Communications
calcd for C17H25NO6: C 60.16, H 7.42, N 4.13; found: C 60.04, H
7.61, N 4.05.
case of 4a. Thus, the reduction of 4a with L-selectride
proceeded at À788C with high stereocontrol to yield the all-
syn-configured b-amino alcohol 7, which in its protected form
belongs to the class of the biologically very important 2-
amino-2-deoxy sugars (Scheme 2).[17c,21] Furthermore, the
polyoxamic acids are directly available from 4b by reduction
of the keto function.[22] They are integral parts of the
polyoxines and also occur in isolated form in nature, and
have attracted interest due to their biological activity.[23]
Received: March 4, 2005
Published online: May 27, 2005
Keywords: amino sugars · asymmetric synthesis ·
.
dihydroxyacetone · Mannich reaction · organocatalysis
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Scheme 2. Diastereoselective reduction of 4a to 7 with L-selectride.
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The efficient asymmetric catalytic method we have
described here starting from simple and commercially avail-
able compounds provides a viable alternative to the conven-
tional, relatively elaborate, and less flexible methods for the
synthesis of amino sugars. Our protocol facilitates the syn-
thesis of different amino pentoses and hexoses with high
diversity in only one to two steps.
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Experimental Section
Unless otherwise stated, all chemicals are commercially available and
were used without further purification with the exception of aldehyde
2g[24] and catalyst 6.[25] All new compounds were fully characterized
(IR, NMR, MS, elemental analysis, optical rotation, melting point).
4a: In a 100-mL round-bottomed flask a 60% aqueous solution of
2a (2.6 g, 15 mmol) was dissolved together with 3 (2.04 g, 16.5 mmol)
and (S)-proline (519 mg, 4.5 mmol) in DMF (55 mL) at 28C. The
solution was stirred for 30 min before 1 (2 g, 15 mmol) was added, and
the mixture was stored for 5 days at 28C. The reaction was quenched
with pH 7 buffer (50 mL) and the mixture stirred for 15 min at
ambient temperature. After extraction of the aqueous phase with
ethyl acetate (3 ꢀ 75 mL), the combined organic layers were dried
over Na2SO4, concentrated, and purified by column chromatography
using silica gel (diethyl ether/pentane, 1:2). The product 4a (4.53 g,
89%) was obtained as a pale yellow solid, which was recrystallized
from heptane/2-propanol (9:1) to afford colorless crystals. M.p. 78–
808C. [a]2D3 = À83.3 (c = 0.98 in CHCl3); IR (CHCl3): n˜ = 3375 (w),
2990 (m), 2938 (m), 2833 (m), 1748 (s), 1617 (s), 1515 (s), 1462 (m),
1378 (m), 1232 (s), 1123 (m), 1094 (m), 1040 (m), 977 (m), 889 (m), 824
(m), 757 (s), 527 cmÀ1 (s); 1H NMR (400 MHz, C6D6): d = 1.27 (s, 3H,
CCH3), 1.29 (s, 3H, CCH3), 3.02 (s, 3H, OCH3), 3.16 (s, 3H, OCH3),
3.55 (s, 3H, OCH3), 3.76 (d, J = 16.4 Hz, 1H, CH2), 3.94 (dd, J =
16.4 Hz, J = 1.4 Hz, 1H, CH2), 4.38 (dd, J = 6.6 Hz, J = 1.6 Hz, 1H,
CH) 4.44 (d, J = 6.6 Hz, 1H, CH(OCH3)2), 4.68 (br, 1H, CH), 6.75
ppm (app-s, 4H, Ar); 13C NMR (100 MHz, C6D6): d = 23.0 (CH3),
24.3 (CH3), 53.3 (OCH3), 54.5 (OCH3), 54.9 (OCH3), 56.3 (CH), 66.9
(CH2), 75.1 (CH), 100.1 (C(CH3)2), 104.4 (CH(OCH3)2), 114.6 (CH),
115.9 (CH), 141.7 (C), 152.8 (C), 207.2 ppm (CO); MS (EI, 70 eV):
m/z (%): 338.8 (11) [M+], 263.9 (10) [M+ÀC3H7O2], 217.9 (100)
[M+ÀC7H7NO], 209.9 (16) [M+ÀC6H9O3], 177.9 (68) [C10H12NO2+],
135.9 (17) [C8H9NO+], 74.9 (31) [C6H4+]; HPLC (Daicel OD,
heptane/iPrOH 95/5, flow rate 0.8 mLminÀ1, major isomer: tR =
11.86 min; minor isomer: tR = 8.78 min; elemental analysis (%):
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organocatalytic carbohydrate syntheses starting from 1 were
4082
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Angew. Chem. Int. Ed. 2005, 44, 4079 –4083