Enantioselective Formation of All-Carbon Quaternary Centers via C–H Functionalization of Methanol: Iridium-Catalyzed Diene Hydrohydroxymethylation

摘要

The first catalytic enantioselective C-C couplings of methanol (> 30× 10⁶ tons/year) are reported. Formal insertion of 2-substituted dienes into the methanol C–H bond occurs in a regioselective manner to form all-carbonyl quaternary centers with excellent levels of enantioselectivity using an iridium-PhanePhos catalyst. Mechanistic studies corroborate a Curtin-Hammett scenario in which methanol dehydrogenation triggers rapid, reversible diene hydrometalation en route to regioisomeric allyliridium-formaldehyde pairs, yet complete levels of regioselectivity are observed.