Ketone activated

In a second attempt to extend the scope of Lewis-acid catalysis of Diels-Alder reactions in water, we have used the Mannich reaction to convert a ketone-activated monodentate dienophile into a potentially chelating p-amino ketone. The Mannich reaction seemed ideally suited for the purpose of introducing a second coordination site on a temporary basis. This reaction adds a strongly Lewis-basic amino functionality on a position p to the ketone. Moreover, the Mannich reaction is usually a reversible process, which should allow removal of the auxiliary after the reaction. Furthermore, the reaction is compatible with the use of an aqueous medium. Some Mannich reactions have even been reported to benefit from the use of water ". Finally, Lewis-acid catalysis of Mannich-type reactions in mixtures of organic solvents and water has been reported ". Hence, if both addition of the auxiliary and the subsequent Diels-Alder reaction benefit from Lewis-acid catalysis, the possibility arises of merging these steps into a one-pot procedure. 

Although the sulfone activated biphenyl and the ketone activated naphthalene moiety for the displacement polymerization have been reported by Attwood et al. [11], these were rediscovered by Cummings et al. [12] and Hergenrother et al. [13], respectively, for the synthesis of poly(aryl ethers). Recently, Singh and Hay [14] reported polymers containing 0-dibenzoyl benzene (1,2,3) moiety by reaction between bis(O-fluorobenzoyl) benzene or substituted benzene with bisphenates of alkali metal salt in DMAC as follows ... 

Similar transformations using a,P-unsaturated ketones activated with a trifluoromethyl group also proved to be highly efficient (e.g., 4 5 <99SL756>, 6- 7 <99TL2541>) for the... 

Aldol reactions.1 The anion generated (BuLi) from chromium carbene complexes undergoes aldol reactions with aldehydes or ketones activated by a Lewis acid. Best results are obtained with ketones in the presence of BF3 etherate, whereas TiCl4 is the preferred catalyst for aldehydes and acetals. 

Keywords aldehyde, ketone, active methylene compound, Knoevenagel condensation, basic alumina, microwave irradiation, olefin... 

The Mukaiyama reaction is a versatile crossed-aldol reaction that uses a silyl enol ether of an aldehyde, ketone, or ester as the carbon nucleophile and an aldehyde or ketone activated by a Lewis acid as the carbon electrophile. The product is a /1-hydroxy carbonyl compound typical of an aldol condensation. The advantages to this approach are that it is carried out under acidic conditions and elimination does not usually occur. 

The reaction of allyl silanes with aldehydes and ketones activated as electrophiles by Lewis acids is a very useful method for preparing homoallylic alcohols. Since allyl silanes are only modestly nucleophilic, strong electrophiles are needed to ensure a good reactivity match. 

For instance, the preparation of isoxazole 4.17 is virtually regiospecific because the reaction commences with the more nucleophilic heteroatom (i.e. nitrogen) attacking the more electrophilic ketone (activated by the electron-withdrawing inductive effect of the adjacent ester group). The reader is encouraged to consider the regiochemical bias in the preparation of isoxazole 4.15 and pyrazole 4.16. 

Trimethylammonium trifluoroacetophenone (19) was found to be a highly effective inhibitor of acetylcholinesterase 37 f The ketone activated by an electron-withdrawing trifluoroacetyl group will enhance the tendency to add a nucleophile (the hydroxyl group of the catalytic serine residue of acetylcholinesterase) to form a tetrahedral adduct as an aldehyde inhibitor. 

Both simple and fused poly substituted pyran-2-ones can be obtained from the reaction between substituted allenyl esters and ketones activated by an electron-withdrawing group. A base-catalysed nucleophilic conjugate addition affords a homoallylic ester and lactonisation completes the one-pot sequence (Scheme 19) <06S2731>. 

Table 5 Bulky Aromatic Ester or Ketone Activation...

Aromatic ketone-activated phospholipid is stored as chloroform solution at -80°C. 

Furan-2,5-dione, or maleic anhydride, can quite reasonably be regarded as furanoquinone, the reduced form being furan-2,5-diol. The carbonyl groups do have some ketonic activity, and in Scheme 23 the key step of a second route to freelingyne (86 in Vol. 30) makes use of this capacity in a reaction with another phosphorus ylide reagent.96 (cf. Scheme 16). Even ordinary (carbonyl stabilized) carbanions will undergo such aldol con-... 

Vapor composition trends are again anticipated by calculation for nonane-methyl isoamyl ketone blends in Figure 11. Predicted compositions are less exact for the 50 wt % blends than for the blends containing both more and less nonane. This is typified by the plot in Figure 12 where experimental and calculated vapor and liquid compositions are each compared. Deviations observed are in line with deviations in isotherm representation high nonane, low ketone activities at high solvent levels, and low nonane activity at low solvent levels. Data for nonane-methyl amyl acetate blends compare closely with calculated values in Figures 13 and 14. 

AlIylFp reagents [where Fp refers to the Fc(C,H5)(CO)2 residue] are examples of such reagents they are obtained by addition of the appropriate allyl chloride or tosylate to a solution of Fc(C5H5)(CO)2Na in THF at —78 "C. Chromatography on alumina allows isolation of the air-and heat-sensitive product in 80-95 % yield. In the presence of a./1-unsa turated ketones activated by an appropriate Lewis acid, cycloaddition provides stereoselectively the Fp-substituted cyclopenlane8. In the case of cyclohexenone as the acceptor, the two isomers formed in equal amounts both have a a. v-ring fusion. The Lewis acid of choice is freshly sublimed aluminum(III) bromide used in catalytic amounts (5 mol%). 

Aliphatic aldehydes are also obtained with high selectivity. Selectivity is lower for primary aliphatic carboxylic acids because of a competing intermolecular decarboxylation reaction which results in ketone formation (Eq. 2) [16]. This ketonization activity of Zr02 was, substantially suppressed by addition of metal ions. 

Substrate 418, which was less hindered without the methyl substituent in the 6-position of the ring, gave slightly higher yield than the analogous reaction of 416 (Scheme 34).102 Deethoxycarboxylation of this class of products was demonstrated by the conversion of 419 to 420. A mixed ester and ketone-activated reagent (421) was also effective for aza-annulation in the construction of 422 at ambient temperature. 

Binary mbctures of acetic, propionic and butyric acid are converted in the vapor phase over zeolite H-T. From hydroxyl stretching vibration. spectra of zeolite H-T with adsorbed butyric acid, it is concluded that the carboxylic acids have access to the different proton locations in this zeolite. The acids undergo ketonization reactions inside the erionite cavities of the zeolite, and dehydration reactions into anhydrides on the outer surface of the zeolite crystal. The ketonization activity and selectivity is rationalized by transition-state shape-selectivity in erionite cages. Zeolite H-T is particularly suitable for converting an equimolar mixture of propionic and butyric acid into 3-hexanone. 

The presence of erionite cages in the zeolite is a prerequisite for ketonization activity and stable catalytic performances [2]. Butyric acid is transformed into 4-heptanone over zeolite T, erionite and ZSM-34 containing this structural element [2]. 

However, Claisen found in 1889 that a second molecule of ethyl acetate (with CH3 hydrogen atoms activated by COOEt) was not the only possible partner for a condensation reaction It could be replaced by a variety of other molecules, such as aldehydes and ketones (activation by CO group) and methyl cyanide and its derivatives (activation by CN group). Many condensation reactions of esters with nitriles were discovered, e.g. diethyl oxalate reacts with methyl cyanide in the presence of sodium ethoxide (Fleischhauer, 189320) ... 

Ketones activated by adjacent carboxyhc ester groups react with thiophenes under high-pressiue... 

Nu = coumarin, nitioalkane, phosphite, TMSCN, pheuol, indole, ketone, active methylene compounds, imide, amide, etc. 

A series of high molecular weight poly(thioether ketone)s (M = 55,000-100,000), eg, (24) and (25), have successfully been prepared from bis(4-mercaptophenyl) ether (4,4 -dimercaptodiphenyl ether) or bis(4-mercaptophenyl) sulfide (4,4 -dimercaptodiphenyl sulfide) by reaction with a series of ketone-activated aromatic fluoro-compoimds in the presence of anhydrous K2CO3. The polymers are amorphous and soluble in common organic solvents. They show TgS from 154 to 251°C and excellent thermal stability [temperatures of 5% weight loss (Tds) even above 500°C] (65). 

Scheme 26 Enamide ketone activation for the construction of discorhabdin core structure...

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