Pyridine, alkynyl

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. 

Moody s synthesis of promothiocin 43 provided evidence that the Bohlmann-Rahtz method can be used for the rapid synthesis of complex pyridines. Oxazaole 44 was treated with alkynyl ketone 45 to afford 46 in 83% yield. The ester moiety of 46 was elaborated into a thiazole substituent providing entry into the northeast quadrant of 43. 

Pyridines 158 have been also prepared by cyclocondensation of alkynyl ketones 157 and amino acrylates in DMSO as the solvent at 170 °C for 20 min (Scheme 56 and Sect. 5.2 for more details) [102,103]. 

Scheme 56 Synthesis of pyridines and pyrimidines from alkynyl ketones...

High density brine completion fluids also often require the use of corrosion inhibitors (8,9). Blends of thioglycolates and thiourea alkyl, alkenyl, or alkynyl phosphonium salts thiocyanate salts mercaptoacetic acid and its salts and the reaction products of pyridine or pyrazine derivatives with dicarboxylic acid monoanhydrides have been used as high density brine corrosion inhibitors. 

Dipolar cycloaddition of 5-aminofuro[3,2-f]pyridinium tosylate 140 and the alkynyl ester 141 yields furo[3,2-f]pyrazolo[l,5- ]pyridine 142 in moderate yield (Equation 33) <1999CCC539>. 

At present, the chemisty of selenophenes and tellurophenes is a relatively scantily studied area. Nevertheless, a number of new valuable contributions dealing with their chemistry have emerged. Electrophilic cyclization of l-(l-alkynyl)-2-(methylseleno)arenes provides a route to a variety of 2,3-disubstituted benzo[fe]selenophenes, as illustrated by the preparation of the system 88. Other useful electrophiles for similar reactions are E or NBS <06JOC2307>. Similar chemistry has also been employed in preparation of 2,3-disubstituted benzo[f>]selenophenes on solid phase <06JCC163>. In addition, syntheses of 2,3-dihydroselenolo[2,3- >]pyridines have been achieved using radical chemistry <06OBC466>. 

Recently, a method for synthesizing substituted pyridines incorporating 3-azadienynes as substrates in ruthenium-catalyzed cycloisomerizations was described <06JA4592>. This route is a two-step process that first converts readily available JV-vinyl or JV-arylamides (e.g., 26) to the corresponding C-silyl alkynyl imines (e.g., 27) and subsequent ruthenium-catalyzed protodesilylation and cycloisomerization results in the formation of the corresponding substituted pyridines (e.g., 28). 

Diethynyl-pyridine was reacted with 2 equiv. of (Me2S)AuCl to give a gold alkynyl as an insoluble coordination polymer of unknown structure. This product could be dissolved in organic solvents with cBuNG to afford the bis(isocyanide) complex with an angular structure (Scheme 50).214... 

A useful method for the preparation of functionalised thiazoles has been described. Palladium catalysed cross coupling reactions between 4-thiazolyl-5-acetyl triflates 36 and alkynes afforded 4-alkynyl-5-acetylthiazoles 37 in good yields (56-82%). If 37 is then treated with ammonia in methanol, thiazolo[5,4-c]pyridines 39 are formed, probably via the intermediate imine 38 which then undergos a regioselective 6-endo dig cyclisation <99EJOC3117>. 

An unusual Sonogashira coupling between an alkynyl bromide and a 4-ethynylpyridine 142 was reported to produce a new complexing agent 143 containing a highly-conjugated pyridine subunit [116]. In addition, alkynylpyridines, as important intermediates in medicinal chemistry,... 

Comins et al. <20010L469> achieved the synthesis of the same allopumiliotoxin 267A 215 by a stereoselective alkynylation of the appropriately substituted 4-MeO-pyridine 226. The C-6 side chain is introduced by an aldol condensation between an aldehyde and indolizidinone 227 (Equation 17). 

Cobaloxime(I), electrochemically regenerated from chloro(pyridine)-cobaloxime (III) (232), has been employed as a mediator in the reductive cleavage of the C—Br bond of 2-bromoalkyl 2-alkynyl ethers (253), giving (254) through radical trapping ofthe internal olefin (Scheme 95) [390]. An interesting feature of the radical cyclization (253) (254) is the reaction in methanol, unlike the trialkyltin hydride-promoted radical reactions that need an aprotic nonpolar solvent. An improved procedure for the electroreductive radical cyclization of (253) has been attained by the combined use of cobaloxime(III) (232) and a zinc plate as a sacrificial anode in an undivided cell [391]. The procedure is advantageous in terms of the turnover of the catalyst and the convenience of the operation. 

Arene-solvated cobalt atoms (U) and (1, obtained by reacting Co vapor and arenes, have been found by Italian workers to promote the conversion of a,d)-dialkynes and nitriles to alkynyl-substituted pyridines [87JOM(326)C33] (Scheme 4). 

Reaction of aldoximes with dimedone derivatives under microwave irradiation leads to partially hydrated acridine derivatives . Eused heterocyclic compounds containing partially hydrogenated pyridine and quinoUne rings were prepared by intramolecular cycloaddition reaction of 5-alkynyl oxime derivatives . (Z)-l,10a-Dihydropyrrolo[l,2-i>]... 

The transformation predominates in Group 9 (Rh, Ir) chemistry. Reactions of RhCl(L)2 2 with 1-alkynes give the q -alkyne complexes which slowly convert to the hydrido(alkynyl)s at room temperature. The latter are sensitive to air and not often isolated. Addition of pyridine affords RhHCl(C=CR)(py)(L)2, which readily lose pyridine in hydrocarbon solvents to give square-planar fran.s-RhCl(=C=CHR)(L)2. Alternatively, the Cp complexes Rh(=C=CHR)(L)Cp can be obtained by reaction of the chloro complexes vdth TlCp. In the iridium series, heating for 36h in refluxing toluene afforded the vinylidenes in 80-90% yields. Table 1.2 lists several examples of reactions in which the q -alkyne complexes have been detected. 

Movassaghi et al. [21[ reported the synthesis of substituted pyridine derivatives via ruthenium-catalyzed cycloisomerization of 3-azadienynes. To avoid the isolation of the chemically active alkynyl imines, trimethysilyl alkynyl amines served as initial substrates, as shown in Scheme 6.19. The formation of ruthenium vinylidene intermediates is accompanied by a 1,2-silyl migration according to controlled... 

While the alkynyl ketone route occurs under mild conditions, and can provide 4-substituted pyrimidines both substituted and unsubstituted at the 6-position, it cannot provide products substituted at the 5-position. However, this can be achieved by use of an oxidative enone cyclization, as demonstrated by the synthesis of the 3-(5-methylpyrimidinyl)pyrazolo[l,5- ]pyridine 1006 from 1002, where air oxidation of the initial adduct was catalyzed by the addition of palladium on carbon <2003T9001>. 

The palladium/copper-catalyzed coupling reaction of 2-iodo-3-methoxy-6-methylpyridine and terminal alkynes leads to the formation of o-methoxyalkynylpyridines which undergo electrophilic cyclization reactions to afford furo[3,2-3]pyridines in moderate yields <2005JOC10292>. A similar Pd/Cu-catalyzed reaction with hydroxypyridines and trimethylsilyl (TMS)-acetylene leads to the formation of alkynyl pyridines which cyclize to form furo[2,3- ]-pyridines in good yields <1998JME1357>. 

Thieno[3,4- ] and [3,4-f]pyridine derivatives can be generated from a cycloaddition reaction of oxazinones with l,4-dichloro-2-butyne to afford polyhalogenated pyridine products which cyclize to thienopyridines (Scheme 39) <2001T4203>. In a similar reaction, pyrazinones, 122, containing alkynyl substituents cyclize to form thieno[3,4-3] and [3,4-i ]pyridine derivatives <2002TL799, 2004T429>. 

Cyclization of 6-acetylenic derivatives constitutes yet another approach to pyrrolo[3,2-.7 pyrimidines. A series of 6-substituted acetylenes 209, prepared by alkynylation of the chloropyrimidine, undergo cyclization to the A -oxides 210 when heated briefly in pyridine (Equation 72) <2003SL1151, 2004CHE1335>. 

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