C–H Methylation of Heteroarenes Inspired by Radical SAM Methyl Transferase

A practical C–H functionalization
method for the methylation
of heteroarenes is presented. Inspiration from Nature’s methylating
agent, S-adenosylmethionine (SAM), allowed for the
design and development of zinc bis­(phenylsulfonylmethanesulfinate),
or PSMS. The action of PSMS on a heteroarene generates a (phenylsulfonyl)­methylated
intermediate that can be easily separated from unreacted starting
material. This intermediate can then be desulfonylated to the methylated
product or elaborated to a deuteriomethylated product, and can divergently
access medicinally important motifs. This mild, operationally simple
protocol that can be conducted in open air at room temperature is
compatible with sensitive functional groups for the late-stage functionalization
of pharmacologically relevant substrates.