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

Cbz-L-Glu(0Me)-OB0 ester 4.69 (0.179 g, 0.47 mmol) was dissolved in dry THF (10
rnL) then cooleci to -78OC whilst stirring under Ar. In a second flask, LiHMDS (1.42
mL, 1.42 mmol, 1.OM in THF) was added to dry THF (15 mL) then cooled to -7S°C
whilst stimng under Ar. The Cbz-LGlu(0Me)-OB0 ester 4.69 was then transferred
dropwise to the second flask via cannuia. The mixture was allowed to stir at -78°C for 1
hour. N-bromosuccinimide (0.092 g, 0.52 mmol) was suspended in THF (10 mL) in a
third fiask and cooled to -78'C. The enolate was then added quickly by cannula to give a
deep purple coloured mixture which was then stimd for approximately 6 houn at -78OC
before king poured into Et20 (70 mL) and extracted with 3% NWI (20 mL), 10%
sodium sulfite (20 mL), saturated NaHC03 (20 mL), bine (20 mL) and dried over
MgSOd. The solvent was removed in vacm to reveal a light yellow oil which was further
purified by flash chromatography (1: 1 Et0Ac:Hex) to give a clear oil in 64% yield (O. 137
8)-
[u]"D = +21.2 (c = 3.00, CH2C12); TLC (1: 1, EtOAc:Hex), Rf = 0.50; 'H NMR (Acetone-
Q, 300 MHz) 6 7.34-7.28 (m, SH, ArH), 5.09-5.04 (m, 2H, CbzCH20), 4.79 (d, 1 H, J =
10.3&, NH), 4.29 (dd, lH, J = 6.1, 8.5H~, po, 4.10 (dt, lH, J = 3.5, 10.3H.z. CECH),
3.85 (s, 6H, OB0 ester Cm), 3.66 (s, 3H, C02CH3), 2.41 (ddd, lH, J = 3.6, 8.6,
lS.OHz, B-CHH), 2.18 (ddd, lH7 J = 3.6, 6.1, lS.OHz, 8-CHH), 0.77 (S. 3H, OB0 ester
13
CC&); C NMR (Acetone& 75 MHz) 6 170.8 @O), 156.4 (TONH), 136.3
230