开发直接转化C(sp3)-H键的方法在合成化学中至关重要,因为它们在各种有机化合物中很普遍。虽然常规方案在很大程度上依赖于过渡金属催化,有机催化的最新进展,特别是在自由基NHC催化下,引起了人们对“惰性”C(sp3)-H键直接官能化的兴趣,以使C-C与羰基部分偶联。该策略涉及C(sp3)-H键的选择性裂解以产生关键的碳自由基,通常通过氢原子转移(HAT)过程实现。通过利用键离解能(BDE)和极性效应,HAT可以使各种C(sp3)-H底物快速官能化,如醚,胺,和烷烃。这篇小型综述总结了通过HAT过程实现的惰性C(sp3)-H键的卡宾有机催化官能化的进展,将它们分为两个部分:1)涉及酰基唑鎓中间体的C-H官能化;和2)通过还原性Breslow中间体将C-H键官能化。
Developing methods to directly transform C(sp3) -H bonds is crucial in synthetic chemistry due to their prevalence in various organic compounds. While conventional protocols have largely relied on transition metal catalysis, recent advancements in
organocatalysis, particularly with radical NHC catalysis have sparked interest in the direct functionalization of \"inert\" C(sp3) -H bonds for cross C-C coupling with carbonyl moieties. This strategy involves selective cleavage of C(sp3) -H bonds to generate key carbon radicals, often achieved via hydrogen atom transfer (HAT) processes. By leveraging the bond dissociation energy (BDE) and polarity effects, HAT enables the rapid functionalization of diverse C(sp3)-H substrates, such as ethers, amines, and alkanes. This mini-review summarizes the progress in carbene organocatalytic functionalization of inert C(sp3)-H bonds enabled by HAT processes, categorizing them into two sections: 1) C-H functionalization involving acyl azolium intermediates; and 2) functionalization of C-H bonds via reductive Breslow intermediates.