Organomagnesiums, 154. with copper halides

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.). 

Some examples to illustrate these categories are listed in Table 8.1. Many examples of reactions between organomagnesium compounds and organic halides are tabulated in General Ref. [A] it should be noted, however, that for many of the earlier experiments, transition metals may have been present as impurities in the magnesium used. While under some circumstances transition metal catalysis may be beneficial, under the conditions commonly used in the early experiments it usually led to a proliferation of products. For reactions with primary alkyl and allylic halides, catalysis with copper(i) salts is often beneficial examples of such reactions are also shown in Table 8.1 and a procedure follows. 

The reaction of organolithiums or organomagnesium halide reagents with gold halides proceeds similarly to the copper halides in a 1 1 ratio. Their phosphine complexes can be isolated and characterized. In a 2 1 ratio, the transmetallation reaction is followed by ate complexation to form organoaurate complexes ... 

Reactions of organomagnesium compounds with dialkyl sulfates or alkyl sulfonates often give satisfactory yields of the products of displacement of sulfate or sulfonate. Side-reactions have been observed, but they can often be avoided for example, an excess of the sulfate or sulfonate should be used with Grignard reagents, as some is consumed by nucleophilic attack by halide ion [A]. The dialkyl sulfates are reactive, but hazardous. Toluenesulfonates (tosylates) are less reactive, but their reactions are catalysed by copper complexes the reactions of trifluoromethanesulfonates (triflates) are catalysed by nickel complexes. Reactions of Grignard reagents with secondary tosylates appear to follow an Sn2 mechanism, with inversion of configuration [43],... 

As mentioned in 5.4.2.2.1(i) the purity of the reagents may be critical for success this also holds for the solvent employed. Ethers should be free of peroxides (washing with aq FeSO ). They are dried by refluxing and distillation from Na wire or Na-K alloy under an inert atmosphere. Absence of O2 and HjO can be achieved by distillation from Na metal and benzophenone (blue benzophenone-ketyl, or better the copper-colored disodium adduct), from LiAlH4 or from organomagnesium-halide reagents, such as CjHsMgBr. 

Organomagnesiums frequently prove superior also in other types of reactions. They may facilitate the oxidation of a carbon-metal to a carbon-oxygen bond, secure clean monoaddition of an acetylide to an activated ester (a critical issue in a monensin synthesis X favor in the presence of a copper catalyst 1,4-addition onto a conjugated enone over 1,2-addition, reorient the attack of formaldehyde on a benzylic entitiy from the a- to the or /to-position, and provide diastereoselectivity in nucleophilic additions onto aldehydes. Furthermore organomagnesiums combine under carbon-carbon linking with a variety of organic halides, tosylates, and acetates if the process is mediated by transition elements such as palladium(O) copper(I), nickel(II) or iron(II) Organoalkalis are often less fit to enter such catalytic cycles. 

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