Dimethylcuprate

The coupling reaction between lithium dimethylcuprate and acyclic enol phosphates must be carried out between -47 and -98 C for stereoselective formation of g-methyl-a,g-unsaturated esters. 

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 C2-symmetric epoxide 23 (Scheme 7) reacts smoothly with carbon nucleophiles. For example, treatment of 23 with lithium dimethylcuprate proceeds with inversion of configuration, resulting in the formation of alcohol 28. An important consequence of the C2 symmetry of 23 is that the attack of the organometallic reagent upon either one of the two epoxide carbons produces the same product. After simultaneous hydrogenolysis of the two benzyl ethers in 28, protection of the 1,2-diol as an acetonide ring can be easily achieved by the use of 2,2-dimethoxypropane and camphor-sulfonic acid (CSA). It is necessary to briefly expose the crude product from the latter reaction to methanol and CSA so that the mixed acyclic ketal can be cleaved (see 29—>30). Oxidation of alcohol 30 with pyridinium chlorochromate (PCC) provides alde-... 

A similar reaction the with rran.v-isomer 3b gave c -3,5-dimethylcyclohexene (4) with very high diastereoselectivity. Accordingly, the stereochemistry of this substitution is anti. Deuterium labeling experiments using the 1-deuterio or 3-deuterio derivative of 3 a showed that the ratio of SN2 /SN2 with lithium dimethylcuprate was about 50 50, while the ratio with lithium cyano(methyl)cupratc was >96 4. 

The reaction of propargylic chiral acetals with a catalytic copper reagent (RMgX/5% CuX) provides the expected alkoxy allenes in quantitative yield (Table 3)61. The diastereomeric excess is highly dependent on the size of the ring of the acetal and on the type of substituents it contains. The best diastereomeric excess is 85% with the acetal derived from cyclooctanediol. The use of lithium dimethylcuprate results in 1,2-addition lo the triple bond and the resulting lithium alkenyl cuprate bearing a cyclic acetal does not eliminate even at reflux temperature ( + 35°C). 

Dimethylcuprate addition was carried out as above, however, 3 mol equiv of chlorotrimethylsilane are added at — 78 °C prior to the substrate addition yield 72% d.r. 95 5. 

The conjugate addition of lithium dimethylcuprate to spiroketone 5 gave predominantly (S j-6 [(S)/(R) 92 8] in which methyl group attacked from the side syn to the oxygen atom, whereas the addition of lithium dimethylcuprate-chlorotrimethylsilane afforded exclusively the anti-adduct (S)-621,... 

The conformational properties of medium and large ring organic molecules have profound consequences on the stereochemical course of dimethylcuprate addition24. The addition to... 

The conjugate addition of lithium dimethylcuprate to chalcone in the presence of (2S)-1-(2,2-dimethyl-l-oxopropyl)-2-diphenylphosphinomethylpyrrolidine gave the corresponding S-adduct with 84% ec in 79% yield79. 

Nucleophilic addition to acetylenic sulfoxides provides a,/ -ethylenic sulfoxides. Treatment of 181 with monoalkyl-copper afforded nearly quantitatively /J-alkylated a, / -ethylenic sulfoxides 182 through cis-addition to the triple bond. The reaction with lithium dimethylcuprate also afforded a similar adduct however, the reaction with lithium di-n-butylcuprate was found to give a small amount of ethyl n-butyl sulfoxide 183 besides the... 

Lithium bis(2-butyl)cupiate [Lithium bis-(l-methylpropyl)cuprate, 55, 112 Lithium dialkylcuprates, 55, 112 Lithium dimethylcuprate, 55, 112 Lithium diphenylcuprate, 55,112 LITHIUM DIPROPENYLCUPRATE, 55, 103,111... 

The 2 1 species are known as cuprates and are the most common synthetic reagents. Disubstituted Cu(I) species have the 3c 10 electronic configuration and would be expected to have linear geometry. The Cu is a center of high electron density and nucleophilicity, and in solution, lithium dimethylcuprate exists as a dimer [LiCu(CH3)2]2.3 The compound is often represented as four methyl groups attached to a tetrahedral cluster of lithium and copper atoms. However, in the presence of Lil, the compound seems to be a monomer of composition (CH3)2CuLi.4... 

Sn2 and SN2 Reactions with Halides and Sulfonates. Corey and Posner discovered that lithium dimethylcuprate can replace iodine or bromine by methyl in a wide variety of compounds, including aryl, alkenyl, and alkyl derivatives. This halogen displacement reaction is more general and gives higher yields than displacements with... 

There have been many applications of conjugate additions in synthesis. Some representative reactions are shown in Scheme 8.2. Entries 1 and 2 are examples of addition of lithium dimethylcuprate to cyclic enones. The stereoselectivity exhibited in Entry 2 is the result of both steric and stereoelectronic effects that favor the approach syn to the methyl substituent. In particular, the axial hydrogen at C(6) hinders the a approach. 

The reaction of lithium dimethylcuprate with 17-A shows considerable 1,4-diastereoselectivity. Offer an explanation, including a transition structure. 

In order to establish the bridgehead carbon configuration with certainty and to demonstrate the usefulness of the method, desilylation and deprotection of 438b in acidic conditions have been performed. Since they are accompanied by double bond migration and loss of chirality, a dimethylcuprate alkylation has been carried out before acid hydrolysis (Scheme 59) [112]. 

Additions to cyclopentenones.5 Conjugate addition of cuprates to 4-substi-tuted cyclopentenones can show moderate to high trarw-diastereoselection, which can be attributed to a steric effect. Surprisingly, addition of lithium dimethylcuprate to (R)-5-methoxy-2-cyclopentenone also shows high frans-diastereoselectivity (equation I). The stereoselectivity is decreased somewhat by addition of ClSi(CH3)3. 

Sn2 -Addition to vinyloxiranes. Lithium dimethylcuprate reacts with vinyl-oxiranes by a highly arm-selective SN2 addition to provide homoallylic alcohols. Examples ... 

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