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.