Communications
for 1 h at room temperature. A saturated aqueous NaHCO3 solution
was added, and the reaction mixture was extracted twice with
dichloromethane. The combined organic layers were dried over
Na2SO4, filtered, and concentrated in vacuo. Crystallization from
EtOH (70 mL)gave 17 (1.56 g, 79%)as a white solid. [ a]2D5 = + 5 (c =
[20]
1 gcmÀ3 in CHCl3)[lit. [ a]D25 = + 1.4 (c = 1 gcmÀ3 in CHCl3)]; m.p.
173–1758C; 1H NMR (CDCl3, 360 MHz): d = 7.59–7.26 (m, 18H, Ar-
H), 5.61 (s, 1H, CH-Ph), 5.09 (dd, J2,1 = 9.7 Hz, J2,3 = 9.0 Hz, 1H, H-2),
4.91 (d, J = 12.2 Hz, 1H, CH2-Ph), 4.75 (d, J1,2 = 9.7 Hz, 1H, H-1), 4.71
(d, J = 12.2 Hz, 1H, CH2-Ph), 4.43 (dd, J6’,5 = 5.0 Hz, J6’,6 = 10.4 Hz,
1H, H-6’), 3.84 (dd, J6,5 = 10.2 Hz, J6,6’ = 10.4 Hz, 1H, H-6), 3.81 (t,
J3,2 = J3,4 = 9.0 Hz, 1H, H-3), 3.78 (t, J4,3 = J4,5 = 9.0 Hz, 1H, H-4), 3.55
Scheme 2. Copper triflate catalyzed one-pot regioselective protection
(ddd, J5,4 = 9.0 Hz, J5,6 = 10.2 Hz, J5,6’ = 5.0 Hz, 1H, H-5), 2.06 ppm (s,
3H, CH3-CO); 13C NMR (CDCl3, 90 MHz): d = 169.3 (CH3-CO),
138.1, 132.7, 132.3, 129.1, 129.0, 128.4, 128.3, 128.2, 127.9, 127.8, 126.1
(18C, Ar-C), 101.3 (CH-Ph), 86.8 (C-1), 81.3 (C-4), 79.8 (C-3), 74.4
(CH2-Ph), 71.4 (C-2), 70.5 (C-5), 68.6 (C-6), 21.0 ppm (CH3-CO); Rf
(pentane/diethyl ether 3:1) = 0.6; ESI HRMS for C28H28O6S1
[M+Na]+: found 515.1499, calcd 515.1499.
of d-glucopyranosides 1 and 6. a) PhCHO (3 equiv), Et3SiH
(1.1 equiv), 1 mol% Cu(OTf)2, CH2Cl2/CH3CN (4:1), room temperature
(X=a-OMe) or 08C (X=b-SPh), 10 min (procedure a), then Ac2O
(3 equiv), CH2Cl2, room temperature, 1 h (16: 78%; 17: 79% after
direct recrystallization) or Bz2O (4 equiv), CH2Cl2, reflux, 24 h (18:
71%; 19: 69%) or Piv2O (4 equiv), CH2Cl2, reflux, 24 h (20: 74%; 21:
70%). b) procedure (a) then BH3·THF (5 equiv), 10 mol% Cu(OTf)2,
room temperature, 3 h (22: 75%; 23: 77%); c) procedure (a) then
Et3SiH (5 equiv), 5 mol% Cu(OTf)2, room temperature, 2 h (2: 58%).
Bz=benzoyl, Piv=pivaloyl.
Received: July 30, 2007
Published online: October 2, 2007
Keywords: carbohydrates · Lewis acids · regioselectivity ·
.
tandem catalysis
“Chemical Synthesis of Glycosides and Glycomimetics” in
Carbohydrates in Chemistry and Biology, Vol. 1 (Eds.: B. Ernst,
G. W. Hart, P. Sinaþ), Wiley-VCH, Weinheim, 2000.
[2] For two selected books on protecting groups, see: a)T. W.
Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis,
3rd ed., Wiley, New York, 1999; b)P. J. Kocienski, Protecting
Groups, 3rd ed., Georg Thieme, Stuttgart, 2005.
3754 – 3760; e)J.-C. Wasilke, S. J. Obrey, R. T. Baker, G. C.
[4] a)N. Grenouillat, B. Vauzeilles, J.-J. Bono, E. Samain, J.-M.
44, 965 – 969; c)A. Malapelle, Z. Abdallah, G. Doisneau, J.-M.
[5] For some selected reports on tandem catalysis with Lewis acids
[6] Acetal formation. TMSOTf: a)T. Tsunoda, M. Suzuki, R.
H. Wataru, J. Org. Chem. 2003, 68, 3413 – 3415; Sc(NTf2)3: K.
839 – 840; Bi(OTf)3: N. M. Leonard, M. C. Oswald, D. A. Frei-
Scheme 3. Iterative preparation of a,b-triglucoside 25. a) 1-Benzenesul-
finyl piperidine (1 equiv), Tf2O (1.1 equiv), 2,4,6-tri-tert-butylpyrimidine
(2 equiv), MS 4 ꢀ, CH2Cl2, À608C, 15 min, then 10 (1.25 equiv) 1 h,
70%. b) The same conditions as in (a) but with 3 (1.25 equiv), 66%
(81% based on recovered donor 24).
In conclusion, we have developed a regioselective one-pot
protection of carbohydrates, which has been optimized on d-
glucopyranosides, by using a single catalyst in a single reaction
vessel. Different building blocks with different substitution
patterns can be obtained in a single flask by fine-tuning the
reaction conditions. This approach should simplify the
synthetic sequences to oligomers as demonstrated by a
rapid iterative assembly that incorporates these building
blocks into a trisaccharide.
Experimental Section
17: A solution of freshly dried copper(II)trifluoromethanesulfonate
in acetonitrile (80 mm, 0.50 mL)was added to an ice-cold solution of
the persilylated thioglucoside 6 (2.32 g, 3.98 mmol)and benzaldehyde
(1.21 mL, 11.95 mmol)in dichloromethane (2 mL). Then, triethylsi-
lane (0.70 mL, 4.38 mmol)was added, and over 30 min the solution
was concentrated to dryness under an argon flow. The resulting yellow
solid was dissolved in dichloromethane (2.00 mL), and the acetic
anhydride (1.13 mL, 11.95 mmol)was added. The mixture was stirred
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2007, 46, 8662 –8665
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