2.6- Naphthyridines from pyrroles

Besides the domino Michael/SN processes, domino Michael/Knoevenagel reactions have also been used. Thus, Obrecht, Filippone and Santeusanio employed this type of process for the assembly of highly substituted thiophenes [102] and pyrroles [103]. Marinelli and colleagues have reported on the synthesis of various 2,4-disubstituted quinolines [104] and [l,8]naphthyridines [105] by means of a domino Michael addition/imine cyclization. Related di- and tetrahydroquinolines were prepared by a domino Michael addition/aldol condensation described by the Hamada group [106]. A recent example of a domino Michael/aldol condensation process has been reported by Brase and coworkers [107], by which substituted tetrahydroxan-thenes 2-186 were prepared from salicylic aldehydes 2-184 and cycloenones 2-185 (Scheme 2.43). 

Starting from 1-methyl-17/-pyrrole-2-carboxylic acid, the tricyclic fused quinolin-4-one and naphthyridin-4-one derivatives 441 were prepared, in only three steps, by an intramolecular Heck cyclization of derivative 440 (Scheme 94) <2005EJ02091>. This reaction was performed in DMA as solvent, with potassium acetate as base and Pd(PPh3)4 as catalyst. The use of microwave irradiation, in some cases, gives better yields of cyclized products. 

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