Development of New Methods for Acyclic Stereocontrol and Their Application

(1)路易斯酸介导的有机铜试剂在反式-烷氧基- α， β -不饱和酯上偶联加成得到反异构体，而在顺式衍生物上加成得到顺式异构体。这种非对映选择性的变化表明了双键几何形状在控制-烷氧基- α， β -不饱和羰基化合物的1,2-不对称诱导中的重要性。RCu（有机铜）和R_2CuLi（有机铜酸盐）与反式-烷基- - -不饱和酯的共轭加成得到反异构体，而铜酸盐与顺式酯的共轭加成得到顺式异构体。这一变化表明在共轭加成过程中，试剂类型对控制1,2-不对称诱导的重要性。综上所述，在共轭加法中提出了过渡态几何的新模型。(2)同样地，我们也研究了共轭还原中的1,2-不对称感应。在这里，试剂类型在控制诱导中起着重要的作用。在单电子事件和双电子事件之间观察到显著的立体化学差异。(3) n -苄基三甲基硅基酰胺锂（LSA）以1,4方式选择性地加入到巴罗酮酸盐中，而普通锂酰胺与α， β -不饱和酯的反应伴随着1,2加成和抽氢。通过LSA进行共轭加成，然后用亲电试剂捕获烯酸酯，产生相应的α -取代-氨基酯，这些氨基酯依次转化为β -内酰胺和α -取代- α， β -不饱和酯。高度立体选择性生成β -氨基酯的Z-和e -烯醇酯的方法是建立在将LSA偶联添加到甲基巴豆酸盐的基础上的。(4) -甲硅氧基- - -不饱和酯与有机氰铜- bf_3试剂反应，产率很高，生成- -烷基- - -不饱和酯。(5)有机金属-路易斯酸配合物（R_4Pb-TiCl_4, R_2Zn-BF_3，…）与乙酰铝离子的反应具有很高的非对映面性和非对映选择性。该反应用于合成他汀类药物。少

(1) The Lewis acid mediated conjugate addition of organocopper reagents to the trans-gamma-alkoxy- alpha, beta-unsaturated ester produces the anti-isomer, while addition to the cis-derivatives gave the syn-isomer. This change in diastereoselectivity indicates the importance of the double bond geometry in controlling the 1,2-asymmetric induction of gamma-alkoxy-alpha, beta-unsaturated carbonyl compounds. The conjugate addition of RCu (organocopper) and R_2CuLi (organocuprate) to the trans-gamma-alkyl-alpha, beta-unsaturated esters produced the anti-isomer, while addition of cuprates to the cis esters gave the syn-isomers. This change indicates the importance of reagent type in controlling 1,2-asymmetric induction during conjugate addition. Taken together, the new models for the transition state geometry have been proposed in the conjugate addition. (2) Quite similarly, the 1,2-asymmetric induction in conjugate reduction has been investigated. Here again, the reagent types play an import … More ant role in controlling the induction. Remarkable stereochemical difference is observed between one- and two-electron events. (3) Lithium N-benzyltrimethylsilylamide (LSA) adds to crotonates selectively in a 1,4-manner, though the reaction of ordinary lithium amides with alpha, beta-unsaturated esters is accompanied with a 1,2-addition and hydrogen abstraction at the gamma-position. The conjugate addition via LSA followed by enolate trapping with electrophiles produces the corresponding alpha-substituted beta-amino esters, which are in turn converted into beta-lactam and alpha-substituted alpha, beta-unsaturated esters. Methods for highly stereoselective generation of both Z- and E-enolates of a beta-amino ester are developed on the basis of a conjugate addition of LSA to methyy crotonate. (4) The reaction of gamma-mesiloxy-alpha, beta-unsaturated esters with organocyanocopper-BF_3 reagents produces alpha-alkyl-beta, gamma-unsaturated esters in very high yields. The substitution proceeds in an anti-S_N2' manner, and this 1,3-chiral transfer always takes place with nearly 100 % ee or de. (5) The reaction of organometallic-Lewis acid complexes (R_4Pb-TiCl_4, R_2Zn-BF_3...) with acyliminium ions proceeds with very high diastereofacial and diastereo-selective manner. The reaction is applied for the synthesis of statine. Less