Facile Synthesis of 3‐Hydroxyglutamic Acids via Cyanation of Chiral N‐Acyliminium Cation Derived From (S)‐Malic Acid

Abstract

Facile synthesis of 3‐hydroxyglutamic acids via cyanation of an N‐acyliminium intermediate derived from (S)‐malic acid is described. The chiral cyclic imide derived from (S)‐malic acid was converted to an acetoxylactam by reduction with sodium borohydride followed by acetylation. The obtained acetoxylactam was treated with trimethylsilyl cyanide in the presence of boron trifluoride etherate to give the corresponding cyanolactam in high yield, even though the diastereoselectivity of the cyanation reaction was moderate. The diastereomers of the cyanolactam were chromatographically separable and were independently converted to (2R,3S)‐ and (2S,3S)‐3‐hydroxyglutamic acids.

Keywords:

• cyanation
• 3‐hydroxyglutamic acid
• malic acid
• N‐acyliminium cation