Enantioselective C-H Amination Catalyzed by Nickel Iminyl Complexes Supported by Anionic Bisoxazoline (BOX) Ligands.
Enantioselective C-H Amination Catalyzed by Nickel Iminyl Complexes Supported by Anionic Bisoxazoline (BOX) Ligands.
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DOI：
10.1021/jacs.0c09839
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发表时间：
2021-01-20
影响因子：
15
通讯作者：
Betley, Theodore A.
中科院分区：
文献类型：
--
作者：
Dong, Yuyang;Lund, Colton J.;Porter, Gerard J.;Clarke, Ryan M.;Zheng, Shao-Liang;Cundari, Thomas R.;Betley, Theodore A.
制备了三烷基取代双恶唑啉（TrHBOX）作为先前报道的具有闭环胺化催化能力的镍双吡啶体系的手性类似物。配体金属化与二价NiI2(py)4，然后钾石墨还原得到单价（TrHBOX）Ni(py)(4)。将1.4等量的1-adamantylazide苯溶液缓慢加入到4中，生成四氮基（TrHBOX）Ni(κ2-N4Ad2)(5)和末端亚胺基加合物（TrHBOX）Ni(NAd)(6)。通过单晶x射线晶体学、核磁共振和EPR光谱以及计算对6进行了研究，发现其具有Ni(II)-亚胺基自由基形式，与其同系物二吡啶酸相似。配合物4表现出分子内C-H键胺化的对映选择性，从4-芳基-2-甲基-2-叠氮戊烷中产生n -杂环产物。催化C - h胺化发生在温和的条件下（5 mol%的催化剂，60°C），在中等ee（高达73%）的条件下，以良好的收率（29%-87%）提供吡咯烷产品。在4-芳基位置上有3,5-二烷基取代的底物使观察到的对映体选择性最大化。采用1H和19F核磁共振光谱对反应机理进行了动力学研究。一个小的分子间动力学同位素效应（1.35±0.03）表明h原子的提取步骤具有不对称过渡态，而反应速率在催化剂浓度下为一级，在底物浓度下为零级。对映体特异性氘标记研究表明，对映体选择性是由h原子抽离和自由基重组步骤决定的，因为自由基旋转和C-N键形成之间的速率相当。此外，理论计算证实了两步反应的竞争因素，其中h -从亲r构型中去除，而碳基的Si面发生优先自由基捕获，可能导致观察到的ee减少。基于这些对映决定步骤，证明了2,5-二叔吡咯烷的催化对映选择性合成具有良好的产率（50-78%）和中等的ee（高达79%）。
The trityl-substituted bisoxazoline (TrHBOX) was prepared as a chiral analogue to previously reported nickel dipyrrin system capable of ring-closing amination catalysis. Ligand metallation with divalent NiI2(py)4 followed by potassium graphite reduction afforded the monovalent (TrHBOX)Ni(py) (4). Slow addition of 1.4 equivalent of a benzene solution of 1-adamantylazide to 4 generated the tetrazido (TrHBOX)Ni(κ2-N4Ad2) (5) and terminal iminyl adduct (TrHBOX)Ni(NAd) (6). Investigation of 6 via single-crystal X-ray crystallography, NMR and EPR spectroscopies, and computations revealed a Ni(II)-iminyl radical formulation, similar to its dipyrrinato congener. Complex 4 exhibits enantioselective intramolecular C–H bond amination to afford N-heterocyclic products from 4-aryl-2-methyl-2-azidopentanes. Catalytic C–H amination occurs under mild conditions (5 mol% catalyst, 60 °C) and provides pyrrolidine products in decent yield (29%–87%) with moderate ee (up to 73%). Substrates with a 3,5-dialkyl substitution on the 4-aryl position maximized the observed enantioselectivity. Kinetic studies to probe the reaction mechanism were conducted using 1H and 19F NMR spectroscopies. A small, intermolecular kinetic isotope effect (1.35 ± 0.03) suggests an H-atom abstraction step with an asymmetric transition state while the reaction rate is measured to be first order in catalyst and zeroth order in substrate concentrations. Enantiospecific deuterium labelling studies show that the enantioselectivity is dictated by both the H-atom abstraction and radical recombination steps due to the comparable rate between radical rotation and C–N bond formation. Furthermore, the competing elements of the two-step reaction where H-removal from the pro-R configuration is preferred while the preferential radical capture occurs with the Si face of the carboradical likely lead to the diminished ee observed, as corroborated by theoretical calculations. Based on these enantio-determining steps, catalytic enantioselective synthesis of 2,5-bis-tertiary pyrrolidines is demonstrated with good yield (50–78%) and moderate ee (up to 79 %).
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影响因子：
15
作者：
Bagh B;Broere DLJ;Sinha V;Kuijpers PF;van Leest NP;de Bruin B;Demeshko S;Siegler MA;van der Vlugt JI
通讯作者：
van der Vlugt JI
影响因子：
56.9
作者：
Carsch, Kurtis M.;DiMucci, Ida M.;Betley, Theodore A.
通讯作者：
Betley, Theodore A.
影响因子：
16.6
作者：
Dai, Xi-Jie;Engl, Oliver D.;Buchwald, Stephen L.
通讯作者：
Buchwald, Stephen L.
影响因子：
4.9
作者：
Dong, Yuyang;Clarke, Ryan M. M.;Betley, Theodore A. A.
通讯作者：
Betley, Theodore A. A.
影响因子：
3.6
作者：
DALE, JA;DULL, DL;MOSHER, HS
通讯作者：
MOSHER, HS