Enolate anions, homoenolates

The o-complexes generated by oxidative addition of haloarenes and haloalkenes to paUadium(O) are electrophilic at the metal-substituted center and can therefore react with nucleophiles other than alkenes, especially with enolate and homoenolate ions to form new C-C bonds [331, 332]. This reaction mode has been termed anion capture [333]. 

The synthetic use of acylsilanes depends to a large extent on the ease of migration of Si to an alternative site in the molecule after addition of a suitable nucleophile. For instance, enolate anions add to the carbonyl carbon atom of a-chloroacyltrimethylsilanes, the McsSi unit migrating to the a-C atom with displacement of Cl. In this case, the product can be desilylated to give a /8-diketone. Alternatively, the Si can migrate to the carbonyl O atom, as in Scheme 14, where either a homoenolate ion is set up for further alkylation or, in the case of 2-furyl-lithium addition, the furyl ring opens to give a cumulated dienolate system. 

Abstract The discovery and development of new A-heterocyclic carbene-catalyzed reaction is described. Based on inspiration from nature, we have taken thiazolium-based approaches to umpolung reactivity and invented a suite of related reactions involving acyl anions, homoenolate, and enolate nucleophiles all generated under catalytic conditions. 

Allyl anion synthons A and C, bearing one or two electronegative hetero-substituents in the y-position are widely used for the combination of the homoenolate (or / -enolate) moiety B or D with carbonyl compounds by means of allylmetal reagents 1 or 4, since hydrolysis of the addition products 2 or 5 leads to 4-hydroxy-substituted aldehydes or ketones 3, or carboxylic acids, respectively. At present, 1-hetero-substituted allylmetal reagents of type 1, rather than 4, offer the widest opportunity for the variation of the substitution pattern and for the control of the different levels of stereoselectivity. The resulting aldehydes of type 3 (R1 = H) are easily oxidized to form carboxylic acids 6 (or their derivatives). 

Just as anions of allyl derivatives can be homoenolate equivalents (chapter 13) so anions of vinyl derivatives can be acyl anion equivalents. Vinyl (or enol) ethers can be lithiated reasonably easily, especially when there is no possibility of forming an allyl derivative, as with the simplest compound 81. The most acidic proton is the one marked and the vinyl-lithium derivative 82 reacts with electrophiles to give the enol ether of the product17 84. However, tertiary butyl lithium is needed and compounds with y-CHs usually end up as the chelated allyl-lithium 85. These vinyl-lithium compounds add directly to conjugated systems but the cuprates will do conjugate addition.18... 

M MeMgCl in THF added to a soln. of startg. chiral c/5-oxazolidine (derived from (R)-N-(4-toluenesulfonyl)phenylglycinol and 2-hydroxymethylenecyclohexanone) in the same solvent below —70°, and stirred at that temp, for 24 h - (rR,2R,2 S,4R)-product. Y 91% (diastereoisomeric purity 95%). F.e. inch reaction of Li-enolates, homoenolates and acyl anion equivalents, also asym. reduction with Zn(BH4)2, s-I. Hoppe et al., Angew. Chem. Intern. Ed. 28, 67-9 (1989). 

An innovative stereoselective synthesis of A-acylhydrazones via an unprecedented A-heterocyclic carbene-catalysed addition of aldehydes to diazo compounds has been presented. Enals exclusively afforded A-acylhydrazones, in yields up to 91% (Scheme 13). The observed regioselectivity was traced back to the reaction of the viny-logous Breslow intermediate via the acyl anion pathway over competing homoenolate, enol, and acyl azolium pathways. This unusual reaction profile was studied based on DFT calculations, which revealed that the reaction is under orbital control, rather than being ruled by charge. 

The power of NHC catalysts lies in the ability of these heterocycles to promote the transient generation of reactive species, such as acyl anion equivalents or activated carboxylates. Using the mechanistic postulates for these processes, it is possible to predict that the combination of an NHC catalyst and an a,p-unsaturated aldehyde could lead to the generation of a wide variety of cata-lytically generated reactive intermediates (Scheme 14.12). Over the past 5 years, the rapid developments of new catalysts and reaction conditions have made possible the selective generation of eaeh of these classes of reactive species, including the synthetically powerful homoenolate and ester enolate equivalents. 

In order to separate structural effects from the electronic differences of these two catalyst classes. Bode synthesized chiral imidazolium salt 57 (Scheme 14.28). This allowed direct comparison of imidazolium versus triazolium precatalysts across a number of different reaction manifolds including those involving the catalytic generation of homoenolate equivalents, ester enolate equivalents, and acyl anions. These studies conclusively demonstrated that imidazolium-derived catalysts are superior for homoenolate reactions with less reactive electrophiles, while the triazolium-derived pre-catalysts are preferred for all other reactions. Interestingly, from the currently published body of the work, it does not appear to be any effects from the counterion of the azolium pre-catalysts in the presence of bases. 

For NHC-catalyzed generation (For NHC-catalyzed generation of homoenolates) of enolates and acyl anions)... 

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