Unsaturated Carbonyl Compounds Conjugate Addition

Chapter 27

a,P-Unsaturated Carbonyl Compounds Conjugate Addition

Structure and properties

• In general, a compound that contains both a carbon-carbon double bond and a carbon-oxygen double bond has properties that are characteristic of both functional groups. At the carbon-carbon double bond an unsaturated ester or unsaturated ketone undergoes electrophilic addition of acids and halogens, hydrogenation, hydroxylation, and cleavage; at the carbonyl group it undergoes the nucleophilic substitution typical of an ester or the nucleophilic addition typical of a ketone.

• In the a,0-unsaturated carbonyl compounds, the carbon-carbon double bond and the carbon-oxygen double bond are separated by just one carbon-carbon single bond; that is, the double bonds are conjugated. Because of this conjugation, such compounds possess not only the properties of the individual functional groups, but certain other properties besides. In this chapter we shall concentrate on the aj8-unsaturated compounds, and on the special reaction's characteristic of the conjugated.

Preparation

• There are several general ways to make compounds of this kind: the aldol condensation, to make unsaturated aldehydes and ketones; dehydrohalogenation of oc-halo acids and the Perkin condensation, to make unsaturated acids. Besides these, there are certain methods useful only for making single compounds. 

• All these methods make use of chemistry with which we are already familiar: the fundamental chemistry of alkenes and carbonyl compounds.

Interaction of functional groups

• We have seen (Sec. 6.11) that, with regard to electrophilic addition, a Carbon carbon double bond is activated by an electron-releasing substituent and deactivated Vy an electron-withdrawing substituent. The carbon-carbon double bond serves ks a source of electrons for the electrophilic reagent; the availability of its electrons is determined by the groups attached to it. More specifically, an electron-releasing substituent stabilizes the transition state leading to the initial carbonium ion by dispersing the developing positive charge; an electron-withdrawing substituent destabilizes the transition state by intensifying the positive charge.

• The O=O, COOH, COOR, and CN groups are powerful electron withdrawing groups, and therefore would be expected to deactivate a Carbon carbon double bond toward electrophilic addition. This is found to be true: a, Jb-unsaturated ketones, acids, esters, and nitriles are in general less reactive than simple alkenes toward reagents like bromine and the hydrogen.

• But this powerful electron withdrawal, which deactivates a carbon-carbon

• double bond toward reagents seeking electrons, at the same time activates toward

• reagents that are electron rich. As a result, the carbon-carbon double bond of an

• <x,j8-unsaturated ketone, acid, ester, or nitrile is susceptible to nucleophilic attack,

• and undergoes a set of reactions, nucleophilic addition, that is uncommon for the

simple alkenes. 

Electrophilic addition

• The presence of the carbonyl group not only lowers the reactivity of the carbon-carbon double bond toward electrophilic addition, but also controls the orientation of the addition.

• In general, it is observed that addition of an unsymmetrical reagent to an a,0-unsaturated carbonyl compound takes place in such a way that hydrogen becomes attached to the a-carbon and the negative group becomes attached to the 0-carbon. For example:

• Electrophilic addition to simple alkenes takes place in such a way as to form the most stable intermediate carbonium ion. Addition to a,j3-unsaturated carbonyl compounds, too, is consistent with this principle; to see that this is so, however, we must look at the conjugated system as a whole. As in the case of conjugated dienes (Sec. 8.20), addition to an end of the conjugated system is preferred, since these yields (step 1) a resonance-stabilized carbonium ion. Addition to the carbonyl oxygen end would yield carbonium ion 1; addition to the 0-cairbon end would yield carbonium ion II.

Nucleophilic addition

• Aqueous sodium cyanide converts, /?-unsaturated carbonyl compounds into 0-cyano carbonyl compounds. The reaction amounts to addition of the elements of HCN to the carbon-carbon double bond. For example:

• The nucleophilic reagent adds (step 1) to the carbon-carbon double bond to yield the hybrid anion I, which then accepts (step 2) a hydrogen ion from the solvent to yield the final product. This hydrogen ion can add either to the a-carbon or to oxygen, and thus yield either the keto or the enol form of the product; in either case the same equilibrium mixture, chiefly keto, is finally obtained.

Comparison of nucleophilic and electrophilic addition

• We can see that nucleophilic addition is closely analogous to electrophilic addition: (a) addition proceeds in two steps; (b) the first and controlling step is the formation of an intermediate ion; (c) both orientation of addition and reactivity are determined by the stability of the intermediate ion, or, more exactly, by the stability of the transition state leading to its formation; (d) this stability depends upon dispersal of the charge.

• The difference between nucleophilic and electrophilic addition is, of course, that the intermediate ions have opposite charges: negative in nucleophilic addition, positive in electrophilic addition. As a result, the effects of substituents are exactly opposite. Where an electron-withdrawing group deactivates a carbon-carbon double bond toward electrophilic addition, it activates toward nucleophilic addition. An electron-withdrawing group stabilizes the transition state leading to the formation of an intermediate anion in nucleophilic addition by helping to disperse the developing negative charge: 

 The Michael addition

• Of special importance in synthesis is the nucleophilic addition of carbanions to a,/?-unsaturated carbonyl compounds known as the Michael addition. Like the reactions of carbanions that we studied in the previous chapter, it results in formation of carbon-carbon bonds. For example:

The Diels-Alder reaction

• a^-Unsaturated carbonyl compounds undergo an exceedingly useful reaction with conjugated dienes, known as the Dette-Alder reaction. This is an addition reaction in which C-l and C-4 of the conjugated diene system become 

• to the doubly bonded carbons of the unsaturated carbonyl compound to form a six-membered ring. A concerted, single-step mechanism is almost certainly involved; both new carbon-carbon bonds are partly formed in the same transition state, although not necessarily to the same extent. The Delalande reaction is the most important example of cycloaddition, which is discuss d further in Sec. 29.9. Since reaction involves a system of 4 rr electrons (the diene) and a system of 2 it electrons (the dienophile), it is known as a [4 + 2] cycloaddition.

• The Diels-Alder reaction is useful not only because a ring is generated, but also because it takes place so readily for a wide variety of reactants. Reaction is favored by electron-withdrawing substituents in the dienophile, but even simple alkenes can react. Reaction often takes place with the evolution of heat when the reactants are simply mixed together. A few examples of the Diels-Alder reaction are:

Quinoes

• a,-Unsaturated ketones of a rather special kind are given the name of quinones: these are cyclic diketones of such a structure that they are converted by reduction into hydroquinone's, phenols containing two OH groups. For example:

• Because they are highly conjugated, quinones are colored; /?-benzoquinone, for example, is yellow.

• Also because they are highly conjugated, quinones are rather closely balanced, energetically, against the corresponding hydroquinone's. The ready interconversion provides a convenient oxidation-reduction system that has been studied intensively. Many properties of quinones result from the tendency to form the aromatic hydroquinone system.

• Quinones some related to more complicated aromatic systems (Chap. 30) have been isolated from biological sources (molds, fungi, higher plants). In many cases they seem to take part in oxidation-reduction cycles essential to the living organism.