Scope and Mechanism of the Redox-Active 1,2-Benzoquinone Enabled Ruthenium-Catalyzed Deaminative α‑Alkylation of Ketones with Amines

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.