Addition to carbon-oxygen double

Protonation of the enolate ion is chiefly at the oxygen, which is more negative than the carbon, but this produces the enol, which tautomerizes. So, although the net result of the reaction is addition to a carbon-carbon double bond, the mechanism is 1,4 nucleophilic addition to the C=C—C=0 (or similar) system and is thus very similar to the mechanism of addition to carbon-oxygen double and similar bonds (see Chapter 16). When Z is CN or a C=0 group, it is also possible for Y to attack at this carbon, and this reaction sometimes competes. When it happens, it is called 1,2 addition. 1,4 Addition to these substrates is also known as conjugate addition. The Y ion almost never attacks at the 3 position, since the resulting carbanion would have no resonance stabilization " ... 

Furthermore, the data from Table 2 allow us to draw several valuable conclusions regarding the mechanism of hydride addition to carbon-oxygen double bonds. 

Carbanions frequently add to the carbonyl double bond. The aldol reaction, Claisen reaction, Dieckmann reaction, Michael reaction, and Knoevenagel condensation are familiar examples of carbanions (as enolates) undergoing nucleophilic addition to carbon-oxygen double bonds. 

As a nucleophile, a carbanion can react readily with a carbon atom bearing a good leaving group, which is a useful method for forming new carbon-carbon bonds. The aldol reaction and the Claisen condensation are familiar examples of carbanions (tis enolates) undergoing nucleophilic addition to carbon-oxygen double bonds. Carbanions may also act as nucleophiles in Sn2 reactions. The reaction of phenylacetic acid (90) with sodium in liquid ammonia leads to a carbanion (91) that reacts with benzyl chloride to produce 23-diphenylpropionic acid (92, equation 5.66). ... 

Many nucleophilic additions to carbon-oxygen double bonds are reversible the overall results of these reactions depend, therefore, on the position of an equilibrium. 

Carbon-sulphur double bonds also undergo nucleophilic attack in a similar fashion to carbon-oxygen double bonds except in the cases of thiophilic addition, where the nucleophile selectively attacks the sulphur56 (Scheme 9). 

Summary of addition reactions to carbon/oxygen double bonds... 

Almost this entire chapter involves additions of nucleophiles to carbon-oxygen double bonds. Many of these reactions are reversible, others are not. It is the reversible reactions that trouble students most, because there seems to be a bewildering array of additions, proton transfers, and ehminations. So there is, but keep your wits about you, and you U learn to push those protons and waters around properly. 

By far the hardest thing about this chapter is the all-too-plentiful detail. To get this material under control it is absolutely necessary to be able to generalize. The easiest mistake to make is to memorize the details and lose the broad picture. Although there is one general principle in this chapter (nucleophiles add to carbon-oxygen double bonds), it is easy to get lost in the myriad protonation, addition, and deprotonation steps. The reversible addition reactions of this chapter are the hardest to keep... 

In this chapter, we explore the chemistry of the a position in the carbonyl compounds we met in Chapters 16-18. Our ability to understand complex reactions and to construct complicated molecules will greatly increase. There really is little fundamentally new chemistry—much of what we find from now on will be applications of reactions we already know, placed in more complicated settings. For example, in Chapter 16 we saw a vast array of additions of nucleophiles to carbon-oxygen double bonds. Here that same reaction appears, when a new nucleophile, an enolate, adds to carbonyl groups to yield products of increased complexity. The reaction is the same old addition, but the context makes it look complicated (Fig. 19.1). 

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... 

Both the carbon-carbon and carbon-oxygen double bonds of fluoroketenes can take part in [2+2] cycloadditions, but with cyclopentadiene, only cyclo butanones are produced via concerted [2 +2 ] additions [J34] (equation 58) Cycloadditions involving the carbon-oxygen double bonds to form oxetanes are discussed on page 855 Difluoroketene is veiy short lived and difficult to intercept but has been trapped successfully by very electron rich addends to give 2 2 di fluorocyclobutanones m moderate yields [/55] (equation 59)... 

The most common reaction of aldehydes and ketones is the nucleophilic addition reaction, in which a nucleophile, Nu , adds to the electrophilic carbon of the carbonyl group. Since the nucleophile uses an electron pair to form a new bond to carbon, two electrons from the carbon-oxygen double bond must move toward the electronegative oxygen atom to give an alkoxide anion. The carbonyl carbon rehybridizes from sp2 to sp3 during the reaction, and the alkoxide ion product therefore has tetrahedral geometry. 

When a carbonyl group is bonded to a substituent group that can potentially depart as a Lewis base, addition of a nucleophile to the carbonyl carbon leads to elimination and the regeneration of a carbon-oxygen double bond. Esters undergo hydrolysis with alkali hydroxides to form alkali metal salts of carboxylic acids and alcohols. Amides undergo hydrolysis with mineral acids to form carboxylic acids and amine salts. Carbamates undergo alkaline hydrolysis to form amines, carbon dioxide, and alcohols. 

Active Substrate. If a new stereogenic center is ereated in a molecule that is already optically active, the two diastereomers are not (except fortuitously) formed in equal amounts. The reason is that the direction of attack by the reagent is determined by the groups already there. For certain additions to the carbon-oxygen double bond of ketones containing an asymmetric a carbon. Cram s rule predicts which diastereomer will predominate (diastereo-selecti vity). ... 

The addition of a negative ion to a carbon-oxygen double bond does not give a carbanion, since the negative charge resides on the oxygen. 

This comparison suggests that of these two similar reactions, only alkene additions are likely to be a part of an efficient radical chain sequence. Radical additions to carbon-carbon double bonds can be further enhanced by radical stabilizing groups. Addition to a carbonyl group, in contrast, is endothermic. In fact, the reverse fragmentation reaction is commonly observed (see Section 10.3.6) A comparison can also be made between abstraction of hydrogen from carbon as opposed to oxygen. 

The description of the carbon-oxygen double bond is analogous, but in addition to the cr-bonds there are unshared pairs of electrons on oxygen so that two excited states are possible, n-n and n-n. For n-n excitation the resultant half-vacant orbital on oxygen should possess electrophilic reactivity, and the electron rich -system should have nucleophilic characteristics. 62>... 

Certain electrophilic carbon-carbon and carbon-oxygen double bonds can undergo an addition reaction with alkenes in which an allylic hydrogen is transferred to the... 

Addition reactions occur in compounds having n electrons in carbon-carbon double (alkenes) or triple bonds (alkynes) or carbon-oxygen double bonds (aldehydes and ketones). Addition reactions are of two types electrophilic addition to alkenes and alkynes, and nucleophilic addition to aldehydes and ketones. In an addition reaction, the product contains all of the elements of the two reacting species. 

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