Nucleophilic Reactivities of Pyrroles

The second‐order rate constants of the reactions of alkyl‐substituted pyrroles with a series of benzhydrylium ions were determined in acetonitrile, and the reaction products were fully characterized by NMR spectroscopy and mass spectrometry. The formation of the σ adducts is the rate‐limiting step of these reactions. Because the second‐order rate constants correlate linearly with the electrophilicity parameters of the benzhydrylium ions, the determination of the nucleophilicity parameters N and s according to the linear free energy relationship log k2 (20 °C) = s(N + E) was achieved. With these findings, a direct comparison of the nucleophilic reactivities of these π‐excessive heterocycles with other nucleophiles became possible, and the pyrroles were integrated into the comprehensive scale of nucleophilicity, covering a range of 8–9 orders of magnitude from N‐(triisopropylsilyl)pyrrole (N = 3.12), the weakest nucleophile of this series, to kryptopyrrole (3‐ethyl‐2,4‐dimethylpyrrole, N = 11.63). Thus, highly reactive pyrroles show similar nucleophilic reactivities as enamines, whereas those of less‐reactive pyrroles are comparable to allylsilanes or indoles. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)