Acetylene carbocupration

Although acetylene carbocupration and conjugate addition have previously been considered to be two separate reactions, they have been shown to share essentially the same reaction mechanism. The kinship of carbocupration, conjugate addition, Sn2 allylation, and Sn2 alkylation has now been established, through the theoretical studies of Nakamura, Mori, and Morokuma. 

Under controlled conditions, divinylcuprates derived from acetylene carbocupration can be converted to the (IZ, 3Z)-bis(dienyl)cuprates using an excess of acetylene. Reacting the divinylcopper intermediates with electrophiles affords conjugated (Z, Z)-dienes in a highly stereoselective manner." ... 

The apparatus must be flushed with acetylene in order to remove all traces of oxygen. Acetylene dissolved in acetone is most appropriate. Acetylene obtained from tanks which contain solvents such as dimethylformamide (or other solvents) gave lower yields of carbocupration. 

Organocopper chemistry is still rapidly expanding its syntlietic scope. Hie scope of carbocupration, previously limited to acetylenes, has recently been extended to olefins [33-36]. 1,6-, 1,8-, 1,10-, and 1,12-Addition and 1,5-Su2" substitution reac-... 

The carbocupration of acetylene takes place smoothly in a cis fashion, providing a reliable synthetic route to vinyl copper species (Eq. 10.8) [24]. Magnesium and zinc,... 

In the addition of Me2CuLi reagents to electron-deficient acetylenes [85-88], DCD-type complexes have been identified by NMR [84, 89]. As shown below, an ynoate affords a vinylcopper intermediate, while an ynone instead affords an allenolate (Eq. 10.9). The origin of this diversity remains unclear. A related carbocupration mechanism has also been proposed for the reaction with allenylphosphme oxide [53]. Olefin carbocupration of dienes [90] and cyclopropenes [34, 36] is known, but these mechanisms also remain unclear. 

The carbocupration of acetylene has been studied systematically for five model species - MeCu, Me2Cu, Me2CuLi, Me2CuLi LiCl, and (Me2CuLi)2 [91] - all of which have been invoked once in a while in discussions of cuprate mechanisms. A few general conclusions have been made regarding the reactivities of these reagents with 71-acceptors ... 

Fig. 10.3. Snapshots of intermediates on the potential energy surface of carbocupration of acetylene.

Fig. 16.17. Mechanism of the carbocupration of acetylene (R = H) or terminal alkynes (R H) with a saturated Gilman cuprate. The unsaturated Gilman cuprate I is obtained via the cuprolithiation product E and the resulting carbolithiation product F in several steps—and stereoselectively. Iodolysis of I leads to the formation of the iodoalkenes J with complete retention of configuration. Note The last step but one in this figure does not only afford I, but again the initial Gilman cuprate A B, too. The latter reenters the reaction chain "at the top" so that in the end the entire saturated (and more reactive) initial cuprate is incorporated into the unsaturated (and less reactive) cuprate (I). - Caution The organometallic compounds depicted here contain two-electron, multi-center bonds. Other than in "normal" cases, i.e., those with two-electron, two-center bonds, the lines cannot be automatically equated with the number of electron pairs. This is why only three electron shift arrows can be used to illustrate the reaction process. The fourth red arrow—in boldface— is not an electron shift arrow, but only indicates the site where the lithium atom binds next.

The basicity of Gilman cuprates is so low that they do not undergo acid/base reactions with acetylene or higher terminal alkynes. Instead, Gilman cuprates effect the car-bocupration of the C=C triple bond (Figures 13.12 and 13.13). This reaction formally resembles the hydroboration of a C=C triple bond ( see example in Figure 13.10). The regioselectivity also is the same hence, the metal is connected to the Cl center of a terminal alkyne. Finally, the reaction shows the same stereoselectivity as in the case of the hydroboration of a C=C triple bond carbocupration occurs as a cis addition. 

Various functionalized alkynes can be submitted to carbocupration reactions, such as alkoxyalkynes,150 alkynyl carbamates,151 acetylenic orthoesters,152 and thioalkynes.153 The carbocupration of orthoesters, for example, 204, has been used to prepare a-substituted esters of the type 206 by acidic hydrolysis of the adduct 205 (Scheme 51).152 This allows the formation of regioisomers that are not accessible by copper-mediated addition to acetylenic esters. A stereoselective synthesis of trisubstituted alkenes has been described by Normant et al.lSd> starting from phenylthio-acetylene 207. Carbocupration with lithium di- -butylcuprate affords the intermediate 208 which, upon addition of /z-butyllithium, undergoes a 1,2-metalate rearrangement to the vinylcuprate 209. The latter can be trapped with various electrophiles, for example, ethyl propiolate, providing product 210 with complete regio- and stereocontrol. 

This reaction illustrates a stereoselective preparation of (Z)-vinylic cuprates, 5 which are very useful synthetic Intermediates. They react with a variety of electrophiles such as carbon dioxide,5,6 epoxides,5,6 aldehydes,6 allylic halides,7 alkyl halides,7 and acetylenic halides 7 they undergo conjugate addition to a,6-unsaturated esters,5 6 ketones,6 aldehydes,6 and sulfones.8 Finally they add smoothly to activated triple bonds6 such as HCSC-OEt, HC3C-SEt, HC=C-CH(0Et)2. In most cases these cuprates transfer both alkenyl groups. The uses and applications of the carbocupration reaction have been reviewed recently.9 The configurational purity in the final product 1s at least 99.951 Z in the above transformations. 

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