Dual Nickel/Photoredox-Catalyzed Deaminative Cross-Coupling of Sterically Hindered Primary Amines
Julia R Dorsheimer1, Melissa A Ashley1, Tomislav Rovis1
1Department of Chemistry, Columbia University, New York, New York 10027, United States.
Abstract:
We report a method to activate α-3° amines for deaminative arylation via condensation with an electron-rich aldehyde and merge this reactivity with nickel metallaphotoredox to generate benzylic quaternary centers, a common motif in pharmaceuticals and natural products. The reaction is accelerated by added ammonium salts. Evidence is provided in support of two roles for the additive: inhibition of nickel black formation and acceleration of the overall reaction rate. We demonstrate a robust scope of amine and haloarene coupling partners and show an expedited synthesis of ALK2 inhibitors.
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