Reagents lithium dialkyl cuprate

You might have been introduced to these compounds in the first semester of organic chemistry. Lithium dialkyl cuprates are carbon nucleophiles, but they are less reactive than Grignard reagents. Lithium dialkyl cuprates will react with acid halides, but not with ketones. And therefore, we can use these reagents to convert acid halides into ketones ... 

Like Grignards and ordinary lithium reagents, lithium dialkyl cuprate (LiR2Cu) reagents behave as if they are a salt consisting of an anionic carbon nucleophile (R ) and a positive counterion ([CuLiR]" ). 

In fact, they have the opposite electrophile preferences from lithium and Grignard reagents. Lithium dialkyl cuprates DO NOT react with aldehydes and ketones, but react very well with alkyl halides. 

DesilylbrominationThis reaction was first used by Fleming et al. (8, 196 11, 75) in connection with protection of enones, but it is also useful for synthesis of chiral 5-alkylcyclohexenones. Thus reaction of (R)-(-)-l with lithium dialkyl-cuprates gives the trans-adduct 2 as the only product. Of several bromination reagents, only CuBr2 in DMF is useful for conversion of 2 to optically active 3. 

R2CuLi /C=C lithium dialkyl cuprate (Gilman reagents) enamine O II H2C=CH —C —H O II H2C=CH—C—R conjugated aldehyde conjugated ketone... 

Yunker, M B, Plaumann, D E, Fraser-Reid, B, The stereochemistry of conjugate addition of lithium dialkyl cuprate reagents to some carbohydrate a-enones. Can. J. Chem., 55, 4002-4009, 1977. Baer, H H, Ong, K S, Raeactions of nitro sugars. IX. The synthesis of branched-chain dinitro sugars by Michael addition. Can. J. Chem., 46, 2511-2517, 1968. 

In a similar fashion, diethyl cyclopropane-1,1-dicarboxylate (4) reacted with lithium dialkyl-cuprate to give the corresponding malonates S in high yields. Byproducts could be formed by the attack of the organometallic reagent at the carbonyl function. With diethyl 2-vinyl-cyclopropane-1,1-dicarboxylate (6), a preference for the 1,7-addition of the dialkylcuprate was found. Similar observations were made with 1-acetyl- (9,R = Me) and 1-benzoyl-2-vinylcyclopropane (9, R = Ph) when reacted with various dialkyl- and diphenylcuprates and with a vinylcyclopropanedicarboxylate fragment incorporated into a polycyclic system to yield compound 11. ... 

Conjugate addition. The reagent undergoes ready 1,4-addition to cyclo-hexenones to form, after quenching with methanol, 3-silylcyclohexanones. The intermediate can be alkylated cleanly (equation I). The reagent has a strong preference for axial addition (equation II). The reagent thus resembles lithium dialkyl cuprates. 

Another transition metal-catalyzed carbon-carbon bond-forming reaction we shall discuss is the Corey—Posner, Whitesides-House reaction. Using this reaction an alkyl halide can be coupled with the alkyl group from a lithium dialkyl cuprate reagent (often called a Gilman reagent). This reaction does not have a catalytic mechanism. 

G.3 THE COREY-POSNER, WHITESIDES-HOUSE REACTION USE OF LITHIUM DIALKYL CUPRATES (GILMAN REAGENTS) IN COUPLING REACTIONS... 

Yunker, M. B., D. E. Plaumann, and B. Fraser-Reid The Stereochemistry of Conjugate Addition of Lithium Dialkyl Cuprate Reagents to Some Carbohydrate a-Enones. Can. J. Chem. 55, 4002 (1977). 

Related Reagents. For related heterocuprates, see lithium methyl(phenylthIo)cuprate for discussion of lithium dialkyl-cuprates, see lithium dimethylcuprate. 

With this in mind, let s now explore the outcome of a reaction in which an enolate ion is used as a nucleophile to attack an a,(3-unsaturated aldehyde or ketone. In general, enolates are less reactive than Grignard reagents but more reactive than lithium dialkyl cuprates. As such, both 1,2-addition and 1,4-addition are observed, and a mixture of products is obtained. In contrast, doubly stabilized enolates are sufficiently stabifized to produce 1,4 conjugate addition exclusively. 

What if the ketone is the desired product We have a problem here, because the Grignard reagent will attack twice. We can t stop it from attacking twice. If we just try to use exactly one equivalent of the Grignard reagent, we will observe a mess of products (some molecules of the acid halide will get attacked twice, and others will not get attacked at all). In order to prepare the ketone, we need a carbon nucleophile that will only react with an acid halide, but will not react with a ketone. And we are in luck, because there is a class of compounds that will do exactly that. They are called lithium dialkyl cuprates (R2CuLi). 

Some textbooks and instructors will teach you a reagent that can achieve this overall transformation in one step (converting from an acid halide into an aldehyde). There are actually many hydride reagents that are sufficiently selective to convert an acid halide into an aldehyde (very much the way lithium dialkyl cuprates are sufficiently selective to convert an acid halide into a ketone, without attacking the carbonyl group a second time). You should look through your textbook and lecture notes to see if you have covered a selective hydride nucleophile. If you haven t, you can always use the two-step method (shown above) for converting an acid halide into an aldehyde. 

G.3 The Corey-Posner, Whitesides-House Reaction Use of Lithium Dialkyl Cuprates (Gilman Reagents) in Coupling Reactions... 

The Corey-Posner, Whitesides-House reaction involves the coupling of a lithium dialkyl-cuprate (called a Gilman reagent) with an alkyl, alkenyl, or aryl halide. The alkyl group of the lithium dialkylcuprate reagent may be primary, secondary, or tertiary. However, the halide with which the Gihnan reagent couples must be a primary or cyclic secondary alkyl halide if it is not alkenyl or aryl. 

Preparation.—The conversion of acid chlorides into ketones using lithium dialkyl cuprates has been studied by two groups the reagents are sufficiently... 

How do lithium dialkyl cuprates differ from Grignard and ordinary lithium reagents )... 

Draw the lithium dialkyl cuprate reagent formed by mixing 2-chlorobutane with lithium metal, followed by treatment with copper iodide. As in Model 8, show it two different ways i) with covalent bonds between carbon and metal, and ii) as a salt. 

Alkyl bromides are the most common starting materials for preparing Grignard, lithium, and lithium dialkyl cuprate reagents, but Cl and I also work. Draw the products of each of the following reactions, and show the products as ions to emphasize the polarization of the carbon-metal bond. 

Construct an explanation for why high-energy nucleophiles such as Grignard and lithium reagents tend to form 1,2-addition products with a,p-unsaturated carbonyl compounds while milder nucleophiles (including lithium dialkyl cuprates) tend to form 1,4-addition products. 

A lithium dialkyl cuprate (LiR2Cu) reagent will... 

To stop at the aldehyde a special reducing agent (such as DIBAH) may be used. To stop at the ketone a lithium dialkyl cuprate reagent may be used. These reactions are summarized at the end of this activity. 

Students often forget that use of excess LiAlHj, lithium, or Grignard reagent with an acid halide, acid anhydride or ester will result in incorporation of two molar equiyalents of nucleophile in the product whereas lithium dialkyl cuprates will deliyer only one equiyalent (except to esters). This is a consequence of the fact that lithium dialkyl cuprates do NOT react with aldehydes, ketones, or... 

Michael reaction (like the one at right) behave more like a Grignard reagent or more like a lithium dialkyl cuprate reagent in terms of the regiochemistrv of where it bonds to an a,p-unsaturated carbonyl compound Explain. 

The resulting ketone is not further attacked by the lithium dialkyl cuprate (unlike a Grignard reagent, which would attack the ketone). For some reason, students commonly propose a similar reaction between an ester and a lithium dialkyl cuprate ... 

---