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

4.4.16 S-Metby1-(2S,4S)-2-[(be~to~~nyI ]amin&th JI-1-(4-methyl-2,6,7-
a.i-onabieyclo[2.2~]OCf-l-yl)pentan~te, Cbz-L-Glu(pEt)(OMe)-OB0 ester, 4.743.
Cbz-L-Glu(0Me)-OB0 ester 4.69 (0.325 g, 0.85 mmol) was dissolved in dry THF (30
mL) then cooled to -78°C whüst stirring under Ar. In a second flask, L iiiDS (2.57
mL, 2.57 mmol, 1.OM in TEIF) was added to dry THF (5 mL) then cooled to -78°C
whilst stimng under Ar. The Cbz-L-Glu(0Me)-OB0 ester 4.69 was then transferred
dropwise to the second flask via cannda. The mixture was allowed to stir at -78°C for 1
hour before ethyl iodide (0.34 mL, 4.25 mmol) was added by syringe. The mixture was
allowed to stir for 6 hours at -78OC before being poured into 3% NH&l (20 mL) and
extracted with Et20 (100 mL). The organic layer was then extracted with 3% WC1 (20
mL), saturated NaHC03 (20 mL), brine (20 mi,) and dried over MgS04. The solvent was
removed in vacuo to reveal a yellow oil which was mer purified by flash
chromatography (1: 1 Et0Ac:Hex. 0.5% Etm to give a clear oil in 68% yield (0.234 g).
[a120D = -25.6 (c = 1.24, EtOAc); TU3 (1: 1, EtOAc:Hex), Rf = 0.61; 'H NMFt (Acetone-
&, 300 MHz) 6 7.42-7.24 (m, 5H, ArH), 5.63 (d, 1 H, J = 10.3i-I~. NH), S.lW.98 (m 2H,
CbzCH20), 3.86 (s, 6H, OB0 ester Cm), 3.88-3.78 (m, 1H, a-CH), 3.53 (s, 3H,
C02CH3), 2.36-2.26 (m, l& yCH). 1.82 (ddd, 1H, J = 3.6. 8.0, 14.1&, fj-CHH), 1.71
(ddd, 1 H, J = 6.4, 1 1.3, 14.1 Hz. B-CHH), 1.64- 1.44 (m, 2H, CH2CH3). 0.79 (t, 3H. J =