Tcyrulnikov Sergei, Kozlowski Marisa C
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
J Org Chem. 2020 Mar 6;85(5):3465-3472. doi: 10.1021/acs.joc.9b03203. Epub 2020 Feb 12.
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 LPd 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.
研究了钯催化的三种模型烯醇盐α-芳基化反应的机理，重点分析了它们截然不同的反应活性。特别探讨了在标准芳基化条件下硝酮酸酯的低反应活性及其对催化体系性质的高敏感性。研究了每个反应体系的三个典型步骤，并描绘了中间体和过渡态稳定性的关键趋势。提出了一个基于分子轨道分析和软硬酸碱（HSAB）理论的框架来解释观察到的反应活性趋势。发现烯醇盐的局部软度是控制烯醇盐-催化剂络合物能量的关键参数。硝基烷烯醇盐的低反应活性归因于还原消除缓慢，这是硝酮酸酯硬性质的结果。对含有布赫瓦尔德配体的钯催化剂催化硝基甲烷α-芳基化反应活性的分析表明，LPd物种的不稳定是一种主要的非烯醇盐特异性加速机制，而电子云密度较低的配体加速还原消除是一种硝酮酸酯特异性机制。概述了有利于碳芳基化而非氧芳基化的相应能量学和可行性。
