Conjugate additions of o-iodoanilines and methyl anthranilates to acetylenic sulfones. A new route to quinolones including first syntheses of two alkaloids from the medicinal herb Ruta chalepensis.
A novel synthesis of 2-substituted 4-quinolones was developed on the basis of the conjugate additions of appropriately ortho-substituted anilines to acetylenic sulfones followed by intramolecular acylation of the corresponding sulfone-stabilized anions. Conjugate additions of variously substituted anilines to alkyl-substituted acetylenic sulfones generally proceeded slowly and in poor yield, especially when the aniline contained an electron-withdrawing substituent such as an ester group. In some cases, the reactions were enhanced by the presence of DMAP and the use of an excess of the sulfone in aqueous DMF. N-Formylanilines proved superior to free anilines. The products were either vinyl or allyl sulfones, depending on the conditions and the structure of the reactants. The acetylenic sulfone exists in equilibrium with its allenic and propargylic isomers under base-catalyzed conditions. Therefore, any of the three unsaturated sulfones can serve as the starting material for the conjugate additions. o-Iodoanilines proved superior to methyl anthranilate derivatives and underwent conjugate additions smoothly. The products were subjected to palladium-catalyzed carbonylation in methanol, and the resulting methyl esters were cyclized by treatment with strong bases such as LiHMDS or LiTMP, followed by reductive desulfonylation with aluminum amalgam. The resulting 2-substituted 4-quinolones included the naturally occurring medicinal compounds 1 and 2 and the O-methyl derivative 3.
Back
Thomas G
TG
Department of Chemistry, University of Calgary, Calgary, Alberta, Canada T2N 1N4. tgback@ucalgary.ca
Parvez
Masood
M
Wulff
Jeremy E
JE
D000114:Acetylene / Q000737:chemistry; D000470:Alkaloids / Q000138:chemical synthesis*; D000814:Aniline Compounds / Q000737:chemistry*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D007202:Indicators and Reagents; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry; D015363:Quinolones / Q000138:chemical synthesis*; D032105:Ruta / Q000737:chemistry; D013450:Sulfones / Q000138:chemical synthesis*; D062367:ortho-Aminobenzoates / Q000737:chemistry
D000470:Alkaloids; D000814:Aniline Compounds; D007202:Indicators and Reagents; D015363:Quinolones; D013450:Sulfones; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D000114:Acetylene