Keto Ester Couplings

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. 

Stitle coupling of 2-carboxyethyl enol inflates with organostannanes.1U In the presence of Pd(OAc)2/P(C6H )3 (1 2) or Pd[P(Q,H5)i]4, the enol triflatcs of /3-keto esters couple with vinyl-, ally -, and alkynyl(tributyl)stannancs, but not with phcnyltributyltin. 

Phosphorus oxychloride (POCI3) has proven useful as a promoter in a range of Pechmann condensations employing sterically encumbered 3-keto ester coupling partners and electronically deactivated phenols, reactions which fail using sulfuric acid as a promoter. Thus POCI3 has been found to successfully promote the condensation of a-benzylacetoacetate and 1-naphthol as well as the reaction of ethyl acetoacetate with 4-acyl-resorcinols. ... 

The reactivity of the p-keto-ester coupling partner toward less electron-rich phenols is enhanced by substitution of the a-carbon with electron-withdrawing groups e.g., the benzoyl group of benzoylacetoacetate... 

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... 

The o -diketone 865 can be prepared by the coupling of the acylstannane 864 with acyl chlorides[738,739]. The a-keto ester 868 is prepared by the coupling of (a-methoxyvinyl)tributylstannane (866) with acyl chloride, followed by ozo-nization of the coupled product 867[740,741],... 

This procedure illustrates a new method for the preparation of 6-alkyl-a,g-unsaturated esters by coupling lithium dialkylcuprates with enol phosphates of g-keto esters. The procedure for the preparation of methyl 2-oxocyclohexanecarboxylate described in Part A Is based on one reported by Ruest, Blouin, and Deslongcharaps. Methyl 2-methyl-l-cyc1ohexene-l-carboxylate has been prepared by esterification of the corresponding acid with dlazomethane - and by reaction of methyl 2-chloro-l-cyclohexene-l-carboxyl ate with lithium dimethylcuprate. -... 

The formation of g-alkyl-a,g-unsaturated esters by reaction of lithium dialkylcuprates or Grignard reagents in the presence of copper(I) iodide, with g-phenylthio-, > g-acetoxy-g-chloro-, and g-phosphoryloxy-a,g-unsaturated esters has been reported. The principal advantage of the enol phosphate method is the ease and efficiency with which these compounds may be prepared from g-keto esters. A wide variety of cyclic and acyclic g-alkyl-a,g-unsaturated esters has been synthesized from the corresponding g-keto esters. However, the method is limited to primary dialkylcuprates. Acyclic g-keto esters afford (Zl-enol phosphates which undergo stereoselective substitution with lithium dialkylcuprates with predominant retention of stereochemistry (usually > 85-98i )). It is essential that the cuprate coupling reaction of the acyclic enol phosphates be carried out at lower temperatures (-47 to -9a°C) to achieve high stereoselectivity. When combined with they-... 

A somewhat different type of coupling is observed when salts of (i-keto esters, arylacetonitriles (ArCH2CN), and other compounds of the form ZCH2Z are treated with an oxidizing agent such as iodine," " or Cu(II) salts." Arylmethanesulfonyl chlorides (ArCH2S02Cl) couple to give ArCH=CHAr when treated with Et N." ... 

Vitamin B12 derivatives are also effective catalysts for the electroreductive cyclization of bromoalkenes in conductive microemulsions,299 300 or for ring-expansion reactions in cyclic a-(bromomethyl)-(3-keto esters in DMF.301 Vitamin Bi2 attached to an epoxy-polymer has been used in electrosynthesis of valeronitrile by reductive coupling of iodoethane and acrylonitrile.302... 

A-Unsubstituted isoxazolidines such as 65 undergo facile decarboxylative peptide couplings with a-keto acids <06JA1452>. The use of water as solvent or cosolvent was particularly beneficial for the formation of amides in high yields. The methyl a-keto esters obtained could be saponified to the corresponding a-keto acids, and the (i-peptide chain could then be extended by reaction with another isoxazolidine. 

Sml2 also effects an intramolecular reductive coupling of certain unsaturated (3-keto esters or amides to cyclopentanes with good stereochemical control at three centers (equation II).5... 

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... 

If a C—H bond is acidic enough, it couples with diazonium salts in the presence of a base, most often aqueous sodium acetate.153 The reaction is commonly carried out on compounds of the form Z—CH2—Z, where Z and Z are as defined on p. 464, e.g., P-keto esters, p-keto amides, malonic ester. 

A somewhat different type of coupling is observed when salts of p-keto esters, aryl-acetonitriles ArCH2CN, and other compounds of the form ZCH2Z are treated with an... 

The reaction of the enol diethylphosphate of a p-keto ester with a primary dialkyl cuprate provides a useful stereoselective synthesis of / -alkyl-a,j -unsaturated esters (equation II).3 This coupling was used in two steps in a recent synthesis of mokupalide, a novel C30-isoprenoid.A... 

---