Formaldehyde with Methanol Outperforms Methanol in Ru(II)-Catalyzed C-Methylation of Ketones

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A robust Ru(II)–p-cymene complex bearing an indole–pyrazole ligand (Ru1) is rapidly synthesized on a gram scale under ambient conditions and efficiently catalyzes the α-methylation of ketones using methanol. The addition of substoichiometric paraformaldehyde [(CH2O)n] or formalin markedly enhances conversion and selectivity compared with methanol alone, enabling efficient α-mono- and α-dimethylation under mild reaction conditions. In situ monitoring, control experiments, and isotopic-labeling studies support that early formation of formaldehyde-derived aldol intermediates promotes productive Ru–H utilization, while continuous formaldehyde generation sustains the catalytic cycle. These findings highlight the importance of coupling C1-intermediate formation with Ru–H utilization and suggest a practical strategy for improving otherwise inefficient methanol-based hydrogen-transfer catalysis, with implications for future catalyst design.