1402 J . Org. Chem., Vol. 67, No. 4, 2002
Notes
with water and saturated sodium bicarbonate solution followed
by brine and dried over MgSO4 and concentrated under reduced
pressure. The pure cyclic sulfate (1.28 g, 87%) was isolated as a
colorless oil by silica gel chromatography with hexanes-ethyl
acetate (60:40 v/v): 1H NMR (300 MHz, CDCl3) δ 5.08 (d, J )
9.3 Hz, 1H), 5.18 (m, 2H), 5.78 (d, J ) 9.0 Hz, 1H), 7.20-7.36
(m, 10H); 13C NMR 68.7, 81.4, 84.4, 127.1, 128.5, 128.7, 128.9,
129.3, 130.7, 131.7, 133.8, 163.9.
J ) 12 Hz, 1H), 6.77-7.34 (m); 13C NMR 28.2, 35.1, 50.7, 55.2,
56.9, 67.1, 80.1, 113.8, 127.9, 128.4, 128.5, 128.6, 129.1, 130.1,
135, 136.8, 155.2, 158.6, 170.1; HRMS MH+ calcd for C29H34O5-
NS 508.2079, found 508.2141.
Ben zyl (2S,3R)-2-Am in o-3-p h en yl-3-(in d ol-3-yl)p r op a n -
oa te (11). Boron trifluoride etherate (0.1 g, 0.72 mmol) was
added dropwise to a solution of 7 (0.12 g, 0.47 mmol) and indole
(0.11 g, 0.94 mmol) in dichloromethane (5 mL) at 0 °C under
argon. After 2 h, a saturated sodium bicarbonate solution (5 mL)
was then added and the aqueous layer was extracted with
dichloromethane. The combined organic layer was washed with
brine and dried over MgSO4. After removal of solvent, the pure
product (83 mg, 48%) was isolated as a colorless oil by silica gel
Ben zyl (2R,3R)-3-Azid o-2-h yd r oxy-3-p h en ylp r op ion a te
(5) a n d Ben zyl (2S,3S)-2-Azid o-3-h yd r oxy-3-p h en ylp r op i-
on a te (6). Meth od A. To a stirred solution of cyclic sulfate 4
(0.54 g, 1.62 mmol) in acetone (10 mL) and water (1 mL) was
added sodium azide (130 mg, 2 mmol) as a solid. The mixture
was stirred at 0 °C for 5 min and room temperature for 2 h. The
mixture was concentrated under reduced pressure. Ethyl ether
(7 mL) was added, and solution was chilled to 0 °C followed by
dropwise addition of a 20% H2SO4 aqueous solution. The solution
was stirred vigorously at 0 °C for 24 h. The organic layer was
collected and washed with sodium bicarbonate and water. After
removal of solvent, the pure products (0.41 g, 85%) were isolated
by silica gel chromatography with hexanes-ethyl acetate (80:
20 v/v). Meth od B. To a stirred solution of cyclic sulfite 3 (320
mg, 1 mmol) in DMF (2.5 mL) was added sodium azide (130 mg,
2 mmol). The temperature was raised to 60 °C for 6 h. The
mixture was concentrated under reduced pressure, and the pure
product (250 mg, 85%) was obtained by silica gel chromatogra-
phy with hexanes-ethyl acetate (70:30 v/v). The products were
a mixture of the regioisomers. The minor product 6 was not
detected. 1H NMR (500 MHz, CDCl3) δ 2.99 (d, J ) 6.5 Hz, 1H),
4.56 (dd, J ) 4.0 Hz, J ) 6.5 Hz, 1H), 4.86 (d, J ) 4.0 Hz, 1H),
5.12 (m, 2H), 7.20-7.27 (m, 10H); HRMS MH+ calcd for
chromatography with hexanes-ethyl acetate (60:40 v/v): [R]20
D
1
) -33.2 (c 0.65, CHCl3); H NMR (500 MHz, CDCl3) δ 1.58 (b,
2H), 4.27 (d, J ) 7.5 Hz, 1H), 4.67 (d, J ) 7 Hz, 1H), 5.00 (s,
2H), 6.99-7.26 (m, 15H), 8.02 (s, 1H); 13C NMR 47.1, 59.0, 66.7,
110.9, 116.3, 119.2, 119.4,122 (m, 2C), 126.9-128 (m, 5C), 135.4,
136.0, 140.1, 174.4; HRMS MH+ calcd for C24H23O2N2 371.1758,
found 371.1760.
Ben zyl (2S,3S)-2-Acetyla m in o-3-p h en yl-3-h yd r oxylp r o-
p a n oa te (12). A mixture of aziridine 7 (0.14 g, 0.56 mmol) and
acetic acid (5 mL) was stirred at 70 °C for 2 h. Excess acetic
acid was removed under reduced pressure; the pure product (154
mg, 88%) was obtained as a colorless oil by silica gel chroma-
tography with hexanes-ethyl acetate (80:20 v/v): [R]20D ) +47.9
1
(c 1.2, CHCl3); H NMR (500 MHz, CDCl3) δ 1.98 (s, 3H), 4.58
(b, 1H), 5.03 (dd, J ) 7.5 Hz, J ) 3.5 Hz, 1H), 5.10 (m, 2H), 5.21
(d, J ) 3.5 Hz, 1H), 6.40 (d, J ) 7 Hz, 1H), 7.09-7.29 (m, 10H);
13C NMR 22.8, 59.1, 67.5, 74.8, 125.8, 128 (m), 134.5, 138.9,
169.2, 171.5; HRMS MH+ calcd for C18H20O4N 314.1314, found
314.1404.
C
16H16O3N3 298.1113, found 298.1196.
Ben zyl (2S,3R)-3-P h en yla zir id in e-2-ca r boxyla te (7). To
(S)-P h en yla la n in e (13). Aziridine 7 (0.25 g, 1 mmol) was
hydrogenated over a catalytic amount of Pd-C in methanol (2
mL) for 12 h at room temperature under an H2 atmosphere (36
psi). The catalyst was filtered off, and the filtrate was concen-
trated in vacuo to give a residue, which was purified by
recrystallization from hexane and ethyl acetate: [R]23D ) -33.3
(c 1.6, H2O); 1H NMR (300 MHz, D2O) δ 3.05-3.29 (m, 2H),
3.94-3.98 (m, 2H), 7.28-7.42 (m, 5H); 13C NMR 31.9, 51.6,
123.3, 124.5, 130.7, 143.4, 169.6; HRMS MH+ calcd for C19H12O2N
166.0810, found 166.0790.
a stirred solution of azido alcohol 5 and 6 (1 g, 3.36 mmol) in
acetonitrile (15 mL) was added PPh3 (0.91 g, 3.48 mmol) as a
solid. The mixture was stirred at 20 °C for 1 h and then refluxed
for 6 h. After removal of solvent, the pure product (0.8 g, 91%)
was isolated by silica gel chromatography with hexanes-ethyl
acetate (80:20 v/v): [R]20 ) +186 (c 0.9, CHCl3); 1H NMR (500
D
MHz, CDCl3) δ 1.93 (b, 1H), 2.64 (b, 1H), 3.29 (b, 1H), 5.23 (m,
2H), 7.25-7.35 (m, 10H); 13C NMR 39.4, 40.5, 67.5, 126.1, 127.7,
128.3, 128.4, 128.5, 128.6, 135.1, 137.6, 171.6; HRMS MH+ calcd
for C16H16O2N 254.1103, found 254.1178.
Ben zen ep r op a n oic Acid , â-Meth yl-r-oxo, Eth yl Ester (9).
To a stirred solution of â-methyl cyclic sulfite 8 (270 mg, 1 mmol)
in DMF (2.5 mL) was added sodium azide (130 mg, 2 mmol).
The temperature was raised to 65 °C for 6 h. The mixture was
concentrated under reduced pressure, the pure product (100 mg,
48%) was obtained, and 80 mg of starting material was recovered
by silica gel chromatography with hexanes-ethyl acetate (80:
Ben zyl Nr-(ter t-Bu tyloxyca r bon yl)-(2R,3S)-3-p h en yl-3-
(4-m eth oxyben zylth io)p r op a n oa te (10). To a stirred solution
of 7 (1.57 g, 6.2 mmol) and 4-methoxybenzylthiol (2.58 mL, 18.6
mmol) in dry methylene chloride (60 mL) at 0 °C was added
anhydrous boron trifluoride diethyl etherate (1.17 mL, 9.3 mmol)
dropwise. The mixture was stirred at 0 °C for 24 h, and then
the reaction was quenched by addition of saturated sodium
bicarbonate. The organic layer was washed with brine and water
and dried over MgSO4. After removal of solvent, the pure product
(1.69 g, 67%) was obtained as colorless oil by silica gel chroma-
tography with hexanes-ethyl acetate (60:40 v/v). The product
was dissolved in 30 mL of THF. The solution was treated with
TEA (420 mg, 4.12 mmol) and di-tert-butyl dicarbonate (0.89 g,
4.12 mmol). The solution was stirred at room temperature
overnight, and then the solvent was evaporated off. The residue
was dissolved in 50 mL of EtOAc, washed with saturated sodium
bicarbonate and brine, and dried over MgSO4. After removal of
20 v/v): [R]20 ) +7.14 (c 0.35, CHCl3); 1H NMR (500 MHz,
D
CDCl3) δ 1.19 (t, J ) 7.2 Hz, 3H), 1.46 (d, J ) 7.2 Hz, 3H), 4.17
(m, 2H), 4.48 (q, J ) 7.2 Hz, 1H), 7.20-7.36 (m, 5H); 13C NMR
13.8, 16.7, 48.4, 62.2, 127.6, 128.5, 128.9, 137.7, 161.3, 194;
HRMS MH+ calcd for C12H15O3 207.1021, found 207.1022.
Ack n ow led gm en t. This work was supported by the
U.S. Public Health Service (DK 17420) and the National
Institute of Drug Abuse (DA 13449). We thank Professor
Dominic V. McGrath for using his group’s polarimeter.
the solvent, the pure product (2.11 g, 67%) was obtained: [R]20
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for compound 2, 7, and 9-12. This material is available
D
) +127 (c 2.25, CHCl3); 1H NMR (500 MHz, CDCl3) δ 1.40 (s,
9H), 3.48 (d, J ) 13 Hz, 1H), 3.62 (d, J ) 13 Hz,1H), 3.76 (s,
3H), 4.14 (d, J ) 5.0 Hz, 1H), 4.85 (dd, J ) 5 Hz, J ) 9.5 Hz,
1H), 4.98 (d, J ) 9.5 Hz, 1H), 5.02 (d, J ) 12.5 Hz, 1H), 5.11 (d,
J O010860D