Base-Mediated Selective Synthesis of Diversely Substituted N-Heterocyclic Enamines and Enaminones by the Hydroamination of Alkynes

摘要

Regio- and stereoselective alkynylation of various N-heterocycles 1a–l using potassium and cesium salts in DMSO is described. Terminal alkynes 2a–k and internal alkynes 4a–f provided the kinetically stable Z-enamines 3a–l and 5a–i in good to excellent yields using KOH at 120 °C. Addition of heterocyclic amines to 1,3- and 1,4-diethynylbenzene 6a–b provided the mixture of E/Z isomers with KOH; however, with Cs2CO3 selectively Z-isomers 7ab–db were obtained by the hydroamination at one triple bond. This developed methodology also provides an easy and novel access for the synthesis of enaminones 10a–c. The detailed work also supports the formation of cis-isomer by preferential addition of o-haloarylalkynes followed by intramolecular C2 arylation in the copper-catalyzed tandem synthesis of indolo and pyrrolo[2,1-a]isoquinolines.