Palladium-catalyzed regio- and stereoselective γ-arylation of tertiary allylic amines: identification of potent adenylyl cyclase inhibitors.

Substituted allylic amines and their derivatives are key structural motifs of many drug molecules and natural products. A general, mild, and practical palladium-catalyzed γ-arylation of tertiary allylic amines, one of the most challenging Heck arylation substrates, has been developed. The γ-arylation products were obtained in excellent regio- and stereoselectivity. Moreover, novel and potent adenylyl cyclase inhibitors with the potential for treating neuropathic and inflammatory pain have been identified from the γ-arylation products.