Catalyst controlled site-selective
C–H functionalization
is a challenging but powerful tool in organic synthesis. Polarity-matched
and sterically controlled hydrogen atom transfer (HAT) provides an
excellent opportunity for site-selective functionalization. As such,
the dual Ni/photoredox system was successfully employed to generate
acyl radicals from aldehydes via selective formyl C–H activation
and subsequently cross-coupled to generate ketones, a ubiquitous structural
motif present in the vast majority of natural and bioactive molecules.
However, only a handful of examples that are constrained to the use
of aryl halides are developed. Given the wide availability of amines,
we developed a cross-coupling reaction via C–N bond cleavage
using the economic nickel and TBADT catalyst for the first time. A
range of alkyl and aryl aldehydes were cross-coupled with benzylic
and allylic pyridinium salts to afford ketones with a broad spectrum
of functional group tolerance. High regioselectivity toward formyl
C–H bonds even in the presence of α-methylene carbonyl
or α-amino/oxy methylene was obtained.