Investigation of the C-N Bond-Forming Step in a Photoinduced, Copper-Catalyzed Enantioconvergent N-Alkylation: Characterization and Application of a Stabilized Organic Radical as a Mechanistic Probe.
Investigation of the C-N Bond-Forming Step in a Photoinduced, Copper-Catalyzed Enantioconvergent N-Alkylation: Characterization and Application of a Stabilized Organic Radical as a Mechanistic Probe.
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DOI：
10.1021/jacs.1c13151
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发表时间：
2022-03-09
影响因子：
15
通讯作者：
Peters, Jonas C.
中科院分区：
文献类型：
--
作者：
Lee, Heejun;Ahn, Jun Myun;Oyala, Paul H.;Citek, Cooper;Yin, Haolin;Fu, Gregory C.;Peters, Jonas C.
而光诱导，铜催化偶联的氮亲核试剂与烷基亲电试剂最近已被证明提供了一个有吸引力的方法来实现各种对映选择性的C-N键结构，这些转换的机理研究滞后于反应发展的进展。在本文中，我们提供了一个以前报道的光诱导，铜催化的咔唑亲核试剂与外消旋叔α-卤代酰胺亲电试剂的对映会聚C-N偶联的机理洞察。在分离出一个铜（II）模型络合物（其EPR参数作为指导）的基础上，我们独立地合成了所提出的催化循环中的两个关键中间体，一个铜（II）金属自由基，（L*CuII（carb'）2）（L* =单齿手性膦配体; carb' =咔唑配体）以及叔α-酰胺有机基团（R·）;用密度泛函理论（DFT）计算了R·的产生和表征，表明它对同偶联是稳定的.连续波（CW）和脉冲EPR研究，沿着与相应的DFT计算，是用来表征这些活性自由基的技术。我们确定这两个自由基确实联合收割机以良好的产率和显著的对映体过量（77%产率，55%ee）提供C-N偶联产物，从而支持这些提出的中间体的化学能力。DFT计算与R·最初通过自由基的闭壳羰基氧原子的配价相互作用与铜（II）结合一致，该配价相互作用定位α碳以直接与铜（II）结合的咔唑N-原子反应，以产生具有对映选择性的C-N键，而不形成烷基铜（III）中间体。
Whereas photoinduced, copper-catalyzed couplings of nitrogen nucleophiles with alkyl electrophiles have recently been shown to provide an attractive approach to achieving a variety of enantioselective C-N bond constructions, mechanistic studies of these transformations have lagged the advances in reaction development. Herein we provide mechanistic insight into a previously reported photoinduced, copper-catalyzed enantioconvergent C–N coupling of a carbazole nucleophile with a racemic tertiary α-haloamide electrophile. Building on the isolation of a copper(II) model complex whose EPR parameters serve as a guide, we independently synthesize two key intermediates in the proposed catalytic cycle, a copper(II) metalloradical, (L*CuII(carb’)2) (L* = a monodentate chiral phosphine ligand; carb’ = a carbazolide ligand), as well as a tertiary α-amide organic radical (R·); the generation and characterization of R· was guided by DFT calculations, which suggested that it would be stable to homocoupling. Continuous-wave (CW) and pulse EPR studies, along with corresponding DFT calculations, are among the techniques used to characterize these reactive radicals. We establish that these two radicals do indeed combine to furnish the C–N coupling product in good yield and with significant enantiomeric excess (77% yield, 55% ee), thereby supporting the chemical competence of these proposed intermediates. DFT calculations are consistent with R· initially binding to copper(II) via a dative interaction from the closed-shell carbonyl oxygen atom of the radical, which positions the α carbon for direct reaction with the copper(II)-bound carbazole N-atom, to generate the C–N bond with enantioselectivity, without the formation of an alkylcopper(III) intermediate.
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DOI：
10.1002/cber.19891220322
发表时间：
1989-03-01
期刊：
CHEMISCHE BERICHTE
影响因子：
--
作者：
DUNNEBACKE, D;NEUMANN, WP;STEWEN, U
通讯作者：
STEWEN, U
影响因子：
15
作者：
EISENBERG, DC;LAWRIE, CJC;NORTON, JR
通讯作者：
NORTON, JR
影响因子：
56.9
作者：
Creutz, Sidney E.;Lotito, Kenneth J.;Peters, Jonas C.
通讯作者：
Peters, Jonas C.
影响因子：
15
作者：
Bartoszewicz, Agnieszka;Matier, Carson D.;Fu, Gregory C.
通讯作者：
Fu, Gregory C.
影响因子：
5.2
作者：
Michelet, Bastien;Deldaele, Christopher;Evano, Gwilherm
通讯作者：
Evano, Gwilherm