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

(ça), 164.0 EONH), 143.3 (Cbz==). 128.3, 127.7, 127.6 (Cbz===), 107.7 (OB0
ester -O), 72.2 (OB0 ester m20), 65.8 (Cb2m20), 53.0 (a-), 50.9 (CO&H3), 32.8
(y-çH), 33.1 (OB0 ester CC&), 29.3 (p-m2), 17.9, 16.3 (yw3), 16.2 (OB0 ester
CCH3) -
4.4024 Methyl-(~4[(bell~ylo~y)carbonyl]amino12-[hydn,xy(pbenyl)metbyI]4-(4-
methyi-2,6,7-tfi0~bi~y~l0[2.2.2 10ct-l-yI)b~tanoate, Cbz-L-Glu(pOHPh)(OMe)-
OB0 ester, 4.91.
Cbz-L-Glu(0Me)-OB0 ester 4.69 (0.107 g, 0.28 mol) was dissolved in dry THF (10
mL) then cooled to -78°C whilst stirring under Ar. h a second flask. LiHMDS (0.87
mL, 0.87 rnmol, 1.OM in THF) was added to dry THF (5 mL) then cooled to -78°C
whilst sturing under Ar. The Cbz-LGlu(0Me)-OB0 ester 4.69 was then transferred
âropwise to the second fiask via cannula The mixture was allowed to stir at -78°C for 1
hour before benzaldehyde (0.14 mL, 1.40 mrnol) was added by syringe. The mixture was
allowed to stir for 6 hours at -78°C before king poured into 3% -1 (10 mL) and
extracted with Et20 (50 mL). The organic layer was then extracted with 3% NH&I (15
m.), saturated NaHC03 (1 5 mL), bnne (1 5 mL) and dried over MgSO4. The solvent was
removed in vacuo to reveal a yellow oil which was further purified by flash
chromatography (1 : 1 Et0Ac:Hex. 0.5% Et3N) to give a clear oil in 7 1 % yield (0.096 g).