Silyl enol ethers and acetals

For some condensations with silylated substrates as starting compounds, trimethylsilyl inflate can be used as a catalyst [103, 104, 105] Atypical example of such a reaction is the aldol type condensation of silyl enol ethers and acetals catalyzed by 1-5 mol% of trimethylsilyl inflate [103] (equation 53)... 

Aldol reaction,6 This triflate is an effective catalyst for an aldol-type reaction between silyl enol ethers and acetals at -78°. The reaction shows moderate to high svn-selectivity regardless of the geometry of the enol ether. 

A further example is the cyclization of 3 with TiClj to give 4, 5a, and 5b in the ratio 2 3 3, respectively (88% combined yield). Only 5a and 5b are formed with SnCU (23% yield). The formation of an eight-membered ring is striking, particularly in the absence of high dilution, and is attributed to coordination of the silyl enol ether and acetal oxygens to the Ti catalyst. 

Aldol-type reactions. Trityl perchlorate catalyzes an aldol-type reaction between silyl enol ethers and acetals or ketals to give p-alkoxy ketones. The yields are comparable to those obtained with TiCU (6, 594). The iyn-aldol is formed predominantly ( 4 1). 

Mukaiyama aldolization. This substance catalyzes reactions between silyl enol ethers and acetals. 

TMSOTf mediates a stereoselective aldol-type condensation of silyl enol ethers and acetals (or orthoesters). The nonbasic reaction conditions are extremely mild. TMSOTf catalyzes many aldol-type reactions in particular, the reaction of relatively non-nucleophilic enol derivatives with carbonyl compounds is facile in the presence of the silyl triflate. The activation of acetals was first reported by Noyori and has since been widely employed (eq 14). ... 

The reaction of silyl enol ethers and acetals to form aldol products has been accomplished by the use of trimethylsilyl trifluoromethanesulphonate as catalyst [equation (47)]. No polycondensation, self-condensation, or enone products were observed. When chiral centres were formed, there was a high stereoselectivity for the erythro-adducXs, irrespective of the geometry of the silyl enol ether,... 

As an extension of this new procedure for carbon-carbon bond formation, the reaction between silyl enol ethers and acetals 50, a typical protecting group of aldehydes, is performed to afford j5-alkoxy carbonyl compound 51 in the presence of titanium(IV) chloride (Eq. (24)) [27]. A variety of substituted furans are readily prepared by application of the TiCU-promoted reaction of a-halo acetals 52 with silyl enol ethers (Eq. (25)) [27]. 

Preparation of o,/3-Unsaturated Carbonyl Compounds by the Reactions of Silyl Enol Ethers and Enol Acetates with Ally Carbonates... 

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. 

Systems usually fluonnated by electropositive fluorine reagents include acti-vated alkenes (enol ethers, enol acetates, silyl enol ethers, and enamines), activated aromatic systems, certain slightly activated carbon-hydrogen bonds, and selected organometallics. 

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]... 

Table 3. Reaction of (5)-3-Ben2yloxy-2-fIuoro-2-methylpropionaldehyde with Silyl Enol Ethers and Silyl Ketene Acetals [6]...

The Lewis acid induced reaction of silyl enol ethers and silyl ketene (thio)acetals with 4-acetoxyazetidinones is often used for introduction of a carbon substituent in the 4-position of the jS-lactam ring. Numerous examples are known, both with and without substituents at nitrogen, some of which are shown. 

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. 

The reactivity pattern (1) of silyl enol ethers and ketene acetals is based largely on their synthetic equivalence to enolate anions. Recently, a different spectrum of behaviour has been revealed, particularly in those reactions that involve direct reaction without prior generation of the enolate anion. Indeed, the historic development of silyl enol ethers can be seen in three separate phases, involving... 

The enolates of other carbonyl compounds can be used in mixed aldol reactions. Extensive use has been made of the enolates of esters, thiol esters, amides, and imides, including several that serve as chiral auxiliaries. The methods for formation of these enolates are similar to those for ketones. Lithium, boron, titanium, and tin derivatives have all been widely used. The silyl ethers of ester enolates, which are called silyl ketene acetals, show reactivity that is analogous to silyl enol ethers and are covalent equivalents of ester enolates. The silyl thioketene acetal derivatives of thiol esters are also useful. The reactions of these enolate equivalents are discussed in Section 2.1.4. 

Lewis acids such as TiCl4 and SnCl4 induce addition of both silyl enol ethers and ketene silyl acetals to aldehydes.49... 

Aldol additions of silyl enol ethers and silyl ketene acetals can be catalyzed by (Cp)2Zr2+ species including [(Cp)2ZrO-/-liu 1 and (Cp)2Zr(03SCF3)2.58... 

Scheme 2.9 gives some examples of use of enantioselective catalysts. Entries 1 to 4 are cases of the use of the oxazaborolidinone-type of catalyst with silyl enol ethers and silyl ketene acetals. Entries 5 and 6 are examples of the use of BEMOL-titanium catalysts, and Entry 7 illustrates the use of Sn(OTf)2 in conjunction with a chiral amine ligand. The enantioselectivity in each of these cases is determined entirely by the catalyst because there are no stereocenters adjacent to the reaction sites in the reactants. 

The scope of the conjugate addition reaction can be further expanded by use of Lewis acids in conjunction with enolate equivalents, especially silyl enol ethers and silyl ketene acetals. The adduct is stabilized by a new bond to the Lewis acid and products are formed from the adduct. 

Silyl enol ethers and silyl ketene acetals also offer both enhanced reactivity and a favorable termination step. Electrophilic attack is followed by desilylation to give an a-substituted carbonyl compound. The carbocations can be generated from tertiary chlorides and a Lewis acid, such as TiCl4. This reaction provides a method for introducing tertiary alkyl groups a to a carbonyl, a transformation that cannot be achieved by base-catalyzed alkylation because of the strong tendency for tertiary halides to undergo elimination. 

A one-pot reaction between a tryptophan ester, benzotriazole, and 2,5-dimethoxytetrahydrofuran in acetic acid gives the diastereomeric benzotriazolyl tetracycles, 349, in good yield. Substitution of the benzotriazole by reaction with silyl enol ethers and boron trifluoride etherate gives the corresponding ketones 350 and 351, and reaction with allylsilanes gives the corresponding alkenes 352 and 353. If the boron trifluoride etherate is added to the mixture before the silane, elimination of benzotriazole from 349 is also observed (Scheme 83) <1999T3489>. 

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... 

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