Ketones, reaction with organocuprates

Several procedures are available for the preparation of the requisite p-hydroxysi-lanes such as addition of a-silyl carbanions to aldehydes and ketones, reaction of organocuprates with a,P-epoxysilanes, reduction of P-ketosilanes, and addition of organometallic regents to P-ketosilanes. The selection of a particular procedure is dictated by the structure and stereochemistry of the desired alkene. 

The reaction of 1,2-allenyl ketones with organocuprates afforded /3,y-unsaturated enones. The reaction with mixed cuprates RR CuLi delivered, depending on the properties of R and R, two products 430 and 431 [192]. 

INT2, Scheme 10.7) undergoes further reaction (Li/Cu transmetalation) and generates a new organocuprate compound. (Note however that this difference could become more subtle since the product of conjugate addition (PD) might behave more like an a-cuprio(I) ketone complexed with a lithium cation [52] than a lithium enolate complexed with copper(I)). In neither reaction was any evidence of radical intermediates (i.e., SET) found by theoretical calculations [79]. 

Coupling with enol esters (7, 93). A new synthesis of an alkyl-substituted alkene involves coupling of a lithium dialkyl cuprate with an enol triflate,1 available from a ketone by reaction with triflic anhydride and 2,6-di-t-butylpyridine.2 A wide variety of organocuprates can be used and the geometry of the enolate is largely retained. Reported yields are in the range 60 100%. 

R. A. J. Smith and A. S. Vellekoop, 1,4-Addition Reactions of Organocuprates with ,/3-Unsat-urated Ketones, in Advances in Detailed Reaction Mechanisms (J. M. Coxon, Ed.), Vol. 3, Jai Press, Greenwich, CT, 1994. 

Ketones from esters. Methylselenol esters, readily available by reaction of carboxylic esters with (CHdiAlSeCH, (8, 182), react with organocuprates to give ketones in generally high yield... 

Ketone synthesis.4 Organocuprates do not ordinarily react with esters at low temperatures, but they react satisfactorily with 2-pyridyl esters to provide ketones. These esters are readily available by reaction of 2-pyridyl chloroformate, an acid, and N(C2H5)3 catalyzed by DMAP. 

Reactions of (3,(3-disubstituteci enones with organocuprates are often not very successful because of steric crowding of the double bond. In these cases, use of R2CuLi-BF3 OEt2 often obviates the problem. " Possibly, the Lewis acid BF3 further polarizes and activates the ketone by coordination. 

A mild and efficient transformation of esters into ketones via selenol esters has been developed. Selenol esters smoothly reacted with organocuprates to produce ketones in excellent yields (equation 18). Reaction with a vinylcopper(I) reagent gave a,p-unsaturated ketones (equation 19). Butylmanganese chloride also transformed selenol esters into ketones, although 3 equiv. of the reagent are required to complete the reaction. MeaCd and PhHgBr were not effective for this transformation. 

Substitution. Reaction of the diepoxides derived from aUenes with organocuprates to afford a-hydroxy ketones is stereoselective. ... 

There are two major reactions of organocuprates, and both give products reminiscent of a carbon nucleophile (1) reaction with alkyl halides and (2) conjugate addition with a,p-unsaturated ketones. Conjugate addition to a, 3-unsaturated ketones is promoted when ether is used as a solvent.381 The substitution reaction is promoted by the use of THF or ether-HMPA as a solvent. l As mentioned earlier, the mechanism of these reactions probably involves a one-electron transfer, although other mechanistic proposals are in the literature,but the synthetic result is that expected of a carbon nucleophile. 85 The general reactivity of organocuprates with electrophiles follows the order ... 

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