Heterocycle Formation with Internal Oxidants

D3 = 26.3 kcal mol ) barriers via the O-bound isomer were 2-3kcalmol higher. The subsequent steps involve diazoester coordination and Nj loss 

In contrast to previous pathways, no Rh(V) species are invoked in this process, but rather a Rh(III)-Rh(I)-Rh(III) pathway is proposed. Experimentally, the reaction proceeds at 70 C [82] and a Ar /Arp KIE of 2.3 is observed. The rate-limiting alkyne insertion implied by the calculations therefore appears inconsistent with this however, an endothermic (i.e., reversible) initial C-H activation step would also be expected to affect the overall rate [83]. The use of kinetic simulations to quantify these effects would be of interest. Calculations comparing the -NH(NHOAc) and -NH(OAc) groups suggest the former is a weaker oxidant that can promote C-N bond coupling with alkynes but not with alkenes. 

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In 2011, Guimond and coworkers published the first computational study of Rh(III)-catalyzed heterocycle formation based on initial C-H activation and subsequent functionahzation [75]. The coupling of benzamides with alkynes to give isoquinolones was considered, with an OR group (OR = OMe, OPiv) installed on the benzamide nitrogen to act as an internal oxidant. B3LYP(MeOH) calculations were performed for the model reaction of iV-acetoxybenzamide with acetylene at a model Rh(OAc)2Cp catalyst (see Figure 1.27). After Af-deprotonation and loss of HOAc, directed C-H activation proceeds with an overall barrier of... 

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