Ketone Silyl enol ether coupling

Six-membered chiral acetals, derived from aliphatic aldehydes, undergo aldol-type coupling reactions with a-silyl ketones, silyl enol ethers," and with silyl ketene acetals " in the presence of titanium tetrachloride with high diastereoselectivities (equation 41) significant results are reported in Table 20. This procedure, in combination with oxidative destructive elimination of the chiral auxiliary, has been applied... 

The in situ cyanosilylation of p-an1saldehyde is only one example of the reaction which can be applied to aldehydes and ketones in general. - The simplicity of this one-pot procedure coupled with the use of inexpensive reagents are important advantages over previous methods. The silylated cyanohydrins shown in the Table were prepared under conditions similar to those described here. Enolizable ketones and aldehydes have a tendency to produce silyl enol ethers as by-products in addition to the desired cyanohydrins. The... 

Cyclic and acyclic silyl enol ethers can be nitrated with tetranitromethane to give a-nitro ketones in 64-96% yield (Eqs. 2.42 and 2.43).84 The mechanism involves the electron transfer from the silyl enol ether to tetranitromethane. A fast homolytic coupling of the resultant cation radical of silyl enol ether with N02 leads to a-nitro ketones. Tetranitromethane is a neutral reagent it is commercially available or readily prepared.85... 

Dialkyl(trimethylsilyl)phosphines undergo 1,4-addition to a,/3-unsaturated ketones and esters to give phosphine-substituted silyl enol ethers and silyl ketene acetals, respectively. A three-component coupling reaction of a silylphosphine, activated alkenes, and aldehydes in the presence of a catalytic amount of GsF affords an aldol product (Scheme 76).290 291... 

Tin enolates of ketones can be generated by the reaction of the enol acetate 733 with tributyltin methoxide[601] and they react with alkenyl halides via transmetallation to give 734. This reaction offers a useful method for the introduction of an aryl or alkenyl group at the o-carbon of ketones[602]. Tin enolates are also generated by the reaction of silyl enol ethers with tributyltin fluoride and used for coupling with halides[603]. 

The conjugate addition of bis(iodozincio)methane to -unsaturated carbonyl compound gives y-zincio substituted enolate. As shown in equation 31, bis(iodozincio)methane reacts with. v-cis a,/3-unsaturated ketone in the presence of chlorotrimethylsilane to afford the silyl enol ether carrying a C—Zn bond. These zinc-substituted silyl enolates can be used for further coupling reactions (equation 32)54. 

The TiCU-induced three-component coupling reaction of an a-haloacylsilane, allylsilane and another carbonyl compound gives 48 in good yield. A silyl enol ether intermediate is suggested (equation 31)82. The reaction of a cyclopropyl ketone with allylsilane yields a mixture of skeletal rearranged products83. 

In contrast, Fleming and coworkers proposed another mechanism involving a Brook rearrangement coupled with desilylative /J-elimination for similar reactions of a-siloxy ketones 131 with phenyldimethylsilyllithium to give silyl enol ethers 132 (equation 87) no trimethylsilyl enol ether 133 was detected in the reaction mixture203. 

Relatively less acidic ketones compared to 1,3-dicarbonyl compounds are also suitable substrates for the palladium catalyzed coupling. a-Aryl ketones are obtained as products. In the early examples, masked ketone enolates such as silyl enol ethers [42] and enol acetates [43-45] were used in the presence of a tin source. These reactions involve tin enolates or acylmethyltins as intermediates and thus proceed by transmetalation (mechanism B in Scheme 1). 

Coupling of ketones with electron-deficient alkenes via a methylene group (cf. II, 315-316). This modified Giese reaction involves cyclopropanation of the silyl enol ether of a ketone, mcrcuration, and finally demercuration and coupling with an alkcnc via a radical chain reaction. 

Coupling of silyl enol ethers or boron enolates with Co2(CO)6-stabilized carbocations, generated via Lewis acid treatment of the appropriate propargyl ethers or aldehydes (aldol reaction), via the Nicholas reaction has been used to obtain large, highly strained, ring ketones. 

In the last years several publications appeared describing palladium-catalyzed a-arylations of ketone enolates for the synthesis of a-aryl ketones, involving ketone eno-lates, silyl enol ethers and intramolecular a-aiylation of ketone enolates . In this process, an enolate is generated from a ketone in the presence of an aryl halide, and a palladium catalyst couples this enolate with the aryl halide. Iwama and Rawal proposed... 

On the other hand, unsaturated aldehydes and ketones were obtained using allylic alcohols as alkene components [68]. Similarly, allyl f-butyldimethylsilyl ether and N-allylamides gave silyl enol ethers [69] and enamides [70], respectively. The ruthenium-catalyzed alkene-alkyne coupling was successfully combined with the palladium-catalyzed intramolecular asymmetric allylic alkylation [71] to provide a novel one-pot heterocyclization method [72]. 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

The presence of two substituents (generally both at the /3-carbon) still allows the reaction to occur in good yields [25,26], and the same is true when three substituents are present. Thus Verlhac et al. described the alkylation of stannylated silyl enol ethers and, after workup, obtained aryl ketones in moderate to good yields (Scheme 4-4) [27], Booth et al. [28] (Scheme 4-5) and Casson and Kocienski [29] reported couplings of heterofunctionalized vinyltins, Takeda et al. [30] prepared a series of highly substituted ajS-unsaturated ketones (Scheme 4-6) and Shi et al. [31] a number of /3-fluoro-a-keto acid derivatives. 

Silyl enol ethers [Eq. (13), Y = OSi(CH3)3] can be dimerized to 1,4-dicarbonyl compounds in good yields. To suppress the methanolysis of the silyl enol ethers, MeCN-5% MeOH is used as solvent and the electrolysis is conducted within 1 h by the use of a capillary gap cell, which allows high currents (Table 6, numbers 7 and 8) [123]. In this way, unsymmetrical ketones can be coupled selectively in the a-or a -position, since the corresponding silyl enol ethers can be prepared regioselec-tively [124],... 

Diarylbutane-ly4-diones, Silyl enol ethers of aryl methyl ketones couple in the presence of C6H5IO-BF3 etherate (1 3) in CH2CI2 or ether to give 1,4-diarylbutane-l,4-diones in moderate yield. 

Alkylation or acylation of ketones, sulfides, and amines. This reagent generally reacts with alcohols or carboxylic acids to form 2,2,2-trifluoroethyl ethers or esters in satisfactory yields, except in the case of alcohols prone to dehydration. The reaction of these ethers provides a simple synthesis of unsymmetrical sulfides (equation I). A similar reaction can be used for preparation of secondary amines or amides (equation II). Enolate anions (generated from silyl enol ethers with KF) can be alkylated or acylated with a or b (equation III). Use of Grignard reagents in this type of coupling results in mediocre yields. 

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