Stereoselectivity of the nucleophilic addition of organocopper reagents to chiral .alpha.,.beta.-unsaturated carbonyl compounds. Ab initio molecular orbital studies of steric and electronic effects
Stereoselectivity of the nucleophilic addition of organocopper reagents to chiral .alpha.,.beta.-unsaturated carbonyl compounds. Ab initio molecular orbital studies of steric and electronic effects
复制标题
有机铜试剂与手性α，β-不饱和羰基化合物的亲核加成的立体选择性。
DOI：
10.1021/ja00199a008
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发表时间：
1989
影响因子：
15
通讯作者：
K. Morokuma
中科院分区：
文献类型：
--
作者：
A. Dorigo;K. Morokuma
对甲基铜与取代烯醛的共轭加成反应进行了从头算分子轨道研究。对甲基铜与（E）-和（Z）-2-丁烯醛加成反应的过渡结构进行了定位，并分析了甲基和羟基取代基对这两种过渡态7-碳原子的影响。在与（E）-和（Z）-2-戊烯醛的反应中，过渡态中最稳定的构象具有与引入的亲核试剂反式的甲基，其中外部位置优先于内部位置。这些构象偏好很容易根据三个位置的相对立体阻碍来合理化。另一方面，发现由羟基基团表现出的构象偏好主要由电子因素决定。因此，在4-羟基-2-丁烯醛的E和Z异构体的加成中，空间上不受阻碍的反位对于羟基是最不利的。结果表明，吸电子基团在反位不稳定的过渡态，而电子供体有利于反位。从这些计算中，我们已经推导出过渡态模型，我们已经使用该模型来预测手性4-烷氧基，β-不饱和羰基化合物的加成的非对映异构体过量。E异构体优选其中烷基和烷氧基分别占据过渡结构中的反位和内侧位置的构象。在Z异构体中，有利的构象是烷基在亲核试剂的外面，烷氧基在里面;这种构象导致另一种非对映异构体的形成。在这两种情况下都发现了与所观察到的立体选择性的良好一致性。我们还进行了模型计算，合理化的立体选择性，除了E和Z异构体轴承上的7-碳芳基。这些计算表明，在E异构体的有利构象具有芳基和甲基基团的反和内部的位置，分别。在Z异构体中，芳基位于外侧，甲基位于反侧，因此预测在两种情况下相同的非对映体是主要产物。这也与最近报道的实验观察结果相一致。最近的文献中出现了一些关于亲核试剂加成羰基化合物的高水平理论研究。这些研究中的许多涉及这些反应的立体化学方面。[1]因此，理论开始赶上自从克拉姆在近40年前开创这一领域以来积累的大量实验证据。[2]克拉姆规则和Karabatsos、[3] Felkin、[4]和Anh [5]的连续重新解释已成为解释和预测反应立体化学过程的指导方针。最近的理论和实验证据都为Felkin和Anh的过渡态模型提供了强有力的支持（图1）。6· 7
Ab initio molecular orbital studies have been conducted on the conjugate additionof methylcopper to substituted enals. Transition structures have been located for the addition of methylcopperto (E)-and (Z)-2-butenal, and the effect of the methyl and hydroxyl substituents on the 7-carbon has been analyzed for both transition states. In the reaction with both (£)-and (Z)-2-pentenal, the most stable conformation in the transition statehas the methyl group anti to the incoming nucleophile, with the outside position being preferred to the inside position. These conformational preferences are readily rationalized in terms of the relative steric encumbrance of the three positions. On the other hand, the conformational preference exhibited by the hydroxyl group is found to be dictated primarily by electronic factors. Thus, in the addition to both E and Z isomers of 4-hydroxy-2-butenal, the sterically unhindered anti position is the least favorable for the hydroxyl group. It is shown that electron-withdrawing groups in the anti position destabilize the transition state, whereas electron donors favor the anti position. From these calculations we have derived transition-state models that we have used to predict the diastereomeric excess of the addition to chiral 4-alkoxy,/3-unsaturated carbonyl compounds. E isomers prefer a conformation in which the alkyl and alkoxy group occupy the anti and inside positions, respectively, in the transition structure. In the Z isomers the favored conformation has the alkyl group outsidethe nucleophile and the alkoxy group inside; this conformation leads to formation of the other diastereoisomer. Good agreement with the observed stereoselectivity has been found in both cases. We have also performed model calculations that rationalize the stereoselectivity of the addition to E and Z isomers bearing an aryl group on the 7-carbon. These calculations suggest that the favored conformation inE isomers has the aryl and methyl groups in the anti and inside positions, respectively. In Z isomers, the aryl group lies outside and the methyl group anti, so that the same diastereomer is predicted tobe the major product in both cases. This is also in agreement with recently reported experimentalobservations.Several high-level theoretical studies of the additionof nu-cleophiles to carbonyl compounds have appeared in the recent literature. Many of these investigations deal with the stereo-chemical aspects of these reactions. 1 Theory is thus starting to catch up with a wealth of experimental evidence accumulated ever since Cram pioneered the field almost forty years ago. 2 Cram’s rule and successive reinterpretations by Karabatsos, 3 Felkin, 4and Anh5 have become guidelines for the interpretation and prediction of the stereochemical course of the reaction. Recent evidence, both theoretical and experimental, provides strong support in favor of Felkin’s and Anh’s transition-state model (Figure l). 6· 7