Synthesis of analogues of GABA. VIII. Selective a-alkylation and γ-halogenation of the dianion from α,β-unsaturated nipecotic acid derivatives

1,2,3,6-Tetrahydropyridine-3-carboxylic acid (3), the β, γ-unsaturated derivative of the GABA uptake inhibitor nipecotic acid (1), has been synthesized by deconjugation via the dilithium salt of the N-t-butyloxycarbonyl-protected intermediate (6). Substitution of the intermediate with alkylating agents or an aldehyde gave predominantly a-alkylated products but chlorination with N-chlorosuccinimide provided a route to the γ-substituted unsaturated amino acid (13a).