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

Boc-Thr OB0 ester 2.45 (0.90 g, 2.97 mmol) was dissolved in fieshly distilled CH2C12
(15 mL) under Ar and cooled to -7g°C in fiask 1. Oxalyl chlonde (0.414 mL. 4.75 mmol,
1.60 equiv) was aâded to CHzCh (20 mL) in a separate round bottom flask (flask 2)
under Ar, and cooled to -7S°C. Dry DMSO (0.70 mL, 9.8 mmol, 3.30 equiv) was added
to the oxalyl chloride solution (flask 2) and the mixture was stirred at -78OC for 15
minutes. The alcohol solution was transferred slowly by cannula to flask 2 over a period
of 45 minutes and then rinsed with CHzClz (5 mL). The resulting cloudy, white mixture
was stirred for 1.5 hours at -7S°C. DIPEA (2.57 mL, 14.9 mmol, 5.0 equiv) was added
and the solution stirred for 30 minutes at -78OC and 10 minutes at O°C. Ice-cold CHzClz
(80 mL) was added and the solution was washed with ice-cold 3% NWI (2 x 50 mL),
saturated NaCl (1 x 50 mL), dried (MgSOa), and evaporated to dryness to yield a light
coloured foam (0.885g) in 99% yield.
[a]%*= - 107.1 (c =1 .SI, EtOAc); TLC (1 : 1, Et0Ac:Hex) Rr = 0.58; 'H NMR (CDC13,
250 MHz) 6 5.37 (br d, IH, J = 8.3Hz, NH), 4.46 (d, IH, J = 8.3Hz, a-CH), 3.89 (s, 6H.
OB0 ester CHD), 2.28 (S. 3H, p-CH3) 1.39 (s, 9H, (CH3)3C), 0.79 (S. 3H, OB0 ester
CC&); I3c NMR (CDCI3, 63 MHz) 6 20 1.6 c=O), 156.6 (CONH), 107.3 (OB0 ester
- C-O) , 80.1 ((CH3)3C), 72.8 (OB0 ester CH20), 63.3 (a-CH), 30.9 (OB0 ester CCH3),
29.8 ($-CH3), 28.2 ((CH3),C), 14.3 (OB0 ester CcH3); IR (cast €rom CH2Clz) 2972,
2883, 17 16, 1506, 1362, 1 167, 1045; HRMS (FAB) calculated for (M + H+) Ci&aO6