Mechanistic insights into radical formation and functionalization in copper/N-fluorobenzenesulfonimide radical-relay reactions.
Mechanistic insights into radical formation and functionalization in copper/N-fluorobenzenesulfonimide radical-relay reactions.
复制标题
对铜/N-氟苯甲酰亚胺自由基反应反应的自由基形成和功能化的机械洞察力。
DOI：
10.1039/d3sc03597b
复制
发表时间：
2024-01-24
期刊：
影响因子：
8.4
通讯作者：
Stahl, Shannon S.
中科院分区：
文献类型：
--
作者：
Mandal, Mukunda;Buss, Joshua A.;Chen, Si-Jie;Cramer, Christopher J.;Stahl, Shannon S.
采用N-氟苯磺酰亚胺（NFSI）作为氧化剂的铜催化自由基接力反应已经成为C（sp3）-H官能化的高效方法。在这里，计算研究与实验数据配对，以调查这些反应的一系列关键的机械特征，重点关注与位点选择性，对映体选择性和C-H底物范围相关的问题。(1)对映选择性苄基C-H氰化反应的全反应能量学进行了探讨，并暗示Cu和N-磺酰亚胺基自由基（stecNSI）之间的加合物是促进C-H底物氢原子转移（HAT）的物种。(2)用不同的HAT试剂：Cu/tecNSI、stecOtBu和Cl tec 3比较了苄基与3° C-H的位点选择性，并且数据提供了对Cu/NFSI催化的C-H官能化反应中苄基C-H键的高选择性的见解。(3)三个自由基官能化途径的能量进行了比较，包括自由基极性交叉（RPC）产生的碳阳离子中间体，还原消除从一个正式的CuIII有机金属配合物，和自由基除了铜结合的配体。优选的机制取决于与铜结合的配体。(4)最后，三种不同的途径，将苄基C-H键转化为苄基阳离子的能量进行了比较，包括HAT/ET（ET =电子转移），与铜/NFSI的RPC机制相关;氢化物转移，参与高电位醌反应;和顺序ET/PT/ET（PT =质子转移），参与催化光氧化还原反应。总的来说，这些结果提供了机理上的见解，为自由基中继C-H官能化反应的进一步发展奠定了基础。采用N-氟苯磺酰胺（NFSI）作为氧化剂的铜催化自由基接力反应已成为C（sp3）-H官能化的高效方法。
Copper-catalysed radical-relay reactions that employ N-fluorobenzenesulfonimide (NFSI) as the oxidant have emerged as highly effective methods for C(sp3)–H functionalization. Herein, computational studies are paired with experimental data to investigate a series of key mechanistic features of these reactions, with a focus on issues related to site-selectivity, enantioselectivity, and C–H substrate scope. (1) The full reaction energetics of enantioselective benzylic C–H cyanation are probed, and an adduct between Cu and the N-sulfonimidyl radical (˙NSI) is implicated as the species that promotes hydrogen-atom transfer (HAT) from the C–H substrate. (2) Benzylic versus 3° C–H site-selectivity is compared with different HAT reagents: Cu/˙NSI, ˙OtBu, and Cl˙, and the data provide insights into the high selectivity for benzylic C–H bonds in Cu/NFSI-catalyzed C–H functionalization reactions. (3) The energetics of three radical functionalization pathways are compared, including radical–polar crossover (RPC) to generate a carbocation intermediate, reductive elimination from a formal CuIII organometallic complex, and radical addition to a Cu-bound ligand. The preferred mechanism is shown to depend on the ligands bound to copper. (4) Finally, the energetics of three different pathways that convert benzylic C–H bonds into benzylic cations are compared, including HAT/ET (ET = electron transfer), relevant to the RPC mechanism with Cu/NFSI; hydride transfer, involved in reactions with high-potential quinones; and sequential ET/PT/ET (PT = proton transfer), involved in catalytic photoredox reactions. Collectively, the results provide mechanistic insights that establish a foundation for further advances in radical-relay C–H functionalization reactions. Copper-catalysed radical-relay reactions that employ N-fluorobenzenesulfonamide (NFSI) as the oxidant have emerged as highly effective methods for C(sp3)–H functionalization.
登录
查看更多内容
影响因子：
16.6
作者：
Knizia, Gerald;Klein, Johannes E. M. N.
通讯作者：
Klein, Johannes E. M. N.
DOI：
10.1002/anie.201805511
发表时间：
2018-09-10
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Klein JEMN;Knizia G
通讯作者：
Knizia G
影响因子：
2.9
作者：
Dereli, Busra;Ortuno, Manuel A.;Cramer, Christopher J.
通讯作者：
Cramer, Christopher J.
影响因子：
15
作者：
KOCHI, JK
通讯作者：
KOCHI, JK
影响因子：
8.4
作者：
Haines BE;Kawakami T;Kuwata K;Murakami K;Itami K;Musaev DG
通讯作者：
Musaev DG