Preparation and use of organozinc halides

It has also been shown recently that it is possible to prepare organozinc halides by transition metal promoted exchange reactions between commercially 

Subsequent developments indicated that transmetallation to copper was also possible in both catalytic and stoichiometric senses, with the use of the THF soluble copper salt CuCN.2LiCl being especially convenient.7 The formation of these functionalized copper reagents has allowed a substantial increase in the range of products which may be prepared from organozinc halides.8 

The most significant obstacle to be overcome in the preparation of organozinc halides by direct insertion of zinc metal into an organic halide is the intrinsic lack of reactivity of commercially available zinc metal. This is primarily due to a surface coating, for example of zinc oxide, which prevents direct reaction with an organic substrate. The success of attempts to insert zinc metal into an organic halide is entirely dependent upon the care with which the zinc metal is 

As a good compromise between preformed zinc/copper couple which is very easy to prepare on large scale, but not especially reactive, and very reactive Rieke zinc, it is possible to activate commercially available zinc dust (Aldrich -325 mesh) by treatment first with 1,2-dibromoethane and then with chlorotrimethylsilane.7 This process, which is routinely carried out in situ, is a reliable and quick method for the preparation of zinc which is sufficiently reactive for many purposes. 

Preparation of organozinc halides using zinc/copper couple 

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The stereocontrolled (at the C—Zn center) preparation and reactions of organozinc compounds are, however, an active field of research. Diastereomeric cyclic secondary organozinc halides were prepared as mixtures of isomers that appear to be configurationally stable under the experimental reaction conditions used, although the distribution of products can be electrophile-dependent Other cyclic and acyclic diastereomerically... 

Under these standard reaction conditions, the acetonitrile/pyridine mixture can replace the DMF/pyridine one. This solvent mixture is also quite convenient for running the preparation of arylzinc halides. Yields are good to excellent (60-90%) and even higher than those obtained in DMF. However, with bromophenol, no organozinc species was formed in acetonitrile as observed in DMF. The formation of arylzinc species is also effective in a mixture of solvents of acetonitrile-DMF-pyridine (8/1/1) in the presence of C0CI2 (13%) as the catalyst precursor and zinc bromide (30%). This method has also been applied to the formation of organozinc halides from alkyl and alkenyl halides. So far, only low yields have been obtained using the standard reaction conditions in DMF-pyridine. Results are reported in Table 8. 

Direct Reaction of Zn with Alkyl Halides. The direct insertion see Insertion) reaction of Zn metal into alkyl halides - alkyl iodides being the ideal snbstrates - is a nseful reaction to prepare simple or polyfunctional organozinc halide compounds (equation 1). With primary alkyl iodides, the reaction requires an excess of Zn dnst (ca. 3 eqniv), previonsly treated with few mol % of 1,2-dibromoethane and TMSCl, and a temperature of 40 °C in THF. In these conditions, secondary alkyl iodides react at room temperatnre and benzylic and allylic bromides at 0 °C. The insertion see Insertion) into less activated C-X bonds may reqnire more reactive forms of zinc (Riecke zinc), higher temperatures, or the use of polar see Polar Compounds) solvent or cosolvent. 

These reactions are reminiscent of those used in the preparation of Grignard reagents and of Frankland s synthesis of organozinc halides. The products, RMX and R2MX2, are often extremely reactive and disproportionate readily. They can be stabilized, however, by complex formation with other ligands... 

Recently, the required heteroaromatic organozinc halides for the Negishi reaction have also been prepared using microwave irradiation [23]. Suna reported that a Zn - Cu couple (activated Zn), prepared using a slightly modified LeGoff procedure from Zn dust and cupric acetate monohydrate, allowed the smooth preparation of (3-pyridinyl)zinc iodide and (2-thienyl)zinc iodide... 

Organozinc reagents prepared from ultrasonic irradiation of organic halides with Li in the presence of ZnBr2 have recently been used for conjugate addition to a-enones [Eqs. (47) and (48)] (234,235). In the... 

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