Solution and Solid Phase Synthesis of Unusual a-Amino Acids From

By Mitsunobu reaction. Cbz-L-Glu(y-OH)(OMe)OBO ester A% (0.100 g, 0.25 -01)
and Ph3P (0.098 g, 0.38 mmol) were combined and dissolved in dry THF (5 mL) and
stirred at O°C under Ar. DEAD (60 pL, 0.38 rnmol) was added dropwise followed by
(0.97 mL, 0.75 rnmol). The reaction was allowed to warm to room temperature and
stir for 18 h before a TLC indicated the reaction complete. The solvent was removed
under reduced pressure with NaOH trapping the residual HN3. The oily residue could be
purified by flash chromatography (1:l Et0Ac:hexanes) to give pure 4.109 (26 mg, 26%
yield) with the remainder contarninated with diethyl amidodicarboxylate.
TLC (1: 1, EtOAc:Hex), Rf = 0.52; 'H NMR (Acetone-a, 300 MHz) 6 7.38-7.23 (m, SH,
AM, 5.88 (d, 1 H, J = 9.7Hz, NH), 5.08 (d, 1 H, CbzCHHO), 5.00 (d, 1 H, CbzCHHO),
4.18 (br dd, lH, J = 6.3, 6.9Hz, NH), 3.97 (ddd, lH, J = 4.4,9.3, 9.7Hz, a-CH), 3.87 (s,
6H, OB0 ester CH20), 3.69 (S. 3H, C@CH3), 2.08 (ddd, lH, 3 = 4.4, 6.9, 14.1Hz, B-
Cm), 1 -80 (ddd, lH, J = 6.3, 9.3, 14.1 Hz, p-CHH), 0.76 (s, 3H, OBO ester CC&); 13c
NMR (Acetone-&. 75 MHz) 6 170.8 (Cd), 156.3 (CONH), 137.8 (Cbz