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

The first catalytic enantioselective C–C couplings of methanol (>30 × 106 tons/year) are reported. Insertion of 2-substituted dienes into the methanol C–H bond occurs in a regioselective manner to form all-carbon 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 single constitutional isomers are formed.