Cyclization upon pyridines

Attention was centered on radical precursors in which the 3-pyridyl moiety was attached at the indole-3-position with the aim of directly producing the pyrido[4,3-b]carbazole skeleton of ellipticine by regioselective cyclization upon the 4-position of the pyridine ring. Satisfactorily, A-methyl and A-benzyl selenoesters 52a and 52b led to the ellipticine quinones 53a and 53b in acceptable yields (60 and 42% yield, respectively), after the radical cyclization and the in situ oxidation at the interannular methylene group. The cyclization was clearly less efficient from A-(methoxymethyl) selenoester 52c and no reaction was observed 

Ellipticine quinones have an intrinsic interest as antitumor agents 04JME4958 and are also known intermediates in the synthesis of ellipticines 02CRV4303 . For instance, ellipticine quinones 53b and 53c have been transformed into the alkaloid ellipticine 80JA1457 90J(P1)1319 98H(48)1593 . Hence, these homolytic pyridine acylations by 2-indolylacyl radicals also constitute formal syntheses of the natural product. 

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In the presence of bis(acetylacetonato)nickel, a-dicarbonyl compounds readily add at the nitrile group of 4-R-substituted l,2,5-oxadiazole-3-carbonitriles 219 to form enaminofurazans 220. The adducts obtained from 4-amino-3-cyanofurazan underwent intramolecular cyclization upon heating with acetic acid in ethanol to give furazano[3,4- ]pyridine 221 derivatives in high yields (Scheme 51) <2001RCB1280>. 

Carboxy-2-pyridylthio)propionic acids, prepared by the reaction of 2-mercatopyridin-3-carboxylic acid with 3-bromopropionic acid in aqueous KOH, undergo cyclization upon treatment with anhydrous sodium acetate and acetic anhydride to afford 2,3-dihydrothiopyrano[2,3-3]pyridin-4(4//)-ones. These products undergo further reaction with phenylhydrazine to give the phenylhydrazone (isolated) and then Fischer indole cyclization to give novel 5/7,1177-pyrido[2, 3 2,3]thiopyrano[4,3-3]indoles <2000JHC379>. 

The photostimulated reactions of vie aminohalo pyridines with acetone or pinacolone enolate ions lead to azaindoles in high yields (75-95%) [67]. When the amino group is protected as pivaloylamino derivative, (as in 17, Sch. 20), the analogs of substitution compounds 18 obtained by the photoinduced reaction of 2-amino-3-iodo-, 3-amino-4-iodo- and 4-amino-3-iodopyridines with acetone or pinacolone enolate ions, afford 5-, 6- and 7-azaindoles in almost quantitative yields by cyclization upon deprotection of the amino group and dehydration under acidic conditions (for example, see Sch. 20) [67]. 

A mixture of 6 g. of dry pyridine hydrochloride and 3 g. of cannabidiol (M. P. 66-67°) was heated at 125° for one hour The Beam test (purple color with 5% alcoholic potassium hydroxide) had entirely disappeared after a relatively short time. The product was then washed with water to free it from pyridine hydrochloride, extracted with ether and the ether solution washed with water. After evaporation of the solvent, the product was distilled in high vacuo, whereupon hydrogen chloride was evolved. The distillate was a highly viscous, colorless oil with a B.P approximately the same as that reported in the experiments using hydrochloric acid in ethanol for cyclization. Upon separating into six fractions, the specific rotations were as follows [a]32D—235 °, - 236 °, - 235 °, —241 °, —244 °, —249 °. 

Various approaches to the synthesis of 2,7-naphthyridines are available. Thus, the dianilide of 3-oxoglutaric acid 133 reacted with malononitrile in the presence of sodium acetate to give pyridone derivative 134, whereas the reaction of 133 with ethyl cyano-acetate in pyridine afforded tetrahydropyridinedione derivative 135. The compounds 134 and 135 underwent cyclization upon heating with triethylamine in DMF to form substituted 2,7-naphthyridine-3,6-diones 136 and 137, respectively (1989JPR745). 

This tricyclic ring system was prepared from the functionalized pyrazo[l,5-n]pyridines. Thus, pyrazo[l,5-n]pyridine-3-carboxylate 462 gave 465 upon mesylation and subsequent reaction with 2-ethoxy-2-lithioxyethy-lene, whose cyclization afforded 466 (94AP435). Intramolecular aldol... 

An alternative approach to thienothienopyridines involves intramolecular electrophilic attack at C-3 of the thiophene ring. In this way, the thienothiophene 82 can be cyclized to the benzothieno[2,3-/]thieno[2,3-c]pyridine 83 upon treatment with polyphosphoric acid (PPA) at 150°C (Equation 3). Similarly, treatment of the amide 84 with POCI3 gives the corresponding 1-alkyl-3,4-dihydro-benzothieno[3,2-g]thieno[3,2-f]pyridine 85 <1999PS(153)401> (Equation 4). 

The (benzimidazol-2-yl)pyridine 312, upon treatment with ethyl chloroformate in pyridine, undergoes cyclization to the benzimidazopyridopyrimidine 313. When the pyridine ring carries a cyano substituent, a further cyclization occurs, to give the pentacycle 314 (Scheme 77) <2000JCCS961>. 

A single report appears in the literature regarding the use of chirally modified palladium catalysts in reductive enyne cyclization.60 Upon exposure of 1,6-enyne 36a to the indicated palladium pyridine-oxazoline complex in the presence of EtjSiH, cyclization product 36b is formed in good yield, but with only modest levels of asymmetric induction (Scheme 26). 

This also may be looked upon as a substituent reaction (see Chapter 2.06) but a few examples are given here. A suitably substituted pyridine will undergo Pschorr cyclization to give 2- and 4-azafluorene and two other products (equation 181) (65CJC940). With a 2-substituted pyridine (287), cyclization on to the pyridine nitrogen is heavily favoured (equation 182) (54JCS4263). Decomposition of 3-(o-azidophenyl)pyridine results in a nitrene... 

The remaining reactions for the establishment of a bond adjacent to the pyridine nitrogen of a potential quinolizinium ring are presumed to involve the attack of the unshared pair of electrons of the nitrogen upon a carbon bearing a halogen atom. The most direct synthesis of this type might involve the cyclization of l-(2-pyridyl)-4-halobutadiene (130)... 

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