Condition-Modulated Regiodivergent Transfer Hydrogenation of Epoxide using Methanol as Sustainable H2 Source.

Regiodivergent reduction of epoxides under mild conditions is highly attractive for selective functionalization in organic synthesis. Notwithstanding the advances in methanol as an H2 source, its use in epoxide transfer hydrogenation holds significant challenges due to its high dehydrogenation energy and strong nucleophilicity, leading to methoxylation instead of hydrogenation. An unprecedented regiodivergent transfer hydrogenation of epoxides using methanol as the sustainable H2 source, using a single Ir(III) catalyst, is reported here. The regioselectivity is controlled by strategic modulation of reaction conditions rather than catalyst variation. While KOTf and 2,2,2-trifluoroethanol (TFE) helped in anti-Markovnikov-selective ring opening, KOH and tAmOH-mediated conditions favored Markovnikov products. This methodology is further extended to a one-pot β-methylation of alcohols. Mechanistic investigations, including control and labeling experiments supported by density functional theory calculations, revealed the key factors governing regioselectivity. This work showcased the art of selective epoxide functionalization with regiodivergence through a strategic reaction condition modulation.