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

4.4.36 1-[(~,4S)-~[(Be11zylo~)carbonyl]amin01l-(metboxyCIVbOny 1)-3-(4-methyl-
2,6,7-trioxabicyc10[2.2.2 ]oct-l-yl)pmpy1]-1~tri~dien-%iurll, Cbz-L-G1u(pN3)-
(0Me)-OB0 ester, 4.106.
Cbz-L-Glu(0Me)-OB0 ester 4.69 (0.600 g, 1.58 mmol) was dissolved in dry THF (5
mL) then cooled to -78°C whilst stimng under Ar. In a second flask, LiHMDS (4.74
mL, 4.74 mrnol, 1.OM in THF) was added to dry THF (15 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 cannula. The mixture was allowed to stir at -78°C for 1
hour before trisyl azide 4.105 (0.825 g, 3.16 mmol) was added, predissolved in dry THF
(10 d), by syringe. The mixtwe was allowed to stir for 6 hours at -78°C before being
poured into 3% W C1 (20 mL) and extnrted with Et20 (100 mi,). The organic layer
was then extracted with 3% m l (20 mL), saturated NaHC03 (20 mL), brine (20 rnL)
and dried over MgS04. The solvent was rpmoved in vacuo to reveal a yellow oil which
was further purified by flash chromatography (1 : 1 EtOAc:Hex, 0.5% Et&) to give a
clear oil in 54% yield (0.08 1 g).
TLC (l:l, EtOAc:Hex), Ur = 0.40; 'H NMR (CDC13, 300 MHz) 6 7.38-7.26 (m, SH,
Am, 5.12-5.02 (m. 2H, CbzC&O), 4.92 (d, IH, J = 10.1Hz, NH), 4.08 (dt, lH, J = 2.9,
10.1 Hz, a-CH), 3.96 (dd, lH, J = 3.7, 10.7 Hz, Y-CH), 3.85 (s, 6H, OB0 ester C&0),
3.71 (s, 3H, Corn3), 2.08 (ddd, 1& J= 2.9, 10.9, 14.5Hz. PCHH), 1.85 (ddd, 1H. J =
224