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Issue 3, 2014
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Enantioselective synthesis of hexahydrofuro[3,2-c] quinolines through a multicatalytic and multicomponent process. A new “aromatic sandwich” model for BINOL-phosphoric acid catalyzed reactions

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Abstract

A new and straightforward metal–organo orthogonal-relay catalytic asymmetric reaction for the enantioselective synthesis of hexahydrofuro[3,2-c]quinolines is reported. The process involves a three-component coupling reaction between an alkynol, an aldehyde and an arylamine catalyzed by a gold complex and a chiral BINOL-derived phosphoric acid. Quantum chemical calculations of the reaction mechanism suggest that the involved acid-catalyzed Povarov reaction is better described as a sequential Mannich/intramolecular Friedel–Crafts process between the 5-phenyl-2,3-dihydrofuran and protonated N-phenylaldimine reactants generated in situ. Moreover, computations of the reaction mechanisms for the formation of the four stereoisomers of the hexahydrofuro[3,2-c]quinoline adduct using (R)-TRIP-suggested a rationale for the face selectivity of the asymmetric Povarov cycloaddition. With a single coordination mode by ion pairing of the chiral phosphoric acid and the imine, the preferred approach of 5-phenyl-2,3-dihydrofuran to the iminium ion results from a combination of more favourable π-stacking and reduced steric interactions in the Re-exo transition state relative to the alternative diastereoisomeric orientations.

Graphical abstract: Enantioselective synthesis of hexahydrofuro[3,2-c] quinolines through a multicatalytic and multicomponent process. A new “aromatic sandwich” model for BINOL-phosphoric acid catalyzed reactions

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Publication details

The article was received on 18 Oct 2013, accepted on 05 Nov 2013 and first published on 06 Nov 2013


Article type: Edge Article
DOI: 10.1039/C3SC52891J
Citation: Chem. Sci., 2014,5, 996-1007
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    Enantioselective synthesis of hexahydrofuro[3,2-c] quinolines through a multicatalytic and multicomponent process. A new “aromatic sandwich” model for BINOL-phosphoric acid catalyzed reactions

    J. Calleja, A. B. González-Pérez, Á. R. de Lera, R. Álvarez, F. J. Fañanás and F. Rodríguez, Chem. Sci., 2014, 5, 996
    DOI: 10.1039/C3SC52891J

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