The Heck reaction (also called the Mizoroki–Heck reaction) is the

chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...

of an unsaturated

halide In chemistry, a halide (rarely halogenide) is a binary chemical compound, of which one part is a halogen atom and the other part is an element or radical that is less electronegative (or more electropositive) than the halogen, to make a fluor ...

(or triflate) with an

alkene In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...

in the presence of a base and a

palladium catalyst Palladium is a chemical element with the symbol Pd and atomic number 46. It is a rare and lustrous silvery-white metal discovered in 1803 by the English chemist William Hyde Wollaston. He named it after the asteroid Pallas, which was itself na ...

(or palladium

nanomaterial-based catalyst Nanomaterial-based catalysts are usually heterogeneous catalysts broken up into metal nanoparticles in order to enhance the catalytic process. Metal nanoparticles have high surface area, which can increase catalytic activity. Nanoparticle catalyst ...

) to form a substituted alkene. It is named after Tsutomu Mizoroki and

Richard F. Heck Richard Frederick Heck (August 15, 1931 – October 9, 2015) was an American chemist noted for the discovery and development of the Heck reaction, which uses palladium to catalyze organic chemical reactions that couple aryl halides with alkenes ...

. Heck was awarded the 2010

Nobel Prize in Chemistry ) , image = Nobel Prize.png , alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...

, 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 reaction In organic chemistry, a cross-coupling reaction is a reaction where two fragments are joined together with the aid of a metal catalyst. In one important reaction type, a main group organometallic compound of the type R-M (R = organic fragment, M = ...

s. 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, phosphinooxazolines, 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 group, vinyl halides. The alkene must contain at least one sp²-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 Strain (chemistry)#Torsional strain, 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 isomer, 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, (bmim)PF₆ 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 Intramolecular reaction, intramolecularly with the end of a diene to form a pyridine compound. The catalyst is tetrakis(triphenylphosphine)palladium(0) and the base is triethylamine.

References

External links

* The Heck reaction at organic-chemistry.or
Article
{{DEFAULTSORT:Heck Reaction Carbon-carbon bond forming reactions Substitution reactions Palladium Name reactions