Pyrrolo pyridinone

Spirocyclopropane isoxazolidines 75, obtained from alkylidenecyclopropane nitrones, underwent thermally induced selective rearrangement to pyrrolo[3,4-A]pyridinones 76 <00TA897>. The same adducts 75 in the presence of a protic acid afforded exclusively p-lactams 77 (57-60% yield) accompanied by ethylene extrusion <00JA8075>. 

Pyrrolo[2,3-/ ]pyridinones react with diethyl cyanomethanylphosphonate to give two different products, depending on the substitution pattern of the starting material. For compounds without substituents in the 2-position, pyrrolo[2,3-3]-pyridinyl acetonitriles, 55, are produced. When the nitrogen atom is protected with a pivaloyl group, alkenyl nitriles, 56, are formed (Scheme 2) <2001T1995>. 

Pyrrolo[2,3- ]pyridinones, 59, undergo an inverse electron demand Diels-Alder reaction with ethyl vinyl ether to generate 6-aza-5-carboline products in excellent yields but low stereoselectivity (Equation 4) <1997S73>. 

Our interest in expanding the acylative pyrrole annulation approach to additional heterocyclic systems has led to an efficient synthesis of pyrrolo[3,2-c]pyridin-2-ones and pyrido[3,4-6]pyrrolizidin-l-ones starting from 4-chloro-N-benzyl-2(l//)-pyridinone and amino acid salts.811 Over the years pyrrolo[3,2-c]pyridines (5-azaindoles)41 have been of interest for applications as elements in new drug design, nucleotide analogues,42 and biochemical tools. However, available synthetic routes to multifunctionalized members from this class of heterocyclic structures are limited.41 43... 

Mesoionic compounds may undergo 1,3-dipolar cycloaddition reactions. Thus anhydro-1 -hydroxythiazolo[3,2-a]guinolinium hydroxide (396) is a substrate for the reaction with DMAD. The formation of the pyrrolo[l,2-a]quinoline (397) from this reaction involves COS elimination from the initial adduct. Ethyl propiolate also reacts in the same fashion. The orientation in the cycloadduct can be arrived at from the ylide form (396a). With fumaronitrile, however, the fused pyridinone (398) is formed by loss of sulfur from the primary cycloadduct (78JOC2700). 

Diaza-compounds. Phenacyl bromide reacts with 2-aminopyridine 1-oxide to yield 2-phenylimidazo[l,2-a]pyridin-3-ol (769) another derivative of this ring system, compound (771), is produced by the action of diphenylketen on the sulphilimide (770), dimethyl sulphide being eliminated.(6-Methyl-2-pyri-dyl)acetyl azide (772) forms the dihydroimidazo[3,4-a]pyridinone (773) on heating." Whereas l-methylpyrrole-2-aldehyde and other heterocyclic aldehydes react with tosylmethyl isocyanide to give oxazoles, e.g. (774), pyrrole-2-aldehyde affords the 6-azaindolizine (775). The action of potassium amide on the derivative (776) of 3-bromopyridine furnishes the pyrrolo[3,4-c]pyridine (777) by cyclization of an intermediate pyridyne." ... 

Condensation of 2-24 with hydrazine hydrate and hydroxylamine hydrochloride was carried out. The pyrrole-fused heterocycles pyrrolo[3,2-ii]pyridazine 2-27 and pyrrolo[2,3-c]pyridinone 2-28 were generated in high isolated yields, respectively (Scheme 2.16). These further applications of 2-24 demonstrate that the two carbonyl groups on the pyrrole ring of 2-24 are useful for the preparation of other valuable pyrrole-fused A -heterocyclic compounds [59, 60]. 

Condensation of 2-24 with hydrazine hydrate in ethanol at 80 °C gave pyrrolo [3,2-(i]pyridazines 2-27 as products. However, condensation of 2-24a with hydroxylamine hydrochloride in refluxing pyridine led to the pyrrolo[2,3-c]pyrid-inone 2-28 as the single product, which was confirmed by single-crystal X-ray structural analysis (Fig. 2.8). The Csps-H bond of f-Pr was coupled with the in situ generated oxime moiety to form the pyridinone ring via intramolecular nucleophilic substitution or bfi-electrocyclization. 

Formation of Pyrrolo[2,3-c]pyridinone 2-28 from Pyrrole-2,3-diones 2-24 and Hydroxylamine Hydrochloride. In a 20-mL Schlenk tube, hydroxylamine hydrochloride (1.5 mmol, 104 mg) was added to the pyridine solution (10 mL) of compound 2-24a (180 mg, 0.5 mmol). After the reaction mixture was refluxed for 4 h, the solvent was evaporated in vacuo to give a yellow sohd, which was subjected to Si02 column using petroleum ether, ethyl acetate, and triethylamine (100 20 1) as the eluent to give product 2-28. 

The intramolecular hydroarylation of A-propargylpyrrole-2-carboxamides under AuCls-catalyzed conditions affords substituted pyrrolo[2,3-c]pyridinone and pyrrolo[3,2-c]pyridinone derivatives arising from direct hydroarylation or from a formal rearrangement of the carboxamide group (Scheme 18.39) [34]. The ratio of these products depends on the polarity of the solvent. The AuCls-catalyzed intramolecular... 

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