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The Heck reaction is a powerful and efficient method of C-C bond formation in which haloarenes and haloalkenes couple with alkenes in the presence of a palladium(0) catalyst. These reactions are often stereo- and regioselective (1). Numerous examples are described in the literature, many involving applications in natural product syntheses (2). Two syntheses for the organic laboratory, which are not Heck reactions but are examples of palladium-catalyzed reactions, are the synthesis of 4-nitro-1-pentynylbenzene described by Brisbois, Batterman, and Kragerud (3) and the oxidation of 2-vinylnaphthalene described by Byers, Ashfaq, and Morse (4).
In the experiment described below, the Heck reaction is used to synthesize isomeric bromocinnamic acids. The following net equation illustrates the overall reaction for synthesis of o-bromocinnamic acid.
The Reaction Mechanism (2, 5-7)
The Heck reaction is an example of a palladium(0)catalyzed bimolecular reaction. Because of its solubility in organic solvents, palladium(II) acetate is selected as a precatalyst (8), which is reduced by triethylamine in situ to palladium(0). Heck and Nolley report that palladium on charcoal may be used in place of palladium(II) acetate, although reactions are slower and yields lower (9). As illustrated by Mechanism I, conversion of Pd^sup 2+^ to Pd^sup 0^ requires a tertiary amine such as triethylamine to function as the reducing agent (7. The amine also assists in the final hydrogen halide elimination step in mechanism II.
In this example of the Heck reaction, an oxidative addition reaction between palladium(0) and an aryl iodide with acrylic acid produces a 6-arylpalladium(II) complex. This complex undergoes an alkene insertion reaction with the acrylic acid. Internal rotation around the C-C bond as indicated positions the sigma-arylpalladium(II) intermediate for subsequent beta-hydride syn elimination, which produces the alkene-aryl iodide coupling product and an iodopalladium hydride. The pd^sup 0^ catalyst is regenerated from this complex by reductive elimination of HI. These four key steps in the Heck reaction mechanism, oxidative addition, alkene insertion, beta-hydride elimination, and reductive elimination, are typical steps in many other syntheses using organometallic catalysts.
The steps in Mechanism II are well documented (2, 5-7). However, some details concerning particular aspects of the mechanism are less certain. Hegedus states: "Mechanistic organometallic chemistry is both more complex and less developed than mechanistic organic chemistry" (7). For example, De Meijere and Meyer mention...