美国康奈尔大学Lin, Song团队报道了使用受抑自由基对的区域选择性脂肪族C–H官能化。相关研究成果发表在2023年7月5日出版的《自然》。

受抑路易斯对（FLPs）被充分证明可以激活小分子，如二氢和二氧化碳。尽管经典FLP化学本质上是异裂的，但最近的工作表明，某些FLPs可以进行单电子转移以提供自由基对。由于空间阻碍和/或弱键结合，这些自由基不会相互湮灭，因此被命名为受抑自由基对（FRPs）。值得注意的初步结果表明，FRPs可能是化学合成中有用的试剂，尽管它们的应用仍然有限。

该文中，研究人员证明了C（sp3）–H键的功能化可以使用由二酰肼供体和N-氧代铵受体产生的一类FRPs来完成。这些物种一起经历单电子转移，产生瞬态和持久的自由基对，能够裂解未活化的C–H键，从而提供氨基氧基化产物。通过调节供体的结构，可以控制区域选择性并调整对叔、仲或伯C–H键的反应性。机制学研究有力地支持了自由基对在靶反应中的形成和参与。

附：英文原文

Title: Regioselective aliphatic C–H functionalization using frustrated radical pairs

Author: Lu, Zhipeng, Ju, Minsoo, Wang, Yi, Meinhardt, Jonathan M., Martinez Alvarado, Jesus I., Villemure, Elisia, Terrett, Jack A., Lin, Song

Issue&Volume: 2023-07-05

Abstract: Frustrated Lewis pairs (FLPs) are well documented for the activation of small molecules such as dihydrogen and carbon dioxide1,2,3,4. Although canonical FLP chemistry is heterolytic in nature, recent work has shown that certain FLPs can undergo single-electron transfer to afford radical pairs5. Owing to steric encumbrance and/or weak bonding association, these radicals do not annihilate one another, and they have thus been named frustrated radical pairs (FRPs). Notable preliminary results suggest that FRPs may be useful reagents in chemical synthesis6,7,8, although their applications remain limited. Here we demonstrate that the functionalization of C(sp3)–H bonds can be accomplished using a class of FRPs generated from disilazide donors and an N-oxoammonium acceptor. Together, these species undergo single-electron transfer to generate a transient and persistent radical pair capable of cleaving unactivated C–H bonds to furnish aminoxylated products. By tuning the structure of the donor, it is possible to control regioselectivity and tailor reactivity towards tertiary, secondary or primary C–H bonds. Mechanistic studies lend strong support for the formation and involvement of radical pairs in the target reaction.

DOI: 10.1038/s41586-023-06131-3

Source: https://www.nature.com/articles/s41586-023-06131-3