title: Asymmetric synthesis of 2-alkyl-substituted 2,5-dihydropyrroles from optically active aza-Baylis-Hillman adducts. Formal synthesis of (-)-trachelanthamidine.
abstract: A series of optically active 2-alkyl-substituted 2,5-dihydropyrroles were prepared via the asymmetric aza-Baylis-Hillman equivalent reaction and subsequent ring-closure metathesis reaction. Optically active aza-Baylis-Hillman adducts underwent a smooth two-step conversion to N-allyl-beta-amino-alpha-methylene esters in high yield, which gave chiral 2,5-dihydropyrroles, potential precursors for the aza-heterocyclic synthesis, almost quantitatively through RCM reaction catalyzed by Grubbs catalyst. The conversion was carried out without loss of the optical purity of the starting material. Synthetic application of the method to (-)-trachelanthamidine was examined. Hydrogenation of 2,5-dihydropyrrole took place smoothly to give the corresponding 2,3-disubstituted pyrrolidine in good yield. The stereoselectivity of the hydrogenation was sensitive to the presence or absence of the protective group in the C2-side chain. The TBS-protected 2,5-dihydropyrrole gave a 1:1 mixture of the cis/trans isomers, while free alcohol afforded the trans-2,3-disubstituted pyrrolidine in a selectivity of 6:1. The formal synthesis of (-)-trachelanthamidine was achieved in 11 steps from a chiral sulfinimine. This methodology provided a convenient procedure for the preparation of C2-alkyl-substituted 2,5-dihydropyroles with retention of high optical purity.
authors.affiliation: Department of Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University, Ube 755-8611, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Noguchi
authors.forename: Akio
authors.initials: A
authors.lastname: Kamimura
mesh_terms: D007097:Imines / Q000737:chemistry; D009904:Optical Rotation; D011758:Pyrroles / Q000138:chemical synthesis*; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis*; D013452:Sulfonium Compounds / Q000737:chemistry
chemical_list: D007097:Imines; D011758:Pyrroles; D011763:Pyrrolizidine Alkaloids; D013452:Sulfonium Compounds; C522016:sulfinimine; C051741:trachelanthamidine