Chiral synthesis of functionalized tetrahydropyridines: gamma-aminobutyric acid uptake inhibitor analogues.
[Chemical reaction: See text] A convenient preparation of functionalized chiral tetrahydropyridine-3-carboxylates from nitriles in 68-90% enantiomeric excess (ee) via allylboration, followed by a conjugate addition-elimination and ring-closing metathesis, has been developed. Thus, the treatment of the acetate derived from vinylalumination of formaldehyde by use of [alpha-(ethoxycarbonyl)vinyl]diisobutylaluminum with chiral beta-substituted and beta-unsubstituted homoallylic amines, prepared in >98% diastereomeric excess (de) and 68-90% ee via allylboration of the corresponding N-aluminoimines, furnished functionalized aminodienes, which underwent ring-closing metathesis to provide chiral C5-C6 disubstituted tetrahydropyridine-3-carboxylates. This methodology has been applied for the synthesis of a chiral C6-substituted tetrahydropyridine with known GABA-inhibiting properties at low concentrations.
Ramachandran
P Veeraraghavan
PV
Herbert C. Brown Center for Borane Research, Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907-2084, USA. chandran@purdue.edu
Burghardt
Thomas E
TE
Bland-Berry
Layla
L
D000535:Aluminum; D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D018756:GABA Antagonists / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D014753:Vinyl Compounds
D000588:Amines; D018756:GABA Antagonists; D011725:Pyridines; D014753:Vinyl Compounds; D000535:Aluminum