Li Kaizhi, Wu Qian, Lan Jingbo, You Jingsong
Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, 29 Wangjiang Road, Chengdu 610064, PR China.
Nat Commun. 2015 Sep 29;6:8404. doi: 10.1038/ncomms9404.
The past decade has witnessed significant advances in C-H bond functionalizations with the discovery of new mechanisms. Non-precious transition-metal-catalysed radical oxidative coupling for C(sp(3))-H bond transformations is an appealing strategy for C-C bond formations. The radical oxidative C(sp(3))-H/C(sp(3))-H cross-coupling reactions of α-C(sp(3))-H bonds of amines with free radicals represent a conceptual and practical challenge. We herein develop the coordinating activation strategy to illustrate the nickel-catalysed radical oxidative cross-coupling between C(sp(3))-H bonds and (hetero)arylmethyl free radicals. The protocol can tolerate a rich variety of α-amino acids and (hetero)arylmethanes as well as arylmethylenes and arylmethines, affording a large library of α-tertiary and α-quaternary β-aromatic α-amino acids. This process also features low-cost metal catalyst, readily handled and easily removable coordinating group, synthetic simplicity and gram-scale production, which would enable the potential for economical production at commercial scale in the future.
在过去十年中，随着新机制的发现，碳氢键官能团化取得了重大进展。非贵金属催化的自由基氧化偶联用于碳（sp(3)）-氢键转化是一种有吸引力的碳-碳键形成策略。胺的α-碳（sp(3)）-氢键与自由基的自由基氧化碳（sp(3)）-氢键/碳（sp(3)）-氢键交叉偶联反应在概念和实践上都具有挑战性。我们在此开发了配位活化策略，以阐明镍催化的碳（sp(3)）-氢键与（杂）芳基甲基自由基之间的自由基氧化交叉偶联。该方案可以耐受多种α-氨基酸和（杂）芳基甲烷以及芳基亚甲基和芳基次甲基，提供了大量的α-叔和α-季β-芳基α-氨基酸库。该过程还具有低成本金属催化剂、易于处理和易于去除的配位基团、合成简单和克级规模生产的特点，这将使未来有可能在商业规模上进行经济生产。
