Direct Oxidative Addition of Reactive Zinc to Functionalized Alkyl, Aryl, and Vinyl Halides

2 Direct Oxidative Addition of Reactive Zinc to Functionalized Alkyl, Aryl, and Vinyl Halides 

The first report of the oxidative addition of zinc metal to organic halides dates back to the work of Frankland [1-4] around 1850. He discovered that dialkylz-inc compounds could be prepared from zinc metal and methyl iodide or ethyl iodide. However, the reaction did not proceed with alkyl bromides or chlorides. Also, no aryl halides were found to undergo the oxidative addition reaction. Several approaches have been reported since that time to increase the reactivity of the zinc metal. The majority of these modifications have employed zinc-copper couples [5-8] or zinc-silver couples. However, all of these procedures still only worked with alkyl iodides. Noller used a mixture of alkyl iodides and bromides but found that the mixture must contain a large percent of alkyl iodide [9]. 

Methods to activate the metal itself include grinding or milling the metal to yield a finely divided metal powder. However, this zinc powder was of limited reactivity and only worked with alkyl iodides. Shriner s approach for activation employed successively washing zinc dust with 20% HCl, water until neutral, then acetone, and finally anhydrous ether [10]. The resulting zinc dust was air dried and used immediately. Cornforth et al. [11] have described a modification of this procedure which involves the washing of zinc dust with 2% HCl, then ethanol, acetone, and finally ether. The resulting zinc dust is dried in vacuo with a crystal of iodine. They reported that the use of this activated zinc in the Reformatsky reaction gave improved yields. 

In 1962, Gaudeman used THF as the solvent for the oxidative reactions and found that the reaction could be extended to allylic and benzylic bromides. Also, alkyl iodides were easily reacted. Knochel has since made considerable advances in activating the metal by using 1,2-dibromoethane and chlorotri-methylsilane [12,13]. Recently, Knochel has reported that adding alkali salts such as LiCl can be used to activate zinc metals. The importance of the alkali salts generated in the Rieke method was pointed out in our first reports in the 1970s. 

Entry Organic halide Zn RX ratio Temperature (°C) Time (h) rield (%) 

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