Grignard reagents and copper

Although aryl chlorides are not usually reactive enough to couple efficiently with alkyl-coppers, heteroaryl chlorides often couple quite well. For example, the most efficient way of alkylating chlorinated phenanthrolines and quinolines, and both 2- and 3-substitued pyridines involves the use of Grignard reagents and copper salts (equation 51)73. 

Chirally modified alkoxycuprates can be generated from organolithium or Grignard reagents and copper(I) salt in the presence of a lithium or magnesium al-... 

A useful method for selective O-acetylation of 5,7-dihydroxyisoflavones has been described. Acetic anhydride and pyridine gives the 7-acetoxy-compound whereas acetic anhydride and perchloric acid yields the 5-acetoxy-isomer nuclear chlorination of the latter occurred at C-8 when it was treated with ethyl AW-dichlorocarbamate. Interaction of isoflavones (222) with Grignard reagents and copper(l) chloride gave the deoxybenzoin (223), which was used in the synthesis of stilbene-like compounds. ... 

An unnecessarily detailed description has been published of the conversion of functionali d carboxylic acids to methyl ketones via the corresponding acid chlorides more significantly functionalized examples of this reaction have been already reported. An explanation has been offered to account for the lack of steric hindrance in the acid chloride in such a ketone synthesis, where the organocopper species is formed in situ from Grignard reagents and copper(i) chloride. The change in relative reactivity... 

When the decalin-epoxide 64 was treated with a large surplus of Grignard reagent and copper iodide, this combination of Lewis acid and nucleophile (see 65) worked as a push-pull system to cleave the epoxide with high regioselectivity, providing the angular substituted diol 66 [21]. 

Butyl Ether. -Butyl ether is prepared by dehydration of -butyl alcohol by sulfuric acid or by catalytic dehydration over ferric chloride, copper sulfate, siUca, or alumina at high temperatures. It is an important solvent for Grignard reagents and other reactions that require an anhydrous, inert medium. -Butyl ether is also an excellent extracting agent for use with aqueous systems owing to its very low water-solubiUty. 

In the cyclic series several examples, as summarized above, have been provided. The diastereoselectivity, l or u, essentially can be controlled by the choice of the halide in the Grignard reagent and the additive, i.e., employing either organomagnesium bromide with copper(I) bromide and a phosphine, or organomagnesium chloride with copper(I) bromide and chlorotrimethylsilane (see also syn/anti selectivity in Section 1.1.1.2.). 

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