Similarly, silylenol ethers generated from ketones may also be used as the nucleophilic partner in aldol reactions. The silylenol ether can be prepared from its parent carbonyl compound by forming a small equilibrium concentration of enolate ion with weak base such as a tertiary amine and trapping the enolate with the very efficient oxygen electrophile (CH3)3SiCl. The silylenol ether is stable enough to be isolated but is usually used immediately without storing. Lewis acid catalyst is needed to get the aldol reaction to work, and a Ti(IV) compound such as TiCl4 is the most popular (Scheme 7).
Scheme 7
In this reaction, the aldehyde presumably coordinates with the Lewis acid TiCl4 which then undergoes a nucleophilic attack by the silylenol ether to form the aldol product (Scheme 8). The reaction pathway probably involves a six membered cyclic transition state as shown below.
Scheme 8
6.2.2.8 Benzoin Condensation
A reaction similar in nature with the aldol reaction but occurs in the presence of a very concentration of base and with substrates lacking an α-H like benzaldehyde, formaldehyde etc. This reaction involves a hydride transfer from one molecule of aldehyde to other leading to an overall disproportionation where one molecule of aldehyde is oxidized to carboxylic acid where as the other is reduced to an alcohol (Scheme 9).
Scheme 9
Aromatic aldehydes in the presence of catalytic amount of cyanide as a nucleophile may undergo benzoin condensation where cyanide first attacks a molecule of aldehyde to form an intermediate. Next, an intramolecular hydride transfer takes place followed a carbanionic attack on another aldehyde molecule. The intermediate so formed undergoes elimination of cyanide to form α-hydroxyketone (Scheme 10).
Scheme 10
Cyanide is considered ideal for catalysing this reaction due to (1) its ability to act as a nucleophile, (2) its ability to act as a leaving group and (c) its ability through electron withdrawal to increase the acidity of the C-H bond and to stabilize the carbanion.
When benzaldehyde is used as reactant in the above reaction the product is called benzoin and hence the reaction has been named benzoin condensation. These α-hydroxyketones may be easily oxidized to the 1,2-diketones which under the action of hydroxylic base undergo rearrangement to form benzilic acid (Scheme 11).
Scheme 11
6.2.2.9 Wittig Reaction
The Wittig reaction is one of the most important reactions of the carbonyl group and is an important synthetic route to alkenes. It involves the addition of a phosphonium ylide to a carbonyl group of an aldehyde or a ketone. The ylide is actually a carbanion having an adjacent heteroatom. Such species are generated by the reaction of an alkyl halide and triaryl phosphine to yield a salt followed by abstraction of a proton from it by a very strong base (Scheme 12).
Scheme 12
The Wittig reagent or ylide then reacts with the carbonyl compound to probably form a oxaphosphatene intermediate which undergo elimination to generate the alkene (Scheme 13).
Scheme 13