Lithium dimethylcuprate cuprate

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). 

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... 

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. 

In the 1952 paper mentioned above [3], Gilman reported on the formation of lithium dimethylcuprate from polymeric methylcopper and methyllithium. These so-called Gilman cuprates were later used for substitution reactions on both saturated [6] and unsaturated [7, 8, 9] substrates. The first example of a cuprate substitution on an allylic acetate (allylic ester) was reported in 1969 [8], while Schlosser reported the corresponding copper-catalyzed reaction between an allylic acetate and a Grignard reagent (Eq. 2) a few years later [10]. 

Reaction of propynyl-substituted ester 1 with lithium dimethylcuprate gives allene 2. The problem investigated in this study148 was the stereochemical course of the cuprate reaction with propynyl esters, and the relative configuration around the allene unit of 2 was determined by chemical methods (see pp 473 and 487). 

The reaction of rac-4 with lithium dimethylcuprate yielded two of the four possible pairs of addition products (rac-5-rac-8) in a 4 1 ratio (see Section 4.3.3.2.2., p411). Treatment of the major stereoisomer with pyridine gave (presumably via the enolale) an 87 13 mixture containing the minor isomer from the cuprate addition as one component. In this case equilibration did not provide a full answer as to the relative configuration but it showed, that either rac-S/rac-6 or rac-1 jrac-% were formed from rac-4, whereas combinations such as rac-5jrac-1 were excluded (see p 480 for further assignment)108. 

Cuprate conjugate additions. One step in a recent synthesis of (-t-)-modhephene (3). a natural sesquiterpene with a (3.3.3)propellane skeleton, involved conjugate addition of lithium dimethylcuprate to 1. The desired reaction proved difficult... 

Although lower-order cuprate reagents will often engage in displacement reactions with alkyl halides, such reactions are usually slow. They are generally much less facile than 1,4-addition reactions to a,P-unsaturated enones or enoates. The latter processes are particularly facile when trimethylsilyl chloride is employed as an additive. It was Corey and Boaz10 who first recognised the accelerating effect of trimethylsilyl chloride on cuprate addition reactions to a,p-unsaturated carbonyls. Buszek therefore capitalised on Corey s earlier observations in his reaction of 10 with lithium dimethylcuprate to obtain 15. 

Diastereoselective 1,6-cuprate addition reactions to chiral dienones66 (Scheme 17) and acceptor-substituted enynes were reported recently. Due to an efficient shielding of the top face of the enyne moiety by the trifluoromethyl residue of the chiral 5-alkynylidene-l,3-dioxan-4-ones 115, the addition of lithium dimethylcuprate occurs preferentially at the underside to provide allene 116 with high diastereoselectivity after protonation with pivalic acid (Scheme 30).7,7a The stereochemical information generated in this step remained intact during the conversion into the chiral vinylallene 117. 

The 13,17-seco-acid lactone (258), obtained from a Baeyer-Villiger oxidation of 5a-androstan-17-one has been reduced to yield 13,17-seco-5a-androstan-13a,17-diol, whose diacetate on pyrolysis furnished the endocyclic seco-olefin (259 R = OAc) as the major reaction product. A minor product is the corresponding A12 13-olefin.115 Hydrolysis of the acetate (259 R = OAc) to its alcohol (259 R = OH) and formation of the tosylate and the iodide (259 R = I), followed by reaction with lithium dimethylcuprate, afforded a route to A1314-13,17-seco-5a-D-homoandrostene (259 R = Me). The [17a,17a,17a-[2H3]androstene (259 R = CD3) was prepared by treating the iodide (259 R = I) with lithium perdeuteriodimethyl-cuprate. 

In 1952 Gilman and co-workers reported that the yellow, ether-insoluble methylcopper dissolved to give a clear colorless solution on addition of a further equivalent of methyllithium 119). The new copper compound, of composition LiCu(CH3)2, is an ate complex now usually known as lithium dimethylcuprate. Mixed cuprates can be prepared from a preformed organocopper compound, RCu, and a lithium reagent 147, 259, 298, 301). 

Compounds with acidic hydrogen atoms react rapidly with cuprates. Phenylacetylene has been mentioned as one example (223). Another is diethyl phenylmalonate (144), which on addition to lithium dimethylcuprate gave a rapid evolution of methane and the formation of a methyl-copper-like precipitate which did not redissolve. Subsequent to the addition of benzoyl chloride and the customary work-up, only acetophenone and the phenylmalonate were isolated. The reaction may be summarized by Eq. (23). The failure to isolate the acylated product may be ascribed to the formation of the enolate, (II). 

Kim has also studied the corresponding acylation of homocuprates by S-(2-pyridyl) thioates, discussed earlier in the context of total synthesis of monensin and erythronolide A (Sections 1.13.2.2 and 1.13.3.2). Under the standard anaerobic conditions necessary for cuprate formation, good yields of ketones could be derived from acylation of lithium dimethylcuprate (or lithium dibutylcuprate) by S-(2-pyridyl) thiobenzoate and other simple S-(pyridyl) thiol esters (equation 71). Interestingly, if the homocuprate is intentionally placed under an oxygen atmosphere before acylation and then reacted with the S-(2-pyridyl) thioate in oxygen at -78 C, one obtains good yields of the ctnresponding ester (equation 72). 

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