Harnessing methanol as a C1 source for tunable C–H functionalization over CdS-based photocatalysts

Achieving divergent synthesis of multiple molecular scaffolds from identical starting materials via a single catalytic system represents a fascinating yet challenging frontier in organic transformation. Herein, we present a heterogeneous photocatalytic strategy that leverages methanol as a green and renewable C1 feedstock to unlock tunable α-C(sp³)-H functionalization of ketones, including α-hydroxymethylation, α-methoxymethylation, and α-methylation. By simply modulting reaction temperature and NiCo-LDH co-catalyst loading, precise control over product selectivity is achieved, with yields up to 98% across three pathways. A gas–liquid-solid segmented flow (PGSF) system enables effective process intensification alongside demonstrated gram-scale scalability with a remarkable turnover number (TON) of 31591. Mechanistic investigations integrating in-situ characterization and DFT calculations revealed that NiCo-LDH incorporation tailors CdS electronic properties to suppress methanol overoxidation, enhancing α-hydroxymethylation efficiency, while modulating the desorption kinetics of reactive intermediates, thereby directing the reaction selectivity between α-methoxymethylation and α-methylation reaction. This strategy establishes a robust platform for methanol-enabled divergent C–H functionalization, expecting to open up new prospects for semiconductor-catalyzed organic synthesis.