LETTER
Synthesis of Enantiopure Amino Polyols and Pyrrolidine Derivatives
407
O
(12) With 2a this procedure led to the formation of a 1:1 mixture
of diastereomeric azido oxazinones. Apparently,
epimerization either of 2a or the resulting azido oxazinone is
considerably faster here.
(13) As a side product 8% of the N,O-diprotected 1,2-oxazine
were obtained.
(14) Ariza, X.; Urpi, F.; Viladomat, C.; Vilarrasa, J. Tetrahedron
Lett. 1998, 39, 9101.
(15) Correct spectroscopical data were obtained for all new
compounds. Correct elemental analysis was achieved for all
stable compounds.
O
O
O
HN
O
9 equiv SmI2
THF, r.t., 5.5 h
HN
O
+
14
O
NHBn
N
HO
O
Bn
18 (21 %)
17 (34 %)
O
+
N
(16) Typical Procedure, anti-1 to 3a: To a solution of NBS
(0.222 g, 1.25 mmol) in CH3CN (13 mL) and H2O (0.8 mL)
a solution of anti-1 (0.382 g, 1.25 mmol) in CH3CN (3 mL)
was added at –40 °C. The mixture was stirred for 1 h at this
temperature and then warmed up to r.t. After quenching with
H2O the solution was extracted with Et2O and the combined
extracts were dried with MgSO4. After removal of the
solvent the crude mixture was dissolved in n-hexane and the
insoluble N-succinimide was separated by filtration. After
evaporating the solvent 3a (dr 93:7, 0.450 g, 97%) was
obtained. Recrystalization with n-hexane led to diastereo-
merically pure 3a as colorless crystals (mp 53–60 °C).
Analytical data of (3R,5R,4′S)-2-Benzyl-5-bromo-3-(2′,2′-
dimethyl-1′,3′-dioxolan-4′-yl)-tetrahydro-1,2-oxazin-4-one
(3a): [α]D20 +46.0 (c 2.3, CHCl3). 1H NMR (CDCl3, 500
MHz): δ = 7.36–7.26 (m, 5 H, Ph), 4.95 (dt, J = 2.9, 7.5 Hz,
1 H, 4′-H), 4.52, 3.76 (2 d, J = 14.6 Hz, 1 H each, CH2Ph),
4.50 (tbrdbr, J ≈ 0.7 Hz, 8.0 Hz, 1 H, 5-H), 4.41 (dbrd, J ≈ 7.5,
11.2 Hz, 1 H, 6-HA), 4.19 (dd, J = 8.8. 11.2 Hz, 1 H, 6-HB),
4.13 (mc, 2 H, 5′-H), 4.03 (dd, J = 0.6, 2.9 Hz, 1 H, 3-H),
1.42, 1.34 (2 s, 3 H each, Me). 13C NMR (CDCl3, 75.5 MHz):
δ = 196.2 (s, C-4), 136.9, 128.6, 128.5, 127.3 (s, 3 d, Ph),
108.9 (s, C-2′), 74.8 (d, C-3), 74.1 (d, C-4′), 73.8 (t, C-6),
64.7 (t, C-5′), 60.7 (t, CH2Ph), 46.6 (d, C-5), 26.0, 24.0 (2 q,
Me). IR (gas phase): ν = 2990–2890 (C-H), 1750 (C=O)
cm–1. MS (EI, 70 eV): m/z (%) = 356 (1) [M+ – 14], 290 (1)
[M+ – Br], 271, 269 (5 each), 190 (62), 101 (24), 91 (100)
[CH2Ph], 43(45) [C3H7]. C16H20BrNO4 (370.2): Calcd C,
51.90; H, 5.44; N, 3.78. Found: C, 51.88; H, 5.46; N 3.84.
Typical Procedure, 3a to 10: To a solution of 3a (0.555 g,
1.50 mmol) in CH2Cl2 (4 mL) and H2O (2 mL) NaN3 (0.487
g, 7.50 mmol) and Me(Oct)3NCl (15 mg) were added. The
mixture was stirred for 3 d at r.t., the layers were separated
and the organic layer was washed with H2O. After drying
with MgSO4 the solvent was evaporated yielding
O
Bn
19 (8 %)
Scheme 8
of highly functionalized carbohydrate mimicking com-
pounds.15,16
Acknowledgment
The authors thank the Deutsche Forschungsgemeinschaft, Fonds
der Chemischen Industrie and Schering AG for financial support of
this research.
References
(1) Schade, W.; Reissig, H.-U. Synlett 1999, 632.
(2) Synthesis: Dondoni, A.; Franco, S.; Junquera, F.; Merchan,
F. L.; Merino, P.; Tejero, T. Synth. Commun. 1994, 24, 2537.
(3) Pulz, R.; Watanabe, T.; Schade, W.; Reissig, H.-U. Synlett
2000, 983; and references cited herein.
(4) Pulz, R.; Al-Harrasi, A.; Reissig, H.-U. Synlett 2002, 817.
(5) Pulz, R.; Al-Harrasi, A.; Reissig, H.-U. Org. Lett. 2002, 4,
2353.
(6) (a) Wong, C.-H.; Halcomb, R. L.; Ichikawa, Y.; Kajimoto,
T. Angew. Chem., Int. Ed. Engl. 1995, 34, 412; Angew.
Chem. 1995, 107, 453. (b) Wong, C.-H.; Halcomb, R. L.;
Ichikawa, Y.; Kajimoto, T. Angew. Chem., Int. Ed. Engl.
1995, 34, 521; Angew. Chem. 1995, 107, 569.
(c) Iminosugars as Glycosidase Inhibitors; Stütz, A. E., Ed.;
Wiley-VCH: Weinheim, 1999. (d) Heightman, T. D.;
Vasella, A. T. Angew. Chem. Int. Ed. 1999, 38, 750; Angew.
Chem. 1999, 111, 794. (e) Asano, N.; Nash, R. J.;
Molyneux, R. J.; Fleet, G. W. J. Tetrahedron: Asymmetry
2000, 11, 1645. (f) Lillelund, V. H.; Jensen, H. H.; Liang,
X.; Bols, M. Chem. Rev. 2002, 102, 515. (g) Gerber-
Lemaire, S.; Popowycz, F.; Rodríguez-García, E.; Asenjo,
A. T. C.; Robina, I.; Vogel, P. ChemBioChem 2002, 3, 466.
(7) Pulz, R.; Schade, W.; Reissig, H.-U.; Rademacher, O. Z.
Kristallogr. NCS 2000, 215, 73.
spectroscopically pure 10 (dr = 92:8, 0.500 g, quant.) as
viscose brown oil.
Analytical data of (3R,5S,4′S)-5-Azido-2-benzyl-3-(2′,2′-
dimethyl-1′,3′-dioxolan-4′-yl)-3,4,5,6-tetrahydro-2H-1,2-
oxazin-4-one (10): 1H NMR (CDCl3, 500 MHz): δ = 7.38–
7.27 (m, 5 H, Ph), 4.59–4.56 (m, 1 H, 4′-H), 4.55 (t, J = 8.7
Hz, 1 H, 5-H), 4.43 (dd, J = 8.7, 10.6 Hz, 1 H, 6-HA), 4.13
(dd, J = 6.2, 8.4 Hz, 1-H, 5′-HA), 4.12, 3.80 (2 d, J = 13.9
Hz, 1 H each, CH2Ph), 3.92 (dd, J = 7.1, 8.4 Hz, 1 H, 5′-HB),
3.74 (dd, J = 8.7, 10.6 Hz, 1 H, 6-HB), 3.53 (d, J = 3.9 Hz, 1
H, 3-H), 1.35, 1.33 (2 s, 3 H each, Me). 13C NMR (CDCl3,
125 MHz): δ = 200.3 (s, C-4), 135.4, 128.7, 128.4, 127.8 (s,
3 d, Ph), 110.4 (s, C-2′), 75.1 (d, C-3), 72.2 (d, C-4′), 70.8 (t,
C-6), 67.4 (t, C-5′), 62.6 (d, C-5), 58.9 (t, CH2Ph), 25.9, 25.6
(2 q, Me). IR (CCl4): ν = 2990–2890 (C-H), 2120 (N3), 1740
(C=O) cm–1. According to 1H NMR and 13C NMR purity
>95%.
(8) Ballestri, M.; Chatgilialoglu, C.; Clark, K. B.; Griller, D.;
Giese, B.; Kopping, B. J. Org. Chem. 1991, 56, 678.
(9) Dehalogenation of α-halo ketones with Raney nickel:
Barrero, A. F.; Alvarez-Manzaneda, E. J.; Chahboun, R.;
Meneses, R.; Romera, J. L. Synlett 2001, 485.
(10) Keck, G. E.; McHardy, S. F.; Wager, T. T. Tetrahedron Lett.
1995, 36, 7419.
(11) 13% of starting material 5 have been isolated.
Synlett 2003, No. 3, 405–407 ISSN 0936-5214 © Thieme Stuttgart · New York