Ethyl diazoacetate ketone homologation

Treatment of benzaldehydes with ethyl diazoacetate and a catalytic quantity of the iron Lewis acid [ -CpFe(CO)2(THF)]+BF4 yields the expected homologated ketone (80). However, the major product in most cases is the aryl-shifted structure (81a), predominantly as its enol tautomer, 3-hydroxy-2-arylacrylic acid (81b). This novel reaction occurs via a 1,2-aryl shift. Although the mechanism has not been fully characterized, there is evidence for loss of THF to give a vacancy for the aldehyde to bind to the iron, followed by diazoacetate attachment. The product balance is then determined by the ratio of 1,2-aryl to -hydride shift, with the former favoured by electron-donating substituents on the aryl ring. An alternative mechanism involving epoxide intermediates was ruled out by a control experiment. 

Homologation of ketones (1, 369-370 6, 252-253 8, 222). Ethyl diazoacetate is recommended as the most useful diazoalkane for monohomologation of cyclic and acyclic ketones without formation of epoxides as by-products. One advantage is that the usually slow reaction can be catalyzed by BF3 etherate (or triethyloxonium tetrafluoro-borate). 

Ethyl diazoacetate has been used extensively in the homologation of ketones to 3-keto esters. Lewis acid is required for the reaction (equation 23). ° There is a tendency for the least-substituted group to migrate, particularly if one group is fully substituted (equation 24). In a total synthesis of ( )-aplysin (20) this selective rearrangement was applied (Scheme 9), and a similar approach was used in a synthesis of (+)-hirsutic acid. Ethyl diazoacetate has also been used in the homologation of acyclic... 

Homologation Acrolein. Carbon monoxide. Cuprous bromide-Diazomethane. Ethyl bromo acetate. Ethyl diazoacetate. Methyl vinyl ketone. Phenylthiomethyllithium. Trimethyl phosphite. 

Ring expansion (1, 369-370 6, 252-253). The ring expansion of ketones to the next higher homolog with ethyl diazoacetate requires hydrolysis and decarboxylation of the intermediate 8-keto ester, a step that is sometimes troublesome. Baldwin and Landmesser have used benzyl diazoacetate and allyl diazoacetate as alternative reagents. The benzyl jS-keto esters are cleaved and decarboxylated on hydrogenation both benzyl and allyl keto esters are reduced by sodium in liquid ammonia to ketones. 

A full paper has been published on the homologation of ketones to /8-keto-esters using ethyl diazoacetate under triethyloxonium fluoroborate catalysis. In the... 

A novel alkoxycarbonylmethylene carbon-carbon insertion process is reported to occur in the triethyloxonium fluoroborate-catalysed homologation of ketones with ethyl diazoacetate i -ketoesters are produced in high yield. Although the analogous reaction with diazoacetone does not occur, the intramolecular counterpart is successful, providing a route to polycyclic /3-diketones, e.g. the conversion of (85) into (86). 

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