Esters, 1,4-keto homoenolates

Internal nucleophilic cyclization is one of the most typical reactions of reactive metal homoenolates (equation 3 and Scheme and provides a convenient route to silyloxycyclopropanes (e.g. 8) through cyclization of 3-halo esters. Zinc homoenolates (9) also cyclize to cyclopropanes under suitable conditions. Treatment of the zinc homoenolate in CHCb with an acid chloride at room temperature gives an 0-acylation product (Scheme 6), instead of a 4-keto ester (see Section 1.14.7.1). The reaction of the zinc homoenolate wifo MesSiCl in a polar solvent gives a silyloxycyclopropane (Scheme 6), providing a very mild route to silyloxycyclopropanes. ... 

The aryl- and heteroarylfluorosilanes 541 can be used for the preparation of the unsymmetrical ketones 542[400], Carbonylation of aryl triflate with the siloxycyclopropane 543 affords the 7-keto ester 545. In this reaction, transme-tallation of the siloxycyclopropane 543 with acylpalladium and ring opening generate Pd homoenolate as an intermediate 544 without undergoing elimination of/3-hydrogen[401],... 

Among isolable metal homoenolates only zinc homoenolates cyclize to cyclo-propanes under suitable conditions. Whereas acylation of zinc alkyls makes a straightforward ketone synthesis [32], that of a zinc homoenolate is more complex. Treatment of a purified zinc homoenolate in CDC13 with acid chloride at room temperature gives O-acylation product, instead of the expected 4-keto ester, as the single product (Eq. (22) [33]). The reaction probably proceeds by initial electrophilic attack of acyl cation on the carbonyl oxygen. A C-acylation leading to a 4-keto ester can, however, be accomplished in a polar solvent Eq. (44)-... 

This homoenolate anion also acylates acid chlorides readily to give y-keto esters (equation I), but does not react with aldehydes or epoxides. 

Zinc homoenolates (9) react rapidly with acid chlorides in ethereal solvents containing a dipolar aprotic solvent to give 1,4-keto esters in high yield (Scheme 23). 9 palladium catalyst (or, less effective, a copper catalyst) ° accelerates the reaction, in contrast to cyclopropane formation in halometh-ane solvents (see Section 1.14.3.1). 

A completely different approach to Y-keto-esters proceeds via Michael additions of carboxylic acid dianions to an a-anilino-acrylonitrile followed by alkylation of the resulting anion and finally acidic hydrolysis (Scheme 13). Overall yields are in the range 47-79% the method is also useful in the synthesis of r-keto-amides. An alternative anion-based route to y-keto-esters utilizes the homoenolate (166) as the interroediate which undergoes smooth acylation by a wide variety of acid chlorides.The homoenolate is obtained from the corresponding iodoester using Zn-Cu couple, and it seems likely that the method can be used to prepare more highly substituted keto-esters although such reactions have not yet been reported. 

In the same way, the bis-homoenolate (167) can also be generated and used to make 6-keto-esters (168). Overall yields are excellent. 

The zinc homoenolate undergoes copper-catalyzed allylation with allylic chlorides. The reaction is not only extremely Sn2 regioselective but stereoselective for 5-chiral allylic chlorides. Arylation and vinylation of the zinc homoenolates proceed in the presence of a palladium-phosphine complex. Similarly, palladium-catalyzed acylation reaction gives y-keto esters (eq 6). 

Acylation and Carbonylation. The zinc homoenolate reacts more rapidly with acyl halides than with a-/3-enones to give 4-keto esters in good yield (X = Cl) (eq The Ni-catalyzed... 

Homoenolate Anion Equivalent. The reaction of (1) with acid chlorides in the presence of titanium(IV) chloride affords the corresponding y-keto aldehydes after hydrolysis (eq 2) O-Acylation to form the 1-silyl allyl ester (17-30%) competes with the Se alkylation of the double bond. Bulkier silyloxy derivatives give y-keto aldehydes in higher yield. 

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