Lithium dialkyl cuprates

TABLE 2. Product distribution for the displacement reaction of allyl sulfones 9 with lithium dialkyl cuprates ... 

DesilylbrominationThis reaction was first used by Fleming et al. (8, 196 11, 75) in connection with protection of enones, but it is also useful for synthesis of chiral 5-alkylcyclohexenones. Thus reaction of (R)-(-)-l with lithium dialkyl-cuprates gives the trans-adduct 2 as the only product. Of several bromination reagents, only CuBr2 in DMF is useful for conversion of 2 to optically active 3. 

The first examples of allene syntheses using copper-mediated SN2 substitution processes are documented for the reaction of propargylic acetates 7 with lithium dialkyl-cuprates, which led to the formation of allenes 8 with moderate to good chemical yields (Scheme 2.2) [2]. 

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. 

Regiospecific route to silyl enol ethers.11 Silyl enol ethers arc formed regio-specifically by reaction of lithium dialkyl cuprates or diaryl cuprates with 2-trimcthylsiloxyallyl halides. An allylic rearrangement occurs in reactions with hindered halides. 

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... 

The regioselectivity of Grignard addition to /V-acylpyridinium salts can often be controlled by changing the conditions. Thus, e.g., the regioselectivity towards C-4 addition products can be enhanced by the presence of catalytic amounts of copper salts. Direct reaction of salt (281, R = OMe) with lithium dialkyl cuprate gives also almost exclusively the 1,4-dihydro product (283, R = OMe, R1 = Me). 

ArSCu(RMgX)n. These heterocuprates are more useful than lithium dialkyl-cuprates for conjugate addition to enones.5 They are also useful for conjugate addition to the less reactive cinnamates and crotonates.6 Yields are markedly improved by use of 2-methoxyphenylthio as the ligand in additions to the crotonates. 

Figure 10.45 also shows that lithium dialkyl cuprates in solutions containing lithium iodide or lithium cyanide—in addition to the dimeric or monomeric Gilman cuprates presented in Figure 10.44—may contain the following species the contact ion pairs A and C in diethyl... 

R2CuLi /C=C lithium dialkyl cuprate (Gilman reagents) enamine O II H2C=CH —C —H O II H2C=CH—C—R conjugated aldehyde conjugated ketone... 

The reaction of propargylic acetates with excess lithium dialkyl-cuprates [Eq. (98)] in ether between —10° and — 5°C affords a novel... 

Reaction with allylic nitro compounds. All. lie nitro compounds such as 1 undergo Sn2 substitution with lithium dialkyl cuprates to form (E)-trisubstitutcd alkenes selectively. 

Reaction with amino acid derivatives N-Protected amino acid esters substituted by I, Br, or OTs at the y-position undergo substitution reactions with lithium dialkyl cuprates without deteetable racemization. 

Reductive decarboxylation. The reaction of y-carbamoyloxy-a.p-unsaturated esters with a lithium dialkyl cuprate (10 equiv.) in cther-HMPT results in loss of CO, and formation of a p,y-unsaturated ester. Zinc-acetic acid has been used for this reaction," but yields are lower. 

Conjugate addUion-cyclization. 3-Substituied 2-carbomethoxycyclopentanones are prepared conveniently in one step from dimethyl (2E)-hexenedioate by conjugate addition of lithium dialkyl cuprates or higher-order cyan[Pg.348]

Yunker, M B, Plaumann, D E, Fraser-Reid, B, The stereochemistry of conjugate addition of lithium dialkyl cuprate reagents to some carbohydrate a-enones. Can. J. Chem., 55, 4002-4009, 1977. Baer, H H, Ong, K S, Raeactions of nitro sugars. IX. The synthesis of branched-chain dinitro sugars by Michael addition. Can. J. Chem., 46, 2511-2517, 1968. 

In a similar fashion, diethyl cyclopropane-1,1-dicarboxylate (4) reacted with lithium dialkyl-cuprate to give the corresponding malonates S in high yields. Byproducts could be formed by the attack of the organometallic reagent at the carbonyl function. With diethyl 2-vinyl-cyclopropane-1,1-dicarboxylate (6), a preference for the 1,7-addition of the dialkylcuprate was found. Similar observations were made with 1-acetyl- (9,R = Me) and 1-benzoyl-2-vinylcyclopropane (9, R = Ph) when reacted with various dialkyl- and diphenylcuprates and with a vinylcyclopropanedicarboxylate fragment incorporated into a polycyclic system to yield compound 11. ... 

Iithio-3-ethoxypyridine, obtained by the reaction of 3-ethoxypyridine with n-butyl-lithium and TMEDA in THE at — 40 °C, reacts with a wide range of electrophiles to give 2,3-disubstituted pyridines. Esters (R COOR ) are obtained by the reaction of 5-2-pyridylthioates (2-CsH4N-S-COR ) with lithium dialkyl-cuprates (R jCuLi) under oxygen. The reaction of these substrates in a nitrogen atmosphere is known to produce ketones (R COR ). 

This reaction followed by reaction with lithium dialkyl cuprates is an attractive route to trisubstituted olefins from disubstituted acetylenes. 

---