Electrophilicity carbonyl halides

The prime functional group for constructing C-C bonds may be the carbonyl group, functioning as either an electrophile (Eq. 1) or via its enolate derivative as a nucleophile (Eqs. 2 and 3). The objective of this chapter is to survey the issue of asymmetric inductions involving the reaction between enolates derived from carbonyl compounds and alkyl halide electrophiles. The addition of a nucleophile toward a carbonyl group, especially in the catalytic manner, is presented as well. Asymmetric aldol reactions and the related allylation reactions (Eq. 3) are the topics of Chapter 3. Reduction of carbonyl groups is discussed in Chapter 4. 

Synthesis Bromination of butanone in acid gives predominantly the isomer we want, (see frames 198-201 of the Carbonyl Programme) and again the reactive a-carbonyl halide is a good electrophile ... 

These ligand have already been met (Chapter 3), including the three key synthetic routes migratory insertion of o-organyl/carbonyl complexes, electrophilic attack at electron rich metals by acyl halides or anhydrides and nucleophilic attack at coordinated CO (Figure 4.12). 

Deviating from the route via nucleophilic attack of the carbanion at the carbon atom of a CO ligand and then reaction of the acylmetallate with an electrophile are those methods which involve (a) addition of the carbanion to the carbon atom of a carbyne ligand, (b) displacement of halides from transition-metal carbonyl halides by cyclohepta-trienyllithium, or derivatives thereof, followed by hydride abstraction or (c) substitution of a coordinated solvent from a metal-carbonyl complex (see also reaction of LiR with carbene complexes). 

In the Sections above, various aspects of the electronic structure of the carbonyl halides have been discussed in some detail, and it is now appropriate to consider what insight this knowledge yields concerning their chemical reactivity. In particular, their reactivity towards nucleophilic and electrophilic substitutions will be examined. 

Thus, on the very limited data set available, it would appear that the formal positive charge at the carbon (see Fig. 17.7) is more important in determining the electrophilic reactivity of a carbonyl halide than the absolute energy of the x (CO) orbital. 

These compounds generally exist in carbonyl forms. The oxygen function can be converted into halogen by phosphorus halides. Reactions with electrophiles are quite complex. Thus urazole (511) reacts with diazomethane quickly to yield (512), which is more slowly converted into (513). 1-Phenylurazole gives (514) however, 4-phenylurazole yields (515). Oxadiazolinones of type (516) can be alkylated at both O- and N-atoms. 

The behavior of such activated halides as alkylating agents under Friedel-Crafts conditions expands the scope of the synthesis. Aluminum chloride enhances the electrophilic character of the a,/S-unsaturated carbonyl system and permits the nucleophilic attachment of the aromatic addendum (Y ) to the carbon bearing the positive charge, with displacement of halogen [Eq. (5)]. Thus,... 

The benzodithiepines 126 and 127 have been used as formyl and acyl anion equivalents, respectively, although the range of electrophiles was restricted to alkyl halides (75S720) and epifluorohydrin (72TL1837). The carbonyl products were formed by hydrolysis with either mercury or copper salts. 

There is no simple answer to this question, but the exact experimental conditions usually have much to do with the result. Alpha-substitution reactions require a full equivalent of strong base and are normally carried out so that the carbonyl compound is rapidly and completely converted into its enolate ion at a low temperature. An electrophile is then added rapidly to ensure that the reactive enolate ion is quenched quickly. In a ketone alkylation reaction, for instance, we might use 1 equivalent of lithium diisopropylamide (LDA) in lelrahydrofuran solution at -78 °C. Rapid and complete generation of the ketone enolate ion would occur, and no unreacled ketone would be left so that no condensation reaction could take place. We would then immediately add an alkyl halide to complete the alkylation reaction. 

Iron-acyl enolates such as 1, 2, and 3 react readily with electrophiles such as alkyl halides and carbonyl compounds (see Houben-Weyl, Vol. 13/9a p418). The reactions of these enolatc species with alkyl halides and similar electrophiles are discussed in Section D.1.1.1.3.4.1.3. To date, only the simple enolates prepared by a-deprotonation of acetyl and propanoyl complexes have been reacted with ketones or aldehydes. 

The decarboxylation reaction usually proceeds from the dissociated form of a carboxyl group. As a result, the primary reaction intermediate is more or less a carbanion-like species. In one case, the carbanion is stabilized by the adjacent carbonyl group to form an enolate intermediate as seen in the case of decarboxylation of malonic acid and tropic acid derivatives. In the other case, the anion is stabilized by the aid of the thiazolium ring of TPP. This is the case of transketolases. The formation of carbanion equivalents is essentially important in the synthetic chemistry no matter what methods one takes, i.e., enzymatic or ordinary chemical. They undergo C—C bond-forming reactions with carbonyl compounds as well as a number of reactions with electrophiles, such as protonation, Michael-type addition, substitution with pyrophosphate and halides and so on. In this context,... 

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. 

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