Lithium cuprates

The regiochcmistry for stoichiometric alkylation with butyl(cyano)copper magnesium bromide is the same as that for the copper cyanide catalyzed reaction. The regiochemistry with dibutyl-copper magnesium bromide is also very similar to that of the copper(I) bromide catalyzed reaction. Lithium cuprates do not exhibit y regioselectivity in this biased system. 

The conjugate addition of lithium cuprates to cinnamates 1 bearing a chiral oxazolidine or imidazolidine ring at the ortho position produced 2 in good to excellent yield upon hydrolysis14. 

Bromo-2-(t-butylsulfonyl)propene (79) reacts with nucleophiles such as lithium benzenethiolate, lithium enolates and Grignard reagents to give a, /(-unsaturated sulfones, which undergo nucleophilic addition of lithium cuprates (equation 68)58. 

The importance of alkali metal binding with available 7r-electron density in the formation of CIPs was also demonstrated by Niemeyer in the structural elucidation of the first monomeric non-solvated lithium cuprate, [(2,6-Mcs2(LI L)2CuLi] 450, formed from the reaction of 2 equiv. of (2,6-Mcs2Gf,I L)Li with /-BuOCu in pentane.447 The complex crystallizes as two different independent molecules in which the C-Cu-C angles differ (171.1° and 173.8°) as does the mode of coordination to the Li cations C pso and rf to one pendant Ph in molecule 1, with an additional rf interaction to a second Ph group in molecule 2. In the second molecule, the Li site is 10% occupied by a Cu ion. 

Scheme 2.8 Mechanistic model for the formation of the reduction product 26 from propargyl oxirane 23 and lithium cuprates.

Scheme 2.9 Influence of copper salt and additives on the SN2 substitution of propargyl oxirane 27 with lithium cuprates. TBS = Si(tBu)Me2.

The 1,5-substitution of l-chloro-2-en-4-ynes with Grignard reagents has been described by Dulcere and co-workers [41] but lacks generality with regard to the nucleophile (see Section 2.3). In contrast, the regioselective reaction of enyne acetates 47 with various lithium cuprates proceeds smoothly in diethyl ether, furnishing exclusively vinylallenes 48 with variable substituent patterns (Scheme 2.17) [42],... 

Ethyl 2,3-epoxypropanoate is a very interesting chiron. It may be opened by various organometallic compounds such as dialkyl, diaryl, and divinyl lithium cuprates, dialkylmagnesium cuprates, trialkylalanes and aluminum acetylides.5 6 The epoxide ring is attacked regiospecifically at the p-position and produces a-hydroxy esters exclusively without racemization. The same result is observed with... 

Scheme 3.10. Diastereoselectivity in 1,4-addition of stannyl-lithium, cuprate, and zincate reagents to enantiopure 4-heteroatom-substituted 2-enoates [59],...

Alkylation reactions reveal a mechanistic aspect of the cuprate reactions different from that of addition reactions. Theoretical analyses of reactions of alkyl halides (Mel and MeBr) [123, 124] and epoxides (ethylene oxide and cyclohexene oxide) [124] with lithium cuprate clusters (Me2CuLi dimer or Me2CuLi-LiCl, Scheme 10.11) resolved long-standing questions on the mechanism of the alkylation reaction. Density functional calculations showed that the rate-determining step of the... 

A similar reaction pathway was found for the Sn2 substitution of an epoxide with a lithium cuprate cluster [124]. In contrast to that in the MeBr reaction, the stereochemistry of the electrophilic carbon center is already inverted in the transition state, providing the reason for the preferred trans-diaxial epoxide-opening widely observed in synthetic studies. The TS for the Sn2 reaction of cyclohexene oxide is shown in Eq. 10.12. 

SCHEME 7. Structures of lithium cuprates and the Schlenck dimer formed by Li reduction of... 

Lithium-cuprate hoherer Ordnung2-5 9-Bora-bicyclo[3.3.1]nonan-Derivate1 aktiviertc aromatische Verbindungen6 Silcium enthaltende Nukleophile6... 

Sodium cuprate yielded less reduction product and less thiophilic addition product than lithium cuprate at both —50 and 0 °C. In the case of silyl thiones chiral at silicon, the reactions with organolithium derivatives and Grignard reagents produce a-silylsulfides with medium to good levels of asymmetric induction and, interestingly, the asymmetry induced at the a-carbon is retained in the subsequent desilylation431 (equation 118), the process being stereoselective. 

The reaction is illustrated by the formation of propiophenone from diphenyl-cadmium and propanoyl chloride (Expt 6.126). Better yields are obtained by carrying out the synthesis in this manner rather than attempting the alternative combination of diethylcadmium with benzoyl chloride. Alternatively an alkyl-lithium cuprate could be used with an aromatic acid chloride (p. 616). 

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