Nickel-Catalyzed Three-Component Cycloadditions of Enoates, Alkynes, and Aldehydes
Nickel-Catalyzed Three-Component Cycloadditions of Enoates, Alkynes, and Aldehydes
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镍催化烯酸酯、炔烃和醛的三组分环加成
DOI：
10.1021/acs.joc.9b02446
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Montgomery, John
中科院分区：
文献类型：
--
作者：
Jenkins, Aireal D.;Robo, Michael T.;Zimmerman, Paul M.;Montgomery, John
发展了一种烯、炔、醛三组分环加成反应的方法。在化学计量生成的金属杂环进行烷基化的基础上，我们报道了一个催化的烷基化[3 + 2]环加成反应。从简单的起始原料，可以快速组装结构复杂的环戊烯酮。对机制（ω B 97 X-D3/cc-pVTZ//ω B 97 X/6- 31 G（d））的计算研究确定了三个能量上可行的途径。基于烯酮形成的相对速率与异构化成七元金属配体相比，最可能的机理已被确定为“烯酮优先”发生，在羟醛加成之前进行碳环化。氘标记研究表明，当使用α-取代的烯酸酯时，七元金属乳糖的形成成为可能。这种观察到的选择性变化是由于包含额外的空间体积的α-取代基而增加了酚盐消除的难度。净转化导致[3 + 2]环加成，伴随着烯酸酯取代基的烷基化。
A method for the three-component cycloaddition of enoates, alkynes, and aldehydes has been developed. Building upon previous work by this group in which stoichiometrically generated metallacycles undergo alkylation, we report a catalytic, alkylative [3 + 2] cycloaddition. From simple starting materials, structurally complex cyclopentenones may be rapidly assembled. Computational investigation of the mechanism (ωB97X-D3/cc-pVTZ//ωB97X/6-31G(d)) identified three energetically feasible pathways. Based on the relative rates of ketene formation compared to isomerization to a seven-membered metallacycle, the most likely mechanism has been determined to occur “ketene-first”, with carbocyclization prior to aldol addition. Deuterium labeling studies suggest that formation of the seven-membered metallacycle becomes possible when an α-substituted enoate is used. This observed change in selectivity is due to the increased difficulty of phenoxide elimination with the inclusion of additional steric bulk of the α-substituent. The net transformation results in a [3 + 2] cycloaddition accompanied by an alkylation of the enoate substituent.