Addition-Elimination Reactions of Aldehydes and Ketones

The mechanistic picture established by study of hydration and alcohol addition reactions sets a pattern that will be evident in a number of other carbonyl reactions. The initial step is usually nucleophilic addition to the carbonyl group. This can be acid-catalyzed or base-catalyzed. Other reactions of carbonyl groups branch out mechanistically from this common nucleophilic addition step, and differ primarily in the fate of the addition intermediate. 

There are other examples of processes that replace the C=0 bond with a C=C bond. These reactions will be discussed primarily in Part B, Chapter 2. 

The hydrolysis of simple imines occurs readily in aqueous acid, and has been studied in great detail by kinetic methods. The precise mechanism is a function of the reactant structure and the pH of the solution. The overall mechanism consists of an addition of water to the C=N bond, followed by expulsion of the amine from a tetrahedral intermediate.  

The relative rates of the various steps are a function of the pH of the solution and the basicity of the imine. In the alkaline range, the rate-determining step is usually 

Complete understanding of the shape of the curves in Fig. 8.1 requires a kinetic expression somewhat more complicated than we wish to deal with here. The nature 

The mechanistic pattern established by study of hydration and alcohol addition reactions of ketones and aldehydes is followed in a number of other reactions of carbonyl compounds. Reactions at carbonyl centers usually involve a series of addition and elimination steps proceeding through tetrahedral intermediates. These steps can be either acid-catalyzed or base-catalyzed. The rate and products of the reaction are determined by the reactivity of these tetrahedral intermediates. 

In general terms, there are three possible mechanisms for addition of a nucleophile and a proton to give a tetrahedral intermediate in a carbonyl addition reaction. 

There are examples of each of these mechanisms, and a three-dimensional potential energy diagram can provide a useful general framework within which to consider specific addition reactions. The breakdown of a tetrahedral intermediate involves the same processes but operates in the opposite direction, so the principles that are developed will apply equally well to the reactions of the tetrahedral intermediates. Let us examine the three general mechanistic cases in relation to the energy diagram in Fig. 8.3. 

Complete understanding of the shapes of the curves in Fig. 8.4 requires a kinetic expression somewhat more complicated than we wish to deal with here. The nature of the extremities of the curves can be understood, however, on the basis of qualitative arguments. The rate decreases with a decrease in pH in the acidic region because formation of the zwitterionic tetrahedral intermediate is required for expulsion of the 

A) Protonation followed by nucleophilic attack on the protonated carbonyl 

B) Nucleophilic addition at the carbonyl group followed by protonation  

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SECTION 8.2. ADDITION-ELIMINATION REACTIONS OF KETONES AND ALDEHYDES... 

Scheme 8.2. Addition-Elimination Reactions of Aldehydes and Ketones...

In Section 7.7.2 we met enamines as products from addition-elimination reactions of secondary amines with aldehydes or ketones. Enamines are formed instead of imines because no protons are available on nitrogen for the final deprotonation step, and the nearest proton that can be lost from the iminium ion is that at the P-position. 

The methylenation of ketones and aldehydes by the Wittig reaction is a well-established and selective methodology. Unlike addition-elimination methods of alkene formation, the Wittig proceeds in a defined sense, producing an alkene at the original site of the carbonyl. The Wittig reaction is not considered here, but is used as the standard by which the methods discussed are measured. The topics covered in the methylenation sections include the Peterson alkenation, the Johnson sulfoximine approach, the Tebbe reaction and the Oshima-Takai titanium-dihalomethane method. 

Some addition-elimination reactions of aldehydes and ketones... 

Recent developments in this area have considerably expanded the scope of the process to include a wide range of ketone and aldehyde components [98-100). Direct proline-catalyzed cross-coupling aldol reactions from ketones (Equation 16) [98] and aldehydes (Equation 17) [101] have been reported. Moreover, domino processes are possible thus, the proline-catalyzed aldol addition reaction of acetaldehyde proceeds through a double aldol addition and elimination to give useful building blocks for asymmetric synthesis (Equation 18) [100], As with any catalytic process, these processes are in essence multivariable problems, consisting of multiple steps and reactive intermediates, the reactivities and stabilities of which are finely balanced. 

The reactions of complex 2a with ketones and aldehydes show a strong dependence on the substituents. With benzophenone, substitution of the silyl-substituted acetylene leads to the r]2-complex 58, which is additionally stabilized by a THF ligand. This complex can serve as an interesting starting material for other reactions. With benzaldehyde and acetophenone, the typical zirconadihydrofuran 59, akin to 2c, is obtained from a coupling reaction. This complex is unstable in the case of benzaldehyde and dimerizes, after elimination of bis(trimethylsilyl)acetylene, to yield 60. In this respect, it is similar to the above discussed complex 2c, since both of them show a tendency to eliminate the bis(trimethyl-silyl)acetylene. The reaction of methacrolein with complex 2a depends strongly on the solvent used [40]. 

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