烷氧基取代芳环上的 Grignard 试剂的反应机理及异常反应理论预测的实验验证。
Mechanism of alkoxy groups substitution by Grignard reagents on aromatic rings and experimental verification of theoretical predictions of anomalous reactions.
机构信息
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1569, USA.
出版信息
J Am Chem Soc. 2013 May 1;135(17):6633-42. doi: 10.1021/ja4015937. Epub 2013 Apr 22.
Abstract
The mechanism of direct displacement of alkoxy groups in vinylogous and aromatic esters by Grignard reagents, a reaction that is not observed with expectedly better tosyloxy leaving groups, is elucidated computationally. The mechanism of this reaction has been determined to proceed through the inner-sphere attack of nucleophilic alkyl groups from magnesium to the reacting carbons via a metalaoxetane transition state. The formation of a strong magnesium chelate with the reacting alkoxy and carbonyl groups dictates the observed reactivity and selectivity. The influence of ester, ketone, and aldehyde substituents was investigated. In some cases, the calculations predicted the formation of products different than those previously reported; these predictions were then verified experimentally. The importance of studying the actual system, and not simplified models as computational systems, is demonstrated.
摘要
通过计算阐明了 Grignard 试剂对乙烯基和芳基酯中烷氧基的直接取代反应的机理，该反应在预期具有更好的甲苯氧基离去基团时并未观察到。该反应的机理被确定为通过金属氧杂环丁烷过渡态，从镁原子内球进攻反应碳上的亲核烷基基团。与反应的烷氧基和羰基形成强镁螯合物决定了观察到的反应性和选择性。研究了酯、酮和醛取代基的影响。在某些情况下，计算预测了与以前报道的不同的产物的形成；然后通过实验验证了这些预测。证明了研究实际体系而不是计算体系中的简化模型的重要性。
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