Positional selectivity in reactions of pyrrole and its N-substituted derivatives with electrophiles

Abstract

Experimental data on the positional selectivity (α:β-ratios) in reactions of N-substituted pyrroles with electrophiles have been considered. Based on the results of quantum chemical calculations of model N-R-pyrroles (R=H, Me, Et, i-Pr, t-Bu, CH=CH 2 , C≡CH, Ph, PhSO 2 , 4-O 2 NC 6 H 4 ) and their α-or β-protonated σ-complexes, carried out using ab initio methods (RHF/6-31G(d), MP2/6-31G(d)//RHF/6-31G(d)), and within the framework of density functional theory (B3LYP/6-31G(d)), it has been shown that the predominant α-or β-orientation is determined by steric factors and charges on the atoms β-С, α-С, N, and on the substituents at the N atom. We conclude that it is not determined by differences in the relative stabilities of the onium state N + depending on the nature of a substituent at the N atom, or reflecting the role of the heteroatom in the stabilization of σ-complexes formed by β-substitution.

Rational design and regioselective synthesis of conformationally restricted furan-derived ligands as potential anti-malarial agents

“…Readily available 3-furanmethanol 4 appeared to be an appropriate substrate for the targeted 2,4disubstituted furan derivatives 3a-c and and 11a-c (Scheme 1). However, electrophilic substitution is favoured at both of the α-positions (C-2 and C-5) in furan 25,26 and regioselective C-5 acylation of 3-furanmethanol 4 (C-2 in the product!) was clearly desirable.…”

Dipyrrolonaphthyridinedione – (still) a mysterious cross-conjugated chromophore

“…However, the fact of decreased reactivity at the α position of a pyrrole ring caused by the presence of electron-withdrawing groups within this ring cannot be excluded. 24 …”

Photophysical Insights of Halogenated Dipyrrolonaphthyridine‐Diones as Potential Photodynamic Therapy Agents†

“…It is important to note that the halogenation reaction led to the observation of specific regioselectivity respective to the size of the halogen atom. In the case of I 2 -DPND, the electrophilic aromatic substitution led exclusively to the β-iodo-pyrrolo product (19,20) relative to the nitrogen atom in the pyrrole. However, for Br 2 -DPND, the α-substitution product was observed exclusively.…”