New Method of Making Tertiary Amines

19 February 2007

Most modern chemists wishing to make aromatic tertiary amines will try the Buchwald Hartwig methodologies involving displacement of a halide or other leaving group by an amine under palladium or copper catalysis. A new method. developed by the group of Knochel at Munich, involves reacting a Grignard reagent with an N-chloroamine. The Nchloroamines are easily prepared by reaction of a secondary amine with N-chlorosuccinimide in hexane. The Grignards need to be prepared by the exchange reaction, which is typical of Knochel’s excellent procedures, namely reaction of an aryl halide with I-PrMgCl-LiCl.

The aminations occur rapidly at minus 45 degrees within 15 minutes with moderate to good yields. Some biaryl is formed as a byproduct in some cases. The strategy is a useful alternative method of making tertiary amines, particularly when all three groups on the nitrogen are different. (P Sinha and P Knochel, SynLett, 2006, 19, 3304-3308). If there is a chiral center adjacent to N in the N-chloroamine, then chirality is retained.