1546 J . Org. Chem., Vol. 67, No. 5, 2002
Lall et al.
1.0, CHCl3). Anal. Calcd for C12H15NO4S: C, 53.52; H, 5.61;
N, 5.20. Found: C, 53.14; H, 5.49; N, 5.09.
from a modified procedure of Gautschi et al.43b To a solution
of t-BuLi (1.88 mL, 1.7 M in pentane, 3.19 mmol) in THF (10
mL) at -78 °C under an atmosphere of argon was added a
precooled solution of dioxanone 23 (0.5 g, 2.90 mmol) in THF
(3 mL) via cannula. The reaction mixture was stirred for 45
min after which it was treated dropwise with p-anisaldehyde
(0.40 mL, 3.77 mmol). The mixture was stirred for a further
24 h at -78 °C after which it was quenched with sat. NH4Cl
(10 mL) and then extracted with EtOAc (3 × 5 mL) and dried
over MgSO4. The solvent was evaporated in vacuo, the crude
product was purified by flash column chromatography (hexane/
Et2O, 3:1) and the product was recrystallized from (Et2O/
hexane) to give a white solid (0.59 g, 66%); mp 157-158 °C IR
N-(P h en ylm eth a n esu lfon yl)-D-a llo-th r eon in e.55 D-allo-
Threonine (0.30 g, 2.52 mmol) was dissolved in water (15 mL)
and treated with Na2CO3 (1.07 g, 10.1 mmol) followed by
R-toluenesulfonyl chloride (0.28 g, 3.02 mmol). The mixture
was stirred for 24 h. The reaction mixture was then washed
with diethyl ether (2 × 10 mL), acidified to pH 2 with 1 N
HCl, and then extracted with ethyl acetate (3 × 10 mL). The
combined organic layers were dried over MgSO4 and evapora-
tion of the volatiles in vacuo followed by recrystallization of
the crude product from MeOH/Et2O/hexane furnished a white
solid (0.95 g, 28%): mp 138-139 °C; IR (µscope) 3489, 3207,
1
2974, 1732, 1696, 1456 cm-1; H NMR (300 MHz, CD3OD) δ
(µscope) 3408, 2960, 2918, 1795, 1720, 1611, 1511 cm-1 1H
;
7.44-7.32 (m, 5H), 4.38 (d, 1H, J ) 13.7 Hz), 4.34 (d, 1H, J )
13.7 Hz), 4.0 (quintet, J ) 5.2 Hz, 1H), 3.90 (d, 1H, J ) 5 Hz),
1.18 (d, 3H, J ) 7.5 Hz); 13C NMR (75 MHz, CD3OD) δ 173.4,
132.1, 131.1, 129.4, 129.3, 69.3, 63.5, 60.5, 19.1; HRMS (EI,
M+) Calcd for C11H15NO5S 273.0671, found 273.0658.
NMR (300 MHz, CDCl3)(1:1 mixture of diastereomers) δ 7.25
(dd, 2H, J ) 8.9, 4.2 Hz), 6.90 (d, 2H, J ) 8.8 Hz), 5.32 (d, 1H,
J ) 3.4 Hz), 4.83 (s, 1H) 3.98-3.88 (m, 1H), 3.80 (s, 3H), 2.78
(dd, 1H, J ) 9.2, 3.4 Hz,), 0.98 (s, 9H), 0.85 (d, 3H, J ) 7.5
Hz); 13C NMR (75 MHz, CDCl3) δ 171.9, 171.4, 159.4, 132.9,
128.8, 128.2, 127.8, 126.9, 114.5, 114.1, 107.7, 102.0, 74.2, 72.5,
71.2, 69.3, 55.4, 55.3, 46.9, 35.1, 34.9, 24.7, 24.4, 23.9, 21.1,
19.2; HRMS (EI, M+) Calcd for C17H24O5 235.0845, found
235.0835. Anal. Calcd for C17H24O5: C, 66.21; H, 7.84; Found:
C, 65.99; H, 7.79.
N-(P h e n ylm e t h a n e su lfon yl)-D-a llo-t h r e on in e -â-la c-
ton e (20). Cyclization of N-(phenylmethanesulfonyl)-D-allo-
threonine (0.10 g, 0.37 mmol) using BOP (0.20 g, 0.45 mmol)
and triethylamine (0.16 mL, 1.12 mmol) as described for 18a
gave â-lactone 20 (0.06 g, 64%) as a white solid after recrys-
tallization from CHCl3/hexane: mp 150-151 °C; [R]26 +47.5°
(2R,3R)-2-(p-Meth oxyben zyl)-3-h yd r oxybu ta n oic a cid
(25) a n d (1′S,2R,3R)-2-(1′-Hyd r oxy-p-m eth oxyben zyl)-3-
h yd r oxybu ta n oic Acid (26). Reaction of dioxanone 24 (0.4
g, 1.95 mmol) and 10% palladium on carbon (0.04 g) for 24 h
as described for N-(phenethylsulfonyl)-D-serine gave 25 (0.13
g, 40%) and 26 (0.14 g, 35%) as white solids after purification
by flash column chromatography (EtOAc/hexane, 2:1 and 1%
AcOH). These materials were recrystallized from (CHCl3/
hexane). Data for 25: mp 107-108 °C; [R]2D6 -39.7° (c 1.0,
CHCl3); IR (CHCl3 cast) 3259, 3059, 2936, 2835, 1696, 1610,
D
(c 0.2, MeOH); IR (CHCl3 cast) 3278, 2926, 1825, 1759, 1495,
1386, 1331 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.52-7.38 (m,
5H), 4.98 (d, 1H, J ) 8.3 Hz), 4.63 (dq, 1H, J ) 6.1, 4.3 Hz),
4.40 (d, 2H, J ) 14 Hz), 4.30 (dd, 1H, J ) 8.4, 4.2 Hz), 1.42 (d,
3H, J ) 6.3 Hz); 13C NMR (125 MHz, CDCl3) δ 166.9, 131.0,
129.3, 129.1, 128.4, 78.3, 65.6, 60.51, 18.5; HRMS (EI, M+)
Calcd for C11H13NO4S 255.0572, found 255.0565. Anal. Calcd
for C11H13NO4S: C, 51.75; H, 5.13; N, 5.49. Found: C, 51.69;
H, 5.07; N, 5.38.
1
1582, 1512 cm-1; H NMR (300 MHz, CDCl3) δ 7.11 (d, 2H, J
N-(P h en ylsu lfon yl)-D-a llo-th r eon in e. Reaction of D-allo-
threonine (0.44 g, 3.69 mmol) with benzenesulfonyl chloride
(0.56 g, 4.43 mmol) and Na2CO3 (1.57 g, 14.7 mmol) as
described for N-(phenylmethanesulfonyl)-D-allo-threonine gave
the title product as a white solid (0.46 g, 48.5%): mp 171-
173 °C; [R]2D6 -17.2° (c 0.3, MeOH), lit.55 [R]2D6 -16.8° (c 1.6,
) 8.6 Hz), 6.79 (d, 2H, J ) 8.6 Hz), 3.85 (dq, 1H, J ) 6.4, 1.2
Hz), 3.75 (s, 3H), 2.92 (d, 2H, J ) 8.6 Hz), 2.62 (dt, 1H,, J )
5.1, 1.9 Hz); 13C NMR (75 MHz, CDCl3) δ 179.2, 158.4, 130.3,
129.9, 114.0, 67.3, 55.3, 54.3, 34.4, 21.8; HRMS (EI, M+) Calcd
for
C12H16O5 240.0998, found 240.0997. Anal. Calcd for
1
MeOH); H NMR (300 MHz, CD3OD) δ 7.84 (d, 2H, J ) 7.5
C
12H16O5: C, 64.85; H, 6.35; Found: C, 64.66; H, 6.34.
Data for 26: mp 128-129 °C; [R]2D6 -5.8° (c 0.9, CHCl3); IR
Hz), 7.60-7.44 (m, 3H), 3.85 (quintet, 1H, J ) 6.4 Hz), 3.78
(d, 1H, J ) 5.9 Hz), 1.38 (d, 3H, J ) 6.3 Hz; HRMS (ES, MNa+)
Calcd for C10H13NO4SNa 282.0412, found 282.0405.
(CHCl3 cast) 3387, 2934, 1708, 1612, 1586, 1456 cm-1; 1H NMR
(300 MHz, CDCl3) δ 7.22 (d, 2H, J ) 11.3 Hz), 6.84 (d, 2H, J
) 11.3 Hz), 5.18 (d, 1H, J ) 6.0 Hz), 4.80 (br q, 1H, J ) 4.5
Hz), 3.78 (s, 3H), 2.70 (dd, 1H, J ) 6.0, 2.3 Hz), 1.24 (d, 3H, J
) 6.6 Hz); 13C NMR (75 MHz, CDCl3) δ 176.0, 159.2, 133.2,
127.3, 113.9, 172.9, 65.7, 57.2, 55.3, 21.4; HRMS (EI, M+) Calcd
for C12H16O4 224.1049, found 224.1053.
N-(P h en ylsu lfon yl)-D-a llo-th r eon in e-â-la cton e (21). Cy-
clization of N-(benzenesulfonyl)-D-allo-threonine (0.44 g, 1.69
mmol) using BOP (0.89 g, 2.03 mmol) and triethylamine (0.71
mL, 5.07 mmol) as described for 18a gave â-lactone 21 (0.26
g, 64%) as a white solid: mp 110-111 °C; [R]2D6 +9.2° (c 0.3,
CHCl3); IR (CHCl3 cast) 3265, 3069, 2916, 1832, 1447, 1335
cm-1; 1H NMR (300 MHz, CDCl3) δ 7.85 (d, 2H, J ) 10.0 Hz),
7.64-7.52 (m, 3H), 5.50 (br d, 1H, J ) 5.5 Hz), 4.68-4.59 (m,
1H), 4.42 (dd, 1H, J ) 7.5, 4.0 Hz), 1.58 (d, 3H, J ) 6.3 Hz);
13C NMR (75 MHz, CDCl3) δ 166.1, 139.2, 133.6, 129.6, 127.2,
78.3, 65.2, 18.7; HRMS (ES, MNa+) Calcd for C10H11NO4SNa
264.0307, found 264.0305. Anal. Calcd for C10H11NO4S; C,
49.78; H, 4.60; N, 5.81. Found: C, 49.52; H, 4.41; N, 5.73.
N-(Ben zyloxycar bon yl)-D-a llo-th r eon in e-â-lacton e (22).
Cyclization of N-Cbz-D-allo-threonine (0.32 g, 1.27 mmol) using
BOP (0.67 g, 1.52 mmol) and triethylamine (0.53 mL, 3.79
mmol) as described for 18a gave â-lactone 22 (0.23 g, 68%) as
a white solid: mp 136-137 °C; [R]2D6 +61.0° (c 0.4, MeOH); IR
(2R,3R)-3-(p-Meth oxyben zyl)-4-m eth yloxetan -2-on e (27).
Cyclization of hydroxy acid 25 (0.14 g, 0.63 mmol) using BOP
(0.33 g, 0.75 mmol) and triethylamine (0.26 mL, 1.87 mmol)
as described for 18a gave â-lactone 27 (0.09 g, 73%) as a white
solid after recrystallization from Et2O/petroleum ether: mp
34-35 °C; [R]2D6 -28.7° (c 1.0, CHCl3); IR (CHCl3 cast) 2975,
2932, 1816, 1612, 1583, 1442, 1385 cm-1; 1H NMR (300 MHz,
CDCl3) δ 7.18 (d, 2H, J ) 10 Hz), 6.82 (d, 2H, J ) 10 Hz), 4.42
(dq, 1H, J ) 6.1, 4.1 Hz), 3.78 (s, 3H), 3.40 (ddd, 1H, J ) 7.2,
5.8, 4.0 Hz), 3.0 (ddd, 2H, J ) 23.5, 14.6, 8.9 Hz), 1.42 (d, 3H,
J ) 10 Hz); 13C NMR (75 MHz, CDCl3) δ 170.7, 158.7, 129.6,
128.9, 114.3, 74.0, 58.7, 55.3, 32.6, 20.1; HRMS (EI, M+) Calcd
for C12H14O3 206.0943, found 206.0941.
(µscope) 3312, 2972, 1830, 1535, 1382 cm-1 1H NMR (300
;
(1′S,2R,3R)-2-(1′-Hyd r oxy-p-m eth oxyben zyl)-4-m eth y-
loxeta n -2-on e (28). Cyclization of hydroxy acid 26 (0.08 g,
0.34 mmol) using BOP (0.19 g, 0.43 mmol) and triethylamine
(0.15 mL, 1.02 mmol) as described for 18a gave â-lactone 28
(0.05 g, 70%) as a white solid after recrystallization from CH2-
Cl2/hexane: mp 88-89 °C; [R]2D6 -85.5° (c 0.3, CHCl3); IR
MHz, CDCl3) δ 7.40 (br s, 5H), 5.40 (br s, 1H), 5.14 (br s, 2H),
4.80-4.68 (m, 1H), 4.65-4.58 (m, 1H), 1.60 (d, 3H, J ) 6.3
Hz); 13C NMR (75 MHz, CDCl3) δ 167.5, 155.3, 135.6, 128.7,
128.6, 128.4, 128.2, 76.7, 67.8, 64.5, 18.9; HRMS (EI, M+) Calcd
for C12H13NO4 235.0845, found 235.0835. Anal. Calcd for
C
12H13NO4: C, 61.27; H, 5.57; N, 5.95. Found: C, 61.16; H,
(CHCl3 cast) 3411, 2984, 2960, 1807, 1612, 1514, 1448 cm-1
;
5.73; N, 5.99.
1H NMR (300 MHz, CDCl3) δ 7.24 (d, 2H, J ) 11.3 Hz), 6.90
(d, 2H, J ) 11.3 Hz), 5.18 (d, 1H, J ) 4.4 Hz), 4.96-4.85 (m,
1H), 3.80 (s, 3H,), 3.52 (t, 1H, J ) 4.4 Hz), 1.42 (d, 3H, J ) 10
Hz); 13C NMR (75 MHz, CDCl3) δ 159.6, 132.6, 126.7, 114.3,
70.6, 69.3, 64.8, 55.4, 20.1; HRMS (EI, M+) Calcd for C12H14O2
(1′RS,2R,5R,6R)-5-[r-p-Meth oxyben zyl]-2-(ter t-bu tyl)-
6-m eth yl-1,3-d ioxa n -4-on e (24). This material was prepared
(55) Maurer, P. J .; Takahata, H.; Rapoport, H. J . Am. Chem. Soc.
1984, 106, 1095-1098.