Accounting for Strong Ligand Sensitivity in Pd-Catalyzed α-Arylation of Enolates from Ketones, Esters, and Nitroalkanes
Accounting for Strong Ligand Sensitivity in Pd-Catalyzed α-Arylation of Enolates from Ketones, Esters, and Nitroalkanes
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考虑到酮、酯和硝基烷烃的钯催化烯醇化α-芳基化中的强配体敏感性
DOI：
10.1021/acs.joc.9b03203
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Kozlowski, Marisa C.
中科院分区：
文献类型：
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作者：
Tcyrulnikov, Sergei;Kozlowski, Marisa C.
研究了钯催化的三种模型烯醇化物的α-芳基化反应机理，重点分析了它们的反应性差异。特别是，在标准的芳基化条件下，其高灵敏度的性质的催化系统的硝基膦酸酯的低反应性得到解决。每个反应系统的三个典型步骤进行检查，并围绕中间体和过渡态的稳定性的关键趋势划定。基于分子轨道分析和软硬酸碱（HSAB）理论的框架来解释所观察到的反应性趋势。发现烯醇化物的局部柔软度是控制烯醇化物-催化剂络合物的能量的关键参数。硝基烷烯醇化物的低反应性归因于缓慢的还原消除，这是硝基膦酸盐的硬性质的结果。对硝基甲烷与含Buchwald配体的Pd催化剂进行α-芳基化反应的反应性分析表明，L2 Pd物种的不稳定是主要的非烯醇化物特异性加速机制，而较少的富电子配体加速还原消除是硝基特异性机制。相应的能量和可行性，有利于C-芳基化与O-芳基化的概述。
The mechanism of the Pd-catalyzed α-arylation of three model enolates is studied focusing on an analysis of their very different reactivities. In particular, the low reactivity of nitronates under standard arylation conditions and their high sensitivity to the nature of catalytic systems are addressed. The three canonical steps for each of the reaction systems are examined, and key trends surrounding the stability of intermediates and transition states are delineated. A framework based on molecular orbital analyses and the hard–soft acid–base (HSAB) theory is advanced to explain the observed reactivity trends. The local softness of the enolates was found to be a key parameter controlling the energy of the enolate–catalyst complexes. The low reactivity of the nitroalkane enolates is attributed to slow reductive elimination, a consequence of the hard nature of the nitronate. Analysis of reactivity of nitromethane in α-arylation with Pd catalysts containing Buchwald ligands reveals destabilization of the L2Pd species as a major non-enolate-specific acceleration mechanism as well as less electron-rich ligands accelerating reductive elimination as a nitronate-specific mechanism. The corresponding energetics and feasibility that favor C-arylation versus O-arylation are outlined.