A.jS-Enones

When the chiral a,jS-enone enoate 98 was treated with magnesiocuprates in the presence of 1.5-2 equivalents of diethylaluminium chloride, the anti addition product 99 was obtained in moderate yield and with good diastereoselectivity (Scheme 6.21) [43, 44]. A reasonable explanation might assume a chelating coordination of the aluminium reagent [45]. Thus, if the enone 98 were to adopt an s-trans conformation, as indicated for complex 100, subsequent front side attack of the nucleophile would furnish the major diastereomer anti-99. 

Asymmetric epoxidation of a,jS-unsaturated ketones represents an efficient method for the preparation of optically active a,jS-epoxy ketonesJ Recently, a new and very efficient catalytic system for enantioselective epoxidation of ( )-a,jS-enones to the corresponding trans-epoxy ketones has been developed based on a BlNOL-zinc complexJ Very high yields and excellent diastereo- and enantioselectivities are achieved at room temperature using cumene hydroperoxide (CMHP) as the terminal oxidant and performing the reaction in diethyl ether. A combination of enantio-merically pure BINOL and diethylzinc readily affords the active catalyst in situ (Figure 6.13). ... 

While double-bond cis-trans isomerization in /3-substituted a,/ enones occurs at both 313 and 254 nm, oxetene forms only when short wavelengths are used (Friedrich and Schuster, 1%9, 1972). This differentiation has been explained on the basis of calculations that revealed a S -So conical intersection lying 15 and 10 kcal/mol above the (n, r ) minimum of s-trans- and s-c/s-acrolein, respectively (Reguero et al., 1994). Oxabicyclobutane, however, has not been detected. This behavior of a,jS-enones is in contrast with that of butadiene, where cyclobutene and bicyclobutane are formed simultaneously. (Cf. Sections 6.2.1 and 7.5.1.)... 

Waligora et have studied the sensitized photo-oxidation of polystyrene by a,jS-enones. These chromophores introduced an induction period due to... 

The nucleophilic epoxidation of a, jS-enones, pioneered by Wynberg et al. in the 1970s [70], has received considerable attention from various groups. In a recent study employing A-(9-anthracenylmethyl)-Ci c/ o a alkaloids as PTC catalysts, 71-90% ees were obtained for a series of a, jS-epoxyketones (Scheme 16) [71]. 

The use of 8 M KCIO at lower temperature in order to reach higher ees and chemical yields has been reported by Corey and Zhang, together with a rationale of the observed stereoselectivity [72]. The chiral cation assembles the oxidant (KCIO) and the a, 6-enone in a three-dimensional arrangement that allows face-selective conjugate addition of ion-paired hypochlorite to the a, jS-enone, held in proximity by electrostatic and van der Waals forces. 

For conjugated carbonyl compounds, such as a,jS-enones, the orbital diagram would be similar, except for the recognition that the HOMO of the ground state is j/2 of the enone system, rather than the oxygen lone-pair orbital. The excited states can sometimes be usefully represented as dipolar or diradieal intermediates ... 

In the Michael addition of achiral enolates and achiral Michael acceptors the basic general problem of simple diastereoselection (see Section D.1.5.1.3.2.), as described in Section 1.5.2.3.2. is applicable. Thus, the intermolecular 1,4-addition of achiral metal enolates to enones, a.jS-unsat-urated esters, and thioamides, results in the formation of racemic syn-1,2 and/or anti-3,4 adducts. 

Acyclic a,jS-unsaturated ketones do not provide much photochemistry, except for facile geometric isomerization about the double bond. Although some also isomerize to /3,y-unsaturated ketones, others, such as mesityl oxide, apparently undergo no net reaction upon absorption of irradiation. Their low reactivity might result from a rapid relaxation to an appreciably more twisted geometry in their triplet states than can be obtained in the cyclic enones. Below are some examples of typical photochemical behavior.426,427... 

Cyclopropane derivatives have been prepared from reactions of arsonium ylides with conjugated enones " and a, jS-unsaturated esters "" . Initial Michael-type reaction is followed by intramolecular elimination of triphenylarsine, e.g. equation 22. These reactions often give high yields and show high stereoselectivity. 

These have been much less popular, but some examples have been reported. These involve only alkenyltins containing one additional moiety on the G-carbon this substituent can be trimethylsilylmethyl (leading to functionalized allylsilanes [37] or divinyl ketones (Scheme 4-10) [38]) or trifluoromethyl [39]. The substituent can also be in the /3-position (E-geometry) examples have been reported by Parrain et al. [40] and Castano et al., the latter having used the coupling reaction of a jS-stannyl enone as the key step in the preparation of the indolizidine alkaloid ( )-monomorine here the coupling step is followed by an immediate in-situ reduction of the intermediate enone, the mechanism of which is unclear (Scheme 4-11) [41J. 

The aldol condensation reaction yields either a jS-hydroxy aldehyde/ketone or an a,jS-unsaturated aldehyde/ketone, depending on the reactant and on the experimental conditions. By learning how to think backward, it s possible to predict when the aldol reaction might be useful in synthesis. Any time the target molecule contains either a -hydroxy aldehyde/ketone or a conjugated enone functional group, it might come from an aldol reaction. 

The jS-hydroxy aldehydes or ketones formed in aldol reactions can be easily dehydrated to yield a,jS-unsaturated products, or conjugated enones. In fact, it s this loss of water that gives the condensation reaction its name, because water condenses out of the reaction when the enone product forms. 

Two alternative mechanisms for the Mannich reaction can be written. In the first alternative mechanism, the ketone attacks the aldehyde directly in an aldol reaction, the aldol undergoes El elimination of H2O (via the enol) to make an a.jS-unsaturated ketone, and then the amine adds to the enone in a Michael fashion to give the product. Evidence against this mechanism Ketones with only a single a-hydrogcn undergo the Mannich reaction, but such ketones cannot be converted into a,j8-unsaturated ketones. 

P-Bromo acetals and ketals. These useful derivatives are generally prepared by addition of an a,/ -unsaturated carbonyl compound to a solution of HBr in the diol. The same products can be obtained by addition of HBr to the a,jS-enal or enone followed by acetalization. The method is improved if only a stoichiometric amount of HBr is used. Dicinnamalacetone (equation I)2 is used to determine the end point. Hydrogen bromide is added to the initially yellow solution until a red color persists. 

Vilsmeier reactions on 1,3-diketones, 1,4-diketones, and conjugated enones give cyclic products as shown by the reactions of compounds 86 (Eq. 81), 87 (Eq. 82), and 88 (Eq. 83). The reaction of the Vilsmeier reagent with a,jS-epoxy ketones also gives benzaldehydes or 1,3-phthalaldehydes (Eq. 83a) ... 

This is a fairly difficult problem because it is not obvious at the outset which of the two possible enolates of benzyl ethyl ketone undergoes conjugate addition to the a,jS-unsaturated ketone. A good idea here is to work backward from the final product—in effect, do a ret-rosynthetic analysis. The first step is to recognize that the enone arises by dehydration of a jS-hydroxy ketone. 

The cleavage of an a.jS-epoxy-tosylhydrazone to give an acetylenic ketone has been employed to generate the 5(10)-seco-compound (386) best yields resulted from epoxidation of the tosylhydrazone of the 5(10)-en-6-one (385), rather than from first forming the epoxy-ketone. Aldol condensation of the derived saturated seco-3,10-dione (387) afforded the A-nor-B-homo-enone (388). The hydrazones derived from a, -epoxy-ketones and 2-phenyl- (389) or trans-23-diphenyl-l-aminoaziridines (390) undergo thermal fission (e.g. in refluxing DMF), also giving acetylenic aldehydes or ketones. ... 

Conjugate allylation of a, enones Titanium(IV) chloride is the most effective activator for conjugate addition of allylsilanes to a,jS-unsaturated ketones. 

To achieve selectivity in these reactions, a steric or electronic bias is required to favour one particular product or (more importantly given the reversible nature of CM) one metal-alkylidene precursor in the catalytic cycle. In particular, it has been known for some time that metathesis reactions involving one highly electron deficient olefin partner can be selective (for the first example using acrylonitrile or styrene and 1 see Ref. [40]) however, readily available potential substrates such as enones, acrylates and acrylamides are generally incompatible with either 1 or 2 (for two reported exceptions see Ref. [41]). This was partially overcome by the use of acrolein acetals as a,jS-unsaturated car-... 

H elimination occurs by the treatment of jr-allylpalladium enolates in boiling MeCN to give a.jS-unsaturated ketones and aldehydes. Shibasaki and co-workers used the enone formation in the total synthesis of strychnine [204], The silyl enol ether 555 was treated with diallyl carbonate 556 in MeCN and the cyclohexanone 557 was obtained in high yield. 

Lithium-ammonia reduction of a,jS-unsaturated ketones (entry 6, Scheme 1.4) provides a very useful method for generating specific enolates. The desired starting materials are often readily available, and the position of the double bond in the enone determines the structure of the resulting enolate. This and other reductive methods for generating enolates from enones will be discussed more fully in Chapter 5. Another very important method for specific enolate generation, the addition of organometallic reagents to enones, will be discussed in Chapter 8. 

During the alkaline degradation of cellulose and cellobiose, a yellow chromo-phore is formed whose spectral properties are dependent on pH e.g. Am 290 nm at pH 12 was shifted to 256 nm at pH 6 for both hydrocellulose and cellobiose. It is suggested that the chromophore is a jS-hydroxy-a-enone which, at acid pH values, tautomerizes to an aliphatic jS-diketone. It was concluded that the chromophore is a minor product since the molar absorption coefficients of such compounds are very large (> 1 x 10 ) and the apparent molar absorption coefficient for hydrocellulose was only about 900. 

The dienol is unstable, and two separate processes have been identified for ketonization. These are a 1,5-sigmatropic shift of hydrogen leading back to the enone and a base-catalyzed proton transfer which leads to the /i. y-enone. The deconjugated enone is formed because of the kinetic preference for reprotonation of the dienolate at the a carbon. Photochemical deconjugation is a synthetically useful way of effecting isomerization of a,jS-unsaturated ketones and esters to the /1, y-isomers. 

Cychc a,jS-unsaturated ketones present a rich array of photochemical reactions, some of which are of considerable synthetic value (see Section 6.4 of Part B). For cyclohex-enones, two prominent reactions are the di-Ti-methane rearrangement (path A) and the lumiketone rearrangement (path B). 

Feringa showed that Michael addition of j6-ketoesters and a-nitro esters to enones and a,jS-unsaturated aldehydes resulted in a quantitative conversion to the corresponding 1,4-adducts when the reaction was performed in water in the presence ofYb(OTf)3 as the catalyst (Scheme 8.11). However the reaction was often sluggish, the conversion being only 10% after 8 h. The use of the Lewis acid surfactant-combined catalyst Sc(03S0Ci2H25)3 allowed the reaction to proceed smoothly in water to give the Michael adducts in high yields. ... 

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