Synthesis of α,γ-Disubstituted γ-Aminobutyric Acid and Pyrrolidine Derivatives

Significance

Intramolecular alkene-carbonyl coupling reactions of N-alkenylcarbamates mediated by a zirconocene-butene complex gave α-methyl-γ-substituted γ-aminobutyric acid (GABA) derivatives. Enantiopure tert-butyl 3-butenyl-carbamates bearing a substituent at the homoallylic position reacted diastereoselectively to favor the anti-GABA products. The intermediate zirconium species can be iodinated resulting in 2,4-disubstituted pyrrolidines with predominant cis-stereo­chemistry. Alternatively, the GABA products could be reduced to the alcohol and transformed to the tosylate, which cyclizes to give the 2,4-trans-substituted pyrrolidines.