Copper chloride with Grignard reagents

Scheme 3 Copper-catalysed AAA of cinnamyl chlorides with Grignard reagents tanploying, as chiral ligands, phosphine-phosphOTamidites...

Copper(I) chloride with Grignard reagents can be a very powerful synthetic tool in organic synthesis, as in /-selective allylic substitutions, regioselective Sn2 substitution to... 

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. ... 

After the air in the flask had been replaced completely with nitrogen, 100 ml of dry diethyl ether, 0.20 mol of the cumulenic ether (see Chapter V, Exps. 7, 8 and 11) and 1 g (note 1) of copper(l) bromide were placed in it. A solution of the Grignard-reagent, prepared from 0.50 mol of the chloride (see Chapter II,... 

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. 

The reaction of tert-alkyl Grignard reagents with carboxylic acid chlorides in the presence of a copper catalyst provides ieri-alkyl ketones in substantially lower yields than those reported here.4,14 The simplicity and mildness of experimental conditions and isolation procedure, the diversity of substrate structural type, and the functional group selectivity of these mixed organocuprate reagents render them very useful for conversion of carboxylic acid chlorides to the corresponding secondary and tertiary alkyl ketones.15... 

Addition of RMgBr to nitriles. Grignard reagents react with nitriles slowly if at all, but even r-butylmagnesium chloride will add to nitriles in refluxing THF when catalyzed by a copper(I) salt. The adduct can be converted to a ketimine by anhydrous protonation, to a primary amine by reduction (Li/NH,), or to a ketone by hydrolysis. The actual reagent may be a cuprate such as R3Cu(MgX)2. 

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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