Two effective procedures for the synthesis of trichloromethyl ketones, useful precursors of chiral α-amino and α-hydroxy acids
E. J. Corey, John O. Link and Yang Shao
*Department of Chemistry and Chemical Biology, Harvard
University, Cambridge, Massachusetts, 02138, Email: corey
chemistry.harvard.edu
E. J. Corey, J. O. Link, Y. Shao, Tetrahedron Lett., 1992, 33, 3435-3438.
DOI: 10.1016/S0040-4039(00)92656-X
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Abstract
Trihaloacetic acids can been converted to trichloromethyl and tribromomethyl ketones in good yield by a catalyzed reaction with aldehydes followed by oxidation. A coupling of organozinc intermediates with trichloroacetyl chloride gives trichloromethyl ketones.
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Details
The document describes two effective procedures for synthesizing trichloromethyl ketones, which are useful precursors for chiral O-amino and -hydroxy acids. The first method involves the catalyzed reaction of trichloroacetic acid (TCA) with aldehydes at 23 °C, followed by oxidation. This process generates trichloromethyl carbinols in high yield, even for sensitive aldehydes, by using a mixture of TCA and sodium trichloroacetate (NaTCA) in dimethyl formamide (DMF). The second method involves coupling organozinc intermediates with trichloroacetyl chloride, which is particularly useful when aldehyde precursors are not readily available. Both methods are efficient and practical, providing high-purity trichloromethyl ketones. Additionally, tribromomethyl ketones can be synthesized using similar procedures with tribromoacetic acid (TBA) and its sodium salt (NaTBA). The document includes experimental details and yields for various aldehydes, demonstrating the simplicity and effectiveness of these methods. The research was supported by grants from the National Institutes of Health and the National Science Foundation.
Key Words
trichloromethyl carbinols, tribromomethyl carbinols, chromic acid, ketones
ID: J72-Y1992-610
