Dimethylsilyl enolates

Because the trimethylsilyl enol ether of cyclohexanone 107 a is considerably more bulky than the corresponding dimethylsilyl enolate 107b, only the latter reacts with the N-tosyhmine 108 in the presence of catalytic amounts of diisopropylamine in DMF/H2O at 78°C or at room temperature to give the Mannich type compounds 109 in high yields [39] (Scheme 3.4). 

It has also been shown that dimethylsilyl enolates can be activated by diisopropylamine and water and exhibit a high reactivity toward iV-tosyl imines to give Mannich-type reaction products in the absence of a Fewis acid or a Bronsted acid.51 For example, the reaction of [(1-cyclohexen-l-yl)oxy]dimethylsilane with 4-methyl-A -(phenylmethylene)benzene sulfonamide gave re/-4-methyl-N- (f )-[(15)-(2-oxocyclohexyl)phenyl-methyl] benzenesulfonamide (anti-isomer) in 91% yield stereoselectively (99 1 anti syn) (Eq. 11.30). On the other hand, Fi and co-workers reported a ruthenium-catalyzed tandem olefin migration/aldol and Mannich-type reactions by reacting allyl alcohol and imine in protic solvents.52... 

High yields of seven-membered rings can be achieved by treating ally] acetates with Lewis acids. The dimethylsilyl enol ether exclusively attacks the least alkylated terminus of the initial allyl cation3. 

Keywords Dimethylsilyl enolates, formaldehyde, scandium(III) fluoride, THF-H2O (9 1), room temperature, hydroxymethylation, p-hydroxy ketones... 

To a solution of scandium fluoride (0.03 mmol 10 mol%) in THF-H2O (0.22 mL) was added 36% aqueous solution of formaldehyde (1 1.5 mmol 5 equiv.) and dimethylsilyl enolate (2 0.3 mmol). The mixture was stirred for 40 h at room temperature to complete the reaction. The mixture was then diluted with water (10 mL), and the aqueous layer was extracted with dichloromethane (3 x 20 mL). The combined organic extracts were washed with brine, and dried over anhyd. sodium sulfate. After filtration, the solvent was removed in vacuo. The crude residue was purified by preparative TLC (elution with n-hexane-EtOAc) to furnish p-hydroxy ketone 3 with good yield (71-93%). All the compounds were characterized from comparison of their physical and spectral properties with those reported for authentic samples in literature. 

Kokubo, M., and Kobayashi, S. (2008). Scandium(III) fluoride as a novel catalyst for hydroxymethylation of dimethylsilyl enolates in aqueous media. Synlett, 1562-1564. 

Since 1973, many Lewis acid-catalyzed aldol reactions have been studied, as described above. There have, however, been few examples of Lewis base-catalyzed aldol reaction using special silyl enolates, e.g. phosphoramide-catalyzed aldol reactions of trichlorosilyl enolates 69 (Eq. (36)) [47] and CaCh-catalyzed reactions of dimethylsilyl enolates 72 in aqueous DMF (Eq. (37)) [56]. 

Prepa ation.—Dimethylsilyl enol ethers of aldehydes and ketones may be prepared by irradiating the carbonyl compounds in the presence of dodecamethyl-cyclohexasilane (MeaSije/ Highly stereoselective formylation of (Z)-enol silyl ethers has been achieved on treatment of acyclic ketones with ethyl tri-methylsilylacetate and tetrabutylammonium fluoride on the other hand lithiation of pentan-3-one with lithium 2,2,6,6-tetramethylpiperidide followed by chloro-trimethylsilane gave mainly (84%) the ( )-enol silyl ether... 

Scheme 3-128. Reaction of dimethylsilyl enol ethers with aldehydes.

Products of the type (24) also result from enolizable ketones without the formation of silyl enol ethers if the reaction is carried out in the presence of tertiary phosphines. The proposed mechanism involves the betaine R3P—SiMe2 as the silylene transfer agent. In preventing a 1,3-hydrogen migration, the phosphine may well induce dimerization prior to oxasilacyclopropane formation. The dioxadisilacyclohexane (24) can be reduced with LiAIHU to give dimethylsilyl-substituted carbinols, so the reaction is of synthetic value (Scheme 34) (78JA7074). 

In place of dtphenylsilane, 1,2-bis(dimethylsilyl)ethane was applied to the reduction of several ketones by the combination of the Py box-rhodium complex and Silver(I) Trifluoromethanesulfonate to give the corresponding silyl enol ether exclusively (eq 6). ... 

Yamamoto and Saito reported that the kinetically controlled generation of the more substituted enolate of unsyimnetrical dialkyl ketones can be realized by the combined use of ATPH and LDA [175]. Precomplexation of ATPH with 2-methyl-cyclohexanone (175) at -78 °C in toluene was followed by treatment with LDA in THF, and the mixture was stirred for 1 h. Subsequent treatment with methyl trifluoro-methanesulfonate (MeOTf) furnished 2,2-dimethylcyclohexanone (177) and 2,6-dimethylcyclohexanone (176) in the ratio 32 1 (53 % isolated yield). Use of ter/-butyl-dimethylsilyl triflate (TBSOTf) in place of alkyl triflates in this alkylation system produced siloxybutylated product 178 as a result of THF ring-opening alkylation occurred similarly at the more hindered a-carbon of the unsymmetrical ketone 175 (Sch. 136) [176]. 

Kobayashi et al. have found that dimethyltrifloxysilyl enolates, prepared in situ from ketones and dimethylsilyl ditriflate in the presence of a tertiary amine, react smoothly with electrophiles such as aldehydes and acetals without catalyst at -78 °C to afford the corresponding aldol adducts in high yields [94]. The use of ethyl ketones as the substrates achieves high levels of syn selectivity (Scheme 10.29). 

We have found that dimethylsilyl (DMS) enolates derived from ketones react with aldehydes without promoter in DMF at 50°C, affording aldol adducts in moderate to good yields (Scheme 10.33) [100]. The corresponding TMS enolates are not so reactive to aldehydes under the same conditions. The high reactivity of DMS enolates could originate from the relatively less crowded silicon center, which would facilitate the coordination of DMF to silicon to enhance fhe nucleophilicity of the enolates. 

The degree of asymmetric induction in the photocycloaddition reaction can be quite high with substrates containing a stereogenic center. Winkler, Scott and Williard have reported that irradiation of 1-tryptophan-derived vinylogous amide 107 led to the isolation of ketoimine 108 in 91% yield as a single diastereomer . Closure to the tetracyclic portion of the aspidosperma ring system 109 was achieved in two steps by formation of the silyl enol ether with LDA and r-butyl dimethylsilyl triflate followed by treatment with tetrabutylammonium fluoride (TBFA). Conversion of 109 to 110 with >97% optical purity was then achieved. As 110 is an intermediate in Biichi s synthesis of vindorosine, the sequence outlined in Scheme 26 represents a formal total synthesis of vindorosine. 

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