Ethyl formate condensation with cyclohexanone

Gtmnal alkylation af ketones. Coates and Sowerby have reported a new method for site-selective geminal alkylation of ketones which involves reduction of the n-butylthiomethylene derivative of the ketone by lithium-ammonia to give a methyl-substituted cnolatc anion which can be alkylated in situ. The ketone, for example cyclohexanone (I), is condensed with ethyl formate and then transformed into the n-butylthiomethylene derivative (2) by reaction with n-butyl mercaptan (2, 53-54). This is then reduced with excess lithium in liquid ammonia at -33° with 2 eq. of a proton donor (water is usually used to avoid ovcralkylation). The lithium cnolate is then... 

In many reactions there is an equilibrium between reactants and products so that only the more stable of the two alkenes is produced. In the Claisen ester condensation of cyclohexanone 8 with ethyl formate, the true product under the conditions of the reaction is the stable enolate 9 and this is reversibly protonated on workup to give the more stable H-bonded enol of the ketoaldehyde Z-10. In the aldol reaction between the same ketone and benzaldehyde, the initial product 7 gives the enolate 6 and dehydration is reversible only the more sterically favourable E isomer of 5 is formed. Note that it is irrelevant that the aldol 7 is a mixture of diastereoisomers all stereochemistry is lost in the formation of the enolate 6. In later parts of this chapter a more specific relationship between 3D and 2D stereochemistry will be established. 

Formyitttion of ketones. The condensation of cyclohexanone with ethyl formate in the presence of either sodium ethoxide or sodium hydride gives a product which can be described as 2-hydroxymethylenecyclohcxanone (I) or the tautomer 2-Tormylcyclohexanone (2) for simplicity Ihe pwcess is described us a formylation. In the procedure cited, formylulion was followed by reaction wllfr hydru/ine to... 

Ethylfluorene, 39, 45 Ethyl formate, 32,32 condensation with cyclohexanone, 39, 27... 

More commonly, sodium hydride is used as a base for carbonyl condensation reactions. For exarrple, Claisen condensations of ethyl acetate and ethyl isovalerate are effected by sodium hydride. Condensations of cyclohexanone with methyl benzoate and ethyl formate (eq 16) are also facile. Sodium hydride can... 

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