title: Study of the cis to trans isomerization of 1-phenyl-2,3-disubstituted tetrahydro-beta-carbolines at C(1). Evidence for the carbocation-mediated mechanism.
abstract: The present study was undertaken to shed light on the mechanism of the epimerization of cis-1,2,3-trisubstituted tetrahydro-beta-carbolines into the trans isomers via a potential carbocationic intermediate at C(1). In order to study the pathway involved in C(1)-N(2) bond cleavage, the electronic character of the carbon atom at C-1 was altered by substitution of electron-rich and electron-poor phenyl rings at this position. This provided direct evidence of the effects of charge at the proposed site of the carbocationic intermediate. In this regard, a diverse set of 1-(phenyl substituted)-2-benzyl-3-ethoxycarbonyl-1,2,3,4-tetrahydro-beta-carbolines has been synthesized via the Pictet-Spengler reaction by condensation of l-tryptophan derivatives with electron-poor and electron-rich aromatic aldehydes. The epimers involved in the isomerization mechanism were investigated by dynamic (1)H and (13)C NMR spectroscopic and X-ray crystallographic analyses. The kinetic studies, which involved conversion of cis diastereomers into their trans counterparts, were carried out in dilute TFA/CH(2)Cl(2). The 1-(4-methoxyphenyl) cis diastereomer epimerized at a much faster rate into the corresponding trans diastereomer than the related 1-(4-nitrophenyl) cis diastereomer epimerized. These observations provide support for the carbocationic intermediate in the C(1)-N(2) scission process. The understanding of this epimerization process is of importance when Pictet-Spengler reactions are carried out under acidic conditions during the synthesis of indole alkaloids.
authors.affiliation: Department of Chemistry, University of Wisconsin-Whitewater, Whitewater, Wisconsin 53190, USA.
authors.forename: Hephzibah J
authors.initials: HJ
authors.lastname: Kumpaty
authors.forename: Michael L
authors.initials: ML
authors.lastname: Van Linn
authors.forename: M Shahjahan
authors.initials: MS
authors.lastname: Kabir
authors.forename: F Holger
authors.initials: FH
authors.lastname: Försterling
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Deschamps
authors.forename: James M
authors.initials: JM
authors.lastname: Cook
mesh_terms: D000478:Alkylation; D002243:Carbolines / Q000737:chemistry*; D004583:Electrons; D006859:Hydrogen / Q000737:chemistry*; D007536:Isomerism; D015394:Molecular Structure
chemical_list: D002243:Carbolines; D006859:Hydrogen