Carbanion addition

A variety of ring syntheses have been devized which depend on carbanion addition to an activated double bond. The examples depicted in Scheme 74 illustrate the use of inter alia cyano and nitro groups which are subsequently eliminated. In appropriate instances the inclusion of additional eliminable groups ensures the formation of fully aromatized products. 

For carbanionic addition, the relative negative charge and the electron densities in the 1- and 3-position in the HOMO of the ambident allylic anion determine, in addition to steric effects, the regioselectivity of the hydroxyalkylation. According to the allopolarization principle13 the following generalizations can be made ... 

Carbanionic additions usually do not provide significant simple synjanti diastereoselectivities. The EjZ geometry is determined by the configuration of the reacting ally lie carbanion. The attack at position 3 conserves the configuration of the 1,2-partial double bond and vice versa. 

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,... 

We have already discussed carbanion addition to RC02Et (Claisen ester condensation, p. 229), and also their reduction by Li AlH4e (p. 214) some further examples of nucleophilic attack will now be considered. 

We have already discussed a large group of reactions in which carbanions add to the C=0 group (cf. pp. 221-234), including examples of intramolecular carbanion addition, e.g. an aldol reaction (p. 226), Dieckmann reaction (p. 230), and the benzilic acid rearrangement (p. 232), and also to the C=C—C=O system, the Michael reaction... 

The ylid intermediate (50) can be trapped by carrying out the decarboxylation in the presence of carbonyl compounds, e.g. PhCOMe, to yield the carbanion addition product, e.g. (52) this process can indeed be used preparatively. The reason for the much easier decarboxylation of (51), than of its 3-, and 4-isomers, is the stabilisation that the N can effect on the adjacent carbanion carbon atom in the intermediate ylid (50). 

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... 

In the absence of a proton donor, the alkoxide ion generated by carbanion addition to the carbonyl function can interact with a carbon-halogen bond in the 8 2 displacement reaction. Reactions of this type have led to some novel carbon chain forming processes. Ketones are converted to homologated enones in good yield by... 

The reactions to be discussed in this section involve carbanion addition to carbonyl centers with a potential leaving group. The tetrahedral intermediate formed in the addition step then reacts by expulsion of the leaving group. The overall transformation results in the... 

The 1,2,5-thiadiazole-l-oxide (335) when treated with a strong base in refluxing xylene gave the 1,2,4-thiadiazole (337) in low yield. The reaction is thought to proceed by carbanion addition to a sulfinylamine intermediate (33(6) (Scheme 74) <86H(24)l 193). 

Markl, Lieb and Merz have described the carbanionic addition of lithium or magnesium organometallic compounds to the P atom of 2.4.6-triphenyl-X -phos-phorins, which form deep red s ts 143. These can be alkylated either at the P atom to form X -phosphorins 144 or at C—2 to yield 1,2-dihydro-X -phosphorins 145. Acylation with benzoylchloride affords the 1,4-dihydro-X -phosphorin derivatives 146. Addition of acids or water leads to the synthetically important intermediates 147 which can be reconverted to the X -phosphorin-salts 143 by 2 N NaOH. 

Not only can the a-methylene carbanion be produced and stabilized, but it can also undergo base-catalyzed aldol-type reactions without decomposition of the chelate ring. The most-studied reactions involve carbanion additions to acetaldehyde to produce threonine and allothreonine. This can be achieved for bis(glycinato)copper(II),48,49 tris(glycinato)cobalt(III)50,51 or glycinato-bis(l,2-diaminoethane)cobalt(III),52 with the best yield being obtained in the last case, where the... 

Examples of carbanion additions to cobalt-coordinated imines will be considered in the next section (7.4.3.2) as chelate ring formation is a consequence in some cases. 

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