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

近年来，利用前手性烯醇酸酯和醛之间的Aldol反应立体选择性地形成多个手性中心的研究引起了人们的极大兴趣。我们在这里公开了一种简便的非对映选择性地构建三个或四个连续的手性中心的方法，该方法利用Lewis酸介导的酰基硅烯醇醚(I)与缩醛的反应以及随后生成的酰基硅烷(II)的羰基上的亲核加成反应。由具有烯醇化亚甲基质子的酰基硅烷衍生的E-或Z-酰基硅烯醇醚(I)与乙醛-二甲缩醛和TiCl4在二氯甲烷中的混合物处理得到相应的2，3-反-3-甲氧基-1-硅基-1-烷酮(II)。E-I与d，1-苯基丙醛的类似反应生成了具有高立体选择性的2，3-芳基-3，4-芳基-3-甲氧基-1-硅基-1-丁醛(V)，然后与烷基或苯基锂发生亲核反应，得到相应的3-甲氧基-1-硅基-1-烷醇，其中3-甲氧基-1-硅基-1-烷醇具有3个和4个连续的不对称中心(分别为III和VI)。用F^-试剂对III和VI进行脱硅反应，得到相应的具有3个和4个相邻不对称中心的1，2-反烷醇，IV和VI的非对映过量为95-99%。

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.