Corey-Link reaction

What is Corey-Link reaction?

The Corey-Link reaction, also known as the Corey-Link amino acid synthesis or Corey-Link procedure, was first reported by Corey and Link in 1992. It is an enantioselective synthesis of α-amino acids achieved through the asymmetric reduction of trichloromethyl ketones using catecholborane and either (R)- or (S)-oxazaborolidine. The resulting alcohols are treated with base and sodium azide, and then the azido group is reduced to an amino group. The trichloromethyl ketones can be prepared from either the nucleophilic addition of trichloromethide to aldehydes followed by oxidation or from acylation of carbon nucleophile by trichloroacetyl chloride.

Corey-Link reaction - general reaction scheme - Corey-Link amino acid synthesis - Corey-Link procedure
Corey-Link reaction (general reaction scheme)

R = alkyl, aryl

The reduction of trichloromethyl ketones by catecholborane with a catalytic amount of either (R)- or (S)-oxazaborolidine is highly selective, with greater than 97:3 of enantioselectivity. Upon treatment with sodium azide and NaOH in aqueous dimethyl glycol, the trichloromethyl carbinol is smoothly converted into α-azido acid with inversion of the configuration. The α-azido acids can then be reduced using palladium-catalyzed hydrogenation, zinc in acetic acid, or possibly by the Staudinger reaction to yield α-amino acids.

The Corey-Link reaction is a useful method for synthesizing α-azido esters, α-azido acids, and α-amino acids with desired stereochemistry using the appropriately chosen chiral catalyst.

References

A general, catalytic, and enantioselective synthesis of α-amino acids
E. J. Corey and John O. Link
Journal of the American Chemical Society 1992 114 (5), 1906-1908
DOI: 10.1021/ja00031a069

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