Palladium-Catalyzed Coupling of Functionalized Primary and Secondary Amines with Aryl and Heteroaryl Halides: Two Ligands Suffice in Most Cases

Abstract

We report our studies on the use of two catalyst systems, based on the ligands BrettPhos (1) and RuPhos (2), which provide the widest scope for Pd-catalyzed C-N cross-coupling reactions to date. Often low catalyst loadings and short reaction times can be used with functionalized aryl and heteroaryl coupling partners. The reactions are highly robust and can be set up and performed without the use of a glovebox. These catalysts should find wide application in the synthesis of complex molecules including pharmaceuticals, natural products and functional materials.

Fig. 1

Ligands and precatalysts used in these studies for Pd-catalyzed C–N bond formation (1 and 3 are used for 1°-amines, 2 and 4 are used for 2°-amines).

Scheme 1

Synthesis of Imatinib base