A versatile synthesis of benzothieno-annelated 1,2-dihydropyridine and 1,2,3,4-tetrahydropyridine derivatives: the effect of the structure of benzothieno-annelated pyridinium salts on their reduction by sodium borohydride

Abstract  

Benzothieno[2,3-c]pyridinium and benzothieno[2,3-c]quinolinium salts were synthesized either by quaternization of benzothieno[2,3-c]pyridines, or recyclization of benzothieno[2,3-c]pyrylium salts with primary amines. One-pot synthesis of benzothieno[3,2-g]indolizinium salts from 1-(3-chloropropyl)-benzothieno[2,3-c]pyrylium included consequent recyclization of the pyrylium core by ammonia into a pyridine intermediate and its further intramolecular quaternization reaction. Depending on the structure of benzothieno-annelated pyridinium salts, their reaction with sodium borohydride in methanol results in reduction of the pyridine core into tetrahydropyridine or dihydropyridine derivatives. Whereas reduction of benzothieno[2,3-c]pyridinium and benzothieno[3,2-g]indolizinium salts readily yields benzothieno-annelated tetrahydropyridines as a complex mixture of stereoisomers, reduction of benzothieno[2,3-c]quinolinium salts results in dihydropyridine derivatives. The structure of the latter, in particular, was confirmed by single-crystal X-ray diffraction analysis.