Ketones P,y-unsaturated

In addition to the normal photochemical reactions of saturated ketones, p,y-unsaturated carbonyl compounds undergo carbonyl migration via a [1,3] shift. Compound 139 in Scheme 45 represents a typical example. Compounds with an alkyl substituent in the P position such as 140 may also undergo a Norrish type II reaction (Kiefer and Carlson, I%7), while for ketones with electron-rich double bonds such as 141, oxetane formation is also observed (Schexnayder and Engel, 1975). 

Akylsilanes undergo highly regioselective acylation to give P,y-unsaturated ketones (177). Acylation of y,y-dialkylallyltrialkylsilane provides a route to the constmction of difficulty accessible quaternary carbon centers. 

Reactions. The chemical properties of cyanoacetates ate quite similar to those of the malonates. The carbonyl activity of the ester function is increased by the cyano group s tendency to withdraw electrons. Therefore, amidation with ammonia [7664-41-7] to cyanoacetamide [107-91-5] (55) or with urea to cyanoacetylurea [448-98-2] (56) proceeds very easily. An interesting reaction of cyanoacetic acid is the Knoevenagel condensation with aldehydes followed by decarboxylation which leads to substituted acrylonitriles (57) such as (29), or with ketones followed by decarboxylation with a shift of the double bond to give P,y-unsaturated nitriles (58) such as (30) when cyclohexanone [108-94-1] is used. 

A polyfluorinated P,y-unsaturated ketone is formed m situ from tributylamine and 3,4-bis(tnfluoromethyl)-3-(pentafluoroethyl)-5,5,6,6,6-pentafluoro-2-hex-anone. The enol form of the unsaturated ketone cyclizes via an intermolecular addition-elimination reaction that involves exclusive attack by oxygen rather than by carbon. This reaction demonstrates the hardness of a F-C= site toward... 

The epoxyketone 3 is a versatile precursor for a variety of tricycloundecane systems having a p,y-unsaturated carbonyl chromophore, which are not so readily accessible. The contiguous epoxy ketone functionality and the double bond present in the five-membered ring provide opportunities for further manipulation. Adduct 3 may be transformed into a variety of molecular frameworks such as linearly fused cis anti cis tricyclopentanoids, protoilludanes, and marasmanes in a stereoselective fashion after suitable chemical and photochemical manipulation.13... 

Unsaturated ketones can be converted to a-halo-a,P-unsaturated ketones by treatment with phenylselenium bromide or chloride, and to a-halo-P,y-unsaturated ketones by two-phase treatment with HOCl. ... 

The reaction has been extended to allylic benzenes (in this case C-3 substituents are not required),to p,y-unsaturated ketones (the latter reaction, which is... 

For internal olefins, the Wacker oxidation is sometimes surprisingly regioselective. By using aqueous dioxane or THF, oxidation of P,y-unsaturated esters can be achieved selectively to generate y-keto-esters (Eq. 3.18).86 Under appropriate conditions, Wacker oxidation can be used very efficiently in transforming an olefin to a carbonyl compound. Thus, olefins become masked ketones. An example is its application in the synthesis of (+)-19-nortestosterone (3.11) carried out by Tsuji (Scheme 3.5).87... 

Allylation of acyloyl-imidazoles and pyrazoles61 with allyl halide mediated by indium in aqueous media provides a facile regioselective synthesis of P, y-unsaturated ketones (Scheme 11.1), which has been applied to the synthesis of the monoterpene artemesia ketone. The same product can be obtained by indium-mediated allylation of acyl cyanide (Eq. 11.35).62 Samarium, gallium, and bismuth can be used as a mediator for the allylation of nitrones and hydrazones to give homoallylic hydroxylamine and hydrazides in aqueous media in the presence of Bu4NBr (Scheme 11.2).63 The reaction with gallium and bismuth can be increased dramatically under microwave activation. 

Intramolecular oxonium ylide formation is assumed to initialize the copper-catalyzed transformation of a, (3-epoxy diazomethyl ketones 341 to olefins 342 in the presence of an alcohol 333 . The reaction may be described as an intramolecular oxygen transfer from the epoxide ring to the carbenoid carbon atom, yielding a p,y-unsaturated a-ketoaldehyde which is then acetalized. A detailed reaction mechanism has been proposed. In some cases, the oxonium-ylide pathway gives rise to additional products when the reaction is catalyzed by copper powder. If, on the other hand, diazoketones of type 341 are heated in the presence of olefins (e.g. styrene, cyclohexene, cyclopen-tene, but not isopropenyl acetate or 2,3-dimethyl-2-butene) and palladium(II) acetate, intermolecular cyclopropanation rather than oxonium ylide derived chemistry takes place 334 ). 

The benzotriazolyl derivative of acrolein acetal, compound 882, is lithiated, treated with chlorodiphenylphosphine, and the obtained intermediate is oxidized with hydrogen peroxide to phosphine oxide 883 (Scheme 145). The relatively acidic proton in derivative 883 is easily removed by a base, and the obtained anion adds to a carbonyl group of aldehyde or ketone. Subsequent rearrangement and elimination of the phosphorane group generates diene 884. For the derivatives of aldehydes (884, R2 = H), (E)-(E) stereoselectivity of the elimination is observed. Acidic alcoholysis of dienes 884 affords esters of P,y-unsaturated carboxylic acids 885 < 1997JOC4131>. 

Enones undergo a variety of photorearrangements 333). In contrast to a,P-unsaturated ketones which react in many different ways, p,y-unsaturated ketones undergo the oxadi-7c-methane rearrangement in sensitized irradiations in complete analogy the products formed are cyclopropyl ketones... 

In the Pd-catalyzed cross-coupling reactions of acylzirconocene chlorides with allylic halides and/or acetates (Section 5.4.4.4), the isolation of the expected p,y-unsaturated ketone is hampered by the formation of the a, P-un saturated ketone, which arises from isomerization of the p,y-double bond. This undesirable formation of the unsaturated ketone can be avoided by the use of a Cu(I) catalyst instead of a Pd catalyst [35], Most Cu(I) salts, with the exception of CuBr - SMe2, can be used as efficient catalysts Thus the reactions of acylzirconocene chlorides with allyl compounds (Table 5 8 and Scheme 5 30) or propargyl halides (Table 5.9) in the presence of a catalytic amount (10 mol%) of Cu(I) in DMF or THF are completed within 1 h at 0°C to give ffie acyl--allyl or acyl-allenyl coupled products, respectively, in good yields. ill... 

In almost the same manner, tandem hydroformylation/aldol condensation aldol condensation of ketoolefins, such as p,y-unsaturated ketones, gives a single cyclization product under acid catalysis. Similar to the stepwise reaction, the in situ generated aldehyde preferentially acts as the electrophilic carbonyl component, while the ketone acts as the nucleophilic enol to form the five-membered ring product. Subsequent dehydration and hydrogenation of the resulting enone readily occurs under the reductive reaction conditions used (Scheme 30) [84],... 

It has been reported that a cationic iridium such as [Ir(cod)2]BARF (BARF = 3,5-(CF3)2C6H3 4B), when combined with l,l -bis(diphenylphosphino)ferrocene (DPPF), catalyzed a hydrogen-mediated reductive carbon-carbon bond formation [68]. Thus, the reaction of alkynes 150 with a-ketoesters 151 produces p.y-unsaturated-a-hydroxy ketones 152 (Equation 10.40). 

The involvement of transition-metal allenylidene complexes in homogeneous catalysis was reported for the first time by B. M. Trost and co-workers in 1992 (Scheme 35) [293-295]. The catalytic reactions allowed the preparation of a wide variety of tetrahydropyranyl and furanyl p,y-unsaturated ketones starting from hydroxy-functionalized alkynols and allylic alcohols, the key step in the catalytic... 

Di-TT-methane reactions are not restricted to 1,4-dienes. Other 1,4-unsatu-rated systems, such as p,y-unsaturated ketones, undergo similar rearrangements yielding cyclopropyl ketones in the oxa-di-TT-methane (ODPM) version of the reaction. The first example of the ODPM reaction was reported in 1966, in which irradiation of ketone 3 affords the cyclopropyl ketone 4 [13] (Scheme 3). 

The large number of smdies carried out in the di-ir-methane area have established that disubstimtion at the central carbon of 1,4-diene substrates is an important structural requirement for efficient rearrangement [1-4,14-16]. In fact, there are only two examples in which p, Y-unsaturated ketones (3 [13] and 64a [57,58]), monosubstituted at the a-position, undergo the ODPM rearrangement. The reactivity observed in these two substrates was attributed to the bulk of the substituent at C-2 that compensates for the absence of disubstimtion at that a-position. 

The ODPM reactivity of aldehydes 65 is surprising because, as mentioned earlier, the only two ODPM reactive acyclic p, Y-unsaturated mono-C-2-substi-mted ketones are compounds 3 and 64a. Each of these substrates contains bulky substiments at C-2. However, the observations made with 65c and 65d, each having ethyl groups at C-2, clearly demonstrates that the bulk of the C-2 substituent is not an important feature in determining the ODPM reactivity of p, Y-unsam-rated aldehydes. However, it should be noted that the isopropyl substituted aldehydes, 65a and 65b, do react more efficiently, in qualitative terms, than 65c and 65d. 

Removal of an a-proton from a P,y-unsaturated ketone generates an enolate anion, and this might be transformed back to the P,y-unsaturated compound by reprotonation at the a-position. However, this does not occur because the enolate anion now has conjugated double bonds, and we can propose an alternative mechanism for reprotonation, invoking... 

Reactions of 5-siloxy-5-en-l-ynes are summarized in Table 5.2. In every case the reaction proceeds at rt in the presence of H2O to give cyclized p,y-unsaturated ketones in good yield without isomerization of the double bond, even using only 10 mol% W(CO)5(thf). The most characteristic feature of this reaction is that the endo mode of cyclization occurs more readily than in other related cyclization reactions such as HgCl2-mediated reactions. 

From a-substituted allylic alcohols, the formation of p,y-unsaturated ketones is favored, whereas conjugated enones are obtained from simple ally alcohol [46]. This transformation of terminal alkynes via coupling with allylic alcohol and formation of a C—C bond with atom economy has been applied to the synthesis and modification of natural compounds such as rosefuran and steroids [48, 49]. 

P,y-Unsaturated ketones7i-Allylnickel halides (4, 33) react with 2-pyridyl-carboxylic acid esters to form a mixture of p,y- and a,/i-unsaturatcd ketones in which the former isomer predominates (equation I). 2-Pyridylbenzoate can be used... 

P,y-Unsaturated ketones. The last step in a synthesis of /J.y-enones involves hydrolysis of a 2-allyl-3-oxazoline-5-one, previously conducted with Ba(OH)2 in variable yield. Recent investigations reveal that treatment with CrfOAclj-HjPOj or reduction with NaBIl4 in TlIE -CIljOH followed by a treatment with citric acid is superior. 

The name of this rearrangement is applied to acid conditions on p-y unsaturated ketones where either (or both) the carbonyl and/or alkene bond is in a strained environment. 

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