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

✍ Scribed by Marcos José S. Carpes; Carlos Roque D. Correia

• Publisher: Elsevier Science
• Year: 2002
• Tongue: French
• Weight: 74 KB
• Volume: 43
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)02267-5

✦ Synopsis

Heck arylation of N-acyl-3-pyrrolines and an N-acyl-tetrahydropyridine with aryldiazonium tetrafluoroborates under phosphine-free conditions proceeded smoothly to give a-hydroxycarbamates (hemiaminals) or a-alkoxycarbamates which were oxidized to the desired gand d-lactams. Acidic hydrolysis of the g-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-d-lactams and higher homologues of baclofen can be obtained.