A-silyl carbonyl compounds

Hernandez, D., Larson, G. L. Chemistry of a-silyl carbonyl compounds. 9. Synthesis of tri- and tetrasubstituted olefins from a-silyl esters. J. Org. Chem. 1984, 49, 4285-4287. 

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. 

As discussed in Chapter 9, various nucleophiles can be introduced at the ortho position of nitroarenes via the VNS process. This provides a useful strategy for the synthesis of indoles. One of the most attractive and general methods of indoles and indolinones would be the reductive cyclization of a-nitroaryl carbonyl compounds (Eq. 10.54). The VNS and related reactions afford a-nitroaryl carbonyl compounds by a simple procedure. For example, alkylation of 4-fluoronitrobenzene with a lactone silyl enol ether followed by reductive cyclization leads to tryptophols (Eq. 10.55).73... 

Oxidation of silyl enol ethers. Oxidation of silyl enol ethers to a-hydroxy aldehydes or ketones is usually effected with w-chloroperbenzoic acid (6, 112). This oxidation can also be effected by epoxidation with 2-(phenylsulfonyl)-3-( p-nitrophenyl) oxaziridine in CHC1, at 25-60° followed by rearrangement to a-silyloxy carbonyl compounds, which are hydrolyzed to the a-hydroxy carbonyl compound (BujNF or H,0 + ). Yields are moderate to high. Oxidation with a chiral 2-arene-sulfonyloxaziridine shows only modest enantioselectivity. 

The preparation of a-hydroxy carbonyl compounds has been accomplished by the oxidation of enolates using both oxygen6 and MoC PyHMPA-(MoOPh).7 Acyl anion equivalents offer another route to this useful class of compounds. The procedure presented here for the synthesis of 6-hydroxy-3,5,5-tr1methyl-2-cyclohexen-l-one illustrates the use of MCPBA oxidation of an enol silyl ether as a method for obtaining an a-hydroxy enone. The procedure is a scaleup of a published synthesis. ... 

Since the double bond placement in enol silyl ethers is predictable and controllable,18 the method allows the regiospecific introduction of a-hydroxy groups. Omission of the fluoride treatment permits isolation of a-trimethylsiloxy carbonyl compounds,17 while treatment of enol silyl ethers, first with HCPBA, then with triethyl ammonium fluorlde/acetic anhydride gives... 

The reaction of nitroarenes with silyl end ethers and ketene silyl acetals in MeCNATiF with 1 equiv. of TASF, followed by in situ oxidation with Br2 or DDQ, provides an easy route to a-nitroaryl carbonyl compounds (Scheme l).12 The use of these compounds as reagents for the synthesis of arylacetic acids, propionic acids, indoles, 2-indolinones and other heterocyclic compounds has recently been described.88... 

Magnesium halides are known to promote rearrangement of a, /J-epoxysilanes 176 to /J-silyl carbonyl compounds 177, as shown in equation 143216,217. 

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. 

Treatment of silyl enolates with methyllithium followed by an addition of gallium trichloride affords the corresponding gallium enolates. The reaction of the resulting gallium enolates with a-halo carbonyl compounds in the presence of triethylborane provides 1,4-dicarbonyl compounds in good yields (Scheme 142).433... 

Conjugate additions. The silyl cuprate rcapcnt (PhMc,Si),CuLi (1) undergoes conjugate addition to a,(3-unsaturated aldehydes, ketones, or esters to form (3-silyl carbonyl compounds. Methylation of the intermediate enolate in acyclic systems is highly dia-stereoselective in favor of the isomer in which the silyl and methyl groups have the anti-... 

OL-Iodo aldehydes and ketones. Enol silyl ethers are converted by this system into a-iodo carbonyl compounds in yields of >80%. 1 he method fails with enamines, and is only marginally useful with enol ethers. This system converts cyclohexene into trans- -chloro-2-iodocyclohexane (66% yield). 

Michael addition of various a, -unsaturated carbonyl compounds to silyl enol ether catalyzed by Ti-beta and TS-1... 

Whereas alkyl enol ethers easily polymerize upon treatment with electrophilic reagents [202], silylated enol ethers are rapidly desilylated after the electrophilic attack, and regeneration of the carbonyl group prevents polymerization. Therefore, silyl enol ethers are frequently used reagents for synthesizing a-substituted carbonyl compounds (Scheme 45) [200,201,203-205]. 

More recently, worlc has been reported showing that silyl enol ethers of ketones, esters and lactones can be efficiently converted to a-sulfonyloxy carbonyl compounds on treatment with either [hydroxy(to-syloxy)iodo]benzene or [hydroxy(mesyloxy)iodo]benzene (equation 23). This method is similar to that used by the same workers to introduce the trifluoromethylsulfonyloxy group a to ketone carbonyl groups via their silyl enol ethers.While the major interest in these developments is the further func-tion zation of the a-position of carbonyl compounds the method clearly offers a route to a. -unsatu-rated species. 

Trifluoromethyl hypofluorite smoothly converts silyl enol ethers into the corresponding a-fluoro carbonyl compounds in good yield (Table 5). ... 

A 2 1 mixture of silver carboxy late and iodine is well known to be a good oxidant in the transformation of enol silyl ethers into the corresponding a-acyloxy carbonyl compounds (139). Five- and six-membered ring enol silyl ethers serve as the best substrates, with larger ring systems forming a-iodo carbonyl compounds as byproducts. 

---