Direct Deaminative Functionalization

Selective functional group interconversions in complex
molecular
settings underpin many of the challenges facing modern organic synthesis.
Currently, a privileged subset of functional groups dominates this
landscape, while others, despite their abundance, are sorely underdeveloped.
Amines epitomize this dichotomy; they are abundant but otherwise intransigent
toward direct interconversion. Here, we report an approach that enables
the direct conversion of amines to bromides, chlorides, iodides, phosphates,
thioethers, and alcohols, the heart of which is a deaminative carbon-centered
radical formation process using an anomeric amide reagent. Experimental
and computational mechanistic studies demonstrate that successful
deaminative functionalization relies not only on outcompeting the
H-atom transfer to the incipient radical but also on the generation
of polarity-matched, productive chain-carrying radicals that continue
to react efficiently. The overall implications of this technology
for interconverting amine libraries were evaluated via high-throughput
parallel synthesis and applied in the development of one-pot diversification
protocols.