Superbase‐catalyzed domino 3H‐pyrroles synthesis from ketoximes and acetylene: DFT study vs experiment

Abstract

Elimination of vinyl alcohol from 5-vinyloxypyrrolines in the presence of superbases (final step of domino 3H-pyrroles synthesis from ketoximes and acetylene) is studied computationally at different levels of theory in DMSO solution (PCM). The sequences of transformations starting from nucleophilic addition of hydroxide ion to carbon-carbon or carbon-nitrogen double bonds are proposed as possible mechanisms. Unusual reactivity of 2,5-dimethylphenyl substituted 5-vinyloxypyrroline is explained within these mechanisms.

Cascade Assembly of 4,5,6,7-Tetrahydroindole from Cyclohexanone Oxime and Acetylene in the KOH/DMSO Superbase Medium: A Quantum Chemical Study

“…Another alternative mechanism with the participation of a hydroxide ion has been demonstrated for the synthesis of 3 H -pyrrole with methyl and aryl substituents . It comprises several steps.…”

“…Another alternative mechanism with the participation of a hydroxide ion has been demonstrated for the synthesis of 3H-pyrrole with methyl and aryl substituents. 24 It comprises several steps. The chain of conversions is triggered by an attack of the CN double bond by a hydroxide ion, with the simultaneous elimination of a vinyl alcohol anion.…”

“…Catalytic cycles of the transformation of 5-vinyloxypyrroline into 3 H -pyrrole initiated by the addition of OH – to the CC (A) or CN (B) bond. X – is base named “true” base by authors …”

“…The activation barrier of this reaction is found to be ΔG ‡ = 35.1 kcal/mol. Alternative routes of the formation of 3H-pyrroles from 5vinyloxypyrroline, with the participation of a base, proceeding via the nucleophilic addition of hydroxide ion to the CN or CC bond, have been investigated by means of density functional theory (DFT) calculations 24 (Figure 1).…”

Game of Aliphatics: A Density Functional Theory Study of Base-Catalyzed Substrate-Controlled Dimerizations of Aliphatic Alkynones

“…The condensed Fukui electrophilicity indices f A + for alkynones 1a–g were obtained as the difference of electron densities (ρ) on atoms of interest between a molecule with one extra electron (ρ N +1 ) and the neutral molecule (ρ N ). The condensed nucleophilicity indices f A – for deprotonated forms 2a–g were calculated as the difference between an anionic molecule (ρ N ) and the radical form (ρ N –1 ), respectively …”