One-pot synthesis of C2-symmetric N,N′-diaryl bis(oxazolidin-2-ones) as precursors for N,N′-diaryl 2,3-diamino-1,4-butanediols

Article abstract of DOI:10.1016/S0957-4166(00)00446-8

A new and general one-pot synthetic method for C₂-symmetric N,N′-aryl-disubstituted bis(oxazolidin-2-ones) has been developed. Highly regioselective intramolecular cyclization reactions of 2,3-di(methanesulfonyloxy)-1,4-dihydroxybutane with ary

Full text of DOI:10.1016/S0957-4166(00)00446-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 4709–4717
One-pot synthesis of C2-symmetric N,N%-diaryl
bis(oxazolidin-2-ones) as precursors for N,N%-diaryl
2,3-diamino-1,4-butanediols
Sang-gi Lee,* Chung Woo Lim, Jae Kyun Lee, Ok-Sang Jung and Young-A Lee
Life Sciences Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang,
Seoul 130-650, South Korea
Received 13 October 2000; accepted 9 November 2000
Abstract
A new and general one-pot synthetic method for C2-symmetric N,N%-aryl-disubstituted bis(oxazolidin-2-
ones) has been developed. Highly regioselective intramolecular cyclization reactions of 2,3-di(methanesul-
fonyloxy)-1,4-dihydroxybutane with arylisocyanates in the presence of sodium hydride afforded the
corresponding C2-symmetric N,N%-aryl-disubstituted bis(oxazolidin-2-ones) in 82–92% yields. Hydrolytic
ring opening of the bis(oxazolidin-2-ones) provided a convenient synthetic route for optically pure
C2-symmetric N,N%-aryl-disubstituted 2,3-diamino-1,4-butanediols (58–86% yields). © 2001 Elsevier Sci-
ence Ltd. All rights reserved.
1. Introduction
Chiral oxazolidin-2-ones have been utilized as chiral auxiliaries for a wide range of asymmet-
ric reactions such as diastereoselective alkylations, aldol reactions, Michael additions and
Diels–Alder reactions.1 Moreover, chiral oxazolidinones gained much interest in their own right
as antibacterial agents2 and precursors for optically active 1,2-aminoalcohols.3 A number of
chiral 1,2-aminoalcohols have been synthesized by hydrolytic ring opening of chiral oxazolidin-
2-ones which derived from the reaction of 2,3-epoxy alcohols with isocyanates.3 During our
study on the development of C2-symmetric chiral ligands,4 we were interested in vicinal diamines
bearing two neighboring stereogenic centers such as (2S,3S)-2,3-diamino-1,4-butanediol4a,5 as a
starting material for C2-symmetric chiral ligands. Many N,N%-disubstituted ethylenediamine
derivatives with C2-symmetry have been synthesized and widely used as chiral tools in several
reactions.6–8 The most common approach was by reductive coupling of the corresponding imine,
isomerization of the meso compound into the dl one, and subsequent resolution of the
* Corresponding author. E-mail: sanggi@kist.re.kr
0957-4166/00/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00446-8

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S. Lee et al. / Tetrahedron: Asymmetry 11 (2000) 4709–4717
racemate.8 Nevertheless, synthetic methods of chiral N,N%-diarylated ethylenediamines have been
scarcely developed.7–9
It can be expected that the hydrolytic ring opening of enantiopure C2-symmetric N,N%-diaryl
bis(oxazolidin-2-ones) 4 may become a convenient synthetic route for N,N%-diaryl vicinal
diamines. However, as far as we know, no such bis(oxazolidin-2-ones) 4 have been reported. In
a previous communication,10 we reported the double intramolecular cyclization of bis(carba-
mate) 3a to furnish 4a which transformed to (5S,5%S)-5,5%-bis(oxazolidin-2-one), water-soluble
C2-symmetric bifunctional chiral auxiliary.11 In this paper, we wish to report detailed experi-
ments of the intramolecular cyclization of bis(carbamate) 3a and a general one-pot synthesis of
C2-symmetric N,N%-diaryl bis(oxazolidin-2-ones) 4 from diol 2, and their conversion to N,N%-
diaryl-2,3-diamino-1,4-butanediols 5 (Scheme 1).
Scheme 1.
2. Results and discussion
Regiocontrolled intramolecular cyclization of hydroxyl ureas are often used in the syntheses
of imidazolidinones and oxazolines.12 The selectivity for N-cyclization versus O-cyclization
during the intramolecular cyclization of carbamates derived from 2,3-epoxy alcohol and
isocyanates depend on the reaction conditions and, thus, afforded oxazolidinones and/or
carbonates.3a,e Under basic conditions, N-cyclized oxazolidinones were formed in preference to
O-cyclized carbonates. However, the intramolecular cyclization of bis(carbamates) 3 is expected
to be more complicated. Four isomers, namely, two that are N-cyclized, bis(oxazolidinone) 4
and fused-bicyclic oxazidinone 6, and two O-cyclized imino carbonates 7 and 8 could be formed.
To investigate the cyclization route shown in Scheme 2, the -tartaric acid-derived (2S,3S)-2,3-
L
di(methanesulfonyloxy)-1,4-dibenzyloxybutane 1 was debenzylated to give 2 which converted to
the bis(carbamate) 3a by reaction with benzylisocyanate in 90% yield.

S. Lee et al. / Tetrahedron: Asymmetry 11 (2000) 4709–4717
4711
Scheme 2.
Initially, sodium hydride (NaH) was added portionwise to a solution of bis(carbamate) 3a in
THF at 0°C, then the reaction mixture was refluxed for 6 h. One major compound 4a was
detected in TLC (n-hexane:EtOAc=1:2) and isolated in 90% yield. However, when the same
reaction was carried out overnight at room temperature, a mixture of N-cyclized products 4a
1
and 6a was formed in 90% yield in a ratio of 9:1, determined by H NMR spectrum analysis.
1
In H NMR, the diastereotopic benzyl protons of relatively less polar 4a were resonated as two
sets of doublets at l 4.38 and 4.19, whereas at l 4.96 and 4.32 for more polar 6a. There was no
sign of O-cyclized products 7a and 8a. After chromatographic separation of 4a and 6a, their
structures were unambiguously determined by X-ray crystallographic analyses (Fig. 1). Employ-
ing t-BuOK or t-BuONa as base under the same reaction conditions exhibited almost the same
selectivity with that of the value obtained with sodium hydride. However, other bases such as
triethylamine, diisopropylethylamine, potassium carbonate and cesium carbonate gave only a
trace amount of 4a, even at elevated reaction temperatures, and most of the starting bis(carba-
mate) 3a was recovered.
Figure 1. ORTEP diagram of compounds 4a and 6a
To avoid the inconvenience of the separation of carbamate 3a, we turned to a one-pot
reaction. Thus, to a solution of mesylate 2 in THF was successively added benzylisocyanate (2.2
equiv.) and NaH (6 equiv.) at 0°C, and the mixture was stirred at room temperature for 10 h
to give 4a (82%) and 6a (8%). We expected to apply this reaction condition to a general
synthesis of N,N%-aryl disubstituted C2-symmetric bis(oxazolidinones) 4b–4g. On the basis of the
above reaction conditions, various arylisocyanates were reacted with 2, and the yields were

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S. Lee et al. / Tetrahedron: Asymmetry 11 (2000) 4709–4717
summarized in Table 1. In contrast with benzylisocyanate, all of the arylisocyanates examined
afforded only 4b–4g with high selectivity. No other compounds including 6b–6g could be
isolated. The X-ray crystal structure of 4e clearly supported that the isolated compounds were
bis(oxazolidinones) 4b–4g.13
Table 1
C2-Symmetric N,N%-aryl-disubstituted bis(oxazolidin-2-ones) 4 and N,N%-aryl-disubstituted 2,3-diamino-1,4-
butanediols 5
Entry
4
Yield (%)
5
Yield (%)
1
2
3
4
5
6
7
a
b
c
d
e
f
82
91
92
84
89
90
87
a
b
c
d
e
f
81
76
86
76
62
58
72
g
g
Once C2-symmetric N,N%-diaryl bis(oxazolidinones) 4a–4g were in hand, the N,N%-aryl-disub-
stituted (2S,3S)-2,3-diamino-1,4-butanediols 5a–5g could be synthesized by simple hydrolytic
ring opening of the corresponding 4a–4g.3,14 Upon treatment with lithium hydroxide, the
oxazolidinone rings of 4a–4g were opened to furnish 5a–5g in moderate to good yields. The
yields after chromatographic purification (n-hexane:EtOAc=2:1) on silica are summarized in
Table 1. Interestingly, the relative polarities on TLC of the diaminodiols 5a–5g are lower than
the corresponding bis(oxazolidinones) 4a–4g.
In conclusion, we have described in detail the regioselective intramolecular cyclization of
bis(carbamate) 3a and the development of a general one-pot method for the synthesis of
C2-symmetric N,N%-diaryl bis(oxazolidin-2-ones) 4 from dihydroxydimesylate 2 and aryliso-
cyanates in the presence of NaH. Hydrolytic ring opening of 4 provided a convenient synthetic
route for enantiomerically pure N,N%-diaryl-(2S,3S)-2,3-diamino-1,4-butanediols 5. Studies on
the synthesis of C2-symmetric chiral ligands using vicinal diamines 5 are underway.
3. Experimental
3.1. General methods
1
NMR spectra were recorded at 300 MHz for H NMR and 75 MHz for 13C NMR with TMS
as internal reference. Chemical analyses were carried out by the Advanced Analysis Center at
Korea Institute of Science and Technology. The Mass Spectrometry Analysis Group at Korea
Basic Science Institute carried out HRMS (FAB) analysis. All solvents were distilled prior to
use. (2S,3S)-2,3-Di(methanesulfonyloxy)-1,4-dibenzyloxybutane 1 has been prepared from -tar-
L
taric acid according to our previously published procedures.4

S. Lee et al. / Tetrahedron: Asymmetry 11 (2000) 4709–4717
4713
3.2. Synthesis of (2S,3S)-2,3-di(methanesulfonyloxy)-1,4-butanediol 2
A solution of 1 (16 g, 53 mmol) in MeOH/EtOAc (1:1, v/v) was stirred in the presence of
Pd(OH)2 (1 g) under an atmosphere of hydrogen at room temperature for 12 h. The catalyst was
removed by filtration through Celite 545. After evaporation of the solvent under reduced
pressure, the oily residue was purified by column chromatography on silica gel (2:1, EtOAc/n-
hexane) to give 2 as colorless oil (10.9 g, 96%) which solidified after prolonged storage in a
refrigerator. Mp 69–70°C; [h]2D5 −2.9 (c 0.42, CH3OH); H NMR (300 MHz, DMSO-d6) l 5.32
1
(t, J=5.3 Hz, 2H), 4.74 (dt, J=6.9, 3.5 Hz, 2H), 3.86 (m, 4H), 3.22 (s, 6H); 13C NMR (75 MHz,
DMSO-d6) l 81.3, 60.6, 39.0. Anal. calcd for C6H14O8S2: C, 25.89; H, 5.07. Found: C, 25.90; H,
5.08.
3.3. Synthesis of (2S,3S)-2,3-di(methanesulfonyloxy)-1,4-di(N,N%-dibenzylaminocarbonyloxy)-
butane 3a
To a solution of 2 (9.2 g, 43 mmol) in THF was added benzylisocyanate (12 g, 94.4 mmol)
at 0°C. The reaction mixture was stirred overnight at room temperature and diluted with
methylene chloride, washed with 2% aqueous HCl solution, water and brine. The organic layer
was dried with MgSO4 and concentrated under reduced pressure to give benzyl bis(carbamate)
1
3a (21 g, 90%) which was recrystallized in ether. Mp 118–120°C; [h]2D5 −101.1 (c 0.6, CHCl3); H
NMR (300 MHz, CDCl3) l 7.32 (m, 10H), 5.42 (m, 2H), 5.06 (m, 2H), 4.53 (d, J=11.8 Hz, 2H),
4.35 (m, 6H), 3.10 (s, 6H); 13C NMR (75 MHz, CDCl3) l 155.8, 138.3, 129.1, 128.1, 127.9, 127.5,
77.9, 63.0, 45.6, 39.3. Anal. calcd for C22H28N2O10S2: C, 48.52; H, 5.18; N, 5.14. Found: C,
47.80; H, 5.36; N, 4.81. IR (KBr) w 1698 cm−1 (CꢀO).
3.4. Intramolecular cyclization of 3a
To a solution of bis(carbamate) 3a (0.54 g, 0.1 mmol) in THF was added 95% NaH (0.1 g,
4.2 mmol) at 0°C, and the reaction mixture was stirred for 10 h at room temperature. The
reaction mixture was quenched carefully with water and extracted with methylene chloride.
Evaporation of the solvent afforded a mixture of 4a and 6a. After chromatographic separation
(1:2, n-hexane/EtOAc, 4a: Rf=0.4 and 6a: Rf=0.3) on silica, each of 4a and 6a was recrystal-
lized from methanol to give single crystals suitable for X-ray crystallographic analysis.
3.4.1. (5S,5%S)-N,N%-Dibenzyl-5,5%-bis(oxazolidin-2-one) 4a
Mp 158–160°C; [h]2D5 −20.3 (c 0.99, CHCl3); 1H NMR (300 MHz, CDCl3) l 7.33–7.36 (m, 6H),
7.08–7.12 (m, 4H), 4.38 (d, J=15.0 Hz, 2H), 4.19 (d, J=15.0 Hz, 2H), 4.09 (dd, J=9.7, 4.9,
2H), 3.87 (dd, J=9.7, 9.8 Hz, 2H), 3.73 (m, 2H); 13C NMR (75 MHz, CDCl3) l 158.5, 135.7,
129.6, 129.0, 128.6, 62.4, 54.2, 48.0. The X-ray data were collected on an Enraf–Nonius CAD-4
,
automatic diffractometer with graphite-monochromated Mo Ka (u=0.71073 A) at 293 K. The
structure was solved by the Patterson method (SHELXS-86) and refined by full-matrix least-
squares technique. C20H20N2O4, M=352.38. Monoclinic, a=11.889(3), b=6.3358(11), c=
,
12.214(3) A, h=90.00(2)°, i=108.14(2)°, k=90.00(2)°, space group=P21/a (no. 14),
3
3
,
V=874.4(4) A , Z=2, Dc=1.338 g/cm , crystal size=0.2×0.2×0.3 mm, F(000)=372, a total of
1049 reflections in the range of 1.75°5q524.96° were measured, the Dzmax and Dzmin are 0.110
and −0.109 e A , goodness-of-fit=1.113, I/|(I)]2.0, R=0.0377.
−3
,

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S. Lee et al. / Tetrahedron: Asymmetry 11 (2000) 4709–4717
3.4.2. (1S,6S)-2,7-Diaza-2,7-dibenzyl-4,9-dioxabicyclo[4,4,01,6]decane-3,8-dione 6a
Mp 210–211°C; [h]2D5 −4.42 (c 1.06, CHCl3); 1H NMR (300 MHz, CDCl3) l 7.31–7.36 (m, 6H),
7.25–7.28 (m, 4H), 4.96 (d, J=15.4 Hz, 2H), 4.32 (d, J=15.4 Hz, 2H), 4.16–4.28 (m, 6H),
3.72–3.77 (m, 2H); 13C NMR (75 MHz, CDCl3) l 153.0, 135.6, 129.1, 128.3, 127.9, 63.5, 50.6,
49.4. The X-ray data were collected on an Enraf–Nonius CAD-4 automatic diffractometer with
,
graphite-monochromated Mo Ka (u=0.71073 A) at 293 K. The structure was solved by the
Patterson method (SHELXS-86) and refined by full-matrix least-squares technique. There are
two independent molecules in the asymmetric region of the monoclinic unit cell and the features
of the two molecules are within error of being identical. C40H40N4O8, M=704.76. Monoclinic,
,
a=6.149(2), b=26.555(2), c=10.484(1) A, h=90.00(2)°, i=90.35(2)°, k=90.00(1)°, space
3
3
,
group=P21/a (no. 14), V=1711.9(6) A , Z=2, Dc=1.367 g/cm , crystal size=0.2×0.2×0.3 mm,
F(000)=744, a total of 1936 reflections in the range of 1.75°5q524.96° measured, the Dzmax
and Dzmin are 0.242 and −0.212 e A , goodness-of-fit=1.132, I/s(I)]2.0, R=0.0531.
−3
,
3.5. One-pot synthesis of (5S,5%S)-N,N%-dibenzyl-5,5%-bis(oxazolidin-2-ones) 4
To a solution of diol 2 (1.42 g, 6.6 mmol) in THF was successively added arylisocyanate (14.6
mmol) and 95% NaH (1 g, 39.6 mmol) at 0°C. The reaction mixture was stirred overnight at
room temperature. After workup as above, the residue was purified by column chromatography
on silica (1:2, n-hexane/EtOAc) to give the bis(oxazolidin-2-ones) 4. For elemental analyses,
compounds 4b–4g were recrystallized in ethanol.
3.5.1. (5S,5%S)-N,N%-Di(p-methoxyphenyl)-5,5%-bis(oxazolidin-2-one) 4b
1
Mp 131–133°C; [h]2D5 −81.0 (c 0.91, CHCl3); H NMR (300 MHz, CDCl3) l 7.20 (d, J=9.0
Hz, 4H), 6.93 (d, J=9.0 Hz, 4H), 4.58–4.60 (m, 2H), 4.41–4.44 (m, 4H), 3.82 (s, 6H); 13C NMR
(75 MHz, CDCl3) l 158.1, 155.7, 127.9, 124.3, 115.0, 61.8, 55.5, 55.2. Anal. calcd for
C20H20N2O6: C, 62.49; H, 5.24; N, 7.29. Found: C, 62.40; H, 5.30; N, 7.16. IR (KBr) w 1742 cm−1
(CꢀO).
3.5.2. (5S,5%S)-N,N%-Di(p-chlorophenyl)-5,5%-bis(oxazolidin-2-one) 4c
1
Mp 240–241°C; [h]2D5 −119.7 (c 1.70, CHCl3); H NMR (300 MHz, CDCl3) l 7.41 (d, J=8.9
Hz, 4H), 7.29 (d, J=8.9 Hz, 4H), 4.69 (t, J=5.3 Hz, 2H), 4.42–4.44 (m, 4H); 13C NMR (75
MHz, CDCl3) l 154.8, 133.9, 132.0, 130.0, 122.9, 61.9, 54.5. Anal. calcd for C18H14Cl2N2O4: C,
54.98; H, 3.59; N, 7.12. Found: C, 54.90; H, 3.69; N, 7.15. HRMS (FAB+) calcd for
C18H15Cl2N2O4 [(M+H)+]: 393.0331. Found: 393.0404. IR (KBr) 1752 cm−1 (CꢀO).
3.5.3. (5S,5%S)-N,N%-Di(p-tolyl)-5,5%-bis(oxazolidin-2-one) 4d
Mp 168–170°C; [h]2D5 −92.9 (c 0.93, CHCl3); 1H NMR (300 MHz, CDCl3) l 7.23–7.26 (m, 8H),
4.68–4.72 (m, 2H), 4.38–4.50 (m, 4H), 2.37 (s, 6H); 13C NMR (75 MHz, CDCl3) l 155.4, 136.4,
132.7, 130.3, 122.0, 61.7, 54.6, 20.8. Anal. calcd for C20H20N2O4: C, 68.17; H, 5.72; N, 7.95.
Found: C, 68.20; H, 5.76; N, 7.92. IR (KBr) 1750 cm−1 (CꢀO).
3.5.4. (5S,5%S)-N,N%-Di(o-fluorophenyl)-5,5%-bis(oxazolidin-2-one) 4e
Mp 171–172°C; [h]2D5 +0.6 (c 0.98, CHCl3); H NMR (300 MHz, CDCl3) l 7.33–7.40 (m, 4H),
1
7.16–7.26 (m, 4H), 4.54–4.57 (m, 4H), 4.80–4.50 (m, 2H); 13C NMR (75 MHz, CDCl3) l 157.6
(d, JC–F=248.9 Hz), 155.7, 130.0 (d, JC–F=8.2 Hz), 128.5, 125.4 (d, JC–F=3.8 Hz), 122.8, 117.1

S. Lee et al. / Tetrahedron: Asymmetry 11 (2000) 4709–4717
4715
(d, JC–F=19.7 Hz), 62.8, 56.3. Anal. calcd for C18H14F2N2O4: C, 60.00; H, 3.92; N, 7.77. Found:
C, 60.10; H, 3.92; N, 7.76. HRMS (FAB+) calcd for C18H15F2N2O4 [(M+H)+]: 361.0922. Found:
361.1002. IR (KBr) 1752 cm−1 (CꢀO). The X-ray data were collected on an Enraf–Nonius
,
CAD-4 automatic diffractometer with graphite-monochromated Mo Ka (u=0.71073 A) at 293
K. The structure was solved by the Patterson method (SHELXS-86) and refined by full-matrix
least-squares technique. C18H14F2N2O4, M=360.31. Orthorhombic, a=11.784(2), b=19.064(2),
3
3
,
,
c=7.316(3) A, space group=P212121 (no. 19), V=1643.5(7) A , Z=4, Dc=1.456 g/cm , crystal
size=0.3×0.35×0.5 mm, F(000)=744, a total of 2536 reflections in the range of 2.03°5q5
24.97° were measured, the Dzmax and Dzmin are 0.275 and −0.224 e A , goodness-of-fit=1.132,
−3
,
I/|(I)]2.0, R=0.045.
3.5.5. (5S,5%S)-N,N%-Di(1-naphthyl)-5,5%-bis(oxazolidin-2-one) 4f
Mp 246–249°C; [h]2D5 −141.1 (c 1.15, CHCl3); H NMR (300 MHz, CDCl3) l 7.85–7.92 (m,
1
4H), 7.40–7.63 (m, 8H), 7.18–7.21 (m, 2H), 4.84–4.89 (m, 2H), 4.75 (m, 2H), 4.45 (m, 2H); 13C
NMR (75 MHz, CDCl3) l 156.4, 134.7, 131.2, 129.6, 128.9, 127.6, 126.9, 125.4, 121.5, 62.9, 57.7.
Anal. calcd for C26H20N2O4: C, 73.30; H, 4.75; N, 6.59. Found: C, 73.57; H, 4.76; N, 6.60.
HRMS (FAB+) calcd for C26H21N2O4 [(M+H)+]: 425.1423. Found: 425.1491. IR (KBr) w 1764
cm−1 (CꢀO).
3.5.6. (5S,5%S)-N,N%-Diphenyl-5,5%-bis(oxazolidin-2-one) 4g
1
Mp 179–180°C; [h]2D5 −58.9 (c 1.04, CHCl3); H NMR (300 MHz, CDCl3) l 7.27–7.49 (m,
10H), 4.76–4.80 (m, 2H), 4.42–4.48 (m, 4H); 13C NMR (75 MHz, CDCl3) l 155.6, 135.8, 130.3,
126.9, 122.2, 62.2, 54.8. Anal. calcd for C18H16N2O4: C, 66.66; H, 4.97; N, 8.64. Found: C, 66.49;
H, 4.99; N, 8.56. IR (KBr) w 1746 cm−1 (CꢀO).
3.6. Synthesis of N,N%-diaryl (2S,3S)-2,3-diamino-1,4-butanediols 5
To a solution of bis(oxazolidinone) 4 (0.26 mmol) in 30% aqueous ethanol solution was added
LiOH·H2O (5.2 mmol) at room temperature. After 48 h reflux, the reaction temperature was
allowed to cool to room temperature and diluted with ethyl acetate. The organic layer was
washed with water, brine and dried with MgSO4. After evaporation of the solvent, the residue
was purified by column chromatography on silica using n-hexane:EtOAc=1:2 as eluent to give
N,N%-diaryl (2S,3S)-2,3-diamino-1,4-butanediols 5.
3.6.1. (2S,3S)-N,N%-Dibenzyl-2,3-diamino-1,4-butanediol 5a
Oil; [h]2D5 −22.2 (c 0.88, CHCl3); H NMR (300 MHz, CDCl3) l 7.28–7.38 (m, 10H), 4.02 (dd,
1
J=9.1, 5.3 Hz, 2H), 3.79 (s, 4H), 3.62 (dd, J=9.1, 3.9 Hz, 2H), 3.23 (pseudo pentet, J=3.8 Hz,
2H); 13C NMR (75 MHz, CDCl3) l 128.5, 128.2, 127.3, 72.7, 64.1, 52.3. HRMS (FAB+) calcd
for C18H25N2O2 [(M+H)+]: 301.1838. Found: 301.1840.
3.6.2. (2S,3S)-N,N%-Di(p-methoxyphenyl)-2,3-diamino-1,4-butanediol 5b
Mp 124–126°C; [h]2D5 +28.6 (c 0.45, CHCl3); 1H NMR (300 MHz, CDCl3) l 7.07 (bs, 2H), 6.75
(s, 8H), 4.15 (dd, J=9.9, 5.4 Hz, 2H), 3.92 (m, 2H), 3.79 (m, 1H), 3.75 (m, 1H+s, 6H); 13C NMR
(75 MHz, CDCl3) l 155.4, 135.5, 118.5, 115.0, 71.4, 61.9, 55.6. Anal. calcd for C18H24N2O4: C,
65.04; H, 7.28; N, 8.43. Found: C, 65.02; H, 7.31; N, 8.40.

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S. Lee et al. / Tetrahedron: Asymmetry 11 (2000) 4709–4717
3.6.3. (2S,3S)-N,N%-Di(p-chlorophenyl)-2,3-diamino-1,4-butanediol 5c
Mp 126–128°C; [h]2D5 +29.1 (c 0.65, CH3OH); H NMR (300 MHz, DMSO-d6) l 7.08 (d,
1
J=8.3 Hz, 4H), 6.67 (d, J=8.3 Hz, 4H), 5.35 (d, J=9.1 Hz, 2H), 4.80 (m, 2H), 3.65–3.70
(m, 2H); 13C NMR (75 MHz, DMSO-d6) l 148.0, 128.7, 118.7, 113.8, 60.4, 54.4. Anal. calcd
for C16H18Cl2N2O2: C, 56.32; H, 5.32; N, 8.21. Found: C, 56.30; H, 5.29; N, 8.25. HRMS
(FAB+) calcd for C16H19Cl2N2O2 [(M+H)+]: 341.0824. Found: 341.0811.
3.6.4. (2S,3S)-N,N%-Di(p-tolyl)-2,3-diamino-1,4-butanediol 5d
1
Oil; H NMR (300 MHz, CDCl3) l 7.04 (d, J=8.2 Hz, 4H), 6.67 (d, J=8.2 Hz, 4H), 4.17 (m,
2H), 3.89 (m, 2H), 3.72 (m, 2H), 2.28 (s, 6H), 1.68 (bs, 4H); 13C NMR (75 MHz, CDCl3) l
144.5, 130.0, 128.0, 114.4, 61.5, 55.8, 20.4. HRMS (FAB+) calcd for C18H25N2O4 [(M+H)+]:
301.1916. Found: 301.1914.
3.6.5. (2S,3S)-N,N%-Di(o-fluorophenyl)-2,3-diamino-1,4-butanediol 5e
Oil; [h]2D5 −31.6 (c 0.98, CHCl3); H NMR (300 MHz, CDCl3) l 6.96–7.03 (m, 4H), 6.80 (td,
1
J=8.6, 1.4 Hz, 2H), 6.64–6.71 (m, 2H), 4.50 (bs, 2H), 3.92 (d, J=10.4 Hz, 2H), 3.70–3.77 (m,
4H), 3.28 (bs, 2H); 13C NMR (75 MHz, CDCl3) l 151.9 (d, JC–F=239.1 Hz), 135.2 (d,
J
C–F=11.6 Hz), 124.7 (d, JC–F=3.5 Hz), 117.8 (d, JC–F=7.0 Hz), 115.0 (d, JC–F=18.8 Hz), 113.1,
60.6, 54.3. HRMS (FAB+) calcd for C16H19F2N2O2 [(M+H)+]: 309.1336. Found: 309.1404.
3.6.6. (2S,3S)-N,N%-Di(1-naphthyl)-2,3-diamino-1,4-butanediol 5f
Oil; [h]2D5 −121.2 (c 0.12, CHCl3); H NMR (300 MHz, CDCl3) l 7.79–7.85 (m, 4H), 7.24–7.48
1
(m, 8H), 6.82 (d, J=7.4 Hz, 2H), 5.10 (bs, 2H), 4.05–4.12 (m, 4H), 3.86–3.90 (m, 2H), 3.24 (bs,
2H); 13C NMR (75 MHz, CDCl3) l 141.9, 134.6, 128.8, 126.5, 125.9, 125.1, 123.8, 119.8, 118.2,
105.5, 60.8, 54.4. HRMS (FAB+) calcd for C24H25N2O2 [(M+H)+]: 373.1838. Found: 373.1908.
3.6.7. (2S,3S)-N,N%-Diphenyl-2,3-diamino-1,4-butanediol 5g
Oil; [h]2D5 −28.2 (c 1.08, CHCl3); H NMR (300 MHz, CDCl3) l 7.22–7.27 (m, 4H), 6.81 (t,
1
J=7.1 Hz, 2H), 6.73 (d, J=7.1 Hz, 4H), 3.88 (m, 6H) 3.70–3.78 (m, 4H); 13C NMR (75 MHz,
CDCl3) l 146.8, 129.5, 118.3, 113.8, 60.9, 54.7. HRMS (FAB+) calcd for C16H21N2O2 [(M+H)+]:
273.1525. Found: 273.1611.
Acknowledgements
We are grateful to the Korea Institute of Science and Technology (2V00443) for support of
this work.
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