Efficient stereocontrolled synthesis of (S)-Fmoc-β-nitroalanine via oxidation of oxime

Stereocontrolled synthesis of (S)-Fmoc-β-nitroalanine (20) was accomplished from (R)-Fmoc-Ser(tBu)-OH (14) in a total of six steps via an oxime. The oxime (17) was obtained from (R)-Fmoc-Ser(tBu)-H (16), which in turn was obtained by reduction of Weinreb amide (15). Oxidation of oxime was realized with peroxytrifluoroacetic acid at a neutral pH at 0 °C. After removal of the tBu protecting group with 90% TFA/H2O, the hydroxyl group was oxidized with Jones reagent to afford (S)-Fmoc-β-nitroalanine (20) in overall good yield.

Graphical abstractStereoselective synthesis of (S)-Fmoc-β-nitroalanine was accomplished from (R)-Fmoc-Ser(tBu)-OH in a total of six steps via oxidation of oxime.Download full-size image