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

2-4-11 MeMgBr addition to 2.46: l-[N~ert-Butoxgcarbonyl-(1S~)-l-smin0-2-
h ydroxypropy~]-4-methy 1-2,6,7-trioxabicycio[2.2.2 ]octane, Boc-L-Ser(Me)OBO
ester, 2.49.
Cnide Boc-L-Ser(a1d) OB0 ester 2-46 (0.478 g, 1.66 mrnol) was dissolved in dry EtzO (5
mL) and CH2C12 (5 mi,) under N2. A solution of MeMgBr in Et20 (1.66 d, 4.98 mmol)
was added quickly by syringe at -78°C and the mixture stirred vigorously. Mer 2 h the
reaction was quenched by pouring into 25 mL of 3% =Cl. CH2C12 (80mL) was added
and the organic Iayer was separated, washed with 3% m l (1 x 50 rnL) and bnne (1 x
50 rnL), dried (MgSO& and evaporated to dryness. The product was punfied by flash
chromatography (4:1, CH2C12:EtOAc) to give 0.307 g of a light oil (6196). A
diastereornetric ratio of 85: 15 threo:erythro was determined using 'H NMR integration of
the threo P-CH3 at 6 1.12- 1 .O7 ppm and the erythro B-C& at 6 1.2 1 - 1.14 ppm in the
crude product. The two diastereomers were separable by flash chromatography, the threo
diastereomer with a RI of 0.39 and eryrhro diastereomer a Rf of 0.34.
[a120578= - 15.4 (C = 1.01, CH2CIZ); TU3 (4: 1, CH2C12:EtOA~) Rf = 0.39: 'H NMR
(CDCl3, 250 MHz, rhreo isomer) 6 5.06 (br d, 1 H, J = 1 O.4EIz, NH), 4.3 1 (br q, 1 H, I =
6.4Hz7 P-CH), 3.89 (s, 6H, OB0 ester CH20), 3.63 (br d, 1H, J = 10.4Hz, a-CH), 2.88,
(br s, 1 H, OH), 1.42 (s, 9H, (CH3)3C), 1 .O6, (d, 3H, J = 6.4H2, B-CH3), 0.77 (s, 3H, OB0
ester CCH3); 13c NMR (CDCk, 63 Mm) 6 155.8 (CONH), 108.4 (OB0 ester -O),
79.1 ((CH3)3Q, 72.5 (OB0 ester w20), 65.6 (p-CH), 59.0 (a-CH), 30.9 (OB0 ester
84