Cascade 4+1 Radical Annulations of 2,6-Disubstituted Phenyl Isonitriles with N-Propargyl-6-Iodopyridones: Scope, Mechanism and Regioselective Synthesis of 7,9-Disubstituted Camptothecin Analogs

Wu Du; Dennis P. Curran

doi:10.1055/s-2003-40327

LETTER

Cascade 4+1 Radical Annulations of 2,6-Disubstituted Phenyl Isonitriles with N-Propargyl-6-Iodopyridones: Scope, Mechanism and Regioselective Synthesis of 7,9-Disubstituted Camptothecin Analogs

Wu Du, Dennis P. Curran*
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
Fax: +1(412)6249861; e-Mail: curran@pitt.edu;

Abstract

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Abstract

The reaction of o,o′-dialkyl-substituted aryl isonitriles with N-propargyl-6-iodopyridones provides 11H-indolizino[1,2-b]quinolin-9-ones with significant regioselectivity in favor of the more crowded product. The usefulness of the method is illustrated with a regioselective synthesis of (20S)-7-trimethylsilyl-9-isopropyl camptothecin.

Key words

cascade radical annulation - isonitrile - camptothecin - mappicine - quinoline

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Referenzen

References

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6

Camptothecin numbering and ring designations are used for consistency throughout the manuscript.

7 A single example of a reaction with a disubstituted isonitrile has been described previously. See ref. and: Liu H. PhD Thesis University of Pittsburgh; USA: 1991.

Fragmentation reactions of cyclohexadienyl-like radicals with rearomatization are well precedented. See, for example:

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9

Supporting Information Available: A print or pdf file of the characterization data for the compounds in this paper can be obtained on request from DPC.