Application of vinylogous carbamates and vinylogous aminonitriles to the regiospecific synthesis of uniquely functionalized pyrroles and quinolones

Abstract

Pyrroles and quinolones represent core structures, which are routinely found in both natural and synthetic bioactive substances. Consequently, the development of efficient and regiospecific methods for the preparation of such heterocycles with unique functionality is of some importance. We describe herein the regiospecific synthesis of 1,2,3,4-tetrasubstituted pyrroles containing polar substituents and such products are prepared from vinylogous carbamates and vinylogous aminonitriles. We also describe the regiospecific synthesis of 3-aryl containing 1,3,6trisubstituted quinolones from vinylogous carbamates. The use of an amine exchange reaction to prepare precursors for the pyrrole and quinolone forming cyclizations represents a key factor in the strategy.

Keywords: Pyrrole; Quinolone; Vinylogous Aminonitrile; Vinylogous Carbamate.

Fig. 1

Biologically Active Pyrroles and Quinolones

Scheme 1.

Preparation of 2-Arylvinylogous Carbamates

Scheme 2.

Preparation of Vinyl Acetate

Scheme 3.

Preparation of Amine Exchaned Vinylogous Carbamates

Scheme 4.

Base Mediated Cyclization of Amine Exchanged Vinylogous Carbamates

Scheme 5.

Preparation of Vinylogous Aminonitriles

Scheme 6.

Preparation of Amine Exchanged Vinylogous Aminonitriles

Scheme 7.

Base Mediated Cyclization of Amine Exchanged Vinylogous Aminonitriles

Scheme 8.

Preparation of Aniline Exchaned Vinylogous Carbamates

Scheme 9.

Preparation of 3-Arylquinolones from Aniline Exchanged Vinylogous Carbamates