Negishi carbometalation

C-C Bond Formation (Part 1) by Addition Reactions through Carbometallation Mediated by Group 4-7 Metals, Pages 251-297, E. Negishi and T. Novak... 

Carbometallation of alkenes and alkynes is attracting considerable interest as a potential new method for C—C bond formation. A general treatment is available by Negishi a leading expert of the field.632... 

Negishi and co-workers developed this carbometalation reaction of alkynes with organoalane-zirconocene derivatives, and it has since turned into an often used route to stereo- and regiodefined... 

Negishi, E.-I. Some Newer Aspects of Organozirconium Chemistry of Relevance to Organic Synthesis. Zr-Catalyzed Enantioselective Carbometalation, Pure Appl. Chem. 2001, 73, 239-242. 

Negishi, E.-i., Kondakov, D. Y., Choueiry, D., Kasai, K., Takahashi, T. Multiple Mechanistic Pathways for Zirconium-Catalyzed Carboalumination of Alkynes. Requirements for Cyclic Carbometalation Processes Involving C-H Activation. J. Am. Chem. Soc. 1996,118, 9577-9588. 

In the Zr-catalyzed enantioselective alkylation reactions discussed above, we discussed transformations that involve the addition of alkylmagnesium halides and alkylaluminum reagents to olefins. With the exception of studies carried out by Negishi and coworkers, all other processes involve the reaction of a C-C n system that is adjacent to a C-0 bond. Also with the exception of the Negishi study [Eqs. (6) and (7)], where direct olefin carbometallation occurs, all enantioselective alkylations involve the intermediacy of a metallacyclopentane (cf. Scheme 3). In this segment of our discussion, we will examine the Ni-catalyzed addition of hard nucleophiles (e.g., alkylmagnesium halides) to olefins that bear a neighboring C-0 unit. These reactions transpire by neither of the above two mechanistic manifolds (metallacyclopentane intermediacy or direct carbometallation). Rather, these processes take place via a Ni-Ti-allyl complex. 

The double arylation reaction (Scheme 10.98, path B) also proceeded in this case to form the desired product 294, albeit in low yield. It has been mentioned that the developed carbozirconation also has a potential application to the regio- and stereoselective synthesis of oHgosubstituted alkenes [79]. A consistent extension of this work disclosing the appUcation of the Negishi reagent [81] in carbometallations of alkynylboronates has been pubHshed recently (Scheme 10.99) [82]. 

For two representative reviews see Negishi, E. Bimetalhc Catalytic Systems Containing Titanium, Zirconium, Nickel and Palladium. Their Apphcations to Selective Organic Syntheses Pure Appl. Chem. 1981, 53,2333-2356. Fallis, A. G. Forgione, P. Metal Mediated Carbometallation of Alkynes and Alkenes Containing Adjacent Heteroatoms Tetrahedron 2001, 57, 5899-5913. 

The carbometalation reaction has been reviewed recently [28-30]. Negishi has demonstrated that zirconium(TV) complexes catalyze the carboalumination of MesAl to various alkynes and enynes [31]. Also the Zr-catalyzed asymmetric carboalumination of aUcenes (ZACA reaction) [32-34] has found important applications in the synthesis of natural products [35-37]. Especially efficient was the asymmetric synthesis of insect pheromones such as (S. / ./ ,S. / ,S)-4,6,8,10,16,18-hexamethyl-docosane (88) (Scheme 8) [38]. 

One of the most successful and general approaches to carbometalation reaction of olefins is the Zr-catalyzed carboalumination process developed by Negishi [81-83], As shown in Equation 19 for the case of 4-methylpent-l-ene (140), the chiral zirconocene 141 catalyzes the addition of trimethylalumi-num to give an intermediate adduct 142 [81]. This reactive species can be oxidized to furnish primary alcohol 143 in 92 % yield and 74 % ee. The process could also be conducted with a variety of other trialkylaluminum reagents, and in many cases these afforded the corresponding adducts, such as 145, in high optical purity (91% ee. Equation 20). 

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