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

mp 80-8 1 OC; [a~~*~a= -67.0 (0 1.55, EtOAc); TLC (4: 1. CH2C12:EtOAc) Rr = 0.45; 'H
NMR (CDCl3, 2M MHz) 6 5.02 (br d. lH, J = 10.6Hz, NH), 3.89 (s, 6H, OB0 ester
Cm), 3.71 (d, IH, J= 10.6Hz. a-CH), 3.38, (br s, lH, OH), 1.41 (s, 9H, (CH3)3C), 1.28
(s, 3H, B-CH3), 1.15 (s, 3H, p-CH3), 0.78 (s, 3H, OB0 ester CCH3); 13c NMR (CDC13,
63 MHz) 6 156.1 (CONH), 109.3 (OB0 ester -O), 79.1 ((CH3)3Q, 72.5 (OB0 ester
- CH20), 72.3 (p-C), 59.8 (a-_CH), 30.4 (OB0 ester cCH3), 28.3 (a3)3C), 28.1 (B-c&),
26.6 (p-GH3), 14.3 (OB0 ester C-3); IR (neat) 3386, 2975, 17 15, 1506, 1365, 1 169,
1049; HRMS (FAB) calcd for (M + H+) Ci5H&J06 318.1917, found 318.1929. Anal.
calcd for C, 56.77; H, 8.57; N, 4.4 1. Found: C, 56.98; H, 8.69; N, 4.73.
2.4.21 Addition of EtMgBr to Boc-Thr(ket)OBO ester 2.47: torf-butyl N4(lS,2R)-2-
hydr0xy-2-metayCl-(4-metby1-2,6,7-tri0~bi~y~lo[2.2.2]~t-l-yl)bu~l]~b~te,
Boc-L-Thr(Et)-OB0 ester, 2.58.
Cnide Boc-L-Thr(ket)-OB0 ester 2.47 (0.3888, 1.29 rnmol) was dissolved in dry Et20
(15 mL) and C&C12 (15 mL) under N2. A solution of EtMgBr in Et20 (1.29 rnL, 3.87
mmol) was added quickly by syringe at -78°C and the mixture stirred vigorously. After 2
h the reaction was quenched by pouring into 3% NWl (25 mL). CH2C12 (100m.L) was
added and the organic layer was separated, washed with 3% N WI (50 mL) and brine
(50 mL), dried (MgS04), and evaporated to dryness. The product was purified by flash
chromatography (4:1, CH2C12:EtOAc) to yield 0.320g (75%) of a white crystalline
product.