Enolization salt effects

Reductions of unsaturated ketones and a-acetoxy ketones usually are effected with an excess of reducing agent. For optimum yields of saturated ketones, the intermediate enolate salt obviously must not become protonated while... 

Detailed studies of the mechanism of these reactions have been performed by Mattay and by Kochi . The former has shown that the endo/exo regiochemistry of the ring closure reaction can be controlled either by variation of the silyl group or by addition of polar molecules such as alcohols (probably the source of hydrogen in equations 37a-c). Based on solvent and salt effects, Kochi has proposed that the oxidation of enols to ketones in the presence of activated chloranil proceeds via photoactivation of chloranil which reacts with the silyl enolate through two competing pathways, namely oxidative elimination to the ketone and oxidative addition to the adduct 51 (equation 38). Non-polar solvents such as dichloromethane favour the oxidative eliminations, while polar solvents such as acetonitrile direct the reaction towards the oxidative addition. More strikingly. 

Typically, nonstabilized ylides are utilized for the synthesis of (Z)-alkenes. In 1986, Schlosser published a paper summarizing the factors that enhance (Z)-selectivity. Salt effects have historically been defined as the response to the presence of soluble lithium salts. Any soluble salt will compromise the (Z)-selectivity of the reaction, and typically this issue has been resolved by the use of sodium amide or sodium or potassium hexamethyldisilazane (NaHMDS or KHMDS) as the base. Solvent effects are also vital to the stereoselectivity. In general, ethereal solvents such as THF, diethyl ether, DME and t-butyl methyl ether are the solvents of choice." In cases where competitive enolate fomnation is problematic, toluene may be utilized. Protic solvents, such as alcohols, as well as DMSO, should be avoided in attempts to maximize (Z)-selectivity. Finally, the dropwise addition of the carbonyl to the ylide should be carried out at low temperature (-78 C). Recent applications of phosphonium ylides in natural product synthesis have been extensively reviewed by Maryanoff and Reitz. 

For Heck reactions catalysed by Pd(OAc)2 associated with dppp, see Ref. [Ig] and (a) Cabri, W., Candiani, I. and Bedeshi, A. (1990) Ligand-controlled a-regioselectivity in palladium-catalyzed arylation of butyl vinyl ether. J. Org. Chem., 55, 3654-5 (b) Cabri, W., Candiani, L, De-Bernardinis, S. et al. (1991) Heck reaction on anthraquinone derivatives ligand, solvent, and salts effects. J. Org. Chem., 56, 5796-800 (c) Cabri, W., Candiani, L, Bedeshi, A. and Santi, R. (1991) Palladium-catalyzed a-arylation of vinyl butyl ether with aryl halides. Tetrahedron Lett., 32, 1753-6 (d) Cabri, W., Candiani, L, Bedeshi, A. et al. (1992) a-Regioselectivity in palladium-catalyzed arylation of acyclic enol ethers. J. Org. Chem., 57, 1481-6 (e) Cabri, W.,... 

The enolate salts, H2C=CH(OM), have been studied at various levels of theory for all of the alkali metals. Several structural and thermodynamic parameters are reported, and the effect of the restriction of enolate resonance by attachment of the cation is described. 

In 2004, researchers from Merck laboratories explored Michael additions on pseudoephedrine carboxamide-derived enolates [41]. A singular salt effect was observed as the presence of LiCl in the reaction mixture led to the syn-adduct, while the absence of LiCl afforded the anti-adduct... 

The leaving group in the alkylating reagent has a major effect on whether C- or O-alkylation occurs. In the case of the lithium enolate of acetophenone, for example, C-alkylation is predominant with methyl iodide, but C- and O-alkylation occur to approximately equal extents with dimethyl sulfate. The C- versus O-alkylation ratio has also been studied for the potassium salt of ethyl acetoacetate as a function of both solvent and leaving group. ... 

Both the Af-fluorosulfonamides and the A -fluoroammonium salts are very effective in the fluormation of enol acetates, enamines, silyl enol ethers, and enolates (Table 2) The reactions are thought to proceed through a mechanism which involves Sf 2 attack on the fluorine atom, but contributions from electron-transfer pathways also exist [65, 68, 73, 75, 76, 79, 80, 81, 82]... 

Phenylmercury derivatives of 3-aminomethylene-l-methyloxindols have also been investigated (79KGS65). For studies of the effect of substituents on the electronic structure of silver and potassium salts of 3-(aryl)imi-nooxindole see 76MI2. The keto-enol and imino-enamine tautomerism of compounds of type 127 (with 128 and 129) has been investigated (85KGS921). 

Diazonium salts react with oximes to give aryl oximes, which are easily hydrolyzed to aldehydes (R = H) or ketones." A copper sulfate-sodium sulfite catalyst is essential. In most cases higher yields (40-60%) are obtained when the reaction is used for aldehydes than for ketones. In another method for achieving the conversion ArNj —> ArCOR, diazonium salts are treated with R4Sn and CO with palladium acetate as catalyst. In a different kind of reaction, silyl enol ethers of aryl ketones, Ar C(OSiMe3)=CHR, react with sohd diazonium fluoroborates, ArNj BF4, to give ketones, ArCHRCOAr. " This is, in effect, an arylation of the aryl ketone. 

Ketones such as methyl cyclohexyl ketone 1284 react with DMSO/TCS 14, via their enol form, to give 21% of the chloroketone 1285 a and 63% of the a-methyl mercaptoketone 1286 [70]. Reaction of 1284 with DMSO/MesSiBr (TBS) 16 affords 85% of the bromo compound 1285 b and 12% hexahydrophenacyl bromide 1287 but no 1286 [71]. Whereas reaction of tra s-4-phenyl-3-buten-2-one (benzalacetone) 1288 with DMSO/TCS 14 gives 81% of the sulfonium salt 1289 [70], the y9-dicar-bonyl compound ethyl acetoacetate furnishes 69% of 1290 [70]. In contrast with DMSO/TCS 14, the combination DMSO/TBS 16 effects selective monobromina-tion of y9-dicarbonyl compounds [71] (Scheme 8.28). 

Fe(OTf)2-catalyzed aziridination of enol silyl ethers with PhlNTs followed by ring opening led to a-N-tosylamido ketones in good yields (Scheme 27) [81]. With silyl ketene ketal (R = OMe) as substrate, the N-tosyl-protected amino acid ester was obtained in 50% yield. In contrast, the copper (I) salt CuClOq was found not effective for this substrate [82]. 

The lanthanide salts are unique among Lewis acids in that they can be effective as catalysts in aqueous solution.61 Silyl enol ethers react with formaldehyde and benzaldehyde in water-THF mixtures using lanthanide triflates such as Yb(03SCF3)3. The catalysis reflects the strong affinity of lanthanides for carbonyl oxygen, even in aqueous solution. 

Y(03SCF3)3 to afford a monoaminoalkylation product in good yield in aqueous media.40 Zinc tetrafluoroborate is also highly effective for such couplings in aqueous THF.41 Kobayashi also reported a Mannich-type reaction of imines with silyl enolates catalyzed by neutral salts such as sodium triflate in water as a suspension medium. Unusual kinetic behavior indicates that the presence of the Mannich adduct facilitates the rate of its formation.42... 

The /3-ketoesters [RC(0 ) CIIC(0)0R] are close analogs which also chelate effectively. A useful general method for synthesis of Co11 compounds of these molecules has been reported, which uses the lithium, caesium, or trimethylsilyl enolate of the /3-ketoester reacting with a Co11 salt in tetrahydrofuran.427... 

DDQ ( red = 0.52 V). It is noteworthy that the strong medium effects (i.e., solvent polarity and added -Bu4N+PFproduct distribution (in Scheme 5) are observed both in thermal reaction with DDQ and photochemical reaction with chloranil. Moreover, the photochemical efficiencies for dehydro-silylation and oxidative addition in Scheme 5 are completely independent of the reaction media - as confirmed by the similar quantum yields (d> = 0.85 for the disappearance of cyclohexanone enol silyl ether) in nonpolar dichloromethane (with and without added salt) and in highly polar acetonitrile. Such observations strongly suggest the similarity of the reactive intermediates in thermal and photochemical transformation of the [ESE, quinone] complex despite changes in the reaction media. 

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