Dual Photoredox/Nickel-Catalyzed Conversion of Aryl Halides to Aryl Aminooxetanes: Computational Evidence for a Substrate-Dependent Switch in Mechanism
Dual Photoredox/Nickel-Catalyzed Conversion of Aryl Halides to Aryl Aminooxetanes: Computational Evidence for a Substrate-Dependent Switch in Mechanism
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DOI：
10.1021/acscatal.9b03596
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发表时间：
2020-01-03
期刊：
影响因子：
12.9
通讯作者：
Huestis, Malcolm P.
中科院分区：
文献类型：
--
作者：
Kolandouzan, Kavoos;Khalaf, Ryan;Huestis, Malcolm P.
通过光氧化还原和镍催化的协同作用，实现了一种温和而直接的构建芳基氨基氧杂环烷的策略。这种方法代表了在光氧化还原/镍交叉偶联中利用具有挑战性的三级自由基的罕见例子。氧杂环己烷在药物化学中经常被用作羰基或宝石-二甲基生物同位素体，但由于缺乏实用的合成方法，它们的可及性受到阻碍。本文报道的策略利用交叉偶联歧管中容易获得的氧杂环己基氨基酸构建块来快速获得具有广泛官能团耐受性的氧杂环己烷支架。计算研究表明，对于与氨氧基自由基的反应，以Ni(0)-Ni(II)氧化加成开始的催化循环，而不是从Ni(0)的自由基加成开始的催化循环。因此，对于基于自由基的光氧化还原/镍催化的交叉偶联，首选的机理途径从根本上取决于自由基的身份。
A mild and direct strategy for the construction of aryl aminooxetanes has been accomplished through the synergistic combination of photoredox and nickel catalysis. This approach represents a rare example of harnessing challenging tertiary radicals in photoredox/nickel cross-coupling. Oxetanes are often employed in medicinal chemistry as carbonyl or gem-dimethyl bioisosteres, but their accessibility is hampered by the lack of practical synthetic methods. The strategy reported here utilizes a readily available oxetanyl amino acid building block in a cross-coupling manifold to rapidly access oxetane scaffolds with broad functional group tolerance. Computational studies reveal that a catalytic cycle beginning with Ni(0)-Ni(II) oxidative addition, rather than radical addition to Ni(0), is operative for reactions with aminooxetanyl radicals. Consequently, for radical-based photoredox/nickel-catalyzed cross-couplings, the preferred mechanistic pathway has a fundamental dependence on the identity of the radical.