Synthesis of alkynyl/alkenyl-substituted pyridine derivatives via heterocyclization and Pd-mediated Sonogashira/Heck coupling process in one-pot: a new MCR strategy

Abstract

A new class of 2-amino-4-(3/2-(alkynyl)/3-(alkenyl)phenyl)-6-phenylnicotinonitriles (6, 7 & 9) has been synthesized with good to excellent isolated yields by the multi-component reaction (MCR) of bromobenzaldehyde (1), malononitrile (2), acetophenone (3), NH₄OAc (4) and a series of terminal alkynes (5)/alkenes (8) in the presence of pyrrolidine and Pd-catalyst in a mixture of H₂O–DME (1 : 4 ratio) under reflux conditions in a single step. The Heck-type coupling with terminal olefins takes place stereoselectively with exclusive formation of E-isomers. This new MCR strategy opens new avenues in the development of (i) a diversity-oriented new cyanopyridine based compound library and (ii) new chemical entities other than the present reported molecules.