Pyridines with nitriles

Scheme 4-25 summarizes the most common metal-promoted /nfe/molecular cyclocoupling reactions of various species with alkynes. The most prominent organic products include arenes, cyclooctatetraenes, cyclohexadienes (with olefins), pyridines (with nitriles), cyclopen-tenones (with olefin ( CO the Pauson-Khand reaction [98]), pyrones (with CO2), and five-membered heterocycles (with X = S, Se) common organometallic products include cyclobutadiene complexes, cyclopentadienone complexes, and metallacyclopentadienes. 

The hydroxy group undergoes 0-acylation and deacylation (79JHC689). These reactions of functionalized hydroxyfurazans are valuable methods for modification of these compounds. Thus, hydroxybifurazan 248 was aroylated with benzoyl chloride in the presence of pyridine with concomitant cleavage of the unsubstituted furazan ring to give nitrile 262 (Scheme 170) (75LA1029). 

Some cycloaddition reactions of 4 are summarized in Scheme 1. This shows that silylene 4 undergoes reactions with nitriles [14], phosphaalkynes [15], silyl azides [16], diazabutadienes [17], 2,2 -bipyridyl and its derivatives [18, 19], a-ketoimines [19], and pyridine-2-aldimines [19]. 

The cobalt-catalyzed cooligomerization of diynes with nitriles allows a simple one-step synthesis222 of condensed pyridine derivatives including difficultly accessible 5,6,7,8-tetrahydroisoquinolines223 The synthesis is a versatile one in that pyridines condensed with five- and seven-membered carbocyclic rings can also be achieved in moderate yield in similar fashion. Additional attractive features of this simple synthesis are the formation of condensed isoquinolines by the use of functionalized nitriles and the pronounced regioselectivity observed when dissymmetrical diacetylenes are employed (Scheme 148).222... 

Bis-cycloadducts 169 and 170 (R = R1 =MeO, Me, Cl) obtained from reactions of respective 4-substituted benzonitrile oxides and pyridine have been described. Crossed adducts, such as 169 (R = H, R1 = MeO R = MeO, R1 = H), were also formed on treating pyridine with mixtures of various nitrile oxides (338). Addition of pyridine to benzoylcarbonitrile oxide affords an unstable... 

Iodoacetylene (prepared in situ from ethynylmagnesium bromide or tributyl (ethynyl)tin with iodine) was used as a dipolarophile in the 1,3-dipolar cycloaddition reactions with nitrile oxides to produce 2-(5-iodoisoxazol-3-yl)pyridine and 3-(4-fluorophenyl)-5-iodoisoxazole in good yield (70%-90%). Subsequently,... 

Reactions of 2-nitrosopyridine with nitrile oxides afford, depending on structure of the latter, either l,2,4-triazolo[l,5-a]pyridine 1,3-di-N-oxides (370) or the corresponding 1.2.4-triazolo, 5-a Ipyridine 3-oxides (371) (419). 

Diynes react with nitriles and aldehydes in the presence of a nickel(0) complex to give pyridines and dienones, respectively (Scheme 93).448,448a,448b... 

Scheme 14.32. Preparation of tetrasubstituted pyridines by the reaction of titanacyclobutenes with nitriles.

BioH14 is a mdo-polyborane, therefore, it is expected that it forms adducts with Lewis bases. This is indeed the case but with concomitant loss of hydrogen as shown in Eq. (51). These adducts of the type BioHi2-2L (L = amines, pyridine, phosphines, nitriles, dialkylsulfides inter alia) proved to be versatile reagents. For instance, when triethylamine is used to replace acetonitrile from the adduct not only does the expected replacement occur but in preference also a proton shift (most likely prior to the base displacement reaction) with cluster closure to the decahydro-doso-decaborate(2—) (Eq. 52) ... 

Furo[2,3- ]pyridines are generated in a cyano [4-1-2] reaction that uses tungsten alkynols and aldehydes which cyclize to 1,3-dienes prior to reaction with nitriles (Scheme 9) <1998JA4520>. The reaction, which is activated by photolysis or with Me3N0-H20, works with unactivated nitriles in both intramolecular and intermolecular reactions to give moderate to good yields of product. 

Thermal rearrangements of 5-spirocyclopropaneisoxazolines, 133, lead to dihydrofuro[2,3-f]pyridines (Scheme 42) <1996JOC1665>. Compound 133 is prepared from the reaction of bicyclopropyl idene, acting as a dipolarophile, with nitrile oxides. A one-pot variation of the reaction beginning with a stable nitrile oxide and bicyclopropyl idene affords higher yields of the furopyridines. 

Scheme 19 Synthesis of pyridine 64 by hetero IEDAR of the diene 61 with nitrile 62 [54]...

Selective cyclotrimerization of alkynes with nitriles produced pentasubstituted pyridines (1) with little formation of benzenoid products (Scheme 1) <94CB(127)2535>. 

In a recently reported synthesis of pyridines, lithiated methoxyallenes react with nitriles in the presence of trifluoroacetic acid (Scheme 107) <2004CEJ4283>. The mechanism is postulated to proceed via initial protonation followed by nucleophilic addition of the trifluoroacetate ion with subsequent intramolecular acyl transfer and aldol condensation to give the pyridine. An additional pyridine formation starting from azaenyne allenes forms a-5-didehydro-3-picoline diradicals, which can be trapped by 1,4-cyclohexadiene, chloroform, and methanol to produce various pyridines <20040L2059>. 

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