A General N-alkylation Platform via Copper Metallaphotoredox and Silyl Radical Activation of Alkyl Halides.
A General N-alkylation Platform via Copper Metallaphotoredox and Silyl Radical Activation of Alkyl Halides.
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DOI：
10.1016/j.chempr.2021.05.005
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发表时间：
2021-07-08
期刊：
影响因子：
23.5
通讯作者：
MacMillan DWC
中科院分区：
文献类型：
--
作者：
Dow NW;Cabré A;MacMillan DWC
通过可见光诱导的金属氧化还原平台，实现了酰胺类、磺胺类、苯胺类、亚胺类或n -杂环类化合物与广谱的电子和立体多样的烷基溴的催化结合。卤素萃取-自由基捕获（HARC）机制的使用允许使用简单的Cu（II）盐在室温下偶联C(sp3)-溴化物，有效地绕过了通常与热诱导SN2或SN1 n -烷基化相关的过高的障碍。该区域和化学选择性方案与bb1010类医学相关的n -亲核试剂兼容，包括已建立的药物制剂，以及结构多样的伯、仲、叔烷基溴。此外，HARC方法通过n -亲核试剂与环丙基溴和未活化的烷基氯的结合（与亲核取代途径不相容的底物），突出了其与传统惰性偶联伙伴的结合能力。初步的机理实验验证了该平台的双催化、开壳性质，使其具有传统卤化物基n-烷基化体系无法达到的反应性。传统的氮亲核试剂和烷基卤化物之间的取代反应在热诱导条件下具有良好的底物依赖性限制和竞争反应途径。在此，我们报告了一种利用卤素提取-自由基捕获（HARC）机制的金属光氧化还原方法，为传统的n-烷基化提供了一种有价值的替代方法。这种可见光诱导的铜催化方案成功地将bbb10类n -亲核试剂与各种伯、仲或叔烷基溴偶联。此外，这种开壳平台缓解了n-烷基化在区域选择性、直接环丙基化和仲烷基氯功能化方面的突出挑战。
The catalytic union of amides, sulfonamides, anilines, imines or N-heterocycles with a broad spectrum of electronically and sterically diverse alkyl bromides has been achieved via a visible light-induced metallaphotoredox platform. The use of a halogen abstraction–radical capture (HARC) mechanism allows for room temperature coupling of C(sp3)-bromides using simple Cu(II) salts, effectively bypassing the prohibitively high barriers typically associated with thermally-induced SN2 or SN1 N-alkylation. This regio- and chemoselective protocol is compatible with >10 classes of medicinally-relevant N-nucleophiles, including established pharmaceutical agents, in addition to structurally diverse primary, secondary and tertiary alkyl bromides. Furthermore, the capacity of HARC methodologies to engage conventionally inert coupling partners is highlighted via the union of N-nucleophiles with cyclopropyl bromides and unactivated alkyl chlorides, substrates that are incompatible with nucleophilic substitution pathways. Preliminary mechanistic experiments validate the dual catalytic, open-shell nature of this platform, which enables reactivity previously unattainable in traditional halide-based N-alkylation systems. Traditional substitution reactions between nitrogen nucleophiles and alkyl halides feature well-established, substrate-dependent limitations and competing reaction pathways under thermally-induced conditions. Herein, we report that a metallaphotoredox approach, utilizing a halogen abstraction-radical capture (HARC) mechanism, provides a valuable alternative to conventional N-alkylation. This visible light-induced, copper-catalyzed protocol is successful for coupling >10 classes of N-nucleophiles with diverse primary, secondary or tertiary alkyl bromides. Moreover, this open-shell platform alleviates outstanding N-alkylation challenges regarding regioselectivity, direct cyclopropylation and secondary alkyl chloride functionalization.
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影响因子：
3.6
作者：
Derosa, Joseph;O'Duill, Miriam L.;Engle, Keary M.
通讯作者：
Engle, Keary M.
DOI：
10.1002/chem.201704169
发表时间：
2017-10-26
期刊：
Chemistry (Weinheim an der Bergstrasse, Germany)
影响因子：
--
作者：
Foley DJ;Craven PGE;Collins PM;Doveston RG;Aimon A;Talon R;Churcher I;von Delft F;Marsden SP;Nelson A
通讯作者：
Nelson A
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：
7.3
作者：
Brow, Dean G.;Bostrom, Jonas
通讯作者：
Bostrom, Jonas
影响因子：
--
作者：
Che, Y;Tsushima, M;Ohsaka, T
通讯作者：
Ohsaka, T