Stereoselective synthesis of cyclobutyl GABA analogues and related compounds from (−)-(S)-verbenone

Synthesis of γ‐Aminobutyric Acid Analogs

“…Similar syntheses of (512) have also been reported from (S)-verbenone [362] and ( þ )-(R)-a-pinene [363]. The highly stereoselective conjugate addition of nitromethane to a,b-unsaturated cyclobutyl esters derived from (À)-(S)-verbenone furnishes 3-substituted cyclobutyl gabapentin analogs [364]. Hydrolysis yields the unsaturated lactam (AE)-(516).…”

Bioactive cyclobutane-containing alkaloids

“…Acid (194) was less effective on all four assays [258]. The highly stereoselective conjugate addition of nitromethane to a,b-unsaturated cyclobutyl esters derived from (-)-(S)-verbenone has been executed to afford the cyclobutyl GABA analog (195) [259]. Structures of compounds (192)- (195) are shown in Fig.…”

Stereoselective synthesis of γ-amino acids

“…Enantiomerically pure b-cyclobutyl c-amino acid 115 from (S)-verbenone was obtained by Ortuñ o et al 59 Thus, the addition of nitromethane to (Z)-and (E)-isomeric conjugated esters 112, which are readily available from (S)-verbenone, 60 in the presence of tetra-n-butylammonium fluoride (TBAF), produced the nitroester derivative 113 as only one diastereoisomer. It is noteworthy that the geometry of the double bound did not influence the p-facial diastereoselection of the nucleophilic addition, since the same product was obtained from the corresponding (Z)-or (E)-isomer.…”