Arylation of Silyl Enolates

Metal-mediated additions of silyl enolates to alkynes also are valuable for intra-and intermolecular vinylation of ketones. The Hg(II)-induced cychzation of alky-nyl-branched SEE provides regio- and stereochemicaUy homogeneous exocychc vinyl mercurial products that can be converted into a variety of functionahzed alkenes [265-267]. Two plausible mechanisms for the intramolecular carbomercura-tion have been proposed, as in the above Pd(II)-mediated cycloaUcenylation-nu-cleophihc enolate addition to the Hg(II)-activated alkyne and concerted addition of an a-keto mercurial species generated by Si-Hg transmetalation. Forsyth et al. have determined that carbomercuration occurs in an anti fashion by the former 

Yamamoto et al. have reported that the EtAlCh-promoted intramolecular addi- 

The proposed mechanism involves die carbometalation of an alkynylstannane with an a-stannylketone, protonation of fhe resultant gem-bisstannylated intermediate, and double bond shift to an allylmetal species. In contrast, the GaCl3-mediated addition of SEE to trimefhylsilylefhyne forms /i. j -unsaturated ketones, vinylation products, without isomerization to u,/I-urisaluraled ketones [272]. A similar mechanism via a gem-bismetalated intermediate formed by carbometalation has been postulated for fhe GaCh-mediated vinylation. 

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Arylation of silyl enol ethers.1 Silyl enol ethers of methyl n- or sec-alkyl ketones undergo arylation when treated with an aryl bromide and tri-n-butyltin fluoride and a... 

Diaryliodonium fluorides can be used as efficient reagents for the arylation of silyl enol ethers [71, 72]. The reaction of silyl enol ethers 95 with o-nitro-phenyliodonium fluoride 96 results in a regiospecific arylation yielding arylke-tones 97 in good yields (Scheme 43) [72]. This arylation has been applied in a new, regiocontrolled synthesis of carbocycle-fused indoles [72]. 

Silyl enolates undergo Pd-catalyzed arylation with aryl halides in the presence of an additive such as Bu3SnF,327 CuF2,328 or ZnF2.329 The arylation of silyl enolates has higher functional group tolerance than that of alkali metal enolates. The ZnF2-promoted arylation is valuable for efficient, stereoselective synthesis of a-arylated esters and imides (Equation (89)). 

Diaryliodonium fluorides (Ar2IF) are effective reagents in arylation of silyl enolates.330 They have been used for the regiocontrolled synthesis of carbocycle-fused indoles (Scheme 26).331 Ph4BiF also serves for efficient regioselec-tive cr-phenylation of carbonyl compounds via silyl enolates.332 This approach can be extended to cr-alkenylation of carbonyl compounds. 

Chae J, Yun J, Buchwald SL (2004) One-pot sequential Cu-catalyzed reduction and Pd-catalyzed arylation of silyl enol ethers. Org Lett 6 4809-4812. doi 10.1021/ol048313c... 

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 relatively unstable / -oxoalkyl(aryl)iodonium salts 46 can be generated by a low temperature reaction of silyl enol ethers with reagent 45 (Scheme 21) [40]. 

The use of aryl-A3-iodanes for C-heteroatom bond formation at the a-carbon atoms of ketones and / -dicarbonyl compounds, and related transformations of silyl enol ethers and silyl ketene acetals, has been exhaustively summarized in recent reviews (Scheme 27) [5,8]. Reactions of this type are especially useful for the introduction of oxygen ligands (e. g., L2 = OH, OR, OCOR, 0S02R, OPO(OR)2), and have been extensively utilized for the synthesis of a-sulfonyl-oxy ketones and a-hydroxy dimethyl ketals. 

Pandey, G., Karthikeyan, M., and Mumgan, A. (1998) New intramolecular a-arylation strategy of ketones by the reaction of silyl enol ethers to photosensitized electron transfer generated arene radical cations construction of benzannulated and benzospiroannulated compounds. Journal of Organic Chemistry, 63, 2867-2872. 

A versatile strategy for efficient intramolecular oc-arylation of ketones was achieved by the reaction of silyle enol ethers with PET-generated arene radical cations. This strategy involved one-electron transfer from the excited methoxy-substituted arenes to ground-state DCN [42]. Pandey et al. reported the construction of five- to eight-membered benzannulated as well as benzospiroannulated compounds using this approach (Sch. 20) [42a]. The course of the reaction can be controlled via the silyl enol ether obtained... 

Silyl enol ethers and ketene silyl acetals react with tetraphenylbismuth fluoride under neutral conditions to give the corresponding a-monophenylated carbonyl compounds in good yields together with triphenylbismuthane and fluorotrimethylsilane (Equation (111)).181 The reaction is likely to be initiated by the nucleophilic attack of the fluoride ion on the silicon atom, and the regiochemistry of arylation is governed by the structure of silyl enolates. 

In summary, the literature survey provides clear evidence for a-carbonyl radical intermediates but no convincing proof for further oxidation to a-carbonyl cation in the vast majority of silyl enol ether radical cation reactions. This suggests that for most cases, silyl enol ethers are more readily oxidized than the corresponding a-carbonyl radicals. Only in oxidations of -aryl substituted silyl enol ethers, a-carbonyl cation intermediates have been invoked. For example, one-electron oxidation of 87d with TTA" " in acetonitrile/MeOH afforded 76 in analogy to the a-Umpolung of ketones via enol radical cations (Scheme 4), and oxidation of 124 with FePHEN provided benzofuran 19 [171]. 

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... 

Ruzziconi and coworkers used the ceric ammonium nitrate promoted C—C forming reaction to prepare polycyclic homo- and heteroaromatics starting from aryl-substituted silyl enolates and, more recently, the same strategy has been applied to the preparation of fluorinated naphthaldehydes and naphthyl ketones . 

Kim, D.Y, Mang, J.Y, and Oh, D.Y, Reaction of silyl enol ethers with phosphite using hypervalent iodine compound. A new synthesis of 2-aryl-2-oxoalkylphosphonates, Synth. Commun., 24, 629, 1994. Hohnquist, C.R., and Roskamp, E.J., Tin(II) chloride catalyzed addition of diazo sulfones, diazo phosphine oxides, and diazo phosphonates to aldehydes. Tetrahedron Lett., 33, 1131, 1992. 

Attempts to produce the analogous carbon-lead compounds by reaction of silyl enol et p-dicarbonyl compounds with aryllead triacetates under similar conditions were unsuccessf only products which were detected were the a-arylated P-dicarbonyl derivatives. 

Reissig and coworkers have devised an indirect method of enantioselective alkylation of ketones via cyclopropanation of silyl enol ethers in the presence of the chiral copper catalyst 16, followed by ring opening to provide the substituted ketones. Overall, the transformation corresponds to alkylation of ketones using methyl diazoacetate as the electrophile. Enantioselectivities up to 88% were realized in the cyclopropanation of aryl substituted olefins, Eq. (20) [63,64]. 

Nucleophilic displacement of chlorine, in a stepwise manner, from cyanuric chloride leads to triazines with heteroatom substituents (see Section 6.12.5.2.4) in symmetrical or unsymmetrical substitution patterns. New reactions for introduction of carbon nucleophiles are useful for the preparation of unsymmetrical 2,4,6-trisubstituted 1,3,5-triazines. The reaction of silyl enol ethers with cyanuric chloride replaces only one of the chlorine atoms and the remaining chlorines can be subjected to further nucleophilic substitution, but the ketone produced from the silyl enol ether reaction may need protection or transformation first. Palladium-catalyzed cross-coupling of 2-substituted 4,6-dichloro-l,3,5-triazine with phenylboronic acid gives 2,4-diaryl-6-substituted 1,3,5-triazines <93S33>. Cyanuric fluoride can be used in a similar manner to cyanuric chloride but has the added advantage of the reactions with aromatic amines, which react as carbon nucleophiles. New 2,4,6-trisubstituted 1,3,5-triazines are therefore available with aryl or heteroaryl and fluoro substituents (see Section 6.12.5.2.4). 

P-Keto sulfoxides. TAS-F promotes the sulfinylation of silyl enol ethers with S-aryl arenethiosulfonate S-oxides. 

The enantioselective protonation of silyl enol ethers, such as (12.39), by a catalyst has been achieved using 2 mol% of the proton source (12.40). The acidity of (12.40) is enhanced by coordination to a Lewis acid. The silyloxy group is activated by fluoride ion and up to 99% ee in the asymmetric protonation of a-aryl substituted cyclic silyl enol ethers such as (12.39) has been obtained using a Lewis acidic BINAP. / F complex.In a similar vein, silyl enol ethers of tetralones and indanones undergo asymmetric protonation with moderate to good ee using catalytic quantities of hydrogen fluoride salts of cinchona alkaloids in the presence of acyl fluorides and ethanol, which act as a stoichiometric source of HE 28... 

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