Pyridines => alkynes

The synthesis of several compounds containing a pyridine alligator clip for incorporation into a molecular electronic device began with compound 21. The synthesis of 22 was accomplished by coupling pyridine 21 with 2,5-dibromonitrobenzene as shown in Scheme 3.56. The low yield may be due to a stable copper acetylide formed after the TMS group is cleaved. If an in situ deprotection was not used, the pyridine alkyne proved to be unstable. 

Anhydro-3-hydroxy-2-phenylthiazolo[2,3-6]thiazolylium hydroxide (407) underwent ready thermal reaction with alkynic and alkenic dipolarophiles in refluxing toluene. With the former dipolarophile sulfur was lost from the intermediate 1 1 cycloadduct (408) to give the substituted 5H-thiazolo[3,2- i]pyridin-5-ones (409). With the latter, the intermediate (410) lost H2S, also forming (409). 

Small shift values for CH or CHr protons may indicate cyclopropane units. Proton shifts distinguish between alkyne CH (generally Sh = 2.5 - 3.2), alkene CH (generally 4, = 4.5-6) and aro-matic/heteroaromatic CH (Sh = 6 - 9.5), and also between rr-electron-rich (pyrrole, fiiran, thiophene, 4/ = d - 7) and Tt-electron-deficient heteroaromatic compounds (pyridine, Sh= 7.5 - 9.5). 

The alkynylation of estrone methyl ether with the lithium, sodium and potassium derivatives of propargyl alcohol, 3-butyn-l-ol, and propargyl aldehyde diethyl acetal in pyridine and dioxane has been studied by Miller. Every combination of alkali metal and alkyne tried, but one, gives the 17a-alkylated products (65a), (65c) and (65d). The exception is alkynylation with the potassium derivative of propargyl aldehyde diethyl acetal in pyridine at room temperature, which produces a mixture of epimeric 17-(3, 3 -diethoxy-T-propynyl) derivatives. The rate of alkynylation of estrone methyl ether depends on the structure of the alkyne and proceeds in the order propar-gylaldehyde diethyl acetal > 3-butyn-l-ol > propargyl alcohol. The reactivity of the alkali metal salts is in the order potassium > sodium > lithium. 

A unique method to generate the pyridine ring employed a transition metal-mediated 6-endo-dig cyclization of A-propargylamine derivative 120. The reaction proceeds in 5-12 h with yields of 22-74%. Gold (HI) salts are required to catalyze the reaction, but copper salts are sufficient with reactive ketones. A proposed reaction mechanism involves activation of the alkyne by transition metal complexation. This lowers the activation energy for the enamine addition to the alkyne that generates 121. The transition metal also behaves as a Lewis acid and facilitates formation of 120 from 118 and 119. Subsequent aromatization of 121 affords pyridine 122. 

It has been shown that even the labile monosubstituted butadiynyl derivatives ean be used as the starting terminal alkynes. Thus, the oxidative eoupling of 3-butadiynyl-l-methyl-, 5-butadiynyl-l-methyl-, and 4-butadiynyl-l,3,5-dimeth-ylpyrazole in pyridine by oxygen in the presenee of CuCl at room temperature leads to eonjugated oetatetraynes in 75%, 83%, and 84.0% yields (69IZV2546 69KGS1055) (Seheme 65, Table XVIII). 

TABLE XXVn. l-Methyl-l,6-dihydropyrazolo[3,4-c]pyridin-7-ones Prepared by Cyclization of Vicinal 4-(Alkyn- l-yl)pyrazole-5-carboxylic Acid Amides [90IZV2089]. 

The mechanism of attack of 1,3-dipolar reagents on fluoroalkenes can be considered to be either stepwise or concerted. Heteroaromatic N-imines react by a stepwise 1,3 addition to perfluoroalkenes and -alkynes to give fluorinated pyrazolo[l,5-a]pyridines [82JCS(P1)1593]. Pyridinium /-butoxycarbonylmethylide with fluoroalkenes gave pyrrolo[l,2-a]pyri-dines [86JCS(P 1) 1769] and indolizines (22) are obtained with pyridinium phenacylide [91JFC(51)407]. 

In the context of pyridin synthesis from alkynes and nitriles homogeneously catalyzed by (cyclopentadienyl)cobalt complexes (Eq. 13), it was found that electron-withdrawing groups on the cyclopentadienyl ring significantly increase the activity [63]. During the screening of various cobalt half-sandwich complexes... 

Scheme 12 General synthesis of 5-dialkylamino-3-ethoxycyclopentadienes 60 from 3-di-alkylamino-l-ethoxypropenylidenechromium complexes 57 and alkynes in a donor solvent. Conditions A pyridine, 55-80 °C, 1.5-4 equiv. of the alkyne B MeCN, 80 °C, slow addition of 2-4 equiv. of the alkyne. For further details see Table 1 [43,44,60,61]...

The reactions of the isopropyl-substituted 3-dimethylaminopropenyli-denechromium complex 109 with terminal alkynes 90 bearing a bulky substituent (e.g., R=ter -butyl, mesityl, adamantyl etc.), in the presence of moist pyridine, yield 2-(acylmethylene)pyrrolidines 110 (Scheme 23) [84]. The dihydroazepinetricarbonylchromium complexes 111 were found to be the key... 

Scheme 35 Formation of 2,5-disubstituted pyridines 162 from a,/ -unsaturated complexes with a primary 3-amino group 160 and alkynes 90 [36,88]...

To avoid problems with the separation of regiomers, dimethyl acetylene dicarboxylate (DMAD) was chosen as a dienophile. The intermolecular Diels-Alder reactions were performed in refluxing dichlorobenzene (bp 132 °C), while the intramolecular reaction of alkyne tethered pyrazinone required a solvent with a higher boiling point (bromobenzene, bp 156 °C). In the case of 3-methoxy or 3-phenyl pyrazinones a mixture of pyridinones and pyridines was obtained, while for the alkyne tethered analogue only the di-hydrofuropyridinone was isolated as the single reaction product. 

Terminal alkynes can be coupled by heating with stoichiometric amounts of cupric salts in pyridine or a similar base. This reaction, which produces symmetrical diynes... 

The alkyne ligand is not displaced by CO or ethene but is substituted by stronger (T-donor ligands like pyridine and 4-picoline, which give the paramagnetic... 

In the racemic version, the reaction of various terminal alkynes 105 with nitrones 106 was carried out using 10 mol % of Cul in pyridine-DMF at room temperature. As expected, the corresponding azetidinones 107 were formed as a mixture of trans and czs-isomers, along with the imines 108 (Scheme 30). 

Unlike the case of the Ni-catalyzed reaction, which afforded the branched thioester (Eq. 7.1), the PdCl2(PPh3)3/SnCl2-catalyzed reaction with 1-alkyne and 1-alkene predominantly provided terminal thioester 6 in up to 61% yield in preference to 7. In 1983, a similar hydrothiocarboxylation of an alkene was also documented by using a Pd(OAc)2/P( -Pr)3 catalyst system with t-BuSH to form 8 in up to 79% yield (Eq. 7.6) [16]. It was mentioned in the patent that the Pt-complex also possessed catalyhc activity for the transformation, although the yield of product was unsatisfactory. In 1984, the hydrothiocarboxylation of a 1,3-diene catalyzed by Co2(CO)g in pyridine was also reported in a patent [17]. In 1986, Alper et al. reported that a similar transformation to the one shown in Eq. (7.3) can be realized under much milder reaction conditions in the presence of a 1,3-diene [18], and the carboxylic ester 10 was produced using an aqueous alcohol as solvent (Eq. 7.7) [19]. 

Alkyne-nitrile cyclotrimerization is a powerful synthetic methodology for the synthesis of complex heterocyclic aromatic molecules.118 Recently, Fatland et al. developed an aqueous alkyne-nitrile cyclotrimerization of one nitrile with two alkynes for the synthesis of highly functionalized pyridines by a water-soluble cobalt catalyst (Eq. 4.62). The reaction was chemospecific and several different functional groups such as unprotected alcohols, ketones, and amines were compatible with the reaction.119 In addition, photocatalyzed [2+2+2] alkyne or alkyne-nitrile cyclotrimerization in water120 and cyclotrimerization in supercritical H2O110121 have been reported in recent years. 

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