Keto esters, McMurry coupling

The McMurry coupling can be applied to intramolecular coupling of keto esters. Because the reactivity between ketone and ester groups is so different, the reaction usually requires individualized optimization, especially in the case of large rings. A combination of TiCls and LiAlH4 in the presence of triethylamine in DME is employed for the... 

The reductive coupling of carbonyl compounds with formation of C-C double bonds was developed in the early seventies and is now known as McMurry reaction [38, 39]. The active metal in these reactions is titanium in a low-valent oxidation state. The reactive Ti species is usually generated from Ti(IV) or Ti(III) substrates by reduction with Zn, a Zn-Cu couple, or lithium aluminum hydride. A broad variety of dicarbonyl compounds can be cyclized by means of this reaction, unfunctionalized cycloalkenes can be synthesized from diketones, enolethers from ketone-ester substrates, enamines from ketone-amide substrates [40-42], Cycloalkanones can be synthesized from external keto esters (X = OR ) by subsequent hydrolysis of the primary formed enol ethers (Scheme 9). 

McMurry has developed a titanium-mediated keto ester coupling (cf, acyloin condensation see R. Brettle, in Comprehensive Organic Synthesis , ed. B. M. Trost, Pergamon Press, Oxford, 1991, vol. 3, chap. 2.7) J. E. McMurry and D. D. Miller, J. Am. Chem. Soc., 1983,105, 1660. 

McMurry reactions will be presented in the following order intermolecular, intramolecular, mixed (tandem) couplings of aldehydes and ketones, and finally keto ester, oxoamide, and acetal couplings. All the compounds which serve as illustrations are listed in Tables 6.1-6.10, along with the titanium reagents and solvents used for their preparation and the yields of isolated products where not specified, the reactions were performed at solvent reflux temperature. 

The McMurry keto ester coupling gives enol ethers, vhich, after acidification, are transformed into the corresponding ketones (Scheme 6.4). 

Scheme 6.4. Synthesis of ketones by McMurry keto ester coupling.

Tab. 6.9. Syntheses by McMurry keto ester coupling reactions.

One of the earliest variations on the traditional McMurry coupling is the McMurry keto ester coupling for the synthesis of enol ethers. Large rings can be prepared by this method, albeit in lower yields, and the cyclic enol... 

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