Ketone From alkyne

A series of 3-hydroxybut-4-ynoic esters (319) has been prepared from alkynic ketones and bromoacid esters in the presence of zinc (61AP234). Ring closure to the pyran-2-one occurs in a mixture of acetic and sulfuric acids. The preparation of 4,6- and 3,4,6-substituted pyranones is possible by this route, the substituents being different or identical, and as such is complementary to the alkynic route to the 3,6-disubstituted compound (57JA2602). 

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

Interestingly, the product actually isolated from alkyne hydration is not the vinylic alcohol, or enol (ene + ol), but is instead a ketone. Although the enol is an intermediate in the reaction, it immediately rearranges to a ketone by a process called keto-enol tautomerisni. The individual keto and enol forms are said to be tautomers, a word used to describe constitutional isomers that interconvert rapidly. With few exceptions, the keto-enol tautomeric equilibrium lies on the side of the ketone enols are almost never isolated. We ll look more closely... 

Most studies on nickel-catalyzed domino reactions have been performed by Ikeda and colleagues [287], who observed that alkenyl nickel species, obtained from alkynes 6/4-41 and a (jr-allyl) nickel complex, can react with organometallics as 6/4-42. If this reaction is carried out in the presence of enones 6/4-43 and TM SCI, then coupling products such as 6/4-44 are obtained. After hydrolysis, substituted ketones 6/4-45 are obtained (Scheme 6/4.12). With cyclic and (5-substituted enones the use of pyridine is essential. Usually, the regioselectivity and stereoselectivity of the reactions is very high. On occasion, alkenes can be used instead of alkynes, though this is rather restricted as only norbornene gave reasonable results [288]. 

Burk et al. showed the enantioselective hydrogenation of a broad range of N-acylhydrazones 146 to occur readily with [Et-DuPhos Rh(COD)]OTf [14]. The reaction was found to be extremely chemoselective, with little or no reduction of alkenes, alkynes, ketones, aldehydes, esters, nitriles, imines, carbon-halogen, or nitro groups occurring. Excellent enantioselectivities were achieved (88-97% ee) at reasonable rates (TOF up to 500 h ) under very mild conditions (4 bar H2, 20°C). The products from these reactions could be easily converted into chiral amines or a-amino acids by cleavage of the N-N bond with samarium diiodide. 

Alkynes. Alkynes are obtained by bisdehydrohalogenation of n c-1,2-dlhromides or gem-dichlorides with solid potassium r-butoxide in petroleum ether in the presence of 0.1 mole % of 18-crown-6. Dichlorides obtained from methyl ketones are converted into I-alkynes only if the 3-position is blocked. Alkynes arc also formed from (F.)-haloalkenes bv. wt-elimination. Yields of alkynes are >80% for the most part. 

I-Alkynes from methyl ketones This reaction can be effected by conversion to Ihe enol phosphate followed by -elimination with LDA (equation I). In the case of a simple ketone such as 2-octanone the yield is low because of formation also of an allene. In such cases lithium tetramethylpiperidide is recommended as base. 

Photochemical reactions of alkynic ketones, e.g. l-phenylprop-2-yn-l-one (111) in alcohols gave 2,5-disubstituted furans, postulated as arising from a 1 1 adduct whose... 

Reaction of carbanions with dialkynic ketones, the so-called skipped diynes, can produce pyranones through an initial Michael condensation. It should be noted however that diynones are vulnerable to attack at several sites and that mixed products can be formed. Addition of the anions derived from diethyl malonate and ethyl cyanoacetate to hepta-2,5-diyn-4-one (313 R1 = Me) gives the pyranones (314 R2 = C02Et or CN Scheme 91) (74JOC843). The former carbanion reacts similarly with the diynone (313 R1 = Bun) (68T4285). The second alkyne moiety appears to have little effect on the course of the reaction, which parallels the synthesis of pyranones from monoalkynic ketones. 

The addition of amines to electron-poor alkynes leads to the formation of enamines (Entry 11, Table 10.6). These acceptor-substituted enamines are more stable towards hydrolysis than enamines derived from unsubstituted ketones. Alkynes devoid of electron-withdrawing groups do not react smoothly with amines, and usually require Hg(II) catalysis to be converted to resin-bound enamines (Entry 12, Table 10.6). 

Tradition reserves the use of the name acid for substances that transfer protons measurably to water. Thus the carboxylic acids stand out from alkynes, halides, alcohols, and simple aldehydes and ketones in giving water solutions that are acidic to indicator papers or pH meters as the result of proton transfers from the carboxyl groups ... 

The involvement of the ketone in the intermediate 50 shows why water adds to one end of the alkyne and not the other. We have already seen above how the cis double bond in molecules of this sort can be made from alkynes and so both main uses of alkynes appear here. 

The asymmetric hydrogenation of enol esters is an alternative to asymmetric ketone hydrogenation. The precursors can be prepared from the ketones but also via ruthenium-catalyzed addition of the carboxylic acids to the 2-postion of terminal alkynes. This latter method allows the study of the effect of the carboxylate on the enantioselectivity of the asymmetric hydrogenation. A remarkable study by Reetz and colleagues established that it is possible to hydrogenate enolate... 

The research reported by Hayashi13 14 indicated a highly efficient route for the preparation of ketones from alkynes via hydration ... 

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