title: Enantioselective total synthesis of (+)-lysergic acid, (+)-lysergol, and (+)-isolysergol by palladium-catalyzed domino cyclization of allenes bearing amino and bromoindolyl groups.
abstract: Enantioselective total synthesis of the biologically important indole alkaloids (+)-lysergol, (+)-isolysergol, and (+)-lysergic acid is described. Key features of these total synthesis include (1) a facile synthesis of a chiral 1,3-amino alcohol via the Pd(0)- and In(I)-mediated reductive coupling reaction between L-serine-derived 2-ethynylaziridine and formaldehyde; (2) the Cr(II)/Ni(0)-mediated Nozaki-Hiyama-Kishi (NHK) reaction of an indole-3-acetaldehyde with iodoalkyne; and (3) Pd(0)-catalyzed domino cyclization of an allene bearing amino and bromoindolyl groups. This domino cyclization enabled direct construction of the C/D ring system of the ergot alkaloids skeleton, as well as the creation of the C5 stereogenic center with transfer of the allenic axial chirality to the central chirality.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Inuki
authors.forename: Akira
authors.initials: A
authors.lastname: Iwata
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohno
mesh_terms: D002384:Catalysis; D003500:Cyclization; D004873:Ergolines / Q000138:chemical synthesis* / Q000737:chemistry; D004876:Ergot Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D008237:Lysergic Acid / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D004873:Ergolines; D004876:Ergot Alkaloids; D007211:Indoles; D010165:Palladium; D008237:Lysergic Acid; C061884:lysergol