Chemistry of the Hexahydropyrrolo[2,3-b]indoles: configuration, conformation, reactivity, and applications in synthesis
David Crich1, Abhisek Banerjee
1Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607-7061, USA.
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.
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