New scheme of the mechanism of Fischer indolization

Some new views on the tautomerisation mechanism

“…47 It was assumed that the hydrazone ± enehydrazine tautomerisation is the rate-determining step of Fischer indolisation, 48 although we do not share this opinion. 36 The results of qualitative and quantitative studies of the imine ± enamine tautomerism and, in particular, the hydrazone ± enehydrazine tautomerism, were comprehensively discussed in the review. 49 Shainyan and Mirskova 49 believed that the proton transfer in these processes occurs through an intermolecular mechanism.…”

“…As can be seen from Table 1, the constants K T for phenylhydrazones 7a ± i have virtually equal values, whereas the constant for cyclohexanone phenylhydrazone 7j is twice as large as these values. The electron-withdrawing (NO 2 ) and electron-donating (Me) substituents in the para position of the benzene ring of both the hydrazine and carbonyl fragments (compounds 7f ± i) exert only a slight effect on K T and DDH # , although it is known 52 that these substituents have a substantial effect on the kinetics of indolisation. In our opinion, this is evidence that the hydrazone ± enehydrazine tautomerisation is not a rate-determining step of Fischer indolisation of arylhydrazones.…”

Why Do Some Fischer Indolizations Fail?

“…Previous computational investigations on the mechanism of the Fischer indole reaction are limited to semiempirical methods, 19 and the effect of substituents on the possible competing pathways has not yet been addressed. Here, we report the first computational study on the mechanism of the Fischer indole reaction using accurate quantum mechanical methods, and demonstrate that substituents on the starting carbonyl compound play a pivotal role in the success or failure of the Fischer indole synthesis.…”

“…Even though it is a widely utilized process, many essential mechanistic details underlying the acid-promoted Fischer indolization remain unclear. Previous computational investigations on the mechanism of the Fischer indole reaction have been limited to semiempirical methods, 19 and the effect of substituents on the possible competing pathways has not been addressed to date. Here we report the first computational study of the mechanism of the Fischer indole reaction using accurate quantum-mechanical methods.…”