Pyridines cycloaddition forms

Pyridine, a six-membered cyclic aromatic amine, has also been studied on Ge(100)-2 x 1 both theoretically [315,316] and experimentally by STM [314]. It adsorbs selectively through a Ge—N dative bond on the surface. Theoretical calculations showed that the dative-bonded adduct is more stable than other possible reaction products (e.g., cycloaddition products) on Ge [315,316]. Furthermore, STM images show formation of a highly ordered monolayer at the surface with a coverage of 0.25 ML. The pyridine overlayer forms a c(4 x 2) structure in which the molecules bind to the down atoms of every other dimer to minimize repulsive interactions between pyridine molecules. 

Takeuchi and coworkers reported an iridium-catalyzed cycloaddition of a,o -diynes and nitriles to give pyridines in 2012 [57]. With [Ir (cod)Cl]2/DPPF or BINAP as the catalytic system, pyridines were formed effectively (Scheme 3.24). A wide range of nitriles (aliphatic and aromatic nitriles) can be applied and reacted smoothly with Q ,a -diynes to give the pyridines. In the case of unsymmetrical diyne bearing two different internal alkyne moieties, high regioselectivity can be achieved which can be explained by the different reactivities of the a-position in iridacyclopentadiene. Terpyridine and quinquepyridine were prepared as well. [Ir(cod)Cl]2/chiral diphosphine catalyst can be applied to enantioselective synthesis. Kinetic resolution of the racemic... 

Whereas in all previously mentioned inverse cycloaddition reactions [h]-fused pyrido annelated systems are formed, some reactions are described which lead to [c]-pyridine annelated bicyclic systems. 5-(Butynylthio)pyrimidines (R = Ph, NHCOCH3) give on heating at 180°C in nitrobenzene 5-R-2,3-dihydrothieno[2,3-c]pyridines (89T803). 5-Propynyloxymethylpyrimidines also readily undergo cycloaddition into l,3-dihydrofuro[3,4-c]pyridines (89T5151) (Scheme 39). Considerable rate enhancements were observed with quaternized pyrimidinium salts. Whereas... 

As an extension of this reaction the intramolecular cycloaddition of 5-propynyloxycycloalkanepyrimidines was studied. It was found that bi-and tricyclic annelated pyridine derivatives are formed by expulsion of either X-CH2-CN and/or HCN, respectively. A marked selectivity in the product formation was observed, depending on the size of the cycloalkane ring. With cyclohexapyrimidines a mixture of A and B is formed, while with the cycloheptapyrimidine derivative exclusive formation of the tricyclic compound B takes place (92T1643, 92T1657) (Scheme 39a). 

Azcpincs under acid conditions reportedly117-225 yield aniline derivatives although ring contraction to pyridines is more usual. Thus, highly substituted 3//-azepines, e.g. 28, with a vacant 7-position, formed by cycloaddition of 2//-azirines with cyclopentadienones, on heating in acetic acid isomerize rapidly to the correspondingly substituted anilines 29.117... 

Treatment of 1,2,4-triazines 91a-91e with the electron-deficient die-nophile dimethyl acetylenedicarboxylate gave products, depending on the substituents [77LA( 10) 1718]. Pyrrolo-[2, -/][ ,2,4]triazines 92 were obtained via [4 + 2]-cycloaddition [77LA(9)1413, 77LA( 10)1718] with 91, but interaction with 91b in the absence of solvent gave, in addition to 92, the pyrido[2,l-/][l,2,4]triazine 93 and [l,3]oxazino[2,3-/][l,2,4]-triazine 94. In case of 91a pyridine and benzene derivatives were also formed in addition to 92 (Scheme 23). 

The scope and efficiency of [4+2] cycloaddition reactions used for the synthesis of pyridines continue to improve. Recently, the collection of dienes participating in aza-Diels Alder reactions has expanded to include 3-phosphinyl-l-aza-l,3-butadienes, 3-azatrienes, and l,3-bis(trimethylsiloxy)buta-l, 3-dienes (1,3-bis silyl enol ethers), which form phosphorylated, vinyl-substituted, and 2-(arylsulfonyl)-4-hydroxypyridines, respectively <06T1095 06T7661 06S2551>. In addition, efforts to improve the synthetic efficiency have been notable, as illustrated with the use of microwave technology. As shown below, a synthesis of highly functionalized pyridine 14 from 3-siloxy-l-aza-1,3-butadiene 15 (conveniently prepared from p-keto oxime 16) and electron-deficient acetylenes utilizes microwave irradiation to reduce reaction times and improve yields <06T5454>. 

Likewise, an efficient one-pot multicomponent synthesis of annelated 2-amino pyridines (e.g., 17) utilizing [4+2] cycloadditions has been described <06JOC3494>. The process involves the in situ generation of 1-aza-1,3-butadiene from a palladium-catalyzed coupling-isomerization reaction of aryl halides (e.g., 18) with propargyl V-tosylamines (e.g., 19). The resulting butadiene then undergoes cycloadditions with V.S -ketene acetals (e.g., 20) to form annelated pyridines (e.g., 17). 

Van der Eycken and coworkers have presented a study describing the microwave-assisted solid-phase Diels-Alder cycloaddition reaction of 2(lH)-pyrazinones with dienophiles [69]. After fragmentation of the resin-bound primary cydoadduct formed by Diels-Alder reaction of the 2(lH)-pyrazinone with an acetylenic dieno-phile, separation of the resulting pyridines from the pyridinone by-products was achieved by applying a traceless linking concept, whereby the pyridinones remained on the solid support with concomitant release of the pyridine products into solution (Scheme 7.58). 

Photochemical [2+2]cycloaddition between benzo[b]furan and 3-cyano-2-alkoxy-pyridines in benzene has been reported to follow a very interesting mechanism supported also by Frontier-MO calculations using the PM3 Hamiltonian. It is believed that the singlet excited state of the pyridine and the ground state benzofuran react to form a [2+2] adduct and is followed by ring opening to the cyclooctatriene, which cyclizes to the secondary endo- and exo-isomers shown below <00CC1201>. 

Cycloaddition to alkynes, cyclobutenones. This ketene when formed in situ from CCI3COCI and Zn/Cu, reacts with alkynes to form 4,4-dichlorocyclobuten-ones,3 which can rearrange in part to 2,4-dichlorocyclobutenones.4 Both products are reduced to the same cyclobutenone by Zn(Cu) in HOAc/pyridine (4 1) or by zinc and acetic acid/TMEDA.5... 

The gas-phase pyrolysis of vinylogous systems of isopropylidene amino-methylenemalonates (1280,1287, and 1290), prepared from the appropriate enaminone or dienaminone and Meldrum s acid in pyridine, was studied by McNab etal. at 500°C and 10 2 torr (87CC140). Flash vacuum pyrolysis of 1280 gave l//-azepinones (1283) in —60% yields, together with a small amount of cyclopentadienone dimer (1284). They suggested that the azepi-nones (1283) were formed by electrocyclization from dipolar intermediates (1282) produced from the methyleneketenes (1281) by hydrogen transfer (Scheme 54). Cycloaddition of 1282 yielded bicyclics (1285), which col-... 

While arylnitrile oxides dimerize in protic solvents and in pure pyridine (cf. 4.04.8.1.3.), they form bis(adducts) (191) and (192) via zwitterions (189) with pyridine in apolar solvents (Scheme 83) <89JHC757,90Gi>. Significantly, the cycloaddition of the nitrile oxide to pyridine to give (190) is not a concerted process. Heterocycles (191) undergo base catalyzed ring cleavage (Scheme 84). 

The triphenyl derivative (91, R = R = R = Ph, R = H) is formed in a mechanistically interesting reaction between benzoyl formic acid anil (Ph-N=CPh-C02H), trifluoroacetic anhydride, and pyridine. Its 1,3-dipolar cycloaddition reactions with alkynes and alkenes have been reported. ... 

Another nonclassical heterocycle, thienol3,4-cJpyrazole, was synthesized, utilizing the ability of mesoionic ring systems to act as 1,3 dipoles in cycloadditions. Condensation of IV-phenylsydnone (162) with dibenzoylacetylene formed 3,4-dibenzoyl-1-phenylpyrazole (163) (85%) with phosphorus pentasulfide in refluxing pyridine, this gave 85% of 2,4,6-triphenyIthieno[3,4-c]pyrazole (164) [Eq. (44)]. The synthesis of 5-methyl-l,3,4,6-tetraphenylthieno[3,4-c]pyrrole is also described. ... 

Reaction with acetylenic dipolarophiles represents an efficient method for the preparation of 2,5-dUiydrothiophenes. These products can be either isolated or directly converted to thiophene derivatives by dehydration procedures. The most frequently used dipolarophile is dimethyl acetylenedicarboxylate (DMAD), which easily combines with thiocarbonyl yhdes generated by the extrusion of nitrogen from 2,5-dihydro-1,3,4-thiadiazoles (8,25,28,36,41,92,94,152). Other methods involve the desUylation (31,53,129) protocol as well as the reaction with 1,3-dithiohum-4-olates and l,3-thiazolium-4-olates (153-158). Cycloaddition of (5)-methylides formed by the N2-extmsion or desilylation method leads to stable 2,5-dUiydrothiophenes of type 98 and 99. In contrast, bicyclic cycloadducts of type 100 usually decompose to give thiophene (101) or pyridine derivatives (102) (Scheme 5.37). 

Zinc chloride-doped natural phosphate was shown to have catalytic behavior in the 1,3-dipolar cycloadditions of nucleoside acetylenes with azides to form triazolonucleosides <99SC1057>. A soluble polymer-supported 1,3-dipolar cycloaddition of carbohydrate-derived 1,2,3-triazoles has been reported <99H(51)1807>. 2-Styrylchromones and sodium azide were employed in the synthesis of 4(5)-aryl-5(4)-(2-chromonyl)-1,2,3-triazoles <99H(51)481>. Lead(IV) acetate oxidation of mixed bis-aroyl hydrazones of biacetyl led to l-(a-aroyloxyarylideneamino)-3,5-dimethyl-l,2,3-triazoles <99H(51)599>. Reaction of 1-amino-3-methylbenzimidazolium chloride with lead(fV) acetate afforded l-methyl-l/f-benzotriazole <99BML961>. Hydrogenation reactions of some [l,2,3]triazolo[l,5-a]pyridines, [l,2,3]triazolo[l,5-a]quinolines, and [l,2,3]triazolo[l,5-a]isoquinolines were studied <99T12881>. 

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