铜催化的乙酰苯胺间位碳氢芳基化反应机理的理论研究

通过系统的理论计算研究了Gaunt报道的一个新颖的间位选择性C-H键芳基化反应的机理. Oxycupration机理含有一个关键的Cu(III)基团和酰胺氧原子对苯环C2=C3键的反式加成步. 但是计算结果表明这个反应路径的活化能太高(>175.56 kJ/mol)，所以是动力学禁阻的. 提出了一个含有关键的酰胺导向的Cu(III)-Aryl对底物C2=C3键的顺式加成步的机理，这一步是反应的决速步，也是决定产物区域选择性的一步. 这个机理的活化能与实验条件是符合的，而且这个机理预测的产物区域选择性与实验

Proposal of an Amide-Directed Carbocupration Mechanism for Copper-Catalyzed meta-Selective C-H Arylation of Acetanilides by Diaryliodonium Salts

We examined the puzzling mechanism for Cu-catalyzed meta-C-H arylation reaction of anilides by diaryliodonium salts through systematic theoretical analysis. The previously proposed anti-oxy-cupration mechanism featuring anti-1,2- or anti-1,4-addition of cuprate and oxygen to the phenyl ring generating a meta-cuprated intermediate was excluded due to the large activation barriers. Alternatively, a new amide-directed carbocupration mechanism was proposed which involves a critical rate- and regio-determining step of amide-directed addition of the Cu(III)-aryl bond across the phenyl C2=C3 double bond to form an ortho-cuprated, meta-arylated intermediate. This mechanism is kinetically the most favored among several possible mechanisms such as ortho- or para-cupration/migration mechanism, direct meta C-H bond cleavage mediated by Cu(III) or Cu(I), and Cu(III)-catalyzed ortho-directed C-H bond activation mechanism. Furthermore, the predicted regioselectivity based on this mechanism has been shown to favor the meta-arylation that is consistent with the experimental observations.