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

• Published in: Beilstein Journal of Organic Chemistry Vol. 10; no. 1; pp. 259 - 270
• Main Authors: Yamabe, Shinichi, Zeng, Guixiang, Guan, Wei, Sakaki, Shigeyoshi
• Format: Journal Article
• Language: English
• Published: Germany Beilstein Institut 23.01.2014; Beilstein-Institut
• Subjects: acetone; acetophenone; Chemistry; DFT calculations; diimine intermediate; Full Research Paper; Organic chemistry; Q; QD241-441; reduction reaction; Science; transition states; Wolff–Kishner; Wolff–Kishner; acetophenone; diimine intermediate; acetone; transition states; reduction reaction; DFT calculations
• ISSN: 1860-5397; 1860-5397
• DOI: 10.3762/bjoc.10.21

Wolff–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 (H 2 N–NH 2 ) and (H 2 O) 8 . A ready reaction channel of acetone → acetone hydrazine (Me 2 C=N–NH 2 ) was obtained. The channel involves two likely proton-transfer routes. However, it was found that the base-free reaction was unlikely at the N 2 extrusion step from the isopropyl diimine intermediate (Me 2 C(H)–N=N–H). Two base-catalyzed reactions were investigated by models of the ketone, H 2 N–NH 2 and OH − (H 2 O) 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 N 2 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.