Dual Nickel/Photoredox-Catalyzed Deaminative Cross-Coupling of Sterically Hindered Primary Amines

J Am Chem Soc. 2021 Nov 24;143(46):19294-19299. doi: 10.1021/jacs.1c10150. Epub 2021 Nov 12.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amines / chemical synthesis*
  • Amines / chemistry
  • Catalysis
  • Molecular Structure
  • Nickel / chemistry*
  • Oxidation-Reduction
  • Photochemical Processes

Substances

  • Amines
  • Nickel