Isotopically labeled compounds are essential in both organic and pharmaceutical chemistry.
The standard methods for synthesizing such molecules often involve the use of deuterated
building blocks, allowing the incorporation of functional groups and deuterium into
the target molecule in one step. In this Synpacts article, we highlight our approach
to accessing various a-deuterated alkyl thianthrenium (TT) salts through a pH-dependent
hydrogen-isotope-exchange process using D2O as a cheap source of deuterium. Through the in situ formation of isotopically labeled
alkyl halides, these TT salts exhibit exceptional compatibility with a range of nickel-catalyzed
hydrodeuteroalkylations of nonactivated olefins and with nickel-catalyzed cross-electrophile
coupling reactions with alkyl, alkenyl, and (het)aryl bromides. This technique has
proven to be invaluable for accessing a range of deuterium-labeled compounds, particularly
those of pharmaceutical significance.
Key words
deuteriation - thianthrenium salts - hydrodeuteroalkylation - nickel catalysis - metallaphotoredox
reaction - pharmaceutical chemistry
