Lithium dialkylcuprates.

Organometallic compounds of copper were known for a long time before their versatil ity in synthetic organic chemistry was fully appreciated The most useful ones are the lithium dialkylcuprates which result when a copper(I) halide reacts with two equivalents of an alkyllithium in diethyl ether or tetrahydrofuran... 

The second molar equivalent of the alkyllithium adds to the alkylcopper to give a neg atively charged dialkyl substituted derivative of copper(I) called a dialkylcuprate It is formed as its lithium salt a lithium dialkylcuprate... 

Lithium dialkylcuprates react with alkyl halides to produce alkanes by carbon-carbon bond formation between the alkyl group of the alkyl halide and the alkyl group of the dialkylcuprate... 

Lithium diarylcuprates are prepared m the same way as lithium dialkylcuprates and undergo comparable reactions with primary alkyl halides... 

A key step in the reaction mechanism appears to be nucleophilic attack on the alkyl halide by the negatively charged copper atom but the details of the mechanism are not well understood Indeed there is probably more than one mechanism by which cuprates react with organic halogen compounds Vinyl halides and aryl halides are known to be very unreactive toward nucleophilic attack yet react with lithium dialkylcuprates... 

Preparation of alkanes using lithium di alkylcuprates (Section 14 11) Two alkyl groups may be coupled together to form an alkane by the reaction of an alkyl hal ide with a lithium dialkylcuprate Both alkyl groups must be primary (or meth yl) Aryl and vinyl halides may be used in place of alkyl halides... 

The preparation and some synthetic applications of lithium dialkylcuprates were described earlier (Section 14 11) The most prominent feature of these reagents is then-capacity to undergo conjugate addition to a p unsaturated aldehydes and ketones... 

Mentally disconnect one of the bonds to the p carbon so as to identify the group that comes from the lithium dialkylcuprate... 

The principal synthetic application of lithium dialkylcuprate reagents IS their reaction with a 3 unsatu rated carbonyl compounds Al kylation of the 3 carbon occurs... 

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 formation of g-alkyl-a,g-unsaturated esters by reaction of lithium dialkylcuprates or Grignard reagents in the presence of copper(I) iodide, with g-phenylthio-, > g-acetoxy-g-chloro-, and g-phosphoryloxy-a,g-unsaturated esters has been reported. The principal advantage of the enol phosphate method is the ease and efficiency with which these compounds may be prepared from g-keto esters. A wide variety of cyclic and acyclic g-alkyl-a,g-unsaturated esters has been synthesized from the corresponding g-keto esters. However, the method is limited to primary dialkylcuprates. Acyclic g-keto esters afford (Zl-enol phosphates which undergo stereoselective substitution with lithium dialkylcuprates with predominant retention of stereochemistry (usually > 85-98i )). It is essential that the cuprate coupling reaction of the acyclic enol phosphates be carried out at lower temperatures (-47 to -9a°C) to achieve high stereoselectivity. When combined with they-... 

Simple nitrQ ilkdnes such as nitroethane, l-nitropropane, or l-nitropropane are geaer illy b d electrophiles for the 3 2 reacdoas. In contrast, nitro groups at dlylic posidons are readily displaced by thlolaie ions fEq. 7.13 or lithium dialkylcuprates fEq. 7.14. ... 

The stoichiometric reaction of lithium dialkylcuprates in diethyl ether with a-substituted /J-methylallyl sulfoxides and sulfones gives the /-substitution product with high regio- and E stereoselectivity82. The reaction provides a stereoselective method for the synthesis of trisubsti-tuted (TQ-olefins. 

Conjugate Addition. To a solution of 1.5 mmol of lithium dialkylcuprate at — 25 CC is added 1 mmol of methyl ( )-3-[(25,45,55)-3-benzyloxycarbonyl-4-methyl-5-phenyl-2-oxazolidinyl]-propenoate dissolved in 1 mL of dry diethyl ether. After 30 ntin at — 25 C, the mixture is treated with an aq NH3/NH4C1 pH 8 buffer solution and then stirred at r.t. for 15 min. After diethyl ether extraction, the organic layers are dried over Na,S()4 and filtered and the solvent is evaporated under reduced pressure. The crude products are checked by H- and l3C-NMR analyses in order to determine the diastereomer ratios (g 95 5) and then purified by flash chromatography (hexane/ethyl acetate 80 20) yield 70-72%. 

One diastereomer 5 was formed in large excess (98-76% de) on addition of the 2-(l-dimethyl-aminoethyl)phenyl group from the corresponding lithium dialkylcuprate and or lithium alkyl(2-thienyl)cuprate to prostereogenic enones64. 

The addition of alkyllithium, lithium dialkylcuprates and lithium trialkylzincates to either ( )-(2-nitroethenyl)benzene or E)- -nitropropene in the presence of the nonracemic chiral solvent, ( + )-(S,S)-2,3-dimethoxy-Af,AhA, iV -tetramethyl-l,4-butanediamine, gave adducts in low enantiomeric excess (15-28%) as determined by HNMR35. 

The central C—C bond in bicyclo[ 1.1.0] butane has a high -character and is known to behave as an olefin. Thus, 1-arylsulfonylbicyclobutanes 312 reacted with Grignard reagents in the presence of lithium dialkylcuprates or cuprous salts (Me2S, CuBr or CuCl) giving 3-alkyl-1-arylsulfonylcyclobutanes 313406. 

Another group of Japanese workers91 found that the sulphoxonium salt, 7, was reducible to sulphoxides with either alkyllithiums or lithium dialkylcuprates, the exact reaction pathway being complicated by halide ions originating from the preparation of the metal alkyls. However, good yields of methyl phenyl sulphoxide were obtained by reduction of 7 with sulphur dioxide or a thiol in pyridine (equation 37). 

---