Aldehydes carbanion addition

The strategies presented in Table 8.1 can be generalized in the following manner (1) carbanion addition to aldimine or ketimine derivatives (2) sequential amination-alkylation of aldehydes (carbanion addition to in situ formed aldimine derivatives) (3) transfer hydrogenation or hydrogenation of imines (4) reductive amination of ketones and (5) N-acetylenamide reduction. Because of the difficulty of their synthesis, a-alkyl,-alkyl substituted amines are highlighted whenever possible. 

Crossed aldol condensations, where both aldehydes (or other suitable carbonyl compounds) have a-H atoms, are not normally of any preparative value as a mixture of four different products can result. Crossed aldol reactions can be of synthetic utility, where one aldehyde has no a-H, however, and can thus act only as a carbanion acceptor. An example is the Claisen-Schmidt condensation of aromatic aldehydes (98) with simple aliphatic aldehydes or (usually methyl) ketones in the presence of 10% aqueous KOH (dehydration always takes place subsequent to the initial carbanion addition under these conditions) ... 

This reaction of aromatic aldehydes, ArCHO, resembles the Cannizzaro reaction in that the initial attack [rapid and reversible—step (1)] is by an anion—this time eCN—on the carbonyl carbon atom of one molecule, the donor (125) but instead of hydride transfer (cf. Cannizzaro, p. 216) it is now carbanion addition by (127) to the carbonyl carbon atom of the second molecule of ArCHO, the acceptor (128), that occurs. This, in common with cyanohydrin formation (p. 212) was one of the earliest reactions to have its pathway established— correctly —in 1903. The rate law commonly observed is, as might be expected,... 

OH—on the adjacent (/ -) carbon atom. The possibility of such an elimination may displace the equilibrium over to the right in a number of simple aldol additions, where it would otherwise lie far over to the left. It is important to remember, however, that the overall process aldol addition + dehydration is reversible, i.e. (88) 4= (96), and that a -unsaturaled carbonyl compounds are thus cleaved by base under suitable conditions. It is also pertinent that (96) is still an aldehyde and can undergo further carbanion addition, followed by dehydration, and so on. This is how low molecular weight polymers are produced on heating simple aliphatic aldehydes with aqueous NaOH to stop at the aldol, the best catalysts are basic ion-exchange resins. 

The formation of this product need not concern us, hut its nature is important, in that it contains the equivalent of R or Ar , i.e. the alkyl or aryl group has been transformed into its carbanion. Addition of an aldehyde or ketone to the solution of the Grignard reagent allows a nucleophilic addition reaction to occur. The reaction resembles that of... 

A few examples of chemoselective additions of allyltitanium reagents to aliphatic and aromatic carbonyl compounds are reported in Table 7. Appreciable chemoselectivity toward the aldehydic function is achieved by the titanium ate conqtlex (23), whereas the reverse chemoselectivity toward ketones is realized using aminotitanium complex (104) and the analogous ate complexes (24) and (25), as is shown in Table 7. This is very interestii since it represents a rare case of chemoselectivity in favor of carbanion addition to ketones. A tentative explanation of this inverse chemoselection considers a fast transfer of the aminyl ligand onto the aldehyde function which becomes protected , as in (105), and thus unreactive in respect to the keto group. Ketones react also selectively compared with esters, as is shown by the reaction of ethyl levulinate (1) with the ate complex (23 equation 40). ... 

The effect of substituents in the benzene ring provides an interesting example of the dual nature of carbanion addition to carbonyl groups. When an electron-releasing group is conjugated with the aldehyde function, a resonance form such as (XIV) apparently lowers the usual positive charge on the carbonyl carbon atom to a point where the addition... 

The method may be of interest because it uses the least expensive chiral ammonia equivalent available (Table 8.2) in essentially equimolar quantities (1.05 equiv) as compared to the limiting reagent, the aldehyde. Additionally, this one-pot process has significant yield advantages over the two-step process (formation of the (R)- or (S)-N-a-methylbenzyl aldimine, isolation of this chiral aldimine, followed by carbanion addition). The reactions are fast (3 h at -78°C), but the low temperature requirements, low reactor volume to product ratio, and the need for 3 equiv of a cuprate (CuBr based) will be considered restrictive. Many times the cuprate can be reduced to 2.0 equiv... 

Since in the interfacial region carbanions are of low activity and low quantity, they can react only with very active electrophiles. Thus, formation of lipophilic ion pairs via ion exchange with TAA salts, which is a diffusion-controlled process, proceeds efficiently as a step in the PTC reactions. The carbanions in the interfacial region can also react with other very active electrophiles such as aldehydes. Since addition of carbanions to aldehydes is a reversible process, completion of the reaction in the interfacial region requires further rapid... 

Coupling reactions have also been carried out in a reversal of the imine strategy, by adding a carbanion to an appropriate aldehyde. Thus addition of anion 7.4.21 to acrolein gave racemic adduct 7.4.22 which could be protected, oxidized, and resolved with (+)-ephedrine to give the protected acids 7.4.23 and 7.4.24 (275). 

Aldol-type condensation of an aromatic aldehyde with activated methylarene or phenylacetic acid is a useful reaction for preparing stilbene derivatives. Starting from para-substituted toluenes or para-substituted aromatic aldehydes, one can obtain 4,4 -disubstituted stilbenes. This reaction is relatively simple but has low yield. As an example, condensation of 2,4-dinitrotoluene and 4-nitrophenylacetic acid with aromatic aldehyde was studied [26]. The reaction involves carbanion addition to the carbonyl group. The carbanion is formed by the extraction of proton from the active methylene group of 2,4-dinitrotoluene by the base (usually, piperidine). The carbanion then adds to carbon atoms of the carbonyl group of the aldehyde. The reaction will therefore be facilitated by the ease of both the formation of the... 

An important feature of aldol addition is that carbon-carbon bond formation occurs between the a carbon atom of one aldehyde and the carbonyl group of another This is because carbanion (enolate) generation can involve proton abstraction only from the a carbon atom The overall transformation can be represented schematically as shown m Figure 18 5... 

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