5- -2,2-dimethyl KETONES, ALDOLIZATION

DIBK can be produced by the hydrogenation of phorone which, in turn, is produced by the acid-catalyzed aldol condensation of acetone. It is also a by-product in the manufacture of methyl isobutyl ketone. Diisobutyl ketone ( 1.37/kg, October 1994) is produced in the United States by Union Carbide (Institute, West Virginia) and Eastman (Kingsport, Teimessee) (47), and is mainly used as a coating solvent. Catalytic hydrogenation of diisobutyl ketone produces the alcohol 2,6-dimethyl-4-heptanol [108-82-7]. 

Aldol condensation of the methoxymethyl ether of m-methoxybenzaldehyde (83) with cyclohexanone affords the conjugated ketone 84. Michael addition of dimethyl amine leads to the ami noketone Reduction of the ketone... 

Due to their tendency to form (Z)-enolates, ketones usually provide syn-aldols, and anti-se ec-tive chiral ketone enolates are rare. When, however, (S)-5,5-dimethyl-4-trimethylsiloxy-3-hex-anone is deprotonated with (V-(bromomagnesio)-2,2,6,6-tetramethylpiperidine, the (E)-enolate la is assumed to be formed. Subsequent addition to aldehydes delivers anh-aldols 2a and 3a in ratios of between 92 8 and 95 5 and yields of 75-85%53b. 

On the other hand, the predominant formation of the diastereomeric aldols 3 b results from the titanium enolate 1 b of (S )-5,5-dimethyl-4-tert-butyldimethylsilyloxy-3-hexanone. For this purpose, the ketone is first deprotonated with A-(bromomagnesio)-2,2,6,6-tetramethylpiperidine and the magnesium enolate, presumably (E) configurated, formed is thereby treated with hexamethylphosphoric triamide and triisopropyloxytitanium chloride. After sonification, the aldehyde is added to give predominantly aldol adducts 3b the diastereomeric ratio of 3b/2b surpasses 95 5 and the chemical yields range from 85 to 88%53b. 

The first element of stereocontrol in aldol addition reactions of ketone enolates is the enolate structure. Most enolates can exist as two stereoisomers. In Section 1.1.2, we discussed the factors that influence enolate composition. The enolate formed from 2,2-dimethyl-3-pentanone under kinetically controlled conditions is the Z-isomer.5 When it reacts with benzaldehyde only the syn aldol is formed.4 The product stereochemistry is correctly predicted if the TS has a conformation with the phenyl substituent in an equatorial position. 

Aldol-type reactions of nitrones (303) occur with electron-deficient ketones, such as a-keto esters, a, 3-diketones, and trifluoromethyl ketones. These reactions are catalyzed by secondary amines. The use of chiral cyclic amines A1-A7 leads to a-(2-hydroxyalkyl)nitrones (304) in moderate yields and rather high optical purity (Scheme 2.120) (381). The mechanism of the nitrone-aldol reaction of iV-methyl-C-ethyl nitrone with dimethyl ketomalonate in the absence and presence of L- proline has been studied by using density functional theory (DFT) (544). 

SYNTHESIS OF p-LACTONES BY ALDOLIZATION OF KETONES WITH PHENYL ESTER ENOLATES 3,3-DIMETHYL-1 -OXASPIRO[3.5]NONAN-... 

Acid Catalyzed. Although ketonic carbonyl groups are less reactive than aldehydic carbonyls in the presence of basic catalysts, this is not the case with acid catalysts. Thus acetone undergoes aldol addition in the presence of sulfuric acid to give mesityl oxide, which then condenses with a third molecule of acetone to give a mixture ofphorone (2,6-dimethyl-2,6-heptadien-4-one) and mesitylene (1,3,5-trimethylbenzene). Ketones also condense with activated aromatic products in the presence of sulfuric acid to give coupled aromatic products. For example, acetone and phenol condense to bisphenol A (4,4 -isopropylidenediphenol), which is used in the manufacture of epoxy resins (qv) and polycarbonates (qv). 

Carbonyl activation and deactivation.1 Aldehydes, but not ketones, undergo aldol condensation with silyl enol ethers at —78° in the presence of dibutyltin bistriflate. In contrast, the dimethyl acetals of ketones, but not of aldehydes, can undergo this condensation (Mukaiyama reaction) with silyl enol ethers at -78° with almost complete discrimination, which is not observed with the usual Lewis-acid catalysts. Thus dibutyltin bistriflate activates aldehydes, but deactivates acetals of... 

CO2-PEG system is also effective for the scandium-catalyzed aldol reactions, and poly(ethylene glycol) dimethyl ether (PEG(OMe)2, MW = 500) is more effective than PEG (Scheme 3.12) [57]. Emulsions in C02-PEG(0Me)2 medium are observed when the concentration of the additive is 1 g/L. Not only benzal-dehyde but also substituted aromatics, aliphatic, and a, /]-unsaturated aldehydes react smoothly, and various silicon enolates derived from a ketones, esters, and thioesters also react well to afford the corresponding aldol adducts in high yields. 

To a mixture of anhydrous dimethyl sulfoxide (4 mL) and ketone donor (1 mL) was added the corresponding aldehyde (0.5 mmol) followed by L-proline (20-30mol%) and the resulting mixture was stirred at room temperature for 4—72 h. The reaction mixture was treated with saturated ammonium chloride solution, the layers were separated, and the aqueous layer was extracted several times with ethyl acetate, dried with anhydrous MgS04, and evaporated. The pure aldol products were obtained by flash column chromatography (silica gel, mixture of hexanes and ethyl acetate). 

Methylation with dimethyl sulfate in alkali gave the methyl derivatives 28 and 29. Although formaldehyde attacks at N-2, aldol condensation of 10 with benzaldehyde gave the 3a-hydroxybenzyl compound (30) which is dehydrated to the 2-acetyl-3-benzylidene compound (31) with acetic anhydride.27 With acid anhydrides the2-acyl derivatives are obtained however, with acid chlorides in pyridine or dimethylaniline the bicyclic ketone (32) is formed.31 Despite the occurrence of the bicyclic product (32) and the bicyclic intermediate (13) there is no evidence for the existence of a bicyclic tautomer of 10.37... 

Several examples of Sc(OTf)3-catalyzed aldol reactions of silyl enolates with aldehydes were been examined. Silyl enolates derived from ketones, thioesters, and esters reacted smoothly with different types of aldehyde in the presence of 5 mol % Sc(OTf)3 to afford the aldol adducts in high yields. Sc(OTf)3 was also found to be an effective catalyst in aldol-type reactions of silyl enolates with acetals. The reactions proceeded smoothly at -78 °C or room temperature to give the corresponding aldol-typc adducts in high )delds without side-reaction products. It should be noted that aldehydes were more reactive than acetals. For example, while 3-phenylpropionalde-hyde reacted with the ketene silyl acetal of methyl isobutyrate at -78 °C to give the aldol adduct in 80 % yield, no aldol-type adduct was obtained at -78 °C in the reaction of the same ketene silyl acetal with 3-phenylpropionaldehyde dimethyl acetal. The acetal reacted with the ketene silyl acetal at 0 °C to room temperature to give the... 

The first enantioselective total synthesis of tetracyclic sesquiterpenoid (+)-cyclomyltaylan-5a-ol, isolated from a Taiwanese liverwort, was accomplished by H. Hagiwara and co-workers. They started out from Hajos-Parrish ketone analogue, (S)-(+)-4,7a-dimethyl-2,3,7,7a-tetrahydro-6/-/-indene-1,5-dione, that could be synthesized from 2-methylcyclopentane-1,3-dione and ethyl vinyl ketone in an acetic acid-catalyzed Michael addition followed by an intramolecular aldol reaction. The intramolecular aldol reaction was carried out in the presence of one equivalent (S)-(-)-phenylalanine and 0.5 equivalent D-camphorsulfonic acid. The resulting enone was recrystallized from hexane-diethyl ether to yield the product in 43% yield and 98% ee. Since the absolute stereochemistry of the natural product was unknown, the total synthesis also served to establish the absolute stereochemistry. 

Aldol reactions. Regioselective aldol reaction at a more highly substituted a-position of a ketone is promoted by TiCl. This Lewis acid also catalyzes the Baylis-Hillman reaction participated by dimethyl sulfide. ... 

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