organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J.; ...

, the Corey–Link reaction is a

name reaction A name reaction is a chemical reaction named after its discoverers or developers. Among the tens of thousands of organic reactions that are known, hundreds of such reactions are well-known enough to be named after people. Well-known examples include ...

that converts a 1,1,1-trichloro-2-keto structure into a 2-aminocarboxylic acid (an alpha amino acid) or other

acyl In chemistry, an acyl group is a moiety derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids. It contains a double-bonded oxygen atom and an alkyl group (). In organic chemistry, the acyl group (IUPAC n ...

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 rest ...

with control of the

chirality Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is distinguishable from ...

at the alpha position. The reaction is named for

E.J. Corey Elias James Corey (born July 12, 1928) is an American organic chemist. In 1990, he won the Nobel Prize in Chemistry "for his development of the theory and methodology of organic synthesis", specifically retrosynthetic analysis. Regarded by many ...

and John Link, who first reported the reaction sequence.

Process

The first stage of the process is the reduction of the carbonyl to give a 1,1,1-trichloro-2-hydroxy structure. The original protocol used

catecholborane Catecholborane (abbreviated HBcat) is an organoboron compound that is useful in organic synthesis. This colourless liquid is a derivative of catechol and a borane, having the formula C6H4O2BH. Synthesis and structure Traditionally catecholborane ...

with a small amount of one enantiomer of

CBS catalyst The CBS catalyst or Corey–Bakshi–Shibata catalyst is an Chiral synthesis, asymmetric catalyst derived from proline. It finds many uses in organic reactions such as the CBS reduction, Diels-Alder reactions and (3+2) cycloadditions. Pro ...

Corey–Itsuno reduction The Corey–Itsuno reduction, also known as the Corey–Bakshi–Shibata (CBS) reduction, is a chemical reaction in which an achiral ketone is enantioselectively reduced to produce the corresponding chiral, non-racemic alcohol. The oxazaborolidine ...

). The choice of chirality of the catalyst thus gives selectivity for one or the other stereochemistry of the alcohol, which subsequently controls the stereochemistry of the amino substituent in the ultimate product. This 2-hydroxy structure then undergoes a

Jocic–Reeve reaction In organic chemistry, the Jocic reaction, also called the Jocic–Reeve reaction (named after Zivojin Jocic and Wilkins Reeve) is a name reaction that generates α-substituted carboxylic acids from trichloromethylcarbinols and corresponding nucleop ...

using

azide In chemistry, azide is a linear, polyatomic anion with the formula and structure . It is the conjugate base of hydrazoic acid . Organic azides are organic compounds with the formula , containing the azide functional group. The dominant applic ...

as the

nucleophile In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...

. The multistep reaction mechanism begins with deprotonation of the alcohol, followed by the oxygen-anion attacking the adjacent trichloromethyl position to form an

epoxide In organic chemistry, an epoxide is a cyclic ether () with a three-atom ring. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. They are produced on a large scale for ...

. The azide then opens this ring by an S_N2 reaction to give a 2-azido structure whose stereochemistry is inverted compared to the original 2-hydroxy. The oxygen, having become attached to the first carbon of the chain during the epoxide formation, simultaneously displaces a second chlorine atom there to form an

acyl chloride In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group . Their formula is usually written , where R is a side chain. They are reactive derivatives of carboxylic acids (). A specific example o ...

. An additional nucleophilic reactant, such as

hydroxide Hydroxide is a diatomic anion with chemical formula OH−. It consists of an oxygen and hydrogen atom held together by a single covalent bond, and carries a negative electric charge. It is an important but usually minor constituent of water. I ...

or an

alkoxide In chemistry, an alkoxide is the conjugate base of an alcohol and therefore consists of an organic group bonded to a negatively charged oxygen atom. They are written as , where R is the organic substituent. Alkoxides are strong bases and, whe ...

, then triggers an

acyl substitution In chemistry, an acyl group is a moiety derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids. It contains a double-bonded oxygen atom and an alkyl group (). In organic chemistry, the acyl group (IUPAC n ...

there to produce a

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...

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 ar ...

. Various other nucleophiles can be used to generate other acyl functional groups. This sequence of steps gives a 2-azido compound, which is then reduced to the 2-amino compound in a separate reaction, typically a

Staudinger reaction The Staudinger reaction is a chemical reaction of an organic azide with a phosphine or phosphite produces an iminophosphorane. The reaction was discovered by and named after Hermann Staudinger. The reaction follows this stoichiometry: :R3P + ...

Bargellini reaction

The

Bargellini reaction The Bargellini reaction is a chemical reaction discovered in 1906 by Italian chemist Guido Bargellini. The original reaction was a mixture of the reagents phenol, chloroform, and acetone in the presence of a sodium hydroxide solution. Prior to B ...

involves the same type of dichloroepoxy intermediate, formed by a different method, that reacts with a single structure containing two nucleophilic groups. It thus gives products such as morpholinones or piperazinones, alpha-amino esters or amides in which the amine is tethered to the acyl substituent group.

References

* {{DEFAULTSORT:Corey-Link reaction Name reactions Chemical synthesis of amino acids