7674 J . Org. Chem., Vol. 65, No. 22, 2000
Notes
29.3, 26.5. Anal. Calcd for C16H15NO7: C, 57.66; H, 4.54; N, 4.20.
Found: C, 57.67; H, 4.58; N, 4.15.
ter t-Bu tyl (R)-5-(ter t-Bu tyld im eth ylsilyloxy)-2-(ben zyl-
oxyca r bon yla m in ooxy)p en ta n oa te (23b). The solution of an
aminooxy ester from the previous experiment (0.44 g, 1.0 mmol),
benzyloxycarbonyl chloride (0.19 g, 1.1 mmol), and DIEA (245
µL) in CH2Cl2 (500 µL) was stirred for 1 h at room temperature.
The reaction mixture was diluted with CH2Cl2 and washed with
H2O and brine, dried (MgSO4), and concentrated in vacuo. The
crude product was purified by flash column chromatography (6:1
hexane/EtOAc) to give 23b in 93% yield as an oil: [R]D +52.8 (c
1.0, CHCl3); 1H NMR (250 MHz, CDCl3) δ 7.88 (s, 1 H), 7.36 (s,
5 H), 5.24-5.08 (m, 2 H), 4.28 (dd, 1 H, J ) 4.3, 7.9 Hz), 3.64-
3.58 (m, 2 H), 1.98-1.50 (m, 4 H), 1.46 (s, 9 H), 0.88 (s, 9 H),
0.03 (s, 6 H); 13C NMR (62.5 MHz, CDCl3) δ 171.0, 156. 9, 135.7,
128.7, 128.5, 128.4, 83.8, 82.2, 67.6, 62.2, 28.3, 28.2, 27.4, 26.0,
18.4, -5.2. Anal. Calcd for C23H39NO6Si: C, 60.89; H, 8.67; N,
3.09. Found: C, 60.81; H, 8.69; N, 3.13.
ter t-Bu tyl (R)-5-(ter t-Bu tyld im eth ylsilyloxy)-2-p h th a l-
im id ooxyp en ta n oa te (21). Treatment of 2025 (1.05 g, 3.5
mmol), PPh3 (3.08 g, 11.7 mmol, 3.4 equiv) and N-hydroxyphthal-
imide (1.41 g, 8.6 mmol, 2.5 equiv) in CH2Cl2 (15 mL) with DIAD
(2.50 g, 11.7 mmol, 3.4 equiv) as described for 3a followed by
flash column chromatography (8:1 hexane/EtOAc) gave 21 in
93% yield as a white solid: mp 52 °C; [R]D +44.1 (c 1.0, CHCl3);
1H NMR (250 MHz, CDCl3) δ 7.85-7.73 (m, 4 H), 4.69 (t, 1 H,
J ) 6.5 Hz), 3.74-3.67 (m, 2 H), 2.08-2.01 (m, 2 H), 1.86-1.78
(m, 2 H), 1.55 (s, 9 H), 0.89 (s, 9 H), 0.06 (s, 6 H); 13C NMR
(62.5 MHz, CDCl3) δ 168.8, 163.3, 134.6, 129.0, 123.7, 85.8, 82.5,
62.4, 28.1, 28.0, 27.8, 26.1, 18.4, -5.2. Anal. Calcd for C23H35
-
NO6Si: C, 61.44; H, 7.85; N, 3.12. Found: C, 61.41; H, 7.92; N,
3.15.
D-P h th N-O-Ar g(Cbz)2-OH (22). To a stirred solution of 21
(0.25 g, 0.6 mmol) in CHCl3 (3 mL) was added BF3‚Et2O (0.12 g,
0.8 mmol). After 50 min at room temperature, the reaction
mixture was diluted with CHCl3, washed with saturated NaH-
CO3, H2O, and brine sequentially, dried (MgSO4), and concen-
trated in vacuo. The crude product was purified by flash column
chromatography (2:1 hexane/EtOAc) to give a TBDMS depro-
ter t-Bu tyl (R)-5-(ter t-Bu tyld im eth ylsilyloxy)-2-(flu or e-
n ylm eth oxyca r bon yla m in ooxy)p en ta n oa te (23c). The solu-
tion of an aminooxy ester from the previous experiment (0.44 g,
1.0 mmol), FMOC-OSu (0.35 g, 1.04 mmol) and DIEA (180 µL)
in CH2Cl2 (500 µL) was stirred for 1 h at room temperature.
The reaction was diluted with CH2Cl2, washed with H2O and
brine, dried (MgSO4), and concentrated in vacuo. The crude
product was purified by flash column chromatography (10:1
hexane/EtOAc) to give 23c in 81% yield as an oil: [R]D +39.5 (c
1.0, CHCl3); 1H NMR (250 MHz, CDCl3) δ 8.18 (s, 1 H), 7.73 (d,
2 H, J ) 7.4 Hz), 7.65 (d, 2 H, J ) 7.4 Hz), 7.40-7.22 (m, 4 H),
4.45 (d, 2 H, J ) 6.9 Hz), 4.27-4.21 (m, 2 H), 3.62 (bs, 2 H),
1
tected 21 in 65% yield as an oil: [R]D +52.2 (c 0.7, CHCl3); H
NMR (250 MHz, CDCl3) δ 7.85-7.74 (m, 4 H), 4.71 (dd, 1 H, J
) 5.8, 6.6 Hz), 3.85-3.68 (m, 2 H), 2.17-1.98 (m, 2 H), 1.95-
1.80 (m, 2 H), 1.47 (s, 9 H); 13C NMR (62.5 MHz, CDCl3) δ 168.6,
163.4, 134.7, 129.0, 123.7, 85.9, 82.8, 62.4, 28.0, 27.9, 27.7. Anal.
Calcd for C17H21NO6 : C, 60.89; H, 6.31; N, 4.18. Found: C,
60.92; H, 6.30; N, 4.19.
2.01-1.50 (m, 4 H), 1.48 (s, 9 H), 0.88 (s, 9 H), 0.03 (s, 6 H); 13
C
NMR (62.5 MHz, CDCl3) δ 171.0, 156.9, 143.5, 141.3, 127.8,
127.1, 125.0, 120.0, 83.7, 82.1, 67.4, 62.2, 47.0, 28.1, 27.4, 25.9,
18.2, -5.2. Anal. Calcd for C30H43NO6Si: C, 66.51; H, 8.00; N,
2.59. Found: C, 66.52; H, 8.01; N, 2.61.
To a stirred solution of a TBDMS deprotected 21 (0.12 g, 0.4
mmol), PPh3 (0.13 g, 0.5 mmol), and N,N′-bis(benzyloxycarbo-
nyl)guanidine (0.12 g, 0.4 mmol) in CH2Cl2 (3 mL) was added
DIAD (0.1 g, 0.5 mmol) at room temperature. After 1 h at the
same temperature, the reaction mixture was concentrated in
vacuo and directly purified by flash column chromatography (8:1
hexane/EtOAc) to give dihydro-DIAD contaminated D-PhthN-
O-Arg(Cbz)2-Ot-Bu. A solution of dihydro-DIAD contaminated
D-PhthN-O-Arg(Cbz)2-Ot-Bu in 50% TFA in CH2Cl2 was stirred
for 1.5 h, and then the solution was concentrated in vacuo. The
concentration step was repeated several times to remove residual
TFA, and then the crude product was purified by short column
chromatography (5:1 to 1:1 hexane/EtOAc) to give 22 in 75%
D-Ns-N-O-P r o-OH (24a ). To a stirred solution of 23a (0.28
g, 0.5 mmol) in CHCl3 (5 mL) was added BF3‚Et2O (0.12 g, 0.8
mmol) at room temperature. After 1 h at the same temperature,
the reaction mixture was diluted with CHCl3, washed with
saturated NaHCO3, H2O, and brine sequentially, dried (MgSO4),
and concentrated in vacuo. The crude product was purified by
flash column chromatography (2:1 to 1:2 hexane/EtOAc) to give
a TBDMS deprotected 23a in 51% yield as a solid: mp 95-97
°C; [R]D -143.4 (c 1.07, CHCl3); 1H NMR (250 MHz, CDCl3) δ
8.45 (s, 1 H), 8.23-8.18 (m, 1 H), 7.94-7.90 (m, 1 H), 7.85-7.77
(m, 2 H), 4.58 (dd, 1 H, J ) 4.2, 8.2 Hz), 3.68 (dd, 1 H, J ) 5.9,
6.2 Hz), 1.92-1.67 (m, 4 H), 1.50 (s, 9 H); 13C NMR (62.5 MHz,
CDCl3) δ 170.2, 148.6, 135.1, 133.5, 133.0, 130.2, 125.7, 84.8,
82.7, 62.0, 28.3, 28.1, 27.4. Anal. Calcd for C15H22N2O8S : C,
46.15; H, 5.68; N, 7.18. Found: C, 46.12; H, 5.78; N, 7.19.
To a stirred solution of a TBDMS deprotected 23b (90 mg,
0.2 mmol), PPh3 (80 mg, 0.3 mmol) in CH2Cl2 (1 mL) was added
DIAD (70 mg, 0.3 mmol) at 20 °C. After 1 h at the same
temperature, the reaction mixture was concentrated in vacuo
and directly purified by flash column chromatography (3:1
hexane/EtOAc) to give dihydro-DIAD contaminated D-Ns-N-O-
Pro-Ot-Bu. A solution of dihydro-DIAD contaminated D-Ns-N-
O-Pro-Ot-Bu in 50% TFA in CH2Cl2 was stirred for 1 h, and then
the solution was concentrated in vacuo. The concentration step
was repeated several times to remove residual TFA, and then
the crude product was purified by short column chromatography
(1:1 hexane/EtOAc to 1:1 EtOAc/MeOH) to give 24a in 85% yield
as a white solid: mp 125-126 °C; [R]D +32.6 (c 0.5, MeOH); 1H
NMR (250 MHz, CD3CO2D) δ 8.19 (d, 1 H, J ) 7.6 Hz), 7.89-
7.66 (m, 3 H), 4.72-4.62 (m, 1 H), 3.70-3.55 (m, 1 H), 3.24-
3.08 (m, 1 H), 2.00-1.73 (m, 4 H); 13C NMR (62.5 MHz,
CD3CO2D) δ 174.1, 150.2, 136.3, 134.1, 132.3, 127.9, 125.0, 80.1,
48.4, 26.8, 23.1. Anal. Calcd for C11H12N2O7S: C, 41.77; H, 3.82;
N, 8.86. Found: C, 41.79; H, 3.77; N, 0.8.79
1
yield as a white solid: mp 66 °C; [R]D +37.2 (c 1.0, CHCl3); H
NMR (250 MHz, CDCl3) δ 9.48 (bs, 1 H), 7.89-7.76 (m, 4 H),
7.44-7.22 (m, 10 H), 5.26 (s, 2 H), 5.12 (d, 1 H, J ) 12.5 Hz),
5.05 (d, 1 H, J ) 12.5 Hz), 4.95-4.85 (m, 1 H), 4.21-4.08 (m, 2
H), 2.15-1.92 (m, 4 H); 13C NMR (62.5 MHz, CDCl3) δ 171.8,
163.5, 162.3, 159.8, 155.6, 136.4, 134.8, 134.5, 128.7, 128.6, 128.4,
128.3, 127.9, 123.8, 84.9, 69.3, 67.4, 44.3, 28.1, 23.9. Anal. Calcd
for C30H28N4O9 : C, 61.22; H, 4.80; N, 9.52. Found: C, 61.20; H,
4.85; N, 9.51.
ter t-Bu tyl (R)-5-(ter t-bu tyld im eth ylsilyloxy)-2-(2-n itr o-
ben zen esu lfon yla m in ooxy)p en ta n oa te (23a ). To a stirred
solution of 21 (0.45 g, 1.0 mmol) was added NH2NH2‚H2O (0.20
g, 4.0 mmol) at room temperature. After 15 min at the same
temperature, the solvent was remove under reduced pressure.
Residual solid was dissolved in 3% Na2CO3 and the solution was
extracted with ether, washed with H2O and brine, dried (Mg-
SO4), and concentrated to give an aminooxy ester, which was
used for the next reaction without further purification. The
solution of an aminooxy ester, 2-nitrobenzenesulfonyl chloride
(0.25 g, 1.1 mmol), and collidine (145 µL) in DMF (600 µL) was
stirred for 17 min at room temperature. The reaction was
quenched with brine and extracted with EtOAc. The combined
organic solution was washed with brine, dried (MgSO4), and
concentrated in vacuo. The crude product was purified by flash
column chromatography (6:1 hexane/EtOAc) to give 23a in 60%
yield as a yellow solid: mp 68 °C; [R]D -115.1 (c 1.0, CHCl3); 1H
NMR (250 MHz, CDCl3) δ 8.40 (s, 1 H), 8.19 (d, 1 H, J ) 7.9
Hz), 7.93-7.89 (d, 1 H, J ) 7.3 Hz), 7.85-7.74 (m, 2 H), 4.55
(dd, 1 H, J ) 4.2, 8.1 Hz), 3.62 (t, 2 H, J ) 5.9 Hz), 1.93-1.80
(m, 1 H), 1.71-1.57 (m, 3 H), 1.49 (s, 9 H), 0.89 (s, 9 H), 0.04 (s,
6 H); 13C NMR (62.5 MHz, CDCl3) δ 170.3, 148.7, 134.9, 133.6,
132.9, 130.5, 125.7, 84.8, 82.5, 62.1, 28.5, 28.2, 27.5, 26.0, 18.4,
-5.2. Anal. Calcd for C21H36N2O8SSi: C, 49.98; H, 7.19; N, 5.55.
Found: C, 49.97; H, 7.23; N, 5.51.
D-Cbz-N-O-P r o-OH (24b). To a stirred solution of 23b (0.23
g, 0.5 mmol) in CHCl3 (3 mL) was added BF3‚Et2O (0.11 g, 0.8
mmol) at room temperature. After 1 h at the same temperature,
the reaction mixture was diluted with CHCl3, washed with
saturated NaHCO3, H2O and brine sequentially, dried (MgSO4),
and concentrated to give a TBDMS deprotected 23b in 75% yield
as an oil: [R]D +69.2 (c 1.02, CHCl3);1H NMR (250 MHz, CDCl3)
δ 7.92 (s, 1 H), 7.36 (s, 5 H), 5.24-5.08 (m, 2 H), 4.35 (dd, 1 H,
J ) 3.8, 8.1 Hz), 3.68 (bs, 2 H), 1.99-1.72 (m, 4 H), 1.47 (s, 9
H); 13C NMR (62.5 MHz, CDCl3) δ 171.0, 157.3, 135.5, 128.5,