Stereoselective Synthesis of (<i>E</i>)‐α,β‐Dehydroamino Acid Esters

Abstract

Abstract Dehydroamino acid (Dhaa) is recognized as a useful tool or substrate for amino acid and peptide research. Although the stereoselective synthesis of the thermodynamically more stable Z ‐Dhaa has been well examined and established, the stereoselective synthesis of E ‐Dhaa has still remained to be a challenging synthetic task. In this paper, a stereoselective synthesis of E ‐Dhaa esters using a new (α‐diphenylphosphono)glycine is described. The characteristic aspects of the new method are summarized as follows: (i) metal additives play an important role in the promotion of E ‐stereoselectivities. (ii) the use of NaI was effected for the synthesis of E ‐Dhaas bearing an aryl substituent and an amino functionality, (iii) MgBr 2 · OEt 2 and ZnCl 2 contributed to improve the E ‐stereoselective synthesis of E ‐Dhaas bearing an alkyl substituent and an oxygen functionality, (iv) various protecting and functional groups were compatible under the reaction conditions, and (v) N ‐Cbz, Boc, and acyl‐α‐(diphenylphosphono)glycines were served for the stereoselective olefination reaction to provide the corresponding E ‐Dhaas.