Copper-catalyzed reactions carbomagnesiation

Since this report on the copper catalysis in carbomagnesiation across acetylene, a variety of Cu-catalyzed carbomagnesiation reactions of afkynes have been reported. However, the applicable aUcynes are somewhat limited to electronically biased (activated) or heteroatom-containing aUcynes, which will be discussed later. 

A number of examples for the copper-catalyzed carbometallation151,300,300a or stannylmetallation61,61a of G-G double or triple bonds have been described in recent years. For example, reaction of ethynyl carbamate 346 with n-butylmagnesium bromide in the presence of 10 mol.% of copper(i)-iodide induced a smooth regio- and stereoselective carbomagnesiation to afford the vinylmagnesium intermediate 347 which can be trapped with benzaldehyde to the allyl alcohol 348 (Scheme 97).151... 

DFT computations showed that the intramolecular addition of the aryllithium generated from 425 occurs on the central carbon atom of the allenic moiety to yield the intermediate 427 from which lithium ethoxide is eliminated to furnish the benzofuran product 426. Both cyclization processes were found to pass through low-lying transition states, as it would be expected for fast reactions at low temperatures [123]. Further explorations on the anti selectivity in the intramolecular carbolithi-ation by DFT computations revealed additional details regarding the mechanism of this carbocyclization and led the authors to conclude that such a transformation is controlled by the appropriate molecular editing [123]. The synthesis of functionalized heterocycles can be relatively easy to achieve by intramolecular carbometallation reactions. For example, Kunz and Knochel [124] recently reported the preparation of benzothiophene scaffolds 429 by copper-catalyzed carbomagnesiation ofalkynyl thioethers 428 (Scheme 10.148). 

Normant and coworkers demonstrated that the intermolecular carbomagnesiation across acetylene (HC=CH) could be catalyzed by a copper salt . The treatment of w-heptylmag-nesium bromide with acetylene in the presence of a catalytic amount of CuBr (5 mol%) in EtgO at —20 °C followed by the reaction with C2H5CHO and quenching with H2O results in the formation of allylic alcohol 12 in 31% yield (Scheme 9) . The carbomagnesiation takes place in a yw-addition manner. 

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