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

4.434 Reformatsky addition to Cbz-L-Ser(dd)-OBO ester 3.42: te*butyl(lS,2R)-l-
[(benzyloxy)carbon y1]amino12-hydn,xy-1-(~metbyI-2,6,7-nio~bi~ycl0[2~2.2]0~t-l-
yl)butanaate, Cbz-L-GIu(p-O~(OtBu)OBO ester, 4.104.
Purified zinc powder (O.Mg, 2.88 mmol) and iodine (1 small crystal) were dissolved in
dry THF (10 rnL) then refluxed for 20 min before a solution of Cbz-Ser(a1d)OBO ester
3-42 (0.153g, 0.48 mol) and t-butylbromoacetate (0.35 rnL, 2.40 mmol) in THF (5 mL)
was quickly added to the refiuxing solution. After 30 min the zinc was filtered off and
the filtrate poured into cold 3% NWI (50 mL) then extracted with Et20 (3 x 50 mL).
The organic layers were combined and extracted with 10% NaHC03 (15 mL), brine (15
mL) and dried over MgS04. The solvent was removed in vacuo and the resulting oil
purified by flash chromatography to give 0.157 g of 4.104 (75% yield over 2 steps) as a
pale oil.
[al2'D = -7.3 (c = 0.9, CH2C12); TU3 (1: 1, EtOAc:Hex), Rf = 0.32; 'H NMR (Acetone-a,
300 MHz) 6 7.40-7.24 (m, SH, ArH), 5.78 (d, lH, J = 10.3Hz, NH), 5.10 (d, IH, J =
12.7Hz, CbzCHHO), 5.03 (d, 1H, J = 12.7Hz, CbzCHHO), 4.51-4.44 (m, lH, $-CH),
3.86 (s, 6H, OB0 ester CH20), 3.79 (dd, 1 H, J = 2.0, 1 O.3H.z. a-CH), 2.3 1-2.24 (m, 2H,
Y-C&), 1 -39 (s, 98 (CH3)3C), 0.80 (s, 3H. OB0 ester CCH3); I3c NMR (Acetone-&, 75
MHz) 6 170.1 (çEO), 156.4 KONH), 137.5 (Cbz