Unsaturated enones, conjugate addition

Vinylcyclopropanation of Enones. Conjugate addition of sulfur-stabilized aUyl carbanions to a. -unsaturated ketones produces enolates that cyclize to vinylcyclopropyl ketones upon treatment with nearly one equivalent of (CuOTf)2-C6H6, i.e. 1.9 equivalents of Cu (eq 68). ... 

Several examples of conjugate addition of carbanions carried out under aprotic conditions are given in Scheme 2.24. The reactions are typically quenched by addition of a proton source to neutralize the enolate. It is also possible to trap the adduct by silylation or, as we will see in Section 2.6.2, to carry out a tandem alkylation. Lithium enolates preformed by reaction with LDA in THF react with enones to give 1,4-diketones (Entries 1 and 2). Entries 3 and 4 involve addition of ester enolates to enones. The reaction in Entry 3 gives the 1,2-addition product at —78°C but isomerizes to the 1,4-product at 25° C. Esters of 1,5-dicarboxylic acids are obtained by addition of ester enolates to a,(3-unsaturated esters (Entry 5). Entries 6 to 8 show cases of... 

Scheme 9.5. Conjugate Addition of AUylic Silanes to a, p-Unsaturated Enones...

The Michael addition of nitroalkanes to a,P-unsaturated ketones followed by the Nef reaction has been extensively used as a method for the conjugated addition of acyl anions to enones (see Section 6.1, Nef Reaction). This strategy is one of the best methods for the preparation of 1,4-dicarbonyl compounds.156a h Various natural products have been prepared via this route.157 For example, r/.v-jasmone is prepared from readily available materials, as shown in Scheme 4.19.156f... 

Enones have also served as latent enols in the hydroalkoxylation process. For example, an Au(m) catalyst has been used to effect the conjugate addition of alcohols (or other nucleophiles) to a,/ -unsaturated ketones, thereby triggering a hydroalkoxylation pathway of the resulting enol to furnish furans as products. (Equation (98)). 

Conjugate additions to enals and enones.1 ClSi(CH,)3/HMPT markedly accelerates the Cu(I)-catalyzed conjugate addition of Grignard reagents to enals, enones, and unsaturated esters. The conjugate addition of organocopper reagents is also facilitated. 

Tandem processes mediated by triethylborane involving conjugate addition to enones followed by aldol reaction are reported (Scheme 52, Eq. 52a). More recently, a tandem process involving addition of an isopropyl radical to an o ,/3-unsaturated oxime ether afforded an azaenolate intermediate that reacts with benzaldehyde in the presence of trimethylaluminum. The aldol product cyclizes to afford an isopropyl substituted y-bulyroloaclonc in 61% overall yield (Scheme 52) [116]. In these reactions, triethylborane is acting as a chain transfer reagent that delivers a boron enolate or azaenolate necessary for the aldolization process. 

Conjugate additions to a, j5-unsaturated ketones and esters are the most important cuprate reactions. Kinetic studies by Krauss and Smith on Me2CuLi and a variety of ketones revealed the following kinetic characteristics (Eq. 10.5), first order both in cuprate dimer and in the enone [60]. 

Photochemical irradiation of a,-unsaturated ketones in the presence of Mc3SiOP(OR)2 (R = Me, Et) gave phosphonosilylation products of 1,4-conjugate additions which are hydrolysed to the phosphono ketones (165). The envisaged initiation step is electron transfer to the triplet excited state of the enone to generate a radical ion pair. 

The first organocatalyzed conjugate addition of a-substituted p-ketoester to a,P-unsaturated ketones was presented by Deng et al. [42] (Scheme 3). Although traditional Cinchona alkaloids were efficient catalysts for conjugate addition of carbon nucleophiles to nitroalkenes and sulfones, replacement of the C(9)-OH with an ester group (Q-7b) showed great improvement in stereoselectivity. The reaction is applicable to a variety of cyclic and acyclic enones (16,18). 

Dicarbonyl donors are excellent Michael donors in asymmetric conjugate addition to a,p-nnsatnrated ketones. Wang and co-workers [79] applied chiral Cinchona-thiourea catalyst 131 to various carbon donors in the addition to aromatic enones. A diverse array of nucleophiles, mainly 1,3-dicarbonyls proceeded smoothly in the conjugate addition to a,p-unsaturated enone 132 (Scheme 29). 

The conjugate additions of thiols to a,p-unsaturated electrophiles was extended by Wang [96]. Catalyst 166 promoted the addition of thioacetic acid to a variety of enones, including aliphatic, aromatic and heteroaromatic substituents (Scheme 42). Wang expanded the scope of the reaction to include asymmetric additions of thioacetic acid to nitro-olefms (Scheme 43) [97]. Thiourea catalyst 166 promoted the addition reactions in high yields and high enantiomeric ratios for a variety of P-substituted nitro-olefms. 

Experimental evidence indicates that cuprates in solution exist largely as dimer (RiCuLi) (25), which is found as the reactive species in conjugate addition. The kinetic results were consistent with the participation of the dimer (R2CuLi)2/enone complex 26 (Figure 24) in the C—C bond-forming process of the conjugate addition. Relatively unreactive a, -unsaturated ketones, esters and nitriles were also found to form complexes represented by 26 in Figure 24. 

Conjugate addition can also be carried out by completely forming the nucleophilic enolate under kinetic conditions. Ketone enolates formed by reaction with LDA in THF react with enones to give 1,5-diketones (entries 1 and 2, Scheme 1.12). Esters of 1,5-dicarboxylic acids are obtained by addition of ester enolates to a,/J-unsaturated esters (entry 5, Scheme 1.12). 

The first naturally occurring tricyclo[6.3.0.0 ]undecane to be synthesized was isocomene (757), a colorless oily sesquiterpene hydrocarbon isolated from several plant sources. In 1979, Paquette and Han reported an efficient, stereospecific approach starting with a preformed bicyclic enone, to which the third five-membered ring was appended with proper attention to stereochemistry and position of unsaturation (Scheme LXXX) The pivotal steps are seen to be the stannic chloride-induced cyclization of aldehyde 732 and the conjugate addition of lithium dimethylcuprate to 733 which sets the stereochemistry of the last methyl group. 

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