title: Chemistry of the Hexahydropyrrolo[2,3-b]indoles: configuration, conformation, reactivity, and applications in synthesis.
abstract: The stereoselective formation of 2-endo-substituted hexahydropyrrolo[2,3-b]indoles from 2-substituted tryptamine derivatives, especially tryptophan, is discussed. Parallels are drawn with the formation of related heterocyclic systems, such as the hexahydrofurano[2,3-b]benzofurans, in which the thermodynamic preference of a substituent at the 2-position is also for the endo-configuration. Functionalization of tryptophan-derived hexahydropyrroloindoles at positions 2-, 3-, and 3a- is discussed with special emphasis on the 2-position, at which both radical and nucleophilic reactions take place preferentially on the endo-face of the diazabicyclo[3.3.0]octane system. The kinetic and thermodynamic preference for the 2-endo-position is considered in terms of the minimization of torsional strain, and parallels are drawn to the Woerpel model for the reactivity of analogous five-membered cyclic oxacarbenium ions. The use of the tryptophan-derived hexahydro[2,3-b]pyrroloindoles in the stereocontrolled synthesis of amino acids and alkaloids is presented.
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607-7061, USA.
authors.forename: David
authors.initials: D
authors.lastname: Crich
authors.forename: Abhisek
authors.initials: A
authors.lastname: Banerjee
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis; D001572:Benzofurans / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry; D026121:Indole Alkaloids / Q000138:chemical synthesis*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D009795:Octanes / Q000737:chemistry; D013237:Stereoisomerism; D013816:Thermodynamics; D014363:Tryptamines / Q000737:chemistry; D014364:Tryptophan / Q000031:analogs & derivatives
chemical_list: D000596:Amino Acids; D001572:Benzofurans; D019086:Bridged Bicyclo Compounds, Heterocyclic; D026121:Indole Alkaloids; D007211:Indoles; D009795:Octanes; D014363:Tryptamines; C429964:hexahydroindolinone; C030820:tryptamine; D014364:Tryptophan