Multicomponent Reactions with Cyclic Tertiary Amines Enabled by Facile C-N Bond Cleavage.

A novel and catalyst-free multicomponent reaction with cyclic tertiary amines, electron-deficient aryl halides or heteroaromatic halides, and Na2 S enabled by facile C-N bond cleavage of the cyclic tertiary amines was developed. This direct and operationally simple method can be applied with a wide range of functional groups and provides an efficient and rapid approach to potentially drug-like products containing amine, azaarene, thioether, or phenol ether functionalities in good to excellent yields. The utility of this method was demonstrated by the rapid synthesis of the analgesic ruzadolane.