DNA-encoded
library (DEL) technology has emerged as a novel interrogation
modality for ligand discovery in the pharmaceutical industry. Given
the increasing demand for a higher proportion of C(sp3)-hybridized
centers in DEL platforms, a photoredox-mediated cross-coupling and
defluorinative alkylation process is introduced using commercially
available alkyl bromides and structurally diverse α-silylamines.
Notably, no protecting group strategies for amines are necessary for
the incorporation of a variety of amino-acid-based organosilanes,
providing crucial branching points for further derivatization.
A general aminoalkylation of aryl
halides was developed, overcoming
intolerance of free amines in nickel-mediated C–C coupling.
This transformation features broad functional group tolerance and
high efficiency. Taking advantage of the fast desilylation of α-silylamines
upon single-electron transfer (SET) facilitated by carbonate, α-amino
radicals are generated regioselectively, which then engage in nickel-mediated
C–C coupling. The reaction displays high chemoselectivity for
C–C over C–N bond formation. Highly functionalized pharmacophores
and peptides are also amenable.
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