Mechanisms of Pyrrole Formation from N-Allyl Ketimines and Arylacetylenes in tBuOK/DMSO Superbasic Medium:...

The mechanisms of polysubstituted pyrrole formation from N-allyl ketimines and arylacetylenes in tBuOK/DMSO superbasic medium have been studied theoretically employing a DFT approach [B2PLYP-D3/6-311 + G(d,p)//B3LYP/6-31 + G(d)] with the IEFPCM solvation model. Two alternative routes of pyrrole assembly have been investigated: (i) via vinylation of the N-allyl ketimine anion with arylacetylene and (ii) via ethynylation of N-vinyl aldimine (tautomer of starting ketimine) with the acetylide ion. It was shown that for the aryl-substituted imine (N-allyl-1-phenylethanimine), the free energies of the transition states that separate the two assembly routes are close. As a result, both routes for pyrrole formation are accessible, but in route i, the assembly is hindered by high barriers to cyclization of the vinylation adduct and isomerization of pyrroline to pyrrole. The influence of the substituent at the imine carbon is assessed by comparison with the alkyl-substituted N-allyl-1-tert-butylethanimine. For the alkyl derivative, the equilibrium is shifted almost completely toward the neutral 2-azadiene (another tautomer of the starting ketimine), rendering route ii kinetically preferred and route i practically inaccessible. The results explain the experimental isolation of intermediates from both routes, the increase in the pyrrole yield with increasing temperature, and how the electronic nature of the substituent at the imine carbon determines the pathway competition.