Y. Kobayashi et al. / Tetrahedron: Asymmetry 19 (2008) 2536–2541
2541
4.5. Liberation of (2S,3S)-2,3-dihydroxy-1,4-
bis(hydroxyamino)butane 1a
N,O-bis(t-butoxycarbonyl)hydroxyamine (12.25 g, 53 mmol) in
dry tetrahydrofuran (175 mL) was dropwise added diisopropyl
azodicarboxylate (11.0 mL, 53 mmol) at 0 °C under an argon
atmosphere. The mixture was stirred at the same temperature
for 3 h and then at room temperature overnight, after which it
was concentrated under reduced pressure, and thoroughly dried
under reduced pressure. An ethanol solution saturated with HCl
(3 mL) was added to the residue at room temperature, and the
solution was stirred overnight at room temperature, after which
it was concentrated under reduced pressure and thoroughly
dried under reduced pressure. The remaining solid was sus-
pended in chloroform (100 mL), and the powdery solid mass
was collected by filtration and dried under reduced pressure.
To a solution of the remaining powder in water (200 mL) was
added Na2CO3 until the pH reached 7, and the aqueous solution
was extracted with ethyl acetate (3 ꢀ 100 mL). The combined ex-
tracts were dried over MgSO4, filtered, and concentrated under
reduced pressure. The remaining solid mass was recrystallized
from hexane/ethyl acetate to give 1b (2.91 g, 8.8 mmol, 50%).
A
solution of (2S,3S)-2,3-dihydroxy-1,4-bis(hydroxyami-
no)butane dihydrochloride 1aꢁ2HCl (1.27 g, 5.6 mmol) in water
(1 mL) was charged on a column filled with a weakly basic ion ex-
change resin (Diaion WA 30, 20 equiv), and the product was eluted
with water (5 mL). The elution was collected, concentrated under
reduced pressure, and dried thoroughly under reduced pressure
to give 1a (0.85 g, 5.6 mmol, quant.) as
¼ þ54:3 (c 1.44, H2O); IR (KBr) 3195, 3094 (br), 1436,
1167, 1080, 1039 cmꢂ1 1H NMR (300 MHz, DMSO-d6) d 2.69–
a white solid.
½ ꢃ
a 2D3:5
;
2.73 (m, 2H), 2.80–2.84 (m, 2H), 3.35 (s, 2H), 3.61 (s, 2H), 5.50
(br s, 2H), 7.19 (s, 2H). HRMS (ESI) calcd for [M (C4H12N2O4)+H]+
153.0875, found 153.0868.
4.6. Synthesis of diethyl (2R,3R)-2,3-dibenzyloxysuccinate 5
Sodium hydride (50% in a mineral oil, 10.2 g, 233 mmol) washed
with hexane (3 ꢀ 200 mL) was suspended in dry tetrahydrofuran
(120 mL) under an argon atmosphere, and a solution of diethyl
(R,R)-tartrate (25.1 g, 122 mmol) in dry tetrahydrofuran (85 mL)
was added dropwise to the suspension at 0 °C over a period of
1.5 h. The reaction mixture was stirred at 0 °C for 4 h and then at
room temperature overnight. To the mixture was successively
added tetrabutylammonium iodide (9.0 g, 24 mmol) and 18-
crown-6 (200 mg, 0.8 mmol). Finally, benzyl bromide (27.7 mL,
233 mmol) was added dropwise to the mixture at 0 °C over a per-
iod of 30 min. The reaction mixture was stirred at room tempera-
ture, after which the reaction was quenched by adding 1 M HCl
aq (300 mL). The resulting reaction mixture was extracted with
ether (3 ꢀ 200 mL), and the combined extracts were successively
washed with satd NaHCO3 (200 mL) and brine (200 mL), dried over
MgSO4, filtered, and concentrated under reduced pressure. The
remaining residue was purified by silica gel column chromatogra-
phy (eluent: hexane/ethyl acetate = 10:1 to 2:1, v/v) to give pure 5
(20.4 g, 53 mmol, 46%) as a colorless oil. 1H NMR (300 MHz,
CD3OD) d 1.18 (t, J = 15 Hz, 6H), 3.9–4.3 (m, 4H), 4.39 (s, 2H),
4.45 (d, J = 12 Hz, 2H), 4.87 (d, J = 12 Hz, 2H), 7.25–7.40 (m, 10H).
Mp 72–73 °C; ½a D23:5
ꢃ
¼ ꢂ36:0 (c 1.03, MeOH); IR (KBr): 3186,
2922, 1455, 1361, 1218, 1089, 1047, 750, 696 cmꢂ1
;
1H NMR
(300 MHz, CD3OD): d 2.92 (dd, J = 4 and 13 Hz, 2H), 3.13 (dd,
J = 6 and 13 Hz, 2H), 3.90–3.92 (m, 2H), 4.64 (d, J = 11 Hz, 2H),
4.70 (d, J = 11 Hz, 2H), 7.26–7.36 (m, 10H). Anal. Calcd for
C18H24N2O4: C, 65.04; H, 7.28; N; 8.43. Found: C, 65.08; H,
7.20; N; 8.31.
Acknowledgment
The present work was supported by the Grant-in-Aid for Scien-
tific Research from the Ministry of Education, Science, Sports and
Culture of Japan (19350064).
References
1. Collet, A. In Comprehensive Supramolecular Chemistry; Reinhoudt, D. N., Ed.;
Pergamon: Oxford, 1996; pp 113–149.
2. Jacques, J.; Collet, A.; Wilen, S. H. Enantiomers, Racemates and Resolutions;
Krieger: Florida, 1994.
3. Kinbara, K.; Saigo, K. In Topics in Stereochemistry; Denmark, S. C., Ed.; Wiley &
Sons: New York, 2003; pp 207–265.
4.7. Synthesis of (2S,3S)-2,3-dibenzyloxy-1,4-butanediol 6
4. Kinbara, K. Synlett 2005, 732.
To a suspension of lithium aluminum hydride (3.1 g, 81 mmol)
in dry ether (45 mL) was added dropwise a solution of diethyl
(2R,3R)-2,3-dibenzyloxysuccinate 5 (14.8 g, 38 mmol) in dry ether
(30 mL) at 0 °C under an argon atmosphere, and the mixture was
stirred for 1 h at room temperature, for 7 h at reflux, and overnight
at room temperature. The remaining lithium aluminum hydride
derivatives were quenched by adding H2O (10 mL) and 6 M HCl
aq (10 mL) successively, and reaction mixture was extracted with
ether (3 ꢀ 50 mL). The combined extracts were dried over MgSO4,
filtered, and concentrated under reduced pressure. The remaining
residue was purified by silica gel column chromatography (eluent:
hexane/ethyl acetate = 5:1, v/v) to give pure 6 (10.8 g, 36 mmol,
93%) as a colorless oil. 1H NMR (300 MHz, CD3OD): d 2.36 (s, 2H),
3.68–3.83 (m, 6H), 4.65 (s, 4H), 7.25–7.38 (m, 10H).
5. Saigo, K.; Kobayashi, Y. Chem. Rec. 2007, 7, 47–56.
6. Molins, E.; Miravitlles, C.; Lopez-Calahorra, F.; Castells, J.; Raventos, J. Acta
Crystallogr., Sect. C 1989, 45, 104–106.
7. Sporer, C.; Ruiz-Molina, K.; Wurst, K.; Kopacka, H.; Veciana, J.; Jaitner, P. J.
Organomet. Chem. 2001, 637–639, 507–513.
8. Kinbara, K.; Sakai, K.; Hashimoto, Y.; Nohira, H.; Saigo, K. J. Chem. Soc., Perkin
Trans. 2 1996, 2615–2622.
9. Crystal data for (2S,3S)-1aꢁ(R)-7a: C13H22N2O6, M = 302.33, monoclinic, space
group P21, a = 8.439(3) Å, b = 7.601(2) Å, c = 12.064(5) Å, V = 770.3(5) Å3, Z = 2,
Dc = 1.303 Mg mꢂ3
, R = 0.0520, Rw = 0.0570. CCDC 694658 contains the
supplementary crystallographic data for this paper.12
10. Crystal data for (2S,3S)-1aꢁ(S)-7b: C14H24N2O6, M = 316.35, monoclinic, space
group P21, a = 8.448(5) Å, b = 6.542(4) Å, c = 14.618(12) Å, V = 805.1(10) Å3,
Z = 2, Dc = 1.305 Mg mꢂ3, R = 0.0480, Rw = 0.0540. CCDC 694657 contains the
supplementary crystallographic data for this paper.12
11. Crystal data for (2S,3S)-1bꢁ(R)-10d: C34H38Cl2N2O10, M = 705.59, monoclinic,
space group C2, a = 33.105(6) Å, b = 4.9790(8) Å, c = 10.995(3) Å, V = 1752.4(6)
Å3, Z = 2, Dc = 1.337 Mg mꢂ3, R = 0.0570, Rw = 0.0610. CCDC 694658 contains
the supplementary crystallographic data for this paper.12
retrieving.html (or from the Cambridge Crystallographic Data Centre, 12, Union
Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033; or deposit@ccdc.
cam.ac.uk).
4.8. Synthesis of (2S,3S)-2,3-dibenzyloxy-1,4-
bis(hydroxyamino)butane 1b
To
a solution of (2S,3S)-2,3-dibenzyloxy-1,4-butanediol 6
(5.29 g, 18 mmol), triphenylphosphine (13.77 g, 53 mmol), and