Enones, 367. reactivity

Johnston and coworkers have explored other dimensions of azide/enone reactivity. Thus, aziridines were obtained in moderate to excellent yields when acyclic enones were... 

Adducts (278) and (279) are derived formally from addition of cw-acetoxy-butenone, whereas the starting material contained ca. 90% of the trans-isomer. Since irradiation of the latter leads to a mixture of 30% cis- and 70 % tra 5-enones, it is possible that (278) and (279) result from the addition to (276) of the more reactive cw-isomer formed by photochemical isomerization prior to cycloaddition. 

A drawback of tlie Z enoates is usually lower reactivity, rehected in prolonged reaction times and bigliet reaction temperatures. Tliis may be overcome by switdi-ing to more reactive enone systems. Tlius, addition of tlie functionalized cyano-G dnian cuprate s7stem 67 to Z enone 66 proceeded smootlily at low temperatures, witli excellent acydic steteocontrol at tlie /J-steteocenter [26, 27]. Stereocontrol upon... 

Wlien tlie diiral molybdenum -K-allyl-substituted enone 147 was treated witli litliium dimetliylciiptate, formation of adduct 148 witli fait selectivity was observed tSdieme 6.29) [69], Interestingly, bigber selectivities were obtained in tlie presetice of boron ttlbuotlde etlierate. It is assumed tliat Lewis acid coordination induces tlie s-trans reactive conformation 149 [64], Consequently, nudeopb de attack anti to tlie molybdetiLim ftagmetit sbould afford tlie major diastereomer 148. 

Data are also available with a-acetylenic aliphatic sulphones, which involve only two steps i.e., saturation of the triple bond without subsequent cleavage of the Caliphalic—S bond, since it is not reactive. However, the introduction of an aromatic ring to the S02 group does not lead, contrary to what is observed with enones, to a potential shift toward less reducing potential values. Thus, the aromatic moiety introduced apparently does not bring any additional conjugation effect but even seems to decrease the activation of the unsaturated bond, as shown by data in Tables 6 and 7 where most of the potentials refer to the same saturated calomel electrode under similar experimental conditions. 

Whereas tropones usually act as dienes in cycloaddition reactions (Section 5.4), tricarbonyl (tropone) iron 59 displays a reactivity that is almost identical to that of a normal enone. High pressure cycloadditions of 59 with 1-oxygen substituted dienes 60 gave the desired cycloadducts 61 in good to excellent yields (Equation 5.9). The subsequent decomplexation of the cycloadducts has been accomplished by treatment with CAN [20]. 

More general processes rely on variations of the Guareschi-Thorpe reaction [14] where condensations between 1,3-dicarbonyls and cyanoacetamide yield functionalized monocyclic 2(lff)-pyridones (a and b. Scheme 2) [15, 16]. Unless the carbonyls are sufficiently different in reactivity, the reaction suffers from poor regioselectivity. The use of 3-alkoxy or 3-amino enones instead of 1,3-dicarbonyls has proven to be a versatile and reliable synthetic methodology where the 1,4-addition controls the regioselective outcome (c and d. Scheme 2) [17-19]. 

Enders and coworkers <96AG(E)1725> have developed an interesting general one-pot method for the asymmetric epoxidation of enones with oxygen in the presence of diethylzinc and (l ,/ )-N-methylpseudoephedrine (30), which provides a, P - epoxyketones in very high yield and high enantiomeric excess (e.g., 33 —> 34). The actual reactive species is believed to be the chirally modified alkoxy(ethylperoxy)zinc 31, which attacks the si face of the s-cis conformation of the (E) enones (cf. 32). 

Route (b) offers a short cut since the reaction between (5) and PhCHO under dehydrating conditions needs no control as (3) is the only possible enone from a ketone enolate attacking the more reactive aldehyde (p T 167). The Michael reaction is also better by this route as explained on p T 171, This is the published synthesis. 

There are many possibilities and I shall simply analyse the published synthesis. Removal of the methyl group from (50) gives ketone (51) which can be made from enone (52) by Michael addition of an ethyl group. Unambiguous cross-condensation between enolisable (54) and reactive (53) gives (52). 

Ferrocen-l,l -diylbismetallacycles are conceptually attractive for the development of bimetal-catalyzed processes for one particular reason the distance between the reactive centers in a coordinated electrophile and a coordinated nucleophile is self-adjustable for specific tasks, because the activation energy for Cp ligand rotation is very low. In 2008, Peters and Jautze reported the application of the bis-palladacycle complex 56a to the enantioselective conjugate addition of a-cyanoacetates to enones (Fig. 31) [74—76] based on the idea that a soft bimetallic complex capable of simultaneously activating both Michael donor and acceptor would not only lead to superior catalytic activity, but also to an enhanced level of stereocontrol due to a highly organized transition state [77]. An a-cyanoacetate should be activated by enolization promoted by coordination of the nitrile moiety to one Pd(II)-center, while the enone should be activated as an electrophile by coordination of the olefinic double bond to the carbophilic Lewis acid [78],... 

The mechanism of conjugate addition reactions probably involves an initial complex between the cuprate and enone.51 The key intermediate for formation of the new carbon-carbon bond is an adduct formed between the enone and the organocopper reagent. The adduct is formulated as a Cu(III) species, which then undergoes reductive elimination. The lithium ion also plays a key role, presumably by Lewis acid coordination at the carbonyl oxygen.52 Solvent molecules also affect the reactivity of the complex.53 The mechanism can be outlined as occurring in three steps. 

The indium-mediated allylation of trifluoroacetaldehyde hydrate (R = H) or trifluoroacetaldehyde ethyl hemiacetal (R = Et) with an allyl bromide in water yielded a-trifluoromethylated alcohols (Eq. 8.56).135 Lanthanide triflate-promoted indium-mediated allylation of aminoaldehyde in aqueous media generated (i-airiinoalcohols stereoselectively.136 Indium-mediated intramolecular carbocyclization in aqueous media generated fused a-methylene-y-butyrolactones (Eq. 8.57).137 Forsythe and co-workers applied the indium-mediated allylation in the synthesis of an advanced intermediate for azaspiracids (Eq. 8.58).138 Other potentially reactive functionalities such as azide, enone, and ketone did not compete with aldehyde for the reaction with the in situ-generated organo-indium intermediate. 

Cycloaddition of 2-cyanoalk-2-enones with several conjugated dienes proceeded under zinc chloride catalysis.636 Zinc halides have also shown reactivity with phenylacetylenes.637 Zinc chloride is an effective Lewis acid catalyst in the Diels Alder reactions of the keto esters and the effects on stereochemistry of catalysts used have been examined.638... 

Domino transformations combining two consecutive anionic steps exist in several variants, but the majority of these reactions is initiated by a Michael addition [1]. Due to the attack of a nucleophile at the 4-position of usually an enone, a reactive enolate is formed which can easily be trapped in a second anionic reaction by, for example, another n,(5-urisalurated carbonyl compound, an aldehyde, a ketone, an inline, an ester, or an alkyl halide (Scheme 2.1). Accordingly, numerous examples of Michael/Michael, Michael/aldol, Michael/Dieckmann, as well as Michael/SN-type sequences have been found in the literature. These reactions can be considered as very reliable domino processes, and are undoubtedly of great value to today s synthetic chemist... 

Although Lewis acid-catalyzed-Diels-Alder reactions of enones are common, there are few reports on the catalysis of Diels-Alder reaction of nitroalkenes. The reaction of nitroalkenes with alkenes in the presence of Lewis acids undergoes a different course of reaction to give cyclic nitronates (see Section 8.3). Knochel reported an enhanced reactivity and selectivity of the intramolecular Diels-Alder reaction using silica gel as Lewis acid in hexane (Eq. 8.19).31... 

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