Tandem Approach to Benzothieno- and Benzofuropyridines from o-Alkynyl Aldehydes via Silver-Catalyzed 6-endo-dig Ring Closure

An operationally simple silver-catalyzed tandem strategy for the synthesis of benzothienopyridines 7a-t and benzofuropyridines 8a-p by the reaction of o-alkynyl aldehyde 4a-t and 5a-p with tert-butylamine 6 under mild reaction conditions is described. The present methodology provides a facile conversion of easily accessible o-alkynyl aldehydes into medicinally useful heterocycles in good to excellent yields under mild and environmentally friendly reaction conditions with excellent regioselectivity. The developed chemistry has been successfully extended for the selective synthesis of C-4 deuterated benzothienopyridines 7u-v and benzofuropyridines 8q-r. The role of the ethanolic proton in the reaction was validated by deuterium-labeling experiments.