反应以及随后的亲核组织添加了结果的酰基硅烷（II）。源自具有可烯烃的亚甲基质子的酰基硅烷的E-OR Z-酰基甲硅烷基乙二胺烯醇（I），二氯甲基乙酰胺的混合物和二氯甲烷中的TICL_4的混合高映射过量的烷烃（II），与使用的双键立体化学无关。 E-I与D，1-苯基丙二醇的类似反应在高立体选择性中提供2,3-Syn-3,4-Syn-Syn-3-Syn-3-甲氧基-1-甲硅烷基-1-丁烷（V）。将-II和2,3-Syn-3,4-Syn-V与烷基或苯基矿体进行亲核反应，以产生相应的3-甲氧基-1-甲硅烷基-1-烷醇，三个和四个连续的不对称中心（IIII III）和vi，分别是立体选择性的。 III和VI的Protiodesilylation用F^ - 试剂提供的，可提供相应的1,2-抗Al- kanols，具有三个和四个连续的不对称中心，IV和VII，在95-99％的映射中过量。