B(C6F5)3-Catalyzed Chemical Tagging of Bioactive N-Alkylamines through β-Amino C(sp3)-H Functionalization
Matthew Chapman1, Changhang Dai1, Yuankai Wang2
1Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, United States.
None:
We present a late-stage functionalization method for arming bioactive N-alkylamines with functional handles for bioconjugation through the transformations of β-amino C(sp3)-H bonds. B(C6F5)3 and a Brønsted base converts N-alkylamines into enamines through sequential hydride abstraction and deprotonation. The resulting enamines, generated in situ, undergo conjugate addition to maleimide-based tagging agents to furnish β-substituted amine derivatives bearing diverse bioconjugation handles. These transformations proceed under redox-neutral conditions and tolerate a range of Lewis acid-sensitive moieties.
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