Carbocupration mechanism

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. 

Carbocupration of alkynes by zirconacyclopentane derivatives can be performed according to the same procedure. Thus, the zirconocyclopentane 135, obtained by treatment of Bu2ZrCp2 with 1,6-heptadiene, reacts at room temperature with phe-nylacetylene to afford the adduct 136 through a carbocupration-reductive elimination mechanism. Cross-coupling followed by intramolecular carbocupration takes place in the case of the reaction with 1-bromohexyne, producing 137 (Scheme 2.66) [143]. 

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 ... 

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. 

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.

Step 4 of the mechanism shown in Figure 13.26 is new. This step consists of the cis-selective addition of the aryl-Pd complex to the C=C double bond of the acrylic acid methyl ester. This is a carbopalladation of the double bond. A related reaction, the cis-selective carbocupration of C=C triple bonds was mentioned in connection with Figures 13.12 and 13.13. The regioselectivity of the carbopalladation of Figure 13.26 is such that the organic moiety is bonded to the methylene carbon and Pd to the methyne carbon of the C=C double bond. The addition product is an alkyl-Pd(II) complex. 

Ohgofunctional zinc-copper reagents such as 110 react efficiently with 1-bromo-and l-iodoalkynes to furnish functionahzed aUcynes such as 111 in good yields (Scheme 4.25). Presumably, the reaction mechanism consists of a two-step sequence involving carbocupration of the alkyne followed by fS-elimination of copper hahde [115]. Regardless of this, the transformation is of synthetic utility... 

While several NMR spectroscopic studies have established the involvement of Jt- and -complexes in CA of organocuprates, littie evidence was obtained for the carbocupration pathway until the early 2000s, when experimental evidence supporting a carbocuprate-Uke intermediate was reported. Reacting cyclohexenone 1 with customised homocuprate 74 bearing an enolate moiety in its structure afforded bicyclic alcohol 75 as major product (Scheme 28) [120]. The formation of 75 is more consistent with a mechanism involving carbocupration intermediate... 

To summarise, all the experimental data obtained tmtil now support a mechanism of CA in which the organocuprate (stoichiometric reagent or formed in catalytic conditions) adds to the a,p-unsaturated carbonyl compounds to first form a jr-complex. Upon formal oxidative addition, the Cu(III)-intermediate is formed, followed by reductive elimination and subsequent formation of the CA product enolate. The alternative mechanism through carbocupration might become predominant only when using an acetylenic or a carbonyl substrate with specific structure and electronic properties. 

Moving on to heterobimetallic cuprates, the structures of lithiocyanocuprates have been a topic in this article in previous years, and last year saw a review published on the role of cuprates in the addition and substitution chemistries of multiply unsaturated substrates, which collated the evidence for mechanisms by which carbocupration, conjugate addition and Sn2 alkylation occur. ... 

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