Substrate dependent reaction channels of the Wolff–Kishner reduction reaction: A theoretical study

Abstract

SummaryWolff–Kishner reduction reactions were investigated by DFT calculations for the first time. B3LYP/6-311+G(d,p) SCRF=(PCM, solvent = 1,2-ethanediol) optimizations were carried out. To investigate the role of the base catalyst, the base-free reaction was examined by the use of acetone, hydrazine (H2N–NH2) and (H2O)8. A ready reaction channel of acetone → acetone hydrazine (Me2C=N–NH2) was obtained. The channel involves two likely proton-transfer routes. However, it was found that the base-free reaction was unlikely at the N2 extrusion step from the isopropyl diimine intermediate (Me2C(H)–N=N–H). Two base-catalyzed reactions were investigated by models of the ketone, H2N–NH2 and OH−(H2O)7. Here, ketones are acetone and acetophenone. While routes of the ketone → hydrazone → diimine are similar, those from the diimines are different. From the isopropyl diimine, the N2 extrusion and the C–H bond formation takes place concomitantly. The concomitance leads to the propane product concertedly. From the (1-phenyl)ethyl substituted diimine, a carbanion intermediate is formed. The para carbon of the phenyl ring of the anion is subject to the protonation, which leads to a 3-ethylidene-1,4-cyclohexadiene intermediate. Its [1,5]-hydrogen migration gives the ethylbenzene product. For both ketone substrates, the diimines undergoing E2 reactions were found to be key intermediates.

Construction of the Benzomesembrine Skeleton: Palladium(0)‐Catalyzed Intermolecular Arylative Dearomatization of α‐Naphthols and Subsequent Aza‐Michael Reaction

“…To further demonstrate the synthetic utility of the newly developed method, several transformations of the benzomesembrine product 3 aa were carried out (Scheme ). The ketone group was reduced under Wolff–Kishner–Huang reaction conditions to afford the benzomesembrane derivative 5 a in 80 % yield. In addition, 3 aa was selectively transformed into the benzomesembranol derivative 6 a in 92 % yield (d.r.…”

“…The ketone group was reduced under Wolff-Kishner-Huang [22] reaction conditions to afford the benzomesembrane derivative 5a in 80 %y ield. The ketone group was reduced under Wolff-Kishner-Huang [22] reaction conditions to afford the benzomesembrane derivative 5a in 80 %y ield.…”

Construction of the Benzomesembrine Skeleton: Palladium(0)‐Catalyzed Intermolecular Arylative Dearomatization of α‐Naphthols and Subsequent Aza‐Michael Reaction

“…To further demonstrate the synthetic utility of the newly developed method, several transformations of the benzomesembrine product 3aa were carried out (Scheme 4). The ketone group was reduced under Wolff-Kishner-Huang [22] reaction conditions to afford the benzomesembrane derivative 5a in 80 %y ield. In addition, 3aa was selectively transformed into the benzomesembranol derivative 6a in 92 %y ield (d.r.…”

Methyl Hydrazinocarboxylate as a Practical Alternative to Hydrazine in the Wolff–Kishner Reaction

“…22,23 In a recent theoretical study, Yamabe identifies imine 7 as the intermediate formed during this protonation rather than the anion 8 favoured by Szmant. 24 Yamabe also identified a mechanistic distinction between substrates such as acetophenone, which give rise to a resonance-stabilised carbanion (with initial protonation occurring in the aromatic ring), and those such as acetone for which the final protonation is concerted, with no carbanion having an independent existence. The competition experiment reported by Taber, in which a Wolff-Kishner reaction was accompanied by a small fraction (ca.…”