Ketones, 3-trimethylsilyloxy

The nucleophilic alkenoylation of a-phenyl-substituted aldehydes and ketones with (methyl-substituted) [l-cyano-l-(trimethylsilyloxy)-2-propenyl]lithium proceeds with good 1,2-induction to afford the j> i-hydroxy ketones109. 

O-Trimethylsilyl nitronates 1036 have been used in fluoride-catalyzed aldol-type condensations with aldehydes and ketones to give a-trimethylsilyloxy-nitro com-... 

Because 2-trimethylsilyloxy sulfides such as 1154 and 1157 are hemiphenyl thioacetals of aldehydes, they are readily hydrolyzed to aldehydes [8-12] or ketones [13]. Thus alkylation of the lithium salt 1162 with cyclohexyhnethylbromide 1163, gives in nearly quantitative yield, the sulfide 1164, which, after oxidation with m-chloroperbenzoic acid and hydrolysis, rearranges in 70% yield to cyclohexylacetal-dehyde 1165 [8] (Scheme 8.2). A more detailed discussion of the formation of aldehydes is given in Section 8.5. 

Conversion of sulfones such as 1955 into their a-sulfonyl anions by treatment with n-BuIi at -78°C in THF then addition of bis(trimethylsilyl)peroxide (BTSP) 1949 afford, via intermediates such as 1956, aldehydes or ketones such as cyclohexanone and HMDSO 7 [146]. This reaction has subsequently been applied to the synthesis of aldehydes [147]. After hthiation with -BuLi thioethers such as phenyl benzyl sulfide 1957 react with BTSP 1949 to give mixtures of the O-silyl 1958 and C-silyl 1959 products [148]. On treatment with -BuLi at -30°C the a,a-bis-(trimethylsilyl)dimethylsulfide 1960 is, hkewise, converted into its anion, which reacts with 1949 to give the a-trimethylsilyloxy sulfide 1961 and MesSiOLi 98 [149] (Scheme 12.41). 

Next is the construction of the D ring. The TMS enol ether of compound 111 undergoes oxidation with m-CPBA, providing the C-5a trimethylsilyloxy ketone 112. Addition of methyl Grignard reagent to the ketone group and subsequent dehydration provides compound 113. Osmylation of the C=C double... 

An outstandingly reactive diene is l-methoxy-3-(trimethylsilyloxy)-l,3-butadiene ( Danishefsky s diene ) 4, prepared by the action of trimethylsilyl chloride on the ketone 3 in the presence of zinc chloride/triethylamine (equation 7)6. The reaction of diethyl mesoxalate with Danishefsky s diene gives the dihydropyran 5 with the (trimethylsily-loxy)dienes 6 and 7, mixtures of dihydropyrans are obtained, in which the meta-isomers predominate (equations 8 and 9)7. 

Trimethylsilylation of enolizable carbonyl compounds and alcohols has also been accomplished by the fluoride ion promoted reaction with hexamethyldisilane and ethyl trimethylsilylacetate [48, 49], with high stereospecificity giving Z-enol ethers from ketones [50]. l-Trimethylsilyl-(l-trimethylsilyloxy)alkanes, produced from the reaction of aldehydes with hexamethyldisilane, undergo acid-catalysed hydrolysis during work up to yield the trimethylsilylcarbinols [51]. In the case of aryl aldehydes, the initially formed trimethylsiloxy carbanion produces the pinacol (Scheme 3.1). 

Next, the TMS enol ether of 53c underwent oxidation with MCPBA to trimethylsilyloxy ketone 57. in 86% yield (86% conversion). Addition of methylmagnesium bromide in methylene chloride proceeded in almost quantitative yield (95%) to give tertiary alcohol 58. Dehydration with Burgess reagent [19] and acidic workup provided the allylic alcohol 59a in 63% yield, which was converted... 

Simple dienes react readily with good dienophiles in Diels-Alder reactions. Functionalized dienes are also important in organic synthesis. One example which illustrates the versatility of such reagents is l-methoxy-3-trimethylsilyloxy-1,3-butadiene (.Danishefsky s diene) 1 Its Diels-Alder adducts are trimethylsilyl enol ethers which can be readily hydrolyzed to ketones. The /j-mcthoxy group is often eliminated during hydrolysis. 

By allowing Cjq to react with 2-trimethylsilyloxy-1,3-butadiene in toluene at reflux [38, 94], another stable Diels-Alder adduct was obtained (Scheme 4.14). The ketone 93 is formed after hydrolysis of the uncharacterized intermediate silyl enol ether under flash chromatographic conditions. 

Bei der Herstellung von a-Hydroxy-ketonen durch Acyloin-Kondensation erzielt man durch Zugabe von Chlor-trimethyl-silan meistens bessere Ausbeuten (vgl. Bd. El5, S. 1294ff.). Die a-Hydroxy-ketone fallen dann als l,2-Bis-[trimethylsilyloxy]-l-alkene an. Diese konnen direkt... 

Trimethylsilyloxy-alkansaure-nitrile In einem Kolben mit Riihrer und Septumkappe gibt man unter Stickstoff 1 mol-equiv. Keton und dann mittels Spritze 1,1 mol-equiv. Cyan-trimethyl-silan, das pro Mol 1-10 mg wasserfreies Zinkjodid als Katalysator enthalt. Die Reaktion wird ohne Solvens oder in... 

Trimethylsilyloxy-substituted alkenes are by far the most widely used enol ethers because of their straightforward preparation from the corresponding ketones (equation 20)78-82 -pjjg electron-rich character of silyl enol ethers allows for highly chemoselective cyclopropanations in the presence of additional double bonds (eqnation 21). ... 

A. 2-Trimethylsilyloxy-l,3-butadiene (1). An oven-dried 500-ml., three-necked, round-bottomed flask is fitted with two oven-dried addition funnels, a glass stopper, and magnetic stirrer, and placed in a 80-90° oil bath. Under an inert atmosphere, methyl vinyl ketone (25.0 g., 0.357 mole) in 25 ml. of dimethylformamide and chlorotrimethylsilane (43.4 g., 0.400 mole) in 25 ml. of dimethylformamide are added over 30 minutes to a magnetically stirred solution of triethylamine (40.5 g., 0.400 mole) in 200 ml. of dimethylformamide (Note 1). The reaction gradually darkens from colorless to yellow or dark brown, and supports a white precipitate of triethylamine hydrochloride. The reaction is set up to run overnight, or ca. 14 hours. 

Butadienes substituted with alkoxy groups in the 2-position, e.g., 2-ethoxy-1,3-butadiene,6 have been prepared from methyl vinyl ketone, but they required several conversions and a tedious spinning-band distillation to purify the product. This slight modification of the House procedure has been used to conveniently prepare 2-trimethylsilyloxy-l,3-butadiene from the readily available methyl vinyl ketone. This one-step procedure has provided large amounts of a new and reactive diene for Diels-Alder reactions, as illustrated in Table I. 

TRIMETHYLSILYLOXY 1,3 BUTA DIENE, A REACTIVE DIENE, 58, 163 1-Trimethylsilylvinyl ketones, 58, 157, 162 1-Tnmethylsilylvinylmagnesium bromide, 58, 157... 

The cycloaddition reactions of 2,5-bis(trimethylsilyloxy)furans have been discussed (Section 3.11.2.7.1). The reactions of these compounds with aldehydes and ketones and with quinone acetals have also been investigated (80TL3431). 

The combination of TMSOTf, dimethyl sulphide and l,2-bis(trimethylsilyloxy)ethane provides a method91 for the selective dioxolanation of ketones in the presence of aldehydes, via intermediate protection of the aldehyde as its silyloxysulphonium salt (equation 19). 

It should be noted that several procedures are available for the preparation of l-(trimethylsilyloxy)cyclohexene. In an original report252 it was prepared by heating a dimethylformamide solution of cyclohexanone under reflux with chlorotrimethylsilane in the presence of triethylamine. This procedure is generally satisfactory for aldehydes and symmetrical ketones, or ketones which can enolise in one direction only. The method described in Expt 5.214 employs lithium sulphide as an additive to increase the silylating power of the chlorotrimethylsilane, so that the reaction proceeds at room temperature acetonitrile is used as the solvent.253... 

E,Z)-1 -MetlK)xy-2-methyT3-trimethylsilyloxy-1,3-pentadiene (1). The diene is prepared by silylation of the corresponding ketone with ClSi(CH3)3 using N(CH3)3-ZnCl2. ... 

A related approach exploited a A-cyanomethyl group to serve in the dual role of a nitrogen protecting group and a latent precursor of the formaldehyde im-inium ion (e.g., 478), and this innovative modification in tactics resulted in a simplified route to the c/.v-3a-aryloctahydroindole 474 (203a,c). To this end, the amino ketone 482 was readily prepared in one step by the reaction of 1,2-bis(trimethylsilyloxy)cyclopentene with A -benzyl-A -cyanomethyl amine. When 482 was exposed to [l-(3,4-methylenedioxyphenyl)ethenyl]lithium, a mixture (1 14) of 483 and 484 was obtained. It is noteworthy that the stereochemical sense... 

Cyclopentanols. Cyclic ketones bearing a , -unsaturated side chain at the a-position undergo five-membered ring annelation to cyclic pentanols on reaction with zinc and chlorotrimethylsilane in the presence of 2,6 lutidine. The reaction probably involves reduction of the keto group to an a-trimethylsilyloxy radical, which adds to the unsaturated center. The bicyclic products have a c/s-ring fusion. 

Trimethylsilyloxy- E15/1, 422 (Keton 4- R3Si-CH2-COOR), 429 (Keton 4- R3Si —Cl), 441 [Keton 4- (R3Si)20], 447... 

Cydohexen 1-Trimethylsilyloxy-Vl/ld, 180/182 (Keton + RjSi-Cl) E1S/1, 418 (Keton + R3SiH), 441 (Keton + RjSi-O-SOj-R) Cyclopentan (Z)- and ( )-2-Hydroxy-1 -(trimethylsilyl-methylene)- E21c, 2730 (1 -SiR2 —... 

Bicyclo 4.1.0]heptan 7-Trimethyl-silylcarbonyl- E17b, 1393 (7-Br/7-SiR3 — 7-H/7-CO—SiR3) Cyclohexan trans-2-Hydroxy-1-(trimethylsilyl-ethinyl)- E19d, 146 (sp-CH - C - Li/Oxiran) Cyclopenten 2-Ethyl-4-methylen-l-trimethylsilyl- E17c, 2251 (Methylen-cyclo propan + In) Ethen l-(l-Cyclohexenyl)- -trimethylsilyloxy- E1S/1, 441 (Keton 4- RjSi—O —S02 —R) Furan 2-Methyl-5-propyl-3-trimethylsilyl- E18, 674 (In-Hydromagnesier./+ R —CN)... 

Cyclohexen 2-Methoxycarbonyl-l-trimethylsilyloxy- El5/1, 446 (Keton + R3 Si — NH — SiR3) Cyclopenten 2-Ethoxycarbonyl-l-trimethylsilyloxy- Vl/ld, 187... 

Butensaure 3-Trimethylsilyloxy- -tert.-butylester E15/1, 447 (Keton R3Si —NR —COOR)... 

Cyclohexen 4,4-Ethylendioxy-2(bzw. 6)-methyl-l -trimethylsilyloxy-E15/1, 432 (Keton + R3Si-Cl) Furan 5-(Diethoxy-methy])-2-trime-thylsilyl- E6a, 145 (Li - SiR3)... 

Oxiran 2-Methyl-3-(4-methyl phenyl)-2-trimethyl-silyl- E19d, 881 (H - Li/ + R-CHO) Propen 2-Methyl-l-phenyl-1-trimethylsilyloxy- E1S/1, 441 (Keton + R3Si —O —S02 —R) Silan Dimethyl-pentanoyl-phenyl-E19d, 570 (Acylierung) Spiro[4.4]nona-2,6-dien 6-Methyl-l -oxo-2(bzw. 3)-trimethylsiiyl-E19c, 221 (3-En-CO-Cl +... 

When 2-substituted (methyl or trimethylsilyloxy) 2-norbornenes and 1,7,7-trimethyl-2-norbor-nenes are allowed to react with singlet oxygen, ene products are efficiently formed53 54. In the case of the trimethylsilyloxy-substituted substrates, migration of the trimethylsilyl group occurs and O-silylated a-hydroperoxy ketones 1 are isolated. The O-silylated a-hydroperoxy ketones 1 arc easily reduced to O-silylated a-hydroxy ketones. 

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