Ketones, unsaturated cuprate reagents

Cheng, K.F., Nagakura, I., and Piers, E. 1982. Reaction of P-halo aP-unsaturated ketones with cuprate reagents. Efficient syntheses of PP-dialkyl ketones and P-alkyl P-unsaturated ketones. A synthesis of (Z)-jasmone. The Canadian Journal of Chemistry, 60(10) 125 6-63. 

The procedure described here illustrates the preparation of mixed lithium arylhetero(alkyl)cuprate reagents and their reactions with carboxylic acid chlorides,4 These mixed cuprate reagents also react with a,a -dibromoketones,12 primary alkyl halides,4 and a,/3-unsaturated ketones,4 with selective transfer of only the alkyl group. 

Carbonylation of the cuprate reagent, R (CN)CuLi2, prepared from copper(I) cyanide and an alkyl-lithium, gives a product which can be used for the direct nucleophilic 1,4-acylation of a,3-unsaturated aldehydes and ketones (equation 16). The reaction works particularly well with cyclic a,p-unsaturated ketones to give high yields of the expected 1,4-diketone. 

Several investigators have attenuated the potent nucleophilic-ity of vinyllithium intermediates by transmetalation or trapping. Vinylstannanes, chromium-carbene complexes, and particularly vinylsilanes have been prepared. Alkenyllithiums react faithfully to give 1,2-addition products with a, -unsaturated ketones, and mixed cuprate reagents have also been prepared with some success by trapping vinyllithiums with phenylthiocopper for 1,4-addition (eq... 

Organonickel intermediates formed from nickel(II) acetylacetonate and trimethylaluminum or tetramethylaluminate behave like cuprate reagents and undergo conjugate addition to a,j8-unsaturated ketones (Ashby and Heinsohn, 1974). 

Conjugate Addition to a, -Unsaturated Carbonyl Compounds Other than Ketones. In addition to a, 8-unsaturated ketones, the silylcuprate reagent also reacts with a, 8-unsaturated aldehydes, esters (eq 13), amides, and nitriles, and with vinyl-sulfoxides without needing Lewis acid catalysis as carbon-based cuprates do. With esters, the intermediate enolates, which have the E geometry (20), may be used directly in highly diastereoselective... 

The carbonyl compound can also contain additional functionality. Thus, treatment of an a,fi- poxy ketone with excess lithium reagent (1) provides the allyl alcohol (2) (eq 2). The use of an a-phenyl selenoaldehyde as electrophile allows either an allyl selenide or a /3-silyl aldehyde to be obtained, depending upon the reaction conditions used with the hydroxysilane (eq 3). With a,/8-unsaturated ketones, the lithium reagent (1) adds in the 1,2-sense the Grignard analog can provide 1,4-addition. The cuprate derived from (1) undergoes the expected reactions for this class of compounds, such as 1,4-addition. ... 

There is also a correlation between the reduction potential of the carbonyl compound and the ease of reaction with cuprate reagents. The more easily reduced, the more reactive is the compound toward organocuprate reagents. Compounds such as a,/3-unsaturated esters and nitriles which are not as easily reduced as a,j3-unsaturated ketones do not react readily with simple alkyl cuprates even though they are good acceptors in conjugate addition reactions involving other types of nucleophiles (Michael reactions). 

All of the mixed organocopper reagents shown in Scheme 6.6 react with a,/3-unsaturated ketones. The efficiency of the reaction can be promoted by the addition of trialkylphosphines. a,/0-Unsaturated esters are borderline in terms of reactivity toward simple cuprates. Unsubstituted and monosubstituted acrylates generally are reactive but more extensively substituted acrylates are not. The R-Cu-BFs reagents are more reactive than simple cuprates toward a,j8-unsaturated esters and also react with a,/3-unsaturated nitriles. Boron trifluoride has been found to catalyze addition of dimethylcuprate to very hindered a,)0-unsaturated ketones.Conjugated acetylenic esters react readily with cuprate reagents, with syn addition being the kinetically preferred mode of addition. ... 

Similarly, copper derivatives of hydrazones add in Michael fashion to cyclic enones to give products that are susceptible to further modification (Scheme 40). Good yields of 1,4-addition products are obtained on addition of the chiral cuprate reagents (26) to unsaturated esters, aldehydes, and ketones the asymmetric induction, however, is <1%. Prolinol has a more pronounced effect in that i -3-methylcyclohexanone is produced in 15.5% optical yield on reaction of... 

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