Insertion of zinc dust

Functionalized organozinc halides are best prepared by direct insertion of zinc dust into alkyl iodides. The insertion reaction is usually performed by addition of a concentrated solution (approx. 3 M) of the alkyl iodide in THF to a suspension of zinc dust activated with a few mol% of 1,2-dibromoethane and MeaSiCl [7]. Primary alkyl iodides react at 40 °C under these conditions, whereas secondary alkyl iodides undergo the zinc insertion process even at room temperature, while allylic bromides and benzylic bromides react under still milder conditions (0 °C to 10 °C). The amount of Wurtz homocoupling products is usually limited, but increases with increased electron density in benzylic or allylic moieties [45]. A range of poly-functional organozinc compounds, such as 69-72, can be prepared under these conditions (Scheme 2.23) [41]. 

Insertion of zinc dust into aryl or heteroaryl iodides is also possible, but polar cosolvents are required in some cases [48, 49]. The use of highly activated zinc (Rieke zinc) prepared by reduction of zinc halides with lithium results in faster insertion (Scheme 2.24) [50-52]. 

In summary, the direct insertion of zinc dust to organic halides is an excellent method for preparing a broad range of polyfunctional organozinc halides bearing various functional groups like an ester" , an ether, an acetate" , a ketone, cyano", halide" , N,N-bis(trimethylsilyl)amino °, primary and secondary amino, amide, phthalimide , sulfide, sulfoxide and sulfone , boronic ester , enone " or a phosphonate . An alternative method is based on transmetalation reactions. 

Interestingly, many electron-defident heterocychc and aryl bromides or iodides are sufRdently activated to react with commercially available zinc powder [14]. In the case of benzylic halides, bromides and even chlorides can be used [12]. Thus, for the functionalized benzylic bromide 12a, the formation of the corresponding benzylic zinc bromide (13a) by the direct insertion of zinc dust is complete within 2h at 5 °C. 

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