One-Carbon Chain Extension of Esters to α-Chloroketones: A Safer Route without Diazomethane
- 11 February 2004
- journal article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 69 (5), 1629-1633
- https://doi.org/10.1021/jo035733r
Abstract
The reaction of a variety of methyl esters with dimethylsulfoxonium methylide at 0-25 degrees C affords the chain-extended beta-keto dimethylsulfoxonium ylides. Subsequent treatment with hydrogen chloride in THF proceeds with loss of DMSO to afford the corresponding alpha-chloroketones. This sequence has been utilized to convert the methyl esters of CBZ-protected alanine and valine to the anti N-protected alpha-amino epoxides, which are important pharmaceutical intermediates. When the same protocol is applied to BOC-protected phenylalanine methyl ester, epimerization occurs so that the use of a more reactive aryl ester is required. This chemistry provides a practical route to alpha-chloroketones that avoids the use of toxic and explosive diazomethane.Keywords
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