Stereoselective Synthesis of α-Fluorinated Amino Acid Derivatives

✍ Scribed by Atsushi Tarui; Kazuyuki Sato; Masaaki Omote; Itsumaro Kumadaki; Akira Ando

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 395 KB
• Volume: 352
• Category: Article
• ISSN: 1615-4150
• DOI: 10.1002/adsc.201000506

✦ Synopsis

Abstract

This account concentrates on our new methodologies for the synthesis of fluorine analogues of amino acids and their derivatives using the Reformatsky‐type reactions of ethyl bromodifluoroacetate and ethyl dibromofluoroacetate with imines promoted by the Wilkinson catalyst. First, we present the rhodium‐catalyzed Reformatsky‐type reaction of ethyl bromodifluoroacetate with imines using diethylzinc for the chemoselective synthesis of α,α‐difluoro‐β‐lactams and non‐cyclized products, 3‐alkylamino‐2,2‐difluorocarboxylates. This reaction was expanded to the asymmetric synthesis of difluoro‐β‐lactams using two types of chiral auxiliaries. To develop another methodology for the synthesis of monofluoro analogues of amino acids and their derivatives, we investigated the reaction of ethyl dibromofluoroacetate with imines using diethylzinc, and found that this Reformatsky‐type reaction proceeded without a rhodium catalyst in diethyl ether to give syn‐α‐bromo‐α‐fluoro‐β‐lactams stereoselectively. Interestingly, by changing the solvent to acetonitrile, the Reformatsky‐type aza‐Darzens products, syn‐2‐fluoroaziridine‐2‐carboxylates, were obtained chemo‐ and stereoselectively.