Cascade condensation, cyclization, intermolecular dipolar cycloaddition by multi-component coupling and application to a synthesis of (±)-crispine A

Abstract

A general approach for the synthesis of various nitrogen-containing heterocyclic compounds is described using an intermolecular dipolar cycloaddition reaction of azomethine ylides and nitrones. Stabilized and non-stabilized azomethine ylide dipoles or the related nitrones were generated by condensation of 4-, 5- or 6-halo-aldehydes with a readily available amino-acid, amino-ester or hydroxylamine to give an imine followed by cyclization and either decarboxylation or loss of a proton. After intermolecular cycloaddition with an activated dipolarophile, bicyclic or polycyclic (if the ylide dipole and/or dipolarophile contain a ring) amines were produced. A short synthesis of the alkaloid (+/-)-crispine A was achieved based on this tandem/domino 3-component coupling chemistry.