Acetylenic Ketones and Esters

The Diels-Alder reaction of oxazoles with alkynes has become a preferred method for the synthesis of substituted furans with diverse applications. A large number of early examples of this reaction have been tabulated. Activated dienophiles such as acetylenic ketones and esters can be used, although unactivated alkyl, aryl, and silyl alkynes have been used as well. In particular, the reaction of 4-phenyloxazole with substituted acetylenes is frequently used for preparing 3,4-disubstimted furans. Cycloadducts derived from 4-phenyloxazole typically decompose under milder conditions than 4-alkyloxazoles, allowing the synthesis of a wider range of functionalized furans. Several examples are shown below. 

Conjugate reductions. This combination (usually 1 3 ratio) effects conjugate reduction of a,p-acetylenic ketones or esters to a, 3-enones or unsaturated esters at -50° with moderate (E)-selectivity. The HMPT is believed to function as a ligand to aluminum and thus to promote hydroalumination to give a vinylaluminum intermediate, which can be trapped by an allylic bromide (equation I).1 The re-... 

Organyl tellurolate anions effect 1,4-additions to acetylenes bearing electron-withdrawing groups such as acetylenic ketones, aldehydes, esters, diacetylenic ketones, " as well as acetylenic phosphonates and sulphones giving 2-substituted vinyl tellurides with Z configuration. 

Selective phosphonate ester dealkylation. Alkyl phosphonate esters are selectively and nearly quantitatively cleaved by bromotrimethylsilane in the presence of alkyl carboxylate esters, carbamates, acetylenes, ketones, and halides. Alkyl iodides do not exchange under the reaction conditions. The resulting bis(trimethylsilyl) phosphonates are hydrolyzed in acetone by a small excess of water. 

The C-H bond cleavage of active methylene compounds with a transition metal catalyst is another method for the functionalization of these C-H bonds. To date, several reactions have been developed. In particular, the asymmetric version of this type of catalytic reaction provides a new route to the enantioselective construction of quaternary carbon centers. One of the most attractive research subjects is the catalytic addition of active methylene C-H bonds to acetylenes, allenes, conjugate ene-ynes, and nitrile C-N triple bonds. The mthenium-catalyzed reaction active methylene compounds with carbonyl compounds involving aldehyde, ketones, and a,y3-unsatu-rated ketones and esters is described in this section. 

Oxodiperoxymolybdenum-pyridine-hexamethylphosphoric triamide, MoOj CjHsN-HMPA (MoOPH), which is prepared from molybdenum trioxide, M0O3 [531,532], hydroxylates the enolates of ketones and esters in the a position with respect to the carbonyl groups [537, 532, 533] and, in the presence of mercuric acetate, converts acetylenes into a-dicarbonyl compounds [534]. 

Syntheses and properties of acetylenic derivatives of pyrazoles 02AHC(82)1. Syntheses of 2-pyrazolines by the reactions of a,/ -unsaturated aldehydes, ketones, and esters with diazoalkanes, nitrile imines, and hydrazines 02JHC1. 

The postulated mechanism for the formation of the 1,4-benzothiazine ring involves the formation of the imine 98, followed by cleavage of the disulfide bond (see Section VI,A,5). This reaction is general for keto compounds, / -keto esters,142 and acetylenic ketones and esters143 the heterocycle is produced in yields of 70-80%. 

Simple a,/3-unsaturated aldehydes, ketones, and esters participate preferentially in inverse electron demand (LUMOdlcne controlled) Diels-Alder reactions with electron-rich, strained, or simple olefinic and acetylenic dienophiles.3 5 The thermal reaction conditions for promoting the [4 + 2] cycloadditions of simple 1-oxabutadienes (R = H > alkyl, aryl > OR), cf. Eq. (1), are relatively harsh (150-250°C), and the reactions are characterized by competitive a,/3-unsaturated carbonyl compound dimerization or polymerization. Usual experimental techniques employed to compensate for poor conversions include the addition of radical inhibitors to the reaction mixture and the use of excess 1-oxabutadiene for promoting the [4 + 2] cycloaddition. Recent efforts have demonstrated that Lewis acid catalysis and pressure-promoted reaction conditions28-30 may be used successfully to conduct the [4 + 2] cycloaddition under mild thermal conditions (25-100°C). 

Cacchi and co-workers reported the synthesis of 1,2-disubstituted 4-quinolones via copper-catalyzed cyelization of l-(2-halophenyl)-2-en-3-amin-l-ones in 2009. Here, the l-(2-bromophenyl)- and l-(2-chloro-phenyl)-2-en-3-amin-l-ones were prepared from allynones and primary amines. The reaction tolerates a variety of useful functionalities including ester, keto, cyano, and chloro substituents. Good to excellent of the desired products were formed (Scheme 3.64a). One year later, Xu and Zhao developed a palladium-catalyzed procedure that could directly use o-haloaryl acetylenic ketones and primary amines (Scheme 3.64b). ... 

Acetylenic aldehydes and ketones or their chloroenone equivalents have been used (58GEP1040040), as have acetylenic esters such as DMAD (e.g. 76JOC1095, 73CPB2014). 

Me3SiI, CH2CI2, 25°, 15 min, 85-95% yield.Under these cleavage conditions i,3-dithiolanes, alkyl and trimethylsilyl enol ethers, and enol acetates are stable. 1,3-Dioxolanes give complex mixtures. Alcohols, epoxides, trityl, r-butyl, and benzyl ethers and esters are reactive. Most other ethers and esters, amines, amides, ketones, olefins, acetylenes, and halides are expected to be stable. 

A two-carbon ring expansion of cyclic ketones was achieved by the addition of acetylenic esters and diesters to the enamine derivatives of the ketones, and reported almost simultaneously from several laboratories (337-343). The intermediate bicyclic adduct could be isolated in some cases. 

The formation of adducts of enamines with acidic carbon compounds has been achieved with acetylenes (518) and hydrogen cyanide (509,519,520) (used as the acetone cyanohydrin). In these reactions an initial imonium salt formation can be assumed. The addition of malonic ester to an enamine furnishes the condensation product, also obtained from the parent ketone (350,521). 

In olefines, acetylenes, aldehydes, ketones, acids and esters, etc. if the proton is present in the positive region, it will be shielded and absorption occurs upfield. On the other hand if the proton is in the negative region, its absorption is downfield. 

The latter method can also be applied to aliphatic or ,/Tunsaturated ketones, to diketones and to aromatic or acetylenic aldehydes. Furthermore, it tolerates a variety of functional groups present in the substrate, as demonstrated by the efficient formation of allenes 174 and 175, which bear an additional nitro and ester group, respectively (Scheme 2.55) [89]. 

Numerous useful transition metal-catalyzed reactions of organic halides are now known. Practical syntheses of esters, acids, amides, aldehydes, olefins, ketones, and acetylenes have been described. In many instances the metal-catalyzed reactions are superior to more conventional, purely organic routes to the same compounds. 

Undheim and Riege267 obtained 1 1 adducts from pyridine-2-thiones (60) and acetylenic amides, esters, and ketones. The reaction rate increases with increase in activation of the acetylenic bond by the adjacent carbonyl group and is affected by the pyridine 6-substituent, which may also affect the stereochemical course. Product-isomer ratios corresponding to kinetic control were obtained in chloroform. Amides gave E isomers, ketones gave Z, and esters a slight preponderance of the E isomers (61). Successive addition of n-butyllithium and DMAD to... 

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