Lithium alkyl cuprates

The alkyls and aryls may be obtained by interaction of copper(I) halides with lithium or Grignard reagents. The alkyls usually decompose readily but methyl copper, a bright yellow polymer insoluble in organic solvents, is reasonably stable it can be used in certain organic syntheses, but the use of lithium alkyl cuprates... 

Lithium Alkyl Cuprates. These important species are commonly used in ether or a similar solvent for a wide variety of organic syntheses. They are especially useful for C—C bond formation by interaction with organic halides ... 

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). 

Ester enolates which contain the chiral information in the acid moiety have been widely used in alkylations (see Section D.1.1.1,3.) as well as in additions to carbon-nitrogen double bonds (sec Section D.1.4.2.). Below are examples of the reaction of this type of enolate with aldehydes720. The (Z)-enolate generated from benzyl cinnamate (benzyl 3-phenylpropcnoate) and lithium (dimethylphenylsilyl)cuprate affords the /h/-carboxylic acid on addition to acetaldehyde and subsequent hydrogenolysis, The diastereoselectivity is 90 10. 

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. 

SECONDARY AND TERTIARY ALKYL KETONES FROM CARBOXYLIC ACID CHLORIDES AND LITHIUM PHENYLTHIO(ALKYL)CUPRATE REAGENTS tert-BUTYL PHENYL KETONE... 

The procedure described here illustrates the preparation of mixed lithium arylhetero(alkyl)cuprate reagents and their reactions with carboxylic acid chlorides,4 These mixed cuprate reagents also react with a,a -dibromoketones,12 primary alkyl halides,4 and a,/3-unsaturated ketones,4 with selective transfer of only the alkyl group. 

For use of other organocopper reagents in converting carboxylic acid chlorides to ketones, see G. H. Posner and C. E. Whitten, Tetrahedron Lett., 1815 (1973) G. H. Posner, C. E. Whitten, and P. E. McFarland, J. Amer. Chem. Soc., 94, 5106 (1972). For a recent report on direct and convenient preparation of lithium phenylthio (alkyl)-cuprate reagents, see G H Posner, D J Brunelle, and L. Sinoway, Synthesis, 662 (1974). 

Lithium, methyl, 55,7, 10 Lithium, phenyl-, 55,11 Lithium phenylthio(alkyl)cuprates, 55,122 LITHIUM, phenyltluo(fe/f-butyl)cuprate [Lithium, phenylthio( 1,1 -dimethyl-ethyl)cupiate, 55,122 Lithium, 1-propenyl-, 55, 111 LITHIUM, ( >l-propenyl-, 55, 103 Lithium thiophenoxide [Ben7enethiol, lithium salt], 55, 122... 

Heterometallic alkali metal phosphide complexes with transition metals have also been reported. The complex [(Cy2P)3Hf(ju.-PCy2)2Li (DME)] results from the reaction of LiPCy2 with HfCl4(THF) (98). This complex persists in solution. Jones et al. have reported the synthesis and reactivity toward a range of electrophiles of a series of lithium di-t-butylphosphido(alkyl)cuprates [RCu(PBu2)Li] (R = Me,... 

Coupling with enol esters (7, 93). A new synthesis of an alkyl-substituted alkene involves coupling of a lithium dialkyl cuprate with an enol triflate,1 available from a ketone by reaction with triflic anhydride and 2,6-di-t-butylpyridine.2 A wide variety of organocuprates can be used and the geometry of the enolate is largely retained. Reported yields are in the range 60 100%. 

Z)-Alkenes. Lithium dialkyl cuprates undergo syn-addition to acetylene to afford (Z)-dialkenyl cuprates in quantitative yield. The products can be alkylated under conditions by which both alkenyl groups are used. In the case of reactive halides 2 equivalents of HMPT is necessary with less reactive halides 3 equivalents of trielhyl phosphite is also necessary (equation 1). The products are essentially only the (7,)-isomers.11... 

Dialkylation of enones. 6 The reaction of a lithium dialkyl cuprate (excess) with an 2,/3-unsaturated ketone substituted by a heteroatom at the / -position (I) results in two successive conjugate additions to introduce an alkyl group at both the ft- and / -position. 

As stated above, intermolecular coupling reactions between carbon atoms are of limited use. In the classical Wurtz reaction two identical primary alkyl iodide molecules are reduced by sodium. n-Hectane (C100H202), for example, has been made by this method in 60% yield (G. Stallberg, 1956). The unsymmetrical coupling of two alkyl halides can be achieved via dialkylcuprates. The first halide, which may have a branched carbon chain, is lithiated and allowed to react with copper(I) salts. The resulting dialkylcuprate can then be coupled with alkyl or aryl iodides or bromides. Although the reaction probably involves radicals it is quite stereoselective and leads to inversion of chiral halides. For example, lithium diphenyl-cuprate reacts with (R)-2-bromobutane with 90% stereoselectivity to form (S)-2-phenylbutane (G.M. Whitesides, 1969). 

Leland and Kotick(87) extended their work to include B/C cis and B/C trans series (82) with antagonist N-substituents (CPM and CBM) in place of methyl and with 8-alkyl substituents. The latter substituents were inserted by reaction of intermediates 87 and 88 with lithium methyl cuprate. Lithium ethyl cuprate gave little of the desired product, and it was found more convenient to proceed to 8-ethyl derivatives by hydrogenation of the more amenable 8-vinyl intermediate. Alkyl functions were assigned the diequatorial conformation by reference to studies on 8-alkylmorphinan-6-ones.<88)... 

Although, as already mentioned, alkylation of several a-lithio cyclopropylsilanes failed 77,78), acetylation and allylation have been successfully effected78) once lithium dibutyl-cuprate (4 eq.) has been added to the THF solution kept at —48 °C (Scheme 26). 

---