Carbozincations processes

The perfect diastereoselectivity observed in these reactions lead to the assumption that they do not proceed via a simple anionic intramolecular cyclization (i.e. carbozincation) as was proposed in earlier61 publications. Cyclizations of non-propargylic substrates15,62 were shown to proceed with significantly lower diastereoselectivity (cis/trans typically 75/25). Thus, in the case of propargylic compounds, e.g. 114, a simple carbozincation process is unlikely to be operative. It was therefore reasoned that the active species in these reactions is not 115-ZnBr but rather its allenic isomer 120, which undergoes a metallo-ene-allene reaction in a chair-like transition state as depicted in equation 5659a. 

Whereas the interpretation of the NMR parameters of di(5-hexenyl)zinc do not suggest any metal-olefin interaction, probably because the chain length is not appropriate to accommodate the latter in the ground state, this interaction may play a crucial role in the reactive complex leading to the intramolecular carbozincation process. Conversely, the chain length is not sufficiently long in the case of di(4-pentenyl)zinc (28) to achieve the requisite conformation for addition to the double bond, but it is favorable for zinc-olefin interaction24,25. 

It has also been reported that treatment of the alkyl iodide 42 with activated zinc led to the spirobicyclic ketone 43. Due to the presence of an activated carbon—carbon bond, THF was a suitable solvent and kinetic studies strongly supported an anionic carbozincation process arising from an open-chain organozinc, although a small part of the cyclic product may derive from an initial radical pathway (equation 15)32. 

In a useful intermolecular carbozincation process, a vinylzinc reagent reacts with allyl halides to give good to excellent yields of the unconjugated 1,4-diene (equation 105)415. The reaction is highly regioselective and occurs at room temperature in 10-20 minutes. 

Thus, the catalytic activity of nickel is explained by the replacement of an unachievable carbozincation by a favorable carbonickelation process, and the catalytic cycle is sustained by two transmetallation reactions. 

The key success of these metal-catalyzed processes lies in the replacement of an unachievable carbozincation by an alternative carbometallation involving the transition metal catalyst, or another pathway such as an alkene-alkene (or alkyne) oxidative coupling promoted by a group IV transition metal complex, followed by transmetallation. An organozinc is ultimately produced and the latter can be functionalized by reaction with electrophiles. 

Due to the low reactivity of alkyl and arylorganozinc reagents towards alkenes and alkynes, it appears clear that the carbozincation chemistry for this class of reagents is intimately associated with transition metal catalysts. Some of the metal-catalyzed/promoted reactions do indeed produce organozinc reagents as the final organometallic species that can further react with an appropriate electrophile, whereas other processes lead to highly functionalized products by an entirely different pathway. 

Recent development of a Ni catalysed alkylzincation of alkynes62 has further expanded the scope of both intramolecular and intermolecular carbozinca-tion. It should be noted, however, that carbozincation may be followed by cross-coupling under the reaction conditions. The current scope of the intramolecular process appears to be limited to five-membered ring formation, and that of the intermolecular version has been limited to phenylethyne derivatives (Scheme 11.18). Further exploration of the scope of this reaction is highly desirable. 

Cyclizations of iodoalkynes have also been demonstrated to proceed with C-C bond formation (Scheme 3-89). Little mechanistic information is available for this process, but a net syn addition across the alkyne was noted. Additionally, intermolecular carbozincations of alkynes were demonstrated under similar... 

The carbozincation reaction of alkenes [97] has so far been mainly used in the case of ethyl group incorporation or in the case of zinc enolates or aza-enolates [98, 99]. By contrast, the Ni-mediated carbozincation of di-substituted alkynes such as 91 is more general, but salt-free diorganozincs are necessary and the regioselectivity of the carbozincation reaction is excellent only for arylacetylenes and TMS-substituted acetylenes (Scheme 4.22) [100]. It is also of interest that the carbozincation of unactivated alkynes can be achieved without a metal catalyst by zinc-atom radical transfer processes [101, 102]. 

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