Rapid Access to 1,2,3,4-Tetrasubstituted Benzenes and 3-Alkenyl-1,2-dihydropyridines

Herein, we report unprecedented protocols for the synthesis of 1,2,3,4-tetrasubstituted benzenes and 3-alkenyl-1,2-dihydropyridines from readily available N-methyl-N-propargyl β-enaminones. When subjected to the reaction with dialkyl acetylenedicarboxylates in refluxing toluene under gold catalysis, N-methyl-N-propargyl β-enaminones afforded 1,2,3,4-tetrasubstituted benzenes. On the other hand, the reaction of N-methyl-N-propargyl β-enaminones with dialkyl acetylenedicarboxylates in refluxing acetonitrile under copper catalysis formed 3-alkenyl-1,2-dihydropyridines as the major product, accompanied by 1,2,3,4-tetrasubstituted benzenes as the minor product. An internal alkyne-tethered N-methyl-N-propargyl β-enaminone yielded a pentasubstituted benzene derivative under both gold and copper catalysis. The skeletal diversity of the synthesized 1,2,3,4-tetrasubstituted benzenes and 3-alkenyl-1,2-dihydropyridines may be of use in medicinal and pharmaceutical chemistry as new and novel molecular entities and structural leads.