Scope and Mechanism of the Redox-Active 1,2-Benzoquinone Enabled Ruthenium-Catalyzed Deaminative α-Alkylation of Ketones with Amines
Pandula T. Kirinde Arachchige, Suhashini Handunneththige, Marat R. Talipov, Nishantha Kalutharage, Chae S. Yi
Abstract
The catalytic system formed in situ from the reaction of a cationic Ru–H complex with 3,4,5,6-tetrachloro-1,2-benzoquinone was found to mediate a regioselective deaminative coupling reaction of ketones with amines to form the α-alkylated ketone products. Both benzylic and aliphatic primary amines were found to be suitable substrates for the coupling reaction with ketones in forming the α-alkylated ketone products. The coupling reaction of PhCOCD3 with 4-methoxybenzylamine showed an extensive H/D exchange on both α-CH2 (41% D) and β-CH2 (21%) positions on the alkylation product. The Hammett plot obtained from the reaction of acetophenone with para-substituted benzylamines p-X-C6H4CH2NH2 (X = OMe, Me, H, F, Cl, CF3) showed a strong promotional effect by the amine substrates with electron-releasing groups (ρ = −0.49 ± 0.1). The most significant carbon isotope effect was observed on the α-carbon of the alkylation product (Cα = 1.020) from the coupling reaction of acetophenone with 4-methoxybenzylamine. The kinetics of the alkylation reaction from an isolated imine substrate led to the empirical rate law: rate = k[Ru][imine]. A catalytically active Ru–catecholate complex was synthesized from the reaction of the cationic Ru–H complex with 3,5-di-tert-butyl-1,2-benzoquinone and PCy3. The DFT computational study was performed on the alkylation reaction, which revealed a stepwise mechanism of the [1,3]-carbon migration step via the formation of a Ru(IV)-alkyl species with a moderate energy of activation (ΔG‡ = 32–42 kcal/mol). A plausible mechanism of the catalytic alkylation reaction via an intramolecular [1,3]-alkyl migration of an Ru-enamine intermediate has been compiled on the basis of these experimental and computational data.