STEREOSELECTIVE ADDITION OF ORGANOCOPPER REAGENTS TO ACETYLENIC ESTERS AND AMIDES - SYNTHESIS OF JUVENILE-HORMONE ANALOGS
STEREOSELECTIVE ADDITION OF ORGANOCOPPER REAGENTS TO ACETYLENIC ESTERS AND AMIDES - SYNTHESIS OF JUVENILE-HORMONE ANALOGS
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DOI：
10.1021/ja00838a039
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发表时间：
1975-01-01
影响因子：
15
通讯作者：
SIDDALL, JB
中科院分区：
文献类型：
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作者：
ANDERSON, RJ;CORBIN, VL;SIDDALL, JB
本文讨论了某些有机铜(I)试剂与3-乙酰基酯的立体选择性共轭加成，得到取代的/3-不饱和酯，用于合成三取代双键，特别是保幼激素类似物甲基(2.E，6 GB)-3，7-二乙基-CZT-10，L 1-环氧基-11-甲基-2，6-十三碳二烯酸酯(JH0，ID)和2E，6E，反式-0异构体18C的制备。概述了反应条件和有机铜试剂的类型对产物立体化学的影响。二正烷基铜酸锂的两个烷基都可以转移到乙酰酯上。由烷基锂制备的聚合铜试剂具有最好的整体效果。甲基(亚铁-丁基)铜酸锂络合物选择性地将叔丁基转移到2-丁酸甲酯。还给出了有机铜(I)试剂与3-乙酰基酰胺的立体选择性共轭加成反应的一些例子。给出了ID和18C对三种昆虫的生物活性，并与已知天然保幼激素的生物活性进行了比较。值得注意的是最近几年三取代双键的立体选择性合成。4最重要的是，Roller等人对C-18 Cecropia保幼激素lc(Jhi)的结构阐明促进了许多此类立体选择性烯烃合成的发展。6观察到LC及其相关化合物的2Z和6Z异构体的生物活性远低于2E和6E异构体，表明天然幼体单体的几何构型对高生物活性是重要的。因此，我们自己和其他实验室开始了研究，以开发合成液晶和相关类似物的立体选择性方法。
The stereoselective conjugate addition of some organocopper (I) reagents to,/3-acetylenic esters to givesubstituted,/3-unsaturated esters is discussed, as applied to the synthesis of trisubstituted double bonds, and in particular the prepara-tion of the juvenile hormone analog methyl (2. E, 6£)-3, 7-diethyl-czT-10, l 1-epoxy-11-methyl-2, 6-tridecadienoate (JH 0, Id) and the 2E, 6E, trans-\0 isomer 18c. The effects of the reaction conditions and of the type of organocopper (I) reagent used on the stereochemistry of the product are outlined. Both alkyl groups of a lithium di-n-alkylcuprate can be transferred to the acetylenic ester. Polymeric copper reagents prepared from alkyllithiums give the best overall results. The lithium methyl-(fert-butyl) cuprate complex selectively transfers the tert-butyl group to methyl 2-butynoate. Some examples are also given for thestereoselective conjugate additionof organocopper (I) reagents to,/3-acetylenic amides. The biological activities of Id and 18c on three insect species are given and compared with those found for the known natural juvenile hormones.Considerable attention has been focusedin the last few years on the stereoselective synthesis of trisubstituted double bonds. 4 More than anything else, the structure elucidation of the C-18 cecropia juvenile hormone lc (JH I) by Roller, et al., 5 prompted the development of many of these stereoselective olefin syntheses. 6 The observation, that the 2Z and 6Z isomers of lc and related compounds showed much lower biological activities than the 2E, 6E isomers, demonstrated that the geometry of the natural juvenile hor-mone was important for high biological activity. 7 Thus, investigations began in our own and in other laboratories to develop stereoselective methods for the synthesis of lc and related analogs.