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 benzothie- no(2,3-c)quinolinium salts were synthesized either by quaternization of benzothieno(2,3-c)pyridines, or recycli- zation of benzothieno(2,3-c)pyrylium salts with primary amines. One-pot synthesis of benzothieno(3,2-g)indolizi- nium salts from 1-(3-chloropropyl)-benzothieno(2,3-c) pyrylium included consequent recyclization of the pyryli- um 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 benzo- thieno(2,3-c)pyridinium and benzothieno(3,2-g)indolizinium salts readily yields benzothieno-annelated tetrahydropyri- dines as a complex mixture of stereoisomers, reduction of benzothieno(2,3-c)quinolinium salts results in dihydropyr- idine derivatives. The structure of the latter, in particular, was confirmed by single-crystal X-ray diffraction analysis.