DFT insights into superelectrophilic activation of α,β-unsaturated nitriles and ketones in superacids

• Published in: Organic & biomolecular chemistry Vol. 2; no. 34; pp. 6799 - 688
• Main Authors: Genaev, Alexander M, Salnikov, George E, Koltunov, Konstantin Yu
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 31.08.2022
• Subjects: Aluminum chloride; Benzene; Carbonyl compounds; Carbonyls; Coordination; Density functional theory; Ketones; Nitriles; Protonation
• ISSN: 1477-0520; 1477-0539; 1477-0539
• DOI: 10.1039/d2ob01141g

Superelectrophilic activation of α,β-unsaturated carbonyl compounds and their isoelectronic analogs, proceeding normally under superacidic conditions, have led to a great variety of beneficial synthetic transformations. However, the essence of such activation is not yet fully recognized, while a number of alternative views on the subject have been discussed at length in the literature. Here, taking the example of virtual reactions of cinnamonitrile and benzalacetone with benzene, their feasible mechanistic variants, including multiple protonation (coordination to AlCl 3 ) of the reactants, were analyzed based on density functional theory (DFT). It is revealed that the most plausible reaction pathways involve the initial N - or O -protonation (coordination to AlCl 3 ) of the activated compounds followed by subsequent protonation on the α-C-atom. Dicationic superelectrophiles thus formed ensure practically barrier-free reactions with benzene in addition to a more favorable energetic profile of their generating, which is in marked contrast to other potential reaction pathways. Density functional theory studies have confirmed that N , C -diprotonation of α,β-unsaturated nitriles, and likewise O , C -diprotonation of isoelectronic ketones, provide the best rationale for their electrophilic reactions with weak nucleophiles, such as benzene.