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 with a small amount of one enantiomer of CBS catalyst (a Corey–Itsuno reduction). 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 using azide as the nucleophile. The multistep reaction mechanism begins with deprotonation of the alcohol, followed by the oxygen-anion attacking the adjacent trichloromethyl position to form an epoxide. The azide then opens this ring by an SN2 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. An additional nucleophilic reactant, such as hydroxide or an alkoxide, then triggers an acyl substitution there to produce a carboxylic acid or ester. 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.
Bargellini reactionedit
The Bargellini reaction 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.
Referencesedit
^Corey, E. J.; Link, John O. (1992). "A general, catalytic, and enantioselective synthesis of α-amino acids". J. Am. Chem. Soc. 114 (5): 1906–1908. doi:10.1021/ja00031a069.
"Corey–Link Reaction (Corey–Link Amino Acid Synthesis)". Comprehensive Organic Name Reactions and Reagents. Vol. 161. Wiley. 2010. pp. 734–737. doi:10.1002/9780470638859.conrr161.
April 14, 2024
corey, link, reaction, organic, chemistry, name, reaction, that, converts, trichloro, keto, structure, into, aminocarboxylic, acid, alpha, amino, acid, other, acyl, functional, group, with, control, chirality, alpha, position, reaction, named, corey, john, lin. In organic chemistry the Corey Link reaction is a name reaction that converts a 1 1 1 trichloro 2 keto structure into a 2 aminocarboxylic acid an alpha amino acid or other acyl functional group with control of the chirality at the alpha position The reaction is named for E J Corey and John Link who first reported the reaction sequence 1 Process editThe 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 with a small amount of one enantiomer of CBS catalyst a Corey Itsuno reduction 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 using azide as the nucleophile The multistep reaction mechanism begins with deprotonation of the alcohol followed by the oxygen anion attacking the adjacent trichloromethyl position to form an epoxide The azide then opens this ring by an SN2 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 An additional nucleophilic reactant such as hydroxide or an alkoxide then triggers an acyl substitution there to produce a carboxylic acid or ester 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 Bargellini reaction editThe Bargellini reaction 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 edit Corey E J Link John O 1992 A general catalytic and enantioselective synthesis of a amino acids J Am Chem Soc 114 5 1906 1908 doi 10 1021 ja00031a069 Corey Link Reaction Corey Link Amino Acid Synthesis Comprehensive Organic Name Reactions and Reagents Vol 161 Wiley 2010 pp 734 737 doi 10 1002 9780470638859 conrr161 Retrieved from https en wikipedia org w index php title Corey Link reaction amp oldid 1133940739, wikipedia, wiki, book, books, library,
