Ketones a-carbon

In reactions with azides, ketones are directly converted to 5-hydroxytriazolines. Ketone enolate 247, generated by treatment of norbornanone 246 with LDA at 0°C, adds readily to azides to provide hydroxytriazolines 248 in 67-93% yield. Interestingly, l-azido-3-iodopropane subjected to the reaction with enolate 247 gives tetracyclic triazoline derivative 251 in 94% yield. The reaction starts from an electrophilic attack of the azide on the ketone a-carbon atom. The following nucleophilic attack on the carbonyl group in intermediate 249 results in triazoline 250. The process is completed by nucleophilic substitution of the iodine atom to form the tetrahydrooxazine ring of product 251 (Scheme 35) <2004JOC1720>. 

There are numerous other syntheses of indoles, and a modern example is the Wender synthesis. Here a 2-bromo-iV-(trifluoroacetyl)aniline in THF is deprotonated by butyllithium and then, in the same pot, reacted with fert-butyllithium to effect halogen-metal exchange to give the dilithiated derivative. To this intermediate is added an a-bromo ketone. A carbon-carbon bond is established first between the reactants, and then cyclization occurs to form a hydroxyindoline. Finally, dehydration generates the indole (Scheme 7.16). 

Norbomenes specifically undergo Pd(0)-catalyzed cyclopropanation by 1 -acetoxy-3-silyl-2-propanones to afford acetylcyclopropane-annelated products349. Methyleneoxazolidinones, ketone a-carbonates and 5-methylene-l,3-dioxolane-2-ones can also be used as the cyclopropanation reagent (equation 157)350 352. 

Palladium(O) catalysed cyclopropanation of electron-rich strained olefins using ketone a-carbonate or cyclic carbonates produce the corresponding cyclopropane adducts136-139. Two examples of this unusual cyclopropanation of norbornene are shown in equations 91 and 92. 

The key step is an intramolecular alkylation reaction of the ketone a-carbon, with the tosylate in the adjacent ring serving as the leaving group. 

The dissonant charge pattern for 2,5-hexanedione exhibits a positive (-1-) polarity at one of the a-carbons, as indicated in the acceptor synthon above. Thus, the a-carbon in this synthon requires an inversion of polarity Umpolung in German) from the negative (-) polarity normally associated with a ketone a-carbon. An appropriate substrate (SE) for the acceptor synthon is the electrophilic a-bromo ketone. It should be noted that an enolate ion might act as a base, resulting in deprotonation of an a-halo ketone, a reaction that could lead to the formation of an epoxy ketone Darzens condensation). To circumvent this problem, a weakly basic enamine is used instead of the enolate. 

Ketone A carbon atom doubly bonded 0 R-CO-R Methyl ethyl... 

The enol immediately rearranges to a ketone. A carbon doubly bonded to an oxygen is called a carbonyl ( car-bo-nil ) group. A ketone is a compound that has two alkyl groups bonded to a carbonyl group. An aldehyde is a compound that has at least one hydrogen bonded to a carbonyl group. 

Again, the achiral base 17 provides a reservoir of amidolithium reagent to allow catalyst turnover by deprotonation of 14 formed in situ (Scheme 3). Clearly, the kinetics of the reaction are such that deprotonation at the ketone a-carbon by the achiral lithium amide 17 is much slower than deprotonation at the 2° nitrogen of the chiral amine 14. Although the catalytic efficiency is modest, it is remarkable that catalysis of this type can be achieved. 

Ketone A carbon compound with a carbonyl group in the middle, rather than at... 

Oxidation of Benzylic Carbons Oxidation of Ketone a-Carbons... 

The a-ethenylation proceeded starting from ketones using a catalytic amount of GaCl3, in which effective proton transfer occurred from the ketone a-carbon to the olefin P-carbon [53]. 

A white solid, m.p. 178 C. Primarily of interest as a brominaling agent which will replace activated hydrogen atoms in benzylic or allylic positions, and also those on a carbon atom a to a carbonyl group. Activating influences can produce nuclear substitution in a benzene ring and certain heterocyclic compounds also used in the oxidation of secondary alcohols to ketones. 

The commercial product, m.p. 53-55°, may be used. Alternatively the methyl -naphthyl ketone may be prepared from naphthalene as described in Section IV,136. The Friedel - Crafts reaction in nitrobenzene solution yields about 90 per cent, of the p-ketone and 10 per cent, of the a-ketone in carbon disulphide solution at — 15°, the proportions ore 65 per cent, of the a- and 35 per cent, of the p-isomer. With chlorobenzene ns the reaction medium, a high proportion of the a-ketone is also formed. Separation of the liquid a-isomer from the solid p-isomer in Such mixtures (which remain liquid at the ordinary temp>erature) is readily effected through the picrates the picrate of the liquid a-aceto compound is less soluble and the higher melting. 

The success of the last reaction depends upon the inertness of the ester carbonyl groups towards the organocadmium compound with its aid and the use of various ester acid chlorides, a carbon chain can be built up to any reasonable length whilst retaining a reactive functional group (the ester group) at one end of the chain. Experimental details are given for l-chloro-2-hexanone and propiophenone. The complete reaction (formation of ketones or keto-esters) can be carried out in one flask without isolation of intermediates, so that the preparation is really equivalent to one step. 

The condensation of aldehydes or ketones with secondary amines leads to "encunines via N-hemiacetals and immonium hydroxides, when the water is removed. In these conjugated systems electron density and nudeophilicity are largely transferred from the nitrogen to the a-carbon atom, and thus enamines are useful electroneutral d -reagents (G.A. Cook, 1969 S.F. Dyke, 1973). A bulky heterocyclic substituent supports regio- and stereoselective reactions. 

Before we start with a systematic discussion of the syntheses of difunctional molecules, we have to point out a formal difficulty. A carbonmultiple bond is, of course, considered as one functional group. With these groups, however, it is not clear, which of the two carbon atoms has to be named as the functional one. A 1,3-diene, for example, could be considered as a 1,2-, 1,3-, or 1,4-difunctional compound. An a, -unsaturated ketone has a 1.2- as well as a 1,3-difunctional structure. We adhere to useful, although arbitrary conventions. Dienes and polyenes are separated out as a special case. a, -Unsaturated alcohols, ketones, etc. are considered as 1,3-difunctional. We call a carbon compound 1,2-difunctional only, if two neighbouring carbon atoms bear hetero atoms. 

The addition of acetylides to oxiranes yields 3-alkyn-l-ols (F. Sondheimer, 1950 M.A. Adams, 1979 R.M. Carlson, 1974, 1975 K. Mori, 1976). The acetylene dianion and two a -synthons can also be used. 1,4-Diols with a carbon triple bond in between are formed from two carbonyl compounds (V. Jager, 1977, see p. 52). The triple bond can be either converted to a CIS- or frans-configurated double bond (M.A. Adams, 1979) or be hydrated to give a ketone (see pp. 52, 57, 131). 

The enamine 315 as a carbon nucleophile reacts with 7r-allylpalladium complexes to give allyl ketones after hydrolysis[265],... 

By analogy to the hydration of alkenes hydration of an alkyne is expected to yield an alcohol The kind of alcohol however would be of a special kind one m which the hydroxyl group is a substituent on a carbon-carbon double bond This type of alcohol IS called an enol (the double bond suffix ene plus the alcohol suffix ol) An important property of enols is their rapid isomerization to aldehydes or ketones under the condi tions of their formation... 

Secondary amines are compounds of the type R2NH They add to aldehydes and ketones to form carbmolammes but their carbmolamme intermediates can dehydrate to a stable product only m the direction that leads to a carbon-carbon double bond... 

In the preceding chapter you learned that nucleophilic addition to the carbonyl group IS one of the fundamental reaction types of organic chemistry In addition to its own reactivity a carbonyl group can affect the chemical properties of aldehydes and ketones m other ways Aldehydes and ketones having at least one hydrogen on a carbon next to the carbonyl are m equilibrium with their enol isomers... 

Step 2 A water molecule acts as a Brpnsted base to remove a proton from the a carbon atom of the protonated aldehyde or ketone... 

Protonation of this anion can occur either at the a carbon or at oxygen Protonation of the a carbon simply returns the anion to the starting aldehyde or ketone Protonation of oxygen as shown m step 2 of Figure 18 3 produces the enol... 

Our experience to this point has been that C—H bonds are not very acidic Com pared with most hydrocarbons however aldehydes and ketones have relatively acidic protons on their a carbon atoms pA s for enolate formation from simple aldehydes and ketones are m the 16 to 20 range... 

A number of novel reactions involving the a carbon atom of aldehydes and ketones involve enol and enolate anion intermediates... 

Substitution of deuterium for hydrogen at the a carbon atom of an aldehyde or a ketone is a convenient way to introduce an isotopic label into a molecule and is readily carried out by treating the carbonyl compound with deuterium oxide (D2O) and base... 

Each act of proton abstraction from the a carbon converts a chiral molecule to an achi ral enol or enolate ion The sp hybridized carbon that is the chirality center m the start mg ketone becomes sp hybridized m the enol or enolate Careful kinetic studies have established that the rate of loss of optical activity of sec butyl phenyl ketone is equal to Its rate of hydrogen-deuterium exchange its rate of brommation and its rate of lodma tion In each case the rate determining step is conversion of the starting ketone to the enol or enolate anion... 

FIGURE 18 7 Nucleophilic addition to a p unsaturated aldehydes and ketones may take place either in a 1 2 or 1 4 manner Direct addition (1 2) occurs faster than conjugate addition (1 4) but gives a less stable product The product of 1 4 addition retains the carbon-oxygen double bond which is in general stronger than a carbon-carbon double bond... 

Esterification of carboxylic acids involves nucleophilic addition to the carbonyl group as a key step In this respect the carbonyl group of a carboxylic acid resembles that of an aldehyde or a ketone Do carboxylic acids resemble aldehydes and ketones m other ways Do they for example form enols and can they be halogenated at their a carbon atom via an enol m the way that aldehydes and ketones can ... 

The enol content of a carboxylic acid is far less than that of an aldehyde or ketone and introduction of a halogen substituent at the a carbon atom requires a different set... 

Like the carbonyl group of aldehydes and ketones the carbon of a C=0 unit m a carboxylic acid is sp hybridized Compared with the carbonyl group of an aldehyde or ketone the C=0 unit of a carboxylic acid receives an extra degree of stabilization from its attached OH group... 

Dialkylation of ethyl acetoacetate can also be accomplished opening the way to ketones with two alkyl substituents at the a carbon... 

Historically carbohydrates were once considered to be hydrates of carbon because their molecular formulas m many (but not all) cases correspond to C (H20) j It IS more realistic to define a carbohydrate as a polyhydroxy aldehyde or polyhydroxy ketone a point of view closer to structural reality and more suggestive of chemical reactivity... 

Carbon-carbon bond formation then occurs between the ketone carbonyl of acetoacetyl coenzyme A and the a carbon of a molecule of acetyl coenzyme A... 

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