STEREOCHEMISTRY OF NUCLEOPHILIC-ADDITION TO CYCLOHEXANONE - THE IMPORTANCE OF 2-ELECTRON STABILIZING INTERACTIONS
STEREOCHEMISTRY OF NUCLEOPHILIC-ADDITION TO CYCLOHEXANONE - THE IMPORTANCE OF 2-ELECTRON STABILIZING INTERACTIONS
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DOI：
10.1021/ja00405a041
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发表时间：
1981-01-01
影响因子：
15
通讯作者：
CIEPLAK, AS
中科院分区：
文献类型：
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作者：
CIEPLAK, AS
本文提出了一个电子给体对羰基亲核加成过渡态的电荷转移稳定化理论。使用Bell-Evans-Polanyi原理，假设对于反应的立体选择性至关重要的这种过渡态的特征是存在与反应中形成的键相关的低位空轨道 *，并且电子离域进入该轨道将稳定过渡态，从而可以提高反应速率：动力学异头效应和动力学α效应被认为是这种稳定相互作用的例子。根据该模型，环己酮亲核加成的立体化学由两个因素决定：有利于赤道途径的空间位阻和从环己酮aCc和oCh键到 *，轨道的电子捐赠，这有利于轴向途径，因为碳-氢键是更好的电子捐赠者。因此，亲核体结构、与羰基氧络合的金属阳离子、溶剂和抗衡离子或其它溶质可通过改变η（*，）来影响反应的立体选择性。此外，委员会认为，结果表明，该模型提供了一个简单而一致的方法来合理化所谓的“远程极性取代基”的动力学和立体化学效应，这种效应不能用空间或静电相互作用来解释，但似乎是由远程电子给体轨道和 * 之间的重叠和能隙控制的。为了解释与环己酮的快速不可逆亲核加成如金属氢化物还原或有机金属化合物加成的立体化学，必须调用至少两个不同的交互。20年前，在对这一专题进行第一次重要审查时就指出了这一必要性，审查的结论如下。“...因此，六元环酮羰基亲核加成反应的空间方向显然由两个竞争因素决定：一个是使取代基进入轴向位置的因素，另一个是与之相反的因素，它取决于空间位阻并使取代基进入赤道位置。它似乎可能是第一个因素是由最终产品的热力学稳定性，但主要是与带电的取向。在极性影响的作用下，例如，与未补偿的偶极子连接
A theory of charge-transfer stabilization of the transition state for nucleophilic addition to a carbonyl group by electron donors is proposed. It is postulated, using the Bell-Evans-Polanyi principle, that the feature of this transition state critical for stereoselectivity of the reaction is the existence of a low-lying vacant orbital*, associated with the bond being formed in the reaction and that electron delocalization into that orbital will stabilize the transition state and may thereby enhance the reaction rate: thekinetic anomeric effect and thekinetic a effect are considered as the examples of such a stabilizing interaction. Stereochemistry of nucleophilic addition to cyclohexanone is determined by two factors according to this model: steric hindrance which favors the equatorial approach and electron donation from the cyclohexanone aCc and oCh bonds into the*, orbital, whichfavors the axial approach since the carbon-hydrogen bonds are better electron donors. Consequently, nucleophile structure, metal cations complexing the carbonyl oxygen, solvent, and counterions or other solutes may influence stereoselectivity of the reaction by changing the «(*,). Furthermore, it is shown that thismodel offers a simple and consistent way to rationalize kinetic and stereochemical effects of the so-called “remote polar substituents” which cannot be explained in terms of steric or electrostatic interactions but appear to be controlled by the overlap and energy gap between the remote electron-donor orbitals and the*„orbital.For an explanation of the stereochemistry of fast irreversible nucleophilic additions to cyclohexanone such as metal hydride reductions or additions of organometallic compounds, at least two different interactions must be invoked. This necessity was pointed out 2 decades ago in the first major review of the topic, which concluded in the following way.“... Thus, the steric direction of reaction of nucleophilic addition to the carbonyl group of cyclic six-membered ketones is determined, apparently, by two competitive factors: a factor directing the entering substituent into the axial position, and a factor op-posing this, depending on steric hindrance and directing the substituent into the equatorial position. It appears probable that the first factor is determined not by thermodynamic stability of the final products but is mainly connected with the orientation of the charged... attacking agent under the action of polar influ-ences... connected for example, with the uncompensated dipole