Efficient and stereoselective synthesis of threo-β-hydroxy-l-glutamic acid via a tandem (Z)-olefination-conjugate addition

threo-β-Hydroxy-l-glutamic acid 1 is an attractive target as a biologically active compound and as a chiral synthon. The required β-hydroxyl group in 1 was efficiently and stereoselectively introduced via an intramolecular conjugate addition of the N-hydroxymethyl group of γ-amino-α,β-unsaturated (Z)-ester 4. While the corresponding (E)-ester 3 gave a lower selectivity of ca. 5:1 in the intramolecular conjugate addition, a selectivity of up to 70:1 was shown with (Z)-ester 4. The tandem (Z)-olefination-conjugate addition could be achieved by simply changing the reaction conditions to give a selectivity of >20:1. Thus, the target compound 1 was obtained as its hydrochloride salt in 70% overall yield over four steps from lactol 2.