Asymmetric synthesis of 3-substituted unsaturated prolines from chiral sulfoximine substituted allyl titanium(IV) complexes

An asymmetric synthesis of the 3-substituted Δ3,4-unsaturated prolines 7a–e and 3-substituted 4-methylene prolines 14a–c starting from the corresponding γ,δ-unsaturated α-amino acids 4a–e and 11a–c, respectively, is described. Amino acid derivatives 4a–e and 11a–d were obtained through aminoalkylation of the corresponding sulfoximine substituted allyl titanium(IV) complexes 2a–e and 10a–d, respectively, with the N-tert-butylsulfonyl imino ester 3. Activation of sulfoximines 4a–e and 11a–c through methylation of the sulfoximine group followed by a KF mediated isomerization of the vinyl aminosulfoxonium salts 5a–e and 12a–c, respectively, to the corresponding allyl aminosulfoxonium salt 6a–e and 13a–c, respectively, and a subsequent intramolecular nucleophilic substitution of the allylic aminosulfoxonium group afforded the enantio- and diastereomerically pure proline derivatives in medium to high yields.