Modular Dual-Tasked C–H Methylation via the Catellani Strategy

We report a dual-tasked
methylation that is based on cooperative
palladium/norbornene catalysis. Readily available (hetero)­aryl halides
(39 iodides and 4 bromides) and inexpensive MeOTs or trimethylphosphate
are utilized as the substrates and methylating reagent, respectively.
Six types of “ipso” terminations can modularly couple
with this “ortho” C–H methylation to constitute
a versatile methylation toolbox for preparing diversified methylated
arenes. This toolbox features inexpensive methyl sources, excellent
functional-group tolerance, simple reaction procedures, and scalability.
Importantly, it can be uneventfully extended to isotope-labeled methylation
by switching to the corresponding reagents CD3OTs or 13CH3OTs. Moreover, this toolbox can be applied
to late-stage modification of biorelevant substrates with complete
stereoretention. We believe these salient and practical features of
our dual-tasked methylation toolbox will be welcomed by academic and
industrial researchers.