A new, general, and practical procedure for the asymmetric synthesis of 4-alkylidenyl glutamic acid derivatives via a catalytic enantioselective tandem conjugate addition-elimination on allylic acetates under chiral phase-transfer conditions is reported. A variety of structural types of allylic acetates have been reacted with the benzophenone imine of glycine tert-butyl ester to give the products in good to excellent yields and enantioselectivities (63-92% yield, 80-97% ee, 8 cases).

[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.

Pyridine derivatives R 0380 Chiral Synthesis of Functionalized Tetrahydropyridines: γ-Aminobutyric Acid Uptake Inhibitor Analogues. -A new method to prepare chiral tetrahydropyridines such as (VI), (VII), and (XII) is developed. -(RAMACHANDRAN*, P. V.; BURGHARDT, T. E.; BLAND-BERRY, L.; J. Org. Chem. 70 (2005) 20, 7911-7918; Dep. Chem., Purdue Univ., West Lafayette, IN 47907, USA; Eng.) -Jannicke 05-135

Contents (65 pages):1. Experimental procedures and product characterization data (pp S2 -S15).2. 1 H and 13 C NMR spectra of 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 4, 5, 6 and 7 (pp S16-S39).3. X-ray spectra and data for compounds (S)-3d and (2S, 4S)-7 (pp S40-S63). References (pp S64-S65)