Oxidative coupling Zinc dust

Copper sulfate, in small amounts, activates the zinc dust by forming zinc—copper couples. Arsenic(III) and antimony(TTT) oxides are used to remove cobalt and nickel they activate the zinc and form intermetaUic compounds such as CoAs (49). Antimony is less toxic than arsenic and its hydride, stibine, is less stable than arsine and does not form as readily. Hydrogen, formed in the purification tanks, may give these hydrides and venting and surveillance is mandatory. The reverse antimony procedure gives a good separation of cadmium and cobalt. 

Only a single example of azofuroxan oxidation to an azoxy derivative is known (99MC15). The most successful way to azoxyfuroxanes is reductive coupling of 4-nitrofuroxans with zinc dust in aqueous acetic acid (Scheme 151). 3-Nitrofuroxans do not form the expected 3,3 -azoxy derivatives the starting compounds decompose under similar conditions (99MC15). 

Zinc dust is frequently covered with a thin layer of zinc oxide which deactivates its surface and causes induction periods in reactions with compounds. This disadvantage can be removed by a proper activation of zinc dust immediately prior to use. Such an activation can be achieved by a 3-4-minute contact with very dilute (0.5-2%) hydrochloric acid followed by washing with water, ethanol, acetone and ether [/55]. Similar activation is carried out in situ by a small amount of anhydrous zinc chloride [156 or zinc bromide [157 in alcohol, ether or tetrahydrofuran. Another way of activating zinc dust is by its conversion to a zinc-copper couple by stirring it (180g) with a solution of 1 g of copper sulfate pentahydrate in 35 ml of water [/55]. 

The Troc group played an important role in Boger s synthesis of Teichopla-nin.243 Considerable effort was expended in optimising the conditions for its removal An example is the deprotection shown in Scheme 8.109. Various metals were used as reductants such as zinc, cadmium and cadmium-lead couple, but the best results (80% yield) were obtained using zinc-lead couple in M aqueous ammonium acetate in THF at room temperature. Zinc-lead couple is easily prepared. Yellow lead oxide is dissolved in warm aqueous acetic acid (1 1) and the solution added to a vigorously stirred suspension of zinc dust in deionised water. The zinc darkens as lead deposits on its surface, and forms clumps that... 

In acetonitrile, methoxybiphenyls are coupled in low yield, but almost quantitatively in dichloromethane-trifluoroacetic acid [135,136]. Yields are low in the first solvent because the cyclized products are more easily oxidized than their precursors and the oxidation products are not stable. In the presence of TEA, the cation radicals derived from the oxidation of cyclized XXII are stable and after reduction with zinc dust, for example, cyclized XXII may be isolated in high yield. 

One of the challenges is to extend the reaction from triflates to less reactive arylsulfonates. The palladium-catalyzed reaction of aryl mesylates results in low yields because of their slow oxidative addition to a palladium(O) complex, but they readily participate in the nickel-catalyzed cross-coupling reaction at 80°-100 °C. A nickel(O) species incorporating dppf ligand, obtained by in situ reduction of 10 mol% of NiCljCdppf) with zinc dust, is recognized as the most effective catalyst (Eq. 43). However, again the reaction needs to be optimized because a... 

Alkyl halides in the presence of a zinc-copper couple, as a mixture of zinc dust and copper(i) iodide, reacted smoothly with a-enones and a-enals in aqueous media (Scheme 4.7). Sonication enhanced the efficiency of the process, leading to 1,4 adduct in good yields (Petrier et al, 1986). Such a conjugate addition was later extended to various electron-deficient alkenes, including a,P-unsaturated esters, amides, nitriles (Dupuy et al., 1991) or phosphine oxides (Pietrusiewicz and Zablocka, 1988). It appeared that the reactivity of the halide (RX) followed the order tertiary > secondary primary and iodide > bromide chloride. The preferred solvent system was aqueous ethanol, but the parameter of highest importance was the solvent composition (Luche and Allavena, 1988a). 

Secondary phosphine oxides have been used in nickel-catalyzed cross-coupling reactions with aryl tosylates and mesylates for the preparation of arylphosphine oxides (Scheme 4.205) [341], These substrates are typically more stable than aryl triflates and can be readily prepared from a wide range of phenols. In terms of the metal catalyst, the authors used a discrete species ((dppONiCl ) and added extra supporting ligand (2 equiv per metal center) to prevent catalyst decomposition. The addition of zinc dust was essential to the success of the reaction, and no arylphosphine oxide was observed without it. 

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