Asymmetric synthesis of α-fluoro-α-sulfenyl-β-ketoesters using DBFOX-Ph/Ni(II) complex

Enantioselective alpha-sulfenylation of alpha-fluoro-beta-ketoesters 4 with phenylsulfenyl chloride catalyzed by DBFOX-Ph/Ni(II) complex afforded the corresponding alpha-fluoro-alpha-sulfenyl-beta-ketoesters 2 in moderate to good yields with excellent enantiomeric excesses up to 93% ee. alpha-Fluoro-alpha-sulfenyl-beta-ketoesters can be effectively converted to tri-fluorinated alpha-sulfenylcarboxylates by the use of DAST, which should be useful intermediates for the synthesis of non-racemized fluorinated isosteres of pharmaceutically attractive SM32. The enantioselective alpha-phenylsulfenylation as well as alpha-pentafluoro-phenylsulfenylation of non-fluorinated beta-ketoesters 5 were also carried out under the same catalyst conditions affording up to 95% ee of the products 6-8. (C) 2009 Elsevier B.V. All rights reserved.