Heck reaction
The Heck reaction (also called the Mizoroki–Heck reaction) is the chemical reaction of an unsaturated halide (or triflate) with an alkene in the presence of a base and a palladium catalyst (or palladium nanomaterial-based catalyst) to form a substituted alkene. It is named after Tsutomu Mizoroki and Richard F. Heck. Heck was awarded the 2010 Nobel Prize in Chemistry, which he shared with Ei-ichi Negishi and Akira Suzuki, for the discovery and development of this reaction. This reaction was the first example of a carbon-carbon bond-forming reaction that followed a Pd(0)/Pd(II) catalytic cycle , the same catalytic cycle that is seen in other Pd(0)-catalyzed cross-coupling reactions. The Heck reaction is a way to substitute alkenes. History. The original reaction by Tsutomu Mizoroki (1971) describes the coupling between iodobenzene and styrene in methanol to form stilbene at 120 °C (autoclave) with potassium acetate base and palladium chloride catalysis. This work was an extension of earlier work by Fujiwara (1967) on the Pd(II)-mediated coupling of arenes (Ar–H) and alkenes and earlier work by Heck (1969) on the coupling of arylmercuric halides (ArHgCl) with alkenes using a stoichiometric amount of a palladium(II) species. In  1972 Heck acknowledged the Mizoroki publication and detailed "independently discovered" work. The reaction conditions differ in catalyst used (palladium acetate) and catalyst loading (0.01 eq.), base used (a hindered amine) and lack of solvent. In these reactions the active catalyst Pd(0) (see reaction mechanism) is formed by Pd coordination to the alkene. In 1974 Heck introduced phosphine ligands into the equation. Catalyst and substrates. The reaction is catalyzed by palladium salts and complexes. Typical catalysts and precatalysts include tetrakis(triphenylphosphine)palladium(0), palladium chloride, and palladium(II) acetate. Typical supporting ligands are triphenylphosphine, PHOX and BINAP. Typical bases are triethylamine, potassium carbonate, and sodium  acetate. The aryl electrophile can be a halide (Br, Cl) or a triflate as well as benzyl or vinyl halides. The alkene must contain at least one sp-C-H bond. Electron-withdrawing substituents enhance the reaction, thus acrylates are ideal. Reaction mechanism. The mechanism involves organopalladium intermediates. The palladium(0) compound required in this cycle is generated in situ from a palladium(II) precursor. For instance, palladium(II) acetate is reduced by triphenylphosphine to bis(triphenylphosphine)palladium(0) (1) and triphenylphosphine is oxidized to triphenylphosphine oxide. Step A is an oxidative addition in which palladium inserts itself in the aryl to bromide bond. Palladium then  forms a π complex with the alkene (3) and in step B the alkene inserts itself in the palladium - carbon bond in a syn addition step. Then follows a torsional strain relieving rotation to the trans isomer (not shown) and step C is a beta-hydride elimination (here the arrows are showing the opposite) step with the formation of a new palladium - alkene π complex (5). This complex is destroyed in the next step. The palladium(0) compound is regenerated by reductive elimination of the palladium(II) compound by potassium carbonate in the final step, D. In the course of the reaction  the carbonate is stoichiometrically consumed and palladium is truly a catalyst and used in catalytic amounts. A similar palladium cycle but with different scenes and actors is observed in the Wacker process. This cycle is not limited to vinyl compounds, in the Sonogashira coupling one of the reactants is an alkyne and in the Suzuki coupling the alkene is replaced by an aryl boronic acid and in the Stille reaction by an aryl stannane. The cycle also extends to the other group 10 element nickel for example in the Negishi coupling between aryl halides and organozinc compounds. Platinum forms strong  bonds with carbon and does not have a catalytic activity in this type of reaction. Stereoselectivity. This coupling reaction is stereoselective with a propensity for trans coupling as the palladium halide group and the bulky organic residue move away from each other in the reaction sequence in a rotation step. The Heck reaction is applied industrially in the production of naproxen and the sunscreen component octyl methoxycinnamate. The naproxen synthesis includes a coupling between a brominated naphthalene compound with ethylene: Variations. Ionic liquid Heck reaction. In the presence of an ionic liquid a Heck reaction proceeds in absence of a  phosphorus ligand. In one modification palladium acetate and the ionic liquid (bmim)PF are immobilized inside the cavities of reversed-phase silica gel. In this way the reaction proceeds in water and the catalyst is re-usable. Heck oxyarylation. In the Heck oxyarylation modification the palladium substituent in the syn-addition intermediate is displaced by a hydroxyl group and the reaction product contains a dihydrofuran ring. Amino-Heck reaction. In the amino-Heck reaction a nitrogen to carbon bond is formed. In one example, an oxime with a strongly electron withdrawing group reacts intramolecularly with the end of a diene to  form a pyridine compound. The catalyst is tetrakis(triphenylphosphine)palladium(0) and the base is triethylamine.