The Nozaki–Hiyama–Kishi reaction is a

nickel Nickel is a chemical element with symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel is a hard and ductile transition metal. Pure nickel is chemically reactive but large pieces are slow ...

/ chromium

coupling reaction A coupling reaction in organic chemistry is a general term for a variety of reactions 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 = ...

forming an alcohol from the reaction of an

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...

with an allyl or

vinyl Vinyl may refer to: Chemistry * Polyvinyl chloride (PVC), a particular vinyl polymer * Vinyl cation, a type of carbocation * Vinyl group, a broad class of organic molecules in chemistry * Vinyl polymer, a group of polymers derived from vinyl ...

halide. In their original 1977 publication, Tamejiro Hiyama and Hitoshi Nozaki reported on a chromium(II) salt solution prepared by reduction of chromic chloride by lithium aluminium hydride to which was added benzaldehyde and

allyl chloride Allyl chloride is the organic compound with the formula C H2=CHCH2 Cl. This colorless liquid is insoluble in water but soluble in common organic solvents. It is mainly converted to epichlorohydrin, used in the production of plastics. It is a chl ...

: : Compared to

Grignard reaction The Grignard reaction () is an organometallic chemical reaction in which alkyl, allyl, vinyl, or aryl-magnesium halides (Grignard reagent) is added to a carbonyl group in an aldehyde or ketone. This reaction is important for the formation of ...

s, this reaction is very selective towards aldehydes with large tolerance towards a range of

functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the re ...

s such as ketones,

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...

s and nitriles. Enals give exclusively 1,2-addition. Solvents of choice are DMF and

DMSO Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula ( CH3)2. This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds ...

, one solvent requirement is solubility of the chromium salts. Nozaki–Hiyama–Kishi reaction is a useful method for preparing medium-size rings. In 1983 the scope was extended by the same authors to include

halides or

triflate In organic chemistry, triflate ( systematic name: trifluoromethanesulfonate), is a functional group with the formula and structure . The triflate group is often represented by , as opposed to −Tf, which is the triflyl group, . For example, ...

s and

aryl In organic chemistry, an aryl is any functional group or substituent derived from an aromaticity, aromatic ring, usually an aromatic hydrocarbon, such as phenyl and naphthyl. "Aryl" is used for the sake of abbreviation or generalization, and "Ar ...

halides. It was observed that the success of the reaction depended on the source of

chromium(II) chloride Chromium(II) chloride describes inorganic compounds with the chemical formula, formula Chromium, CrChlorine, Cl2(H2O)n. The anhydrous solid is white when pure, however commercial samples are often grey or green; it is hygroscopic and readily disso ...

and in 1986 it was found that this is due to nickel impurities. Since then

nickel(II) chloride Nickel(II) chloride (or just nickel chloride) is the chemical compound NiCl2. The anhydrous salt is yellow, but the more familiar hydrate NiCl2·6H2O is green. Nickel(II) chloride, in various forms, is the most important source of nickel for che ...

is used as a

co-catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

. : In the same year

Yoshito Kishi is a Japanese chemist who is the Morris Loeb Professor of Chemistry at Harvard University. He is known for his contributions to the sciences of organic synthesis and total synthesis. Kishi was born in Nagoya, Japan and attended Nagoya Univers ...

et al. independently discovered the beneficial effects of nickel in his quest for palytoxin: :

Palladium acetate Palladium(II) acetate is a chemical compound of palladium described by the formula d(O2CCH3)2sub>n, abbreviated d(OAc)2sub>n. It is more reactive than the analogous platinum compound. Depending on the value of n, the compound is soluble in man ...

was also found to be an effective cocatalyst.

Reaction mechanism

Nickel is the actual

catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

when small amounts of a nickel salt are added to the reaction. Nickel(II) chloride is first reduced to nickel(0) with 2 equivalents of

(as sacrificial catalyst) leaving

chromium(III) chloride Chromium(III) chloride (also called chromic chloride) describes any of several chemical compounds with the formula CrCl3, where can be 0, 5, and 6. The anhydrous compound with the formula CrCl3 is a violet solid. The most common form of the tric ...

. The next step is

oxidative addition Oxidative addition and reductive elimination are two important and related classes of reactions in organometallic chemistry. Oxidative addition is a process that increases both the oxidation state and coordination number of a metal centre. Oxid ...

of nickel into the carbon to halide bond forming an alkenylnickel R–Ni(II)–X intermediate followed by a

transmetallation Transmetalation (alt. spelling: transmetallation) is a type of organometallic reaction that involves the transfer of ligands from one metal to another. It has the general form: :M1–R + M2–R′ → M1–R′ + M2–R where R and R′ can be, but ...

step exchanging NiX with a Cr(III) group to an alkenylchromium R–Cr(III)–X intermediate and regenerating Ni(II). This species reacts with the

carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containi ...

group in a nucleophilic addition. : The amount of nickel used should be low as a direct alkene coupling to a

diene In organic chemistry a diene ( ) (diolefin ( ) or alkadiene) is a covalent compound that contains two double bonds, usually among carbon atoms. They thus contain two alk''ene'' units, with the standard prefix ''di'' of systematic nomenclature. ...

is a side reaction. Related reactions are the

(magnesium), the

Barbier reaction The Barbier reaction is an organometallic reaction between an alkyl halide (chloride, bromide, iodide), a carbonyl group and a metal. The reaction can be performed using magnesium, aluminium, zinc, indium, tin, samarium, barium or their salts. ...

(zinc) and addition reactions involving

organolithium reagent In organometallic chemistry, organolithium reagents are chemical compounds that contain carbon–lithium (C–Li) bonds. These reagents are important in organic synthesis, and are frequently used to transfer the organic group or the lithium atom ...

References

{{DEFAULTSORT:Nozaki-Hiyama-Kishi Nickel Chromium Coupling Reaction Carbon-carbon bond forming reactions Name reactions