Dimethyl cuprate

Many other organometaUic compounds also react with carbonyl groups. Lithium alkyls and aryls add to the ester carbonyl group to give either an alcohol or an olefin. Lithium dimethyl cuprate has been used to prepare ketones from esters (41). Tebbe s reagent, Cp2TiCH2AlCl(CH2)2, where Cp = clyclopentadienyl, and other metal carbene complexes can convert the C=0 of esters to C=CR2 (42,43). 

Although ethereal solutions of methyl lithium may be prepared by the reaction of lithium wire with either methyl iodide or methyl bromide in ether solution, the molar equivalent of lithium iodide or lithium bromide formed in these reactions remains in solution and forms, in part, a complex with the methyllithium. Certain of the ethereal solutions of methyl 1ithium currently marketed by several suppliers including Alfa Products, Morton/Thiokol, Inc., Aldrich Chemical Company, and Lithium Corporation of America, Inc., have been prepared from methyl bromide and contain a full molar equivalent of lithium bromide. In several applications such as the use of methyllithium to prepare lithium dimethyl cuprate or the use of methyllithium in 1,2-dimethyoxyethane to prepare lithium enolates from enol acetates or triraethyl silyl enol ethers, the presence of this lithium salt interferes with the titration and use of methyllithium. There is also evidence which indicates that the stereochemistry observed during addition of methyllithium to carbonyl compounds may be influenced significantly by the presence of a lithium salt in the reaction solution. For these reasons it is often desirable to have ethereal solutions... 

The synthesis in Scheme 13.41 is also built on the desymmetrization concept but uses a very different intermediate. cA-5,7-Dimethylcycloheptadiene was acetoxylated with Pd(OAc)2 and the resulting all-cA-diacetate intermediate was enantioselectively hydrolyzed with a lipase to give a monoacetate that was protected as the TBDMS ether. An anti Sw2 displacement by dimethyl cuprate established the correct configuration of the C(2) methyl substituent. Oxidative ring cleavage and lactonization gave the final product. 

The results for conjugate additions to pseudodipeptides 83 and 86 may be interpreted along similar lines. Thus, addition of the fairly slim lithium dimethyl-cuprate nucleophile proceeded non-selectively (84, Scheme 6.17) [34, 35]. Con-... 

Ss2 reaction with a,fi-epoxy ketones.6 The enolate 1 of 2,3-epoxycyclohexanone reacts with methyllithium to give, after acidic work-up, 2-methy -2-cyclohexenone (3), the product of SN2 addition. Reaction of 1 with lithium dimethyl cuprate on the other hand results in 6-methyl-2-cyclohexcnonc (2), the product of Sv2 addition. 

Substitution of alfylic sulfoxides. Lithium dimethyl cuprate and di-n-butyl cuprate react with allylic sulfoxides or sulfones mainly by y-substitution to give tri-substituted alkenes (equation I).15... 

Chloromagnesium dimethyl cuprate, (CH3)2CuMgCI (1). This mixed cuprate is prepared by reaction of CH3MgCl (2 equivalents) with CuBr (1 equivalent) in THF. Most lithium dialkyl cuprates react with cc,/ -unsaturated aldehydes to give a mixture of 1,2- and 1,4-adducts, but 1 tends to form mainly the latter adducts.25... 

H. Yamamoto, H. Sasaki, and S. Inokawa, Reaction of lithium dimethyl cuprate with methyl 2,3-anhydro-5-deoxy-a-D-ribofuranoside. A new, convenient route for the preparation of 2,5-dideoxy-2-C-methyl-D-arabinofuranose derivatives, Carbohydr. Res. 100 C44 (1982). 

House and Fischer (38) have found that lithium dimethyl cuprate reacts with enone 108 and yields a mixture of trans and cis 3,5-dimethyl-cyclohexanones 109 and 110 in a 98 2 ratio. Similar results were observed by Allinger and Riew (39) using methylmagnesium iodide in the presence of copper(I) chloride. In another case, Heathcock and co-workers (AO) observed the exclusive formation of the trans isomer V[2 from enone 111 no cis isomer was detected. Thus, the preferred mode of approach by cuprate reagent is also 76 + 78 which leads to a chair-like enolate ion. 

A report of House, Respess and Whitesides (47) showed that the reaction of lithium dimethyl cuprate with the unsaturated ketone 135 gave exclusively the ketone J36 having the methyl trans to the t-butyl group. In this case where the double-bond is exocyclic, stereoelectronic effects allow equal attack from either face. Thus, the exclusive formation of 136 must be due to steric reasons only, the equatorial approach being favored. 

D. R. Hicks, R. Ambrose, and B. Fraser-Reid, Lithium dimethyl cuprate cleavage of diastereomeric 2,3-anhydro sugars a route to 2- and 3-C-methyl hex-2-enopyranosides,... 

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

Mori started with the early introduction of the chiral centre [298] in using (3-oxidation of pentanoic acid A by the yeast, Candida rugosa, IFO 0750 [299]. The obtained (R)-3-hydroxypentanoic acid B was transformed into C in a few conventional steps. The second building block was prepared from methyl 2-pentynoate D conjugate addition of lithium dimethyl cuprate yielded E, which was further converted into the frans-configured vinyl bromide F. Hydro-boration of C yielded G which upon Suzuki s palladium catalysed cross-coupling with F furnished 157 after treatment of the reaction product with hydrochloric acid followed by chromatographic purification. The synthesis of ent-157 used (S)-3-hydroxypentanoic acid. 

Allenes are activated by a diphenylphosphine oxide substituent towards nucleophilic substitution at the j3-carbon atom. Lithium dimethyl-cuprate adds quickly to the 1,2-bond to give, on hydrolysis, the olefin in 16-84% yield, according to the nature of the substituents (76). Optimum conditions were not reported. The intermediate a-copper compound resulting from the addition can be dimerized or reacted with methyl iodide [Eq. (106)]. Similar reactions involving methyllithium are complicated. 

The preparation of a 7-substituted morphinan in high yield was first accomplished in 1980.(82) Thebaine (78) was reacted with lithium dimethyl-cuprate to yield (90%) 7/3-methyldihydrothebaine- > (79) together with 4% of the 7a-epimer. Previously, dihydrothebaine(83) and the enol acetate of dihydrocodeinone(84) had been shown to react with methyl Grignard reagents affording predominantly 5-methyldihydrothebainone with only a trace of the 7-methyl isomer.(85) The production of 79 gave entry into a new series of morphinans. 

Several other techniques have been used to determine the structure or aggregation state of organocuprates. Cryoscopic studies in THF found that discrete monomeric species were formed when RLi (R = Me, t-Bu) was added to CuCN in various ratios. A dimeric species resulted, however, when PhLi was used for cuprate formation. X-ray absorption spectroscopy (XAS) was utilized in an investigation of Cul- and CuCN-based dimethyl cuprates. " Both extended... 

Addition von Lithium-dimethyl-cuprat XIII/9a, 275 (t/2-Alken)-(>j5-cyclopentadienyl)-dicarbonyl-Addition von... 

The influence of solvent and additives on yield and selectivity has been examined.The conjugate addition of dimethyl cuprate in the presence of a chiral ligand, such as 144, is an example. The use of chiral ligands with Mgl2/l2 and BuaSnl gave conjugate addition products with a,(3-unsaturated amides with... 

Exo- and endo-cyclic ring closure reactions using 0-nucleophiles transform oxocarbenium ions into cyclic acetals. As an example of an endocyclic cyclization, epoxide ring opening of (96) with lithium dimethyl cuprate, and subsequent treatment of the resulting alcohol with acid, smoothly gives the bicyclic acetal (97), ° a key intermediate in the total synthesis of tirandamycic acid (Scheme 47). ... 

A range of diverse substituted allyl phenyl sulfoxides, which are available by addition of dimethyl cuprate to allenyl sulfoxides or more generally by alkylation of simpler analogs, - have been converted into allylic alcohols possessing predominantly ( )-stereochemistry (E Z 90 10) following simple admixture with trimethyl phosphite - or thiophenolate (MeOH, 60 C, 7 h Scheme 98 Scheme 99 for a lower selectivity see Scheme 98, entry a). ... 

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