Zinc-1,2-Dibromoethane

RCu(CN)ZnI.u These new copper reagents are prepared by reaction of primary or secondary iodides with zinc that has been activated with 1,2-dibromoethane and chlorotrimethylsilane. The resulting organozinc compounds are then allowed to react with the THF-soluble CuCN-2LiCl (equation I). Because of the mild conditions, these new reagents can be prepared from iodides containing keto, ester, and nitrile groups. 

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]. 

Russian chemists [228] found that trimethylsilyl groups protect adjacent triple bonds against hydrogenation with poisoned Pd-catalysts. A similar effect is shown in reductions of trimethylsilylated 1,3-diynes with (activated) zinc powder [226]. One disadvantage of the zinc method is that the zinc salts present in the reaction mixture can cause cleavage of the =C-Si bond (this was shown in a separate experiment in which a trimethylsilylated 1,3-diyne was heated with a solution of zinc bromide or chloride in ethanol [2]). It seems therefore important to keep reaction times of the reductions with zinc as short as possible and to activate the zinc powder with a limited amount of dibromoethane. 

To a mixture of 30 g of zinc powder (Merck, analytical grade) and 30 ml of absolute ethanol is added 3.5 ml of 1.2-dibromoethane. The mixture is heated until an exothermic reaction (evolution of ethene and temporary reflux) starts. The activation is completed by heating the mixture for an additional 10 min under reflux. After cooling to about 50 C, the trimethylsilylated diyne (0.05 mol, see Chap. VI for silylation methods) is added in one portion. The introduction of N2 is started and the mixture is heated for 30 min under reflux. After cooling to room temperature, the work-up is carried out in a way similar to that in exp. 2 (no aqueous ammonia is nsed). Z-CjH- CI CHC CSiMe, b.p. 75 020 mmHg, njy(20 ) 1.4592, is obtained in a high yield. 

Zinc powder (30 g, Merck, analytical grade) is activated with dibromoethane (3.5 ml) in 100% ethanol (35 ml) as described in the previous experiments. After cooling to -30 C the protected diyne alcohol (0.10 mol), prepared as described in p. 213) is added in three equal portions over 5 min, while introducing N2- The temperature of the suspension rises fast and... 

The zinc(II) ions can either be introduced in the reaction mixture before running the experiment (from commercially available ZnBr2 or ZnCl2), or generated in situ, in an undivided electrochemical cell, by oxidation of a zinc anode in the presence of 1,2-dibromoethane (Scheme 5). 

This last procedure allows the preparation of anhydrous zinc bromide in the solvent used (CH3CN, DMF etc.). Note that, simultaneously to the electroreduction of dibromoethane,... 

It can be pointed out that results are not reproducible, depending on the quality of the cobalt salt used and particularly of the ZnBr2. This last species should be produced preferably by cathodic reduction of 1,2-dibromoethane combined with the anodic oxidation of a zinc anode according to Scheme 5 (see Section . ). 

Activation of zinc dust in THF with 1,2-dibromoethane and trimethylsilyl chloride... 

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. 

The realization that zinc dust can be activated by treatment, sequentially, with 1,2-dibromoethane and chlorotrimethylsilane, has had a significant impact on... 

Reduction of alkynes.1 Zinc powder activated by 1,2-dibromoethane reduces conjugated diynes to (Z)-enynes in 70% yield. Triple bonds conjugated with an aryl group are also reduced (80-90% yield). A more active, but less selective, reagent is obtained by activation with dibromoethane and then with CuBr and LiBr. This activated zinc reduces monoacetylenic compounds substituted by OH, NR2, and OR groups to the (Z)-alkenes. 

REDUCTION, REAGENTS Bis(N-methylpi-perazinyl)aluminum hydride. Borane-Di-methyl sulfide. Borane-Tetrahydrofurane. Borane-Pyridine. n-Butyllithium-Diisobu-tylaluminum hydride. Calcium-Amines. Diisobutylaluminum hydride. 8-Hydroxy-quinolinedihydroboronite. Lithium aluminum hydride. Lithium 9-boratabicy-clo[3.3.1]nonane. Lithium n-butyldiisopro-pylaluminum hydride. Lithium tri-j c-butylborohydride. Lithium triethylborohy-dride. Monochloroalane. Nickel boride. 2-Phenylbenzothiazoline. Potassium 9-(2,3-dimethyl-2-butoxy)-9-boratabicy-clo[3.3.1]nonane. Raney nickel. Sodium bis(2-methoxyethoxy)aluminum hydride. Sodium borohydride. Sodium borohy-dride-Nickel chloride. Sodium borohy-dride-Praeseodymium chloride. So-dium(dimethylamino)borohydride. Sodium hydrogen telluride. Thexyl chloroborane-Dimethyl sulfide. Tri-n-butylphosphine-Diphenyl disulfide. Tri-n-butyltin hydride. Zinc-l,2-Dibromoethane. Zinc borohydride. 

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. 

Violent reactions with ammonium salts, chlorate salts, beryllium fluoride, boron diiodophosphide, carbon tetrachloride + methanol, 1,1,1-trichloroethane, 1,2-dibromoethane, halogens or interhalogens (e.g., fluorine, chlorine, bromine, iodine vapor, chlorine trifluoride, iodine heptafluoride), hydrogen iodide, metal oxides + heat (e.g., beryllium oxide, cadmium oxide, copper oxide, mercury oxide, molybdenum oxide, tin oxide, zinc oxide), nitrogen (when ignited), silicon dioxide powder + heat, polytetrafluoroethylene powder + heat. 

To a suspension of zinc dust (1.3 g, 20 mmol, —325 mesh Aldrich) previously activated with 1,2-dibromoethane (3mol%) and TMSCl (lmol%) in THF (3mL) was added 4-iodobutyl pivalate (2.84 g, 10mmol) in THF (1 mL). The reaction mixture was stirred for... 

Primary and secondary alkylzinc iodides (RZnI) are best prepared by direct insertion of zinc metal (zinc dust activated by 1,2-dibromoethane or chlorotrimethylsilane) into alkyl iodides or by treating alkyl iodides with Rieke zinc. The zinc insertion shows a remarkable functional group tolerance, permitting the preparation of polyfunctional... 

Zinc dust was previously activated by the addition of carcinogenic 1,2-dibromoethane [0.026 equiv relative to zinc dust (Zn)] followed by chlorotrimethylsilane (TMSCl) (0.018 equiv relative to Zn), which gave rise to serious issues of poor reproducibility and requirement of excess iodide 80 (2.5 equiv relative to 8). Because the Fukuyama coupling reaction has been reported not to proceed with dialkyl zinc (R2Zn), the Schlenk equilibrium of the zinc reagent should lie to the left to achieve... 

---