One-carbon chain extension of esters to α-chloroketones -α safer route

21 May 2004

A recent publication from the BMS Process R&D Group describes an alternative route for converting an ester in to an ?-chloroketone. Typically a methyl ester is reacted with dimethylsulphoxonium methylide, formed by reacting trimethylsulphoxonium chloride with potassium tert-butoxide, to generate a β-keto sulphur ylide. Yields were >80% (10-15% lower if the ylide is formed from trimethylsulphoxonium iodide). Heating the intermediate with anhydrous HCl in THF gave the desired a -chloroketones in >90% yield.

This methodology was extended to include N-protected a -amino acid esters as substrates in good yield and optical purity. For phenylalanine derivatives racemisation was observed unless a p-nitrophenyl ester was used as substrate. In this case no yield drop was observed when trimethylsulphoxonium iodide was used in place of the chloride.

J. Org. Chem. , 2004 , 69 (5) , 1629-1633.