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

4m4.11 5-Methyl-(~,~-2-[(betl~gIo~)carbonyl]~&~~yl-l-(4~thyl-2,6,7-
hiox~bicycio[2~2~]0~t-l-yl)pentan~te, Cbz-L-Giu(yMe)(OMe)-OB0 ester, 4.73.
Cbz-L-Glu(0Me)-OB0 ester 4.69 (0.M g, 1.12 rnmol) was dissoived in dry THF (40
mL) then cwled to -78OC whilst stimng under Ar. In a second flask, LiHMDS (3.48
mL, 3.48 mrnol, 1.OM in THF) was added to dry THF (10 mL) then cooled to -78OC
whilst stirring 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 methyl iodide (0.28 mL, 5.60 mmol) was added by syringe. The mixture was
allowed to stir for 4 hours at -78°C before king poured into 3% N&Cl (20 mL) and
extracted with Et20 (10 mL). The organic layer was then extracted with 3% WC1 (20
rd), saturated NaHCO3 (20 mL), bnne (20 mL) and dned over MgSO*. The solvent was
removed in vacuo to reveal a yellow oil which was fùrthcr purified by flash
chromatography (1:l EtOAc:Hex, 0.5% Et3N) to give a clear oil in 82% yield (0.358 g).
The product was crystailized h m Et0Ac:Hexanes to give 0.3 16 g of white needles (72%
yield after crystallization).
mp 75-76OC, [UJ*~II = -25.6 (c = 1.02, CHzCl*); TLC ( 1 : 1, EtOAcHex), Rf = 0.60; 'H
NMR (Acetone-&, 300 MHz) 6 7.43-7.26 (m. SH, AH), 5.71 (d 1H, J = 10.2H., NH),
5.15-5.05 (m, 2H, CbzCH20), 3.9 1-3.85 (s + rn, 7H, OB0 ester CH20, a-CH), 3.58 (s,
3H, C02CH3). 2.50-2.38 (m. lH, yCH), 1.84 (ddd, lH, J = 5.1, 11.3, 14.OHz, P - 0 ,
197