Magnesium-halogen exchange

Remarkably, halogen-magnesium exchange can also be extended to aryl and heteroaryl bromides [24, 25], Thus, the functionalized aryl bromides 28 and 29 (Scheme 2.7) were converted, at 0 °C and at —30 °C, respectively, into the corresponding Grignard reagents. After treatment with CuCN, the copper derivative 30 and 31 were obtained. Subsequent treatment with typical electrophiles such as benzoyl bromide or allyl bromide furnished the products 32 and 33, in 70 and 80% yields. 

The presence of bis[2-(A,A-dimethylamino)ethyl]ether allows a selective halogen-magnesium exchange of iodo- and bromoaromatics at ambient temperature using iso-propylmagnesium chloride. Sensitive carboxylic ester and cyano groups are well tolerated (equations 29 and 30). ... 

Halogen-magnesium exchange reactions with triorganomagnesates were reported independently from academia" and industry in 2001. 

TABLE 9. Halogen-magnesium exchange of dihaloarenes followed by reaction with propanal... 

Preparation of some azulenylmagnesium species was achieved by the halogen-magnesium exchange reactions of iodoazulenes with lithium tributylmagnesate at low temperatures (equations 29-33) . The reactions offer access to a variety of functionalized azulenes including azulenylphosphine, -stannane and -boronic ester. 

A. Generation of Magnesium Carbenoids by Halogen-Magnesium Exchange Reaction... 

An intramolecular 1,5-C,H insertion reaction was reported from substituted bromo-iodoalkane and halogen-magnesium exchange reaction (equation 24) °. Indeed, treatment of bromoiodoalkane (86) with i-PrMgCl in ether at —78°C to —20°C resulted in the formation of magnesium carbenoid 87. The 1,5-C,H insertion of 87 took place to afford a cyclopentane derivative (88) however, the yield was not satisfactory. 

Convenient alternatives to direct deprotonation of ethers are tin-lithium exchange [199, 258-261], halogen-magnesium exchange [262], or reductive cleavage of 0,Se-acetals [263, 264], Another synthetic equivalent of a-metalated ethers are (alkoxymethyl)phosphonium salts [265]. 

Acrylic acid derivatives with a heteroatom (N, O, S, Hal) at C-3 can be cleanly deprotonated at this position with BuLi or LDA at low temperatures [329, 333-338] (Scheme 5.37). Some of these anions rearrange to the a-metalated acrylates on warming [329], but can also decompose (see Section5.4.7). Non-heteroatom-substi-tuted lithium /3-lithioacrylate [329] or /3-magnesioacrylic acid derivatives [339, 340] have been prepared by bromine-lithium or halogen-magnesium exchange. 

Oshima, K. Selective halogen—magnesium exchange reaction via organomagnesium ate 483 complexes./. Org. Chem. 2001, 66, 4333—4339. 

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