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

Abstract

An asymmetric synthesis of the 3-substituted Δ 3,4-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.