Heck arylations of N-acyl-3-pyrroline and N-acyl-1,2,5,6-tetrahydropyridine with aryldiazonium salts. Short syntheses of aryl γ- and δ-lactams, baclofen, homobaclofen and analogues

Abstract

Heck arylation of N-acyl-3-pyrrolines and an N-acyl-tetrahydropyridine with aryldiazonium tetrafluoroborates under phosphine-free conditions proceeded smoothly to give α-hydroxycarbamates (hemiaminals) or α-alkoxycarbamates which were oxidized to the desired γ- and δ-lactams. Acidic hydrolysis of the γ-lactams produced a series of arylated GABA derivatives, including baclofen, a useful therapeutic drug, in only three steps with an overall yield of 63–76%. Starting from N-acyl-tetrahydropyridine, aryl-δ-lactams and higher homologues of baclofen can be obtained.