Cuprates, lithium dialkyl, reaction with

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%. 

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). 

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. 

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. 

It is noteworthy that in diethyl ether both the methyl and vinyl groups of (1) are transferred to C3 of 2-cyclopentenone. Also note that even in THF (1) undergoes coupUng reactions with acid chlorides and epoxides with preferential transfer of the methyl group. At the present time the selectivity of organic group transfer of mixed lithium dialkyl cuprates is not well understood. ... 

Another transition metal-catalyzed carbon-carbon bond-forming reaction we shall discuss is the Corey—Posner, Whitesides-House reaction. Using this reaction an alkyl halide can be coupled with the alkyl group from a lithium dialkyl cuprate reagent (often called a Gilman reagent). This reaction does not have a catalytic mechanism. 

With this in mind, let s now explore the outcome of a reaction in which an enolate ion is used as a nucleophile to attack an a,(3-unsaturated aldehyde or ketone. In general, enolates are less reactive than Grignard reagents but more reactive than lithium dialkyl cuprates. As such, both 1,2-addition and 1,4-addition are observed, and a mixture of products is obtained. In contrast, doubly stabilized enolates are sufficiently stabifized to produce 1,4 conjugate addition exclusively. 

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