The Halogen-Magnesium Exchange Reaction

This procedure had significant advantages compared to the oxidative addition, such as higher yields or less side reactions and is still one of the best methods for the synthesis of perfluorinated Grignard reagents [34]. 

The use of iPrMgBr allows the preparation of Grignard reagent 27 at 0 °C within 30 min starting from the readily available aryl bromide 28. Inverse addition to a solution of acetic anhydride furnishes substituted acetophenone 29 in 88% yield. This procedure is also suitable for a mtdtildlogram scale-up. 

Unprotected acids, amides or benzylic alcohols can be tolerated as well using a combination of organo-magnesium and -lithium reagents [58]. 

An anti-S T substitution is observed with Grignard reagent 116, readily available from aryl iodide 118, providing the cis-tetrahydrocarbazole 119 in almost quantitative yield. In this case, the Grignard reagent undergoes the ring closure in the absence of a catalyst [76]. 

Iodo-substituted pyridines,48,49 uracils,48,50 purines,51 imidazoles, 

Bach has used the selective exchange reaction on 2,4-dibromothiazole for the synthesis of substituted 4-bromothia-zoles.59,59a Lithium magnesiates, prepared by the reaction of an organolithium reagent (2 equiv.) and an 

Treatment of (dibromomethyl)methyldiphenylsilane with Bu3MgLi at — 78 °C leads to a smooth exchange reaction. Addition of CuCN-LiCl causes migration of the butyl group affording a-silyl substituted magnesium species. They react with allyl bromide, acyl chlorides, or a/i-cnoncs in the presence of a copper catalyst.79,7911 

TMSO CN /PrMgCI-LiCI TMSO CN CuCN-2LiCI 

XJ i THF,-40 °C, Pent X MgCI-LiCI ii, PhCOCI Pent Kent 2 h iii, Bu4NF 

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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. 

The halogen-magnesium exchange reaction can be easily applied to solid-phase synthesis, affording polymer-bound Grignard reagent, otherwise unavailable (Scheme 27). 

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