Aryl amination using ligand-free Ni(II) salts and photoredox catalysis

Abstract

Over the past two decades, there have been major developments in transition metal-catalyzed aminations of aryl halides to form anilines, a common structure found in drug agents, natural product isolates, and fine chemicals. Many of these approaches have enabled highly efficient and selective coupling through the design of specialized ligands, which facilitate reductive elimination from a destabilized metal center. We postulated that a general and complementary method for carbon-nitrogen bond formation could be developed through the destabilization of a metal amido complex via photoredox catalysis, thus providing an alternative approach to the use of structurally complex ligand systems. Here, we report the development of a distinct mechanistic paradigm for aryl amination using ligand-free nickel(II) salts, in which facile reductive elimination from the nickel metal center is induced via a photoredox-catalyzed electron-transfer event.

Figure 1. Proposed approach to C–N cross-coupling – promotion of reductive elimination via single-electron transfer

Figure 2. Proposed mechanism for the metallaphotoredox-catalyzed amination reaction

L, DABCO or amine; SET, single-electron transfer.

Figure 3. Metallaphotoredox-catalyzed amination: amine and arene scope

For each entry number (in boldface), data are reported as percent isolated yield. R, H, alkyl, or aryl substrate; Y, C, CH, or N; X, CI or Br; DABCO, 1,4-diazabicyclo[2.2.2]octane; MTBD, 7-methyl-1,5,7-triazabicyclo [4.4.0]dec-5-ene; LED, light-emitting diode; Me, methyl; n-pent, n-pentyl; Boc, tert-butoxycarbonyl. *Run at ambient temperature. †Reaction heated to 55 °C. ‡DMSO used as solvent. §MTBD used as base. ‖0.002 mol% 1 used. ¶10 mol% pyrrolidine included. #See Supplementary Materials for details.

Figure 4. High throughput metallaphotoredox-catalyzed aryl amination using a chemistry informer library

For each compound numbered in bold, the cross-coupling was performed with piperidine using DABCO as a base. Ac, acetyl; Bn, benzyl; Boc, tert-butoxycarbonyl; Et, ethyl; Me, methyl; n-Pr, n-propyl; t-Bu, tert-butyl. Conversion was quantified by ultra pressure liquid chromatography/mass spectrometry (UPLC/MS) using an internal standard. See Supplementary Materials for exact yields and conditions.