This study demonstrates that the remote cascade functionalization of 2,4-dienones can be realized by employing Brønsted base catalysis. The developed cascade involving 1,6-addition followed by the intramolecular aldol reaction provides a straightforward access to polysubstituted tetrahydrothiophene derivatives of biological and synthetic importance. Target products, bearing three contiguous stereocenters including one quaternary, have been obtained with excellent yields (up to 98%) and with good to high stereocontrol (>20 : 1 dr, up to 97 : 3 er) with the reaction cascade being promoted by a simple and readily available cinchona alkaloid cinchonine.