Carbanions carbonyl addition reactions

In reactions in which separated ion pairs are involved, e.g., R4N+, K or Na +, and as a borderline case, Li +, the cation does not contribute to the adjustment of the reaction partners in a dense, well-ordered transition state poor selcctivities arc usually the result of these carbanionic carbonyl additions. Further, the high basicity of such carbanionic species may cause decomposition or racemization of sensitive reactions partners. 

D. M. Huryn, Carbanions of Alkali and Alkaline Earth Cations (ii) Selectivity of Carbonyl Addition Reactions, in Comprehensive Organic Synthesis (B. M. Trost, I. Fleming, Eds.), Vol. 1, 49, Pergamon Press, Oxford, 1991. 

Alkyltitanium complexes can be obtained from metal carbanions via titanation. Introduction of chirality at the titanium center or on the ligand (or a combination of both) (Sch. 2) enables the possibility of asymmetric induction in the carbonyl addition reaction. 

Carbanions of Alkali and Alkaline Earth Cations (II) Selectivity of Carbonyl Addition Reactions... 

Evidence for a radical coupling mechanism (as opposed to a carbanionic carbonyl addition mechanism) in the intramolecular Smh-promoted Barbier reactions has come from studies on appropriately functionalized substrates in the 3-keto ester series. It is well known that heterosubstituents are rapidly eliminated when they are adjacent to a carbanionic center. Indeed, treatment of a 3-methoxy organic halide (suitably functionalized for cyclization ) with an organolithium reagent leads only to alkene (equation 48). No cyclized material can be detected. On the other hand, treatment of the same substrate with Sml2 provides cyclized product and a small amount of reduced alcohol, with none of the alkene detected by gas chromatographic analysis (equation 49). ... 

Although the reaction of hydroxide or alkoxide ions with carbonyl compounds to abstract a proton from a carbon atom adjacent to the carbonyl group is thermodynamically unfavourable, and the equilibria in reactions such as (4.11) and (4.12) lie well over to the left, the high reactivity of the carbanion intermediates formed makes reactions of this type of vital importance in a number of cases, especially in halogenation (reaction 4.14) and in some carbonyl addition reactions, e.g. reactions (4.20) and (4.30). 

In addition reactions to chiral carbonyl compounds, the stereochemical course taken by resonance-stabilized alkali metals or magnesium benzyl anions resembles that taken by localized carbanions of similar bulk. Thus, conditions can be delineated which lead to either the steric approach or chelation control the following serve as examples. 

The addition reaction of enolates and enols with carbonyl compounds is of broad scope and of great synthetic importance. Essentially all of the stabilized carbanions mentioned in Section 1.1 are capable of adding to carbonyl groups, in what is known as the generalized aldol reaction. Enolates of aldehydes, ketones, esters, and amides, the carbanions of nitriles and nitro compounds, as well as phosphoms- and sulfur-stabilized carbanions and ylides undergo this reaction. In the next section we emphasize the fundamental regiochemical and stereochemical aspects of the reactions of ketones and aldehydes. 

Nucleophilic additions to carbonyl groups lead to alcohols which on dehydration, furnish alkenes70,71. This two-step protocol has been extremely useful for diene and polyene synthesis with wide variation in the carbonyl substrate and the nucleophilic addendum. Diene synthesis using aldol-type condensation as well as phenyl sulphonyl carbanion (the Julia reaction) are also discussed in this section. 

The acetylacetone carbanion undergoes addition to the imine carbon atom of complex (92) but subsequent cyclization and deacylation processes occur (Scheme 42).212 The apical ammonia group is the most acidic and consequently is favoured to cyclize on to the carbonyl group. In the bis-(1,2-diaminoethane) complex related to the imine chelate (92), the two apical nitrogen atoms are no longer geometrically equivalent. Thus two products are formed when hydrogen cyanide is added to the complex and subsequent cyclization takes place (Scheme 43).213 However, the cyclization reaction is stereoselective. 

In general, the mechanisms of nucleophilic additions to double bonds have not been as much studied or systemized as those of electrophilic addition. Reactions 7.51 and 7.52 are examples of the very useful Michael condensation, in which a carbanion adds to an a,/ -unsaturated carbonyl or nitrile compound. The usefulness of these reactions arises from the fact that the number of ways of building longer carbon chains from smaller ones is limited. 

Intramolecular addition reactions of carbanions to a carbonyl group. 

Unlike previous alkyne-aldehyde additions [23], the generation of an alkynyl carbanion is unlikely owing to the large pK, difference between the terminal acetylene and the solvent water [24]. A mechanism was proposed involving the simultaneous activation of the C-H bond of alkyne by the ruthenium catalyst and the aldehyde carbonyl by the indium ion. The ruthenium intermediate then underwent Grignard-type addition followed by an in situ hydrolysis in water to give the desired carbonyl addition product and regenerated the ruthenium and indium catalysts to catalyze further reactions (Fig. 3). 

The carbanions being electron rich behave like nucleophiles and add to the carbonyl group, for example, aldol condensation (see Chapter 3 for the addition reactions of carbanion to the carbonyl group) (Scheme 2.18). 

Stereoselective formation of the C—Sn bond is usually observed in the addition of a trialkylstan-nyl anion to a C-C double bond or carbonyl group. Reactions are also described where a new C—Sn bond is stereoselectively formed via migration of the stannyl group or by stannylation of a chiral carbanion. 

---