Pyrrolo pyridones

The aldehyde ester (90) is converted into the fused pyridone (91), which can be further transformed to the unsubstituted pyrrolo[3,2-c]pyridine (92 Scheme 31) (B-72MI30900). 

Lead tetraacetate oxidation of diethyl IV-alkylaminofumarates led to the formation of the unusual dihydropyrrolo[3,2-b ]pyrrole derivatives (343), along with the pyrroles (344) and pyridones (345). In addition, the oxidative dimers (346) and (347) were also isolated (Scheme 119). Although the pyrroles (344) and pyridones (345) can be derived from the dimers (346) and (347), the mechanism of formation of the pyrrolo[3,2-6]pyrroles from three moles of starting material is obscure (77CC854). 

A series of JV-alkylamino fumarates have been oxidized by LTA in the presence of trifluoroacetic acid as a catalyst, leading to mixtures of pyrroles, pyridones and pyrrolo [3,2-fr]pyrroles given in Scheme 4970. In some cases acyclic oxidative dimers were isolated. The enamine molecules in them are linked through their -carbon atoms (Scheme 49). 

Thermal cydization of enaminones 542 gives pyrrolo[3,2-6]pyridines 543, which may be N-alkylated to give pyrrolo[3,2-b]pyridones 545. Alternatively, 542 may be A-methylated to give the new enaminones 544, which are cyclized in polyphosphoric ester (PPE) to the pyrrolopyridones 545 (R2 = Me), Scheme 147 (85JHC83 90JHC1201). 

To build the central ABC core present in 1, two main synthetic strategies have been used Diels-Alder reactions and asymmetric synthesis. This tricyclic subunit was chosen as the first synthetic target because it contains all five stereogenic carbons. A central pyrrolo-isoquinoline skeleton (ABC) was initially synthesized by the high-pressure Diels-Alder reaction of 3-alkyl-5,6-dihydro-2-pyridones with Danishefsky s diene, followed by deprotection and spontaneous pyrrolidine ring closure (see Scheme 16) [77]. 

Free radicals can also be generated by the photolysis of thiohydroxamate systems derived from thiazolones and thiopyridones. Photolysis of the thiazolone derivative (236) yields the pyrrolo[l,2-ajindole (238), together with a trace of the related indoline and some dimeric product (239). Reaction of the pyridone thiohydroxamate (237) gives a dimer as the major product (Scheme 72) <93JOC2768>. 

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