Stereocontrolled Oxidative Additions upon 1,4-Dihydropyridines: Synthesis of Hexahydrofuro[2,3-b]pyridine and Hexahydropyrano[2,3-b]pyridine Derivatives

Abstract

trans-α-Alkoxy-β-halotetrahydropyridines are synthesized in a very efficient single step by stereocontrolled N-halosuccinimide (NXS)–promoted alcohol addition to the enamine group in N-alkyl-1,4-dihydropyridines. These compounds are cyclized using sodium cyanoborohydride in the presence of 2,2′-azobis(2-methylpropionitrile), azabisisobutyronitrile (AIBN) (cat.), and tributylstannane (cat.), affording hexahydrofuro[2,3-b]pyridine and hexahydropyrano[2,3-b]pyridine derivatives. The cyclized product undergoes ring-opening reaction by a nucleophile in the presence of Lewis acid to afford highly functionalized tetrahydropyridines.

GRAPHICAL ABSTRACT

Keywords:

• 1,4-Dihydropyridines
• enamine
• iminium ion reactions
• radical cyclizations

ACKNOWLEDGMENT

We thank the University Grant Commission (UGC), New Delhi, for financial support.