Chromium(II)-Catalyzed Amination of N-Heterocyclic Chlorides with Magnesium Amides
Received: 16 December 2014
Accepted after revision: 22 January 2015
26 February 2015 (online)
We report a ligand-free chromium(II)-catalyzed amination reaction of various N-heterocyclic chlorides. CrCl2 regioselectively catalyzes the reaction of chloropyridines and dichloropyridines, dichloroquinolines, dichloroisoquinolines and dichloroquinoxalines with a range of aliphatic, allylic, benzylic and saturated (hetero)cyclic magnesium amides in the presence of lithium chloride as additive. The reactions were performed at 50 °C in THF and led to the desired aminated products in 56–96% yield.
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- 15 However, a longer reaction time (20 h at 50 °C) also led to full conversion.
- 16a Typical procedure for the Cr-catalyzed amination using CrCl2 : The previously prepared solution of the magnesium amide was transferred via syringe to a second dry and argon-flushed Schlenk tube, containing water-free CrCl2 (0.1 equiv) and the N-heterocyclic halide in THF (1 equiv, 2 M in THF) at 23 °C. The resulting reaction mixture was stirred at 50 °C until the N-heterocyclic halide was consumed. The solvent was evaporated in vacuo and the crude product was purified on silica gel to afford the desired product.
- 16b Typical procedure for the Cr-catalyzed amination using Cr(acac)3 : The previously prepared solution of the magnesium amide was transferred via syringe to a second dry and argon-flushed Schlenk tube, containing Cr(acac)3 (0.1 equiv) and the N-heterocyclic halide in THF (1 equiv, 2 M in THF) at 23 °C. The resulting reaction mixture was stirred at 50 °C until the N-heterocyclic halide was consumed. The solvent was evaporated in vacuo and the crude product was purified on silica gel to afford the desired product.
- 17 No diamination product was observed in the aminations involving 1c, 1d, 1e and 1h.
- 18 Magnesium chloride indolin-1-ide (2e) reacted rapidly with 1d but the related magnesium chloride methylanilide underwent the amination reaction in only 32% yield, showing the limits of the CrCl2 catalysis.