Silyl enol ethers enolates from

Fig. 13.21. Generation of enolates from silyl enol ethers.

D. Cahard, P. Duhamel, Alkoxide-Mediated Preparation of Enolates from Silyl Enol Ethers and Enol Acetates - From Discovery to Synthetic Applications, Eur. J. Org. Chem. 2001, 1023-1031. 

A useful catalyst for asymmetric aldol additions is prepared in situ from mono-0> 2,6-diisopropoxybenzoyl)tartaric acid and BH3 -THF complex in propionitrile solution at 0 C. Aldol reactions of ketone enol silyl ethers with aldehydes were promoted by 20 mol % of this catalyst solution. The relative stereochemistry of the major adducts was assigned as Fischer- /ir o, and predominant /i -face attack of enol ethers at the aldehyde carbonyl carbon atom was found with the (/ ,/ ) nantiomer of the tartaric acid catalyst (K. Furuta, 1991). 

The silyl enol ether 940 is prepared from the Q-bromo ketone 939 by the transmetahation with trimethylsilyltributyjtin[784J. 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

Although ethereal solutions of methyl lithium may be prepared by the reaction of lithium wire with either methyl iodide or methyl bromide in ether solution, the molar equivalent of lithium iodide or lithium bromide formed in these reactions remains in solution and forms, in part, a complex with the methyllithium. Certain of the ethereal solutions of methyl 1ithium currently marketed by several suppliers including Alfa Products, Morton/Thiokol, Inc., Aldrich Chemical Company, and Lithium Corporation of America, Inc., have been prepared from methyl bromide and contain a full molar equivalent of lithium bromide. In several applications such as the use of methyllithium to prepare lithium dimethyl cuprate or the use of methyllithium in 1,2-dimethyoxyethane to prepare lithium enolates from enol acetates or triraethyl silyl enol ethers, the presence of this lithium salt interferes with the titration and use of methyllithium. There is also evidence which indicates that the stereochemistry observed during addition of methyllithium to carbonyl compounds may be influenced significantly by the presence of a lithium salt in the reaction solution. For these reasons it is often desirable to have ethereal solutions... 

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]... 

Examine the eleetrostatic potential map of eaeh nueleophile (enamine, silyl enol ether, lithium enolate and enol) with emphasis on the face of the nucleophilic alkene carbon. Rank the nucleophiles from most electron rich to least electron rich. What factors are responsible for this order (Hint For each molecule, consider an alternative Lewis structure to that given above that places a negative charge on the nucleophilic carbon.)... 

Nucleophilicity is determined by HOMO energy the higher the energy the more reactive the nucleophile. HOMO energies (in au) for these nucleophiles are -0.275 (enamine), -0.266 (lidiium enolate), -0.337 (silyl enol ether), and -0.339 (enol). Rank the nucleophiles from most reactive to least reactive. How does this ranking compare to that based on electrostatic potential ... 

The first asymmetric Mn(salen)-catalyzed epoxidation of silyl enol ethers was carried out by Reddy and Thornton in 1992. Results from the epoxidation of various silyl enol ethers gave the corresponding keto-alcohols in up to 62% ee Subsequently, Adam and Katsuki " independently optimized the protocol for these substrates yielding products in excellent enantioselectivity. 

Nitradon of the potassium enolates of cycloalkanones with pentyl n silyl enol ethers with nitroniiim tetraflnoroborate " provides a method for the preparadon of cydic ct-nitro ketones. Tnflnoroacetyl nitrate generated from tnflnoroacedc anhydnde and ammonium nitrate is a mild and effecdve nitradug reagent for enol acetates fEq. 2.411. ... 

Cyclic and acyclic silyl enol ethers can be nitrated with tetranitromethane to give ct-nitro ketones in 64-96% yield fEqs. 2.42 and 2.43. " The mechanism involves the electron transfer from the silyl enol ether to tetranitromethane. A fast homolydc conphng of the resultant cadon radical of silyl enol ether with NO leads tn ct-nitro ketones. Tetranitromethane is a neutral reagent it is commercially available or readdy prepared. " ... 

The synthetic problem is now reduced to cyclopentanone 16. This substance possesses two stereocenters, one of which is quaternary, and its constitution permits a productive retrosynthetic maneuver. Retrosynthetic disassembly of 16 by cleavage of the indicated bond furnishes compounds 17 and 18 as potential precursors. In the synthetic direction, a diastereoselective alkylation of the thermodynamic (more substituted) enolate derived from 18 with alkyl iodide 17 could afford intermediate 16. While trimethylsilyl enol ether 18 could arise through silylation of the enolate oxygen produced by a Michael addition of a divinyl cuprate reagent to 2-methylcyclopentenone (19), iodide 17 can be traced to the simple and readily available building blocks 7 and 20. The application of this basic plan to a synthesis of racemic estrone [( >1] is described below. 

Trifluoro-2-nitrosopropene can be generated in situ from 1 -bromo-3,3,3-trifluoropropan-2-one 2-oxime. It is a highly reactive nitrosoalkene that readily undergoes cycloaddition with silyl enol ethers and other die-nophiles to give CF3- substituted 1,2-oxazines (92JOC339). 

An interesting example from carbohydrate chemistry is the boron trifluoride-diethyl ether complex catalyzed nucleophilic addition of silyl enol ethers to chiral imines (from n-glyceralde-hyde or D-serinal)22. This reaction yields unsaturated y-butyrolactones with predominantly the D-arabino configuration (and almost complete Cram-type erythro selectivity). 

The chiral (V-camphanoyl iminium ion 7, prepared by hydride abstraction from 2-camphanoyl-l,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline 6 (see Appendix) with triphenylcarbenium te-trafluoroborate, reacts with silyl enol ethers to give 1-substituted tetrahydroisoquinoline derivatives with reasonable diastereoselectivity, 0°. On addition of titanium(IV) chloride, prior to the addition of the silyl enol ether, the diastereoselectivity gradually rises to an optimum at 2.5 equivalents of the Lewis acid, but the yield drops by 20%. 

This valuable method utilizes the O-TMS enol ethers derived from either pentane-2,4-dione or methyl acetoacetate, the former being the more reactive. Even t-alcohols are rapidly and quantitatively silylated in DMF at room temperature. A similar technique can be used to introduce the TBDMS group, although here ptsa catalysis is required (4). 

Example of use with dimethylphenylsilane (11). A mixture of the (i/l-unsaturated ketone (1.05mmol), dimethylphenylsilane (l.lmmol) and tris(triphenylphosphine)rhodium(i) chloride (0.002 mmol) was heated at 55°C for 1 h. The silyl enol ether was distilled directly from the reaction. 

Silyl enol ethers and ketene acetals derived from ketones, aldehydes, esters and lactones are converted into the corresponding o/i-unsaturated derivatives on treatment with allyl carbonates in high yields in the catalytic presence of the palladium-bis(diphenylphosphino)ethane complex (32). A phosphinc-free catalyst gives higher selectivity in certain cases, such as those involving ketene acetals. Nitrile solvents, such as acetonitrile, are essential for success. 

This area of reactivity has been the subject of excellent reviews (J5). Silyl enol ethers are not sufficiently nucleophilic to react spontaneously with carbonyl compounds they do so under the influence of either Lewis acids or fluoride ion, as detailed above. Few clear trends have emerged from the somewhat limited number of definitive studies reported so far, with ambiguities in diastereoisomeric assignments occasionally complicating the issue even further. 

The enol acetates, in turn, can be prepared by treatment of the parent ketone with an appropriate reagent. Such treatment generally gives a mixture of the two enol acetates in which one or the other predominates, depending on the reagent. The mixtures are easily separable. An alternate procedure involves conversion of a silyl enol ether (see 12-22) or a dialkylboron enol ether (an enol borinate, see p. 560) to the corresponding enolate ion. If the less hindered enolate ion is desired (e.g., 126), it can be prepared directly from the ketone by treatment with lithium diisopropylamide in THE or 1,2-dimethoxyethane at —78°C. ... 

Vinylic lithium reagents (26) react with silyl peroxides to give high yields of silyl enol ethers with retention of configuration. Since the preparation of 26 from vinylic halides (12-37) also proceeds with retention, the overall procedure is a... 

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