Communications
nucleophile, then as a S+-electrophile, and finally as a leaving
group to fulfill turnover. Investigations are currently under-
way to further probe the scope and mechanism of this novel
mode of sulfoxide catalysis as well as expand it to other
oxygen activation/substitution reactions in synthesis.[15]
Experimental Section
General glycosylation procedure with nBu2SO catalyst/(PhSO2)2O:
15: Benzenesulfonic anhydride (59.9 mg, 0.20 mmol) was added to a
solution of 2,3,4,6-tetra-O-benzyl-d-mannopyranose (92.1mg,
0.17 mmol), n-butyl sulfoxide (7.0 mg, 0.04 mmol), and 2,4,6-tri-tert-
butylpyridine (104.6 mg, 0.42 mmol) in dichloromethane (1.3 mL) at
238C. After the reaction mixture had stirred for 1h, a solution of
benzyl 2,3-di-O-isopropylidene-a-L-rhamnopyranoside (70.3 mg,
0.24 mmol) in dichloromethane (400 mL) was added by syringe and
the reaction mixture was then allowed to stir for an additional 19 h.
The reaction was then quenched with triethylamine (235 mL,
1.69 mmol), concentrated under high vacuum, and purified by silica
gel flash chromatography (5% ! 17% ethyl acetate in benzene) to
afford the (1!4) a-disaccharide 15 (116.3 mg, 84%) as a single
anomer. Rf = 0.19 (5% ethyl acetate in benzene); 1H NMR
(500 MHz, CDCl3): d = 7.18–7.42 (m, 25H), 5.03 (s, 1H), 4.96 (d,
1H, J = 1.5 Hz), 4.92 (d, 1H, J = 10.5 Hz), 4.80 (d, 1H, J = 12.6 Hz),
4.77 (d, 1H, J = 12.2 Hz), 4.72 (d, 1H, J = 12.6 Hz), 4.69 (d, 1H, J =
11.7 Hz), 4.68 (d, 1H, J = 11.9 Hz), 4.65 (d, 1H, J = 11.8 Hz), 4.57 (d,
1H, J = 10.6 Hz), 4.52 (d, 1H, J = 12.8 Hz), 4.50 (d, 1H, J = 12.1 Hz),
4.24 (t, 1H, J = 9.7 Hz), 4.12 (d, 1H, J = 5.7 Hz), 4.05 (m, 1H), 4.02
(dd, 1H, J = 5.8, 7.3 Hz), 3.92 (dd, 1H, J = 3.0, 10.9 Hz), 3.87 (dd, 1H,
J = 3.0, 9.8 Hz), 3.76 (dd, 1H, J = 2.0, 3.0 Hz), 3.70 (dd, 1H, J = 1.9,
10.7 Hz), 3.64 (qd, 1H, J = 6.3, 10.1 Hz), 3.36 (dd, 1H, J = 7.4, 9.9 Hz),
1.49 (s, 3H, CH3), 1.27 (s, 3H), 1.06 ppm (d, 3H, J = 6.3 Hz);
13C NMR (126 MHz, CDCl3): d = 138.7, 138.7, 138.5, 138.3, 137.0,
128.5, 128.4, 128.3, 128.2, 128.2, 128.1, 128.0, 127.9, 127.7, 127.6, 127.5,
127.4, 109.0, 98.9, 96.1, 80.2, 80.0, 76.0, 75.2, 74.7, 74.0, 73.4, 72.6, 72.3,
71.8, 69.0, 68.6, 65.0, 28.1, 26.3, 17.2 ppm; FTIR (neat film): n˜ = 2932
(w), 1496 (w), 1454 (w), 1381 (w), 1220 (w), 1093 (s), 1052 (s),
1028 cmꢀ1 (m); HRMS (FAB) m/z: calcd for C50H56O10Na [M+Na]+
839.3771; found 839.3770.
Scheme 5. Glycoconjugates obtainable by the described reaction;
ꢀ
[a] 0.25 equivalents of nBu2SO; [b] Nu H=dihydrocholesterol; [c] 0.20
equivalents of nBu2SO.
Received: September 1, 2003 [Z52761]
Keywords: glycosylation · homogeneous catalysis ·
reaction mechanisms · sulfonylation · synthetic methods
pling is amenable to the construction of a diverse array of
glycoconjugates (Scheme 5) in a procedure conveniently
conducted entirely at room temperature. In terms of nucle-
ophile variability, primary, secondary, and tertiary alcohols
are glycosylated in good yields.[12,13] The range of a:b ratios in
the glycoconjugates indicates that the anomeric selectivities
vary with the nature of the substrate, although the process
does appear to respond to the effects of neighboring group
participation (i.e., 16). Notably, the method tolerates acid-
sensitive functionalities such as those present in glycal
nucleophiles (18). Moreover, the successful couplings with
glycals (18) as well as nucleophiles bearing latent leaving
groups such as sulfide (19) and fluoride (20) underscore the
potential of this reaction to engage in orthogonal glycosyla-
tion approaches to oligosaccharide construction.[14]
.
[1] a) E. F. V. Scriven, Chem. Soc. Rev. 1983, 12, 129 – 161; b) E.
Vedejs, S. T. Diver, J. Am. Chem. Soc. 1993, 115, 3358 – 3359;
c) E. Vedejs, O. Daugulis, J. Am. Chem. Soc. 1999, 121, 5813 –
5814; d) J. C. Ruble, H. A. Latham, G. C. Fu, J. Am. Chem. Soc.
1997, 119, 1492 – 1493; e) T. Kawabata, M. Nagato, K. Takasu, K.
Fuji, J. Am. Chem. Soc. 1997, 119, 3169 – 3170; f) S. J. Miller,
G. T. Copeland, N. Papaioannou, T. E. Horstmann, E. M. Ruel,
J. Am. Chem. Soc. 1998, 120, 1629 – 1630; g) G. C. Fu, Acc.
Chem. Res. 2000, 33, 412 – 420; h) Y. Chen, S.-K. Tian, L. Deng, J.
Am. Chem. Soc. 2000, 122, 9542 – 9543; i) D. Basavaiah, A. J.
Rao, T. Satyanarayana, Chem. Rev. 2003, 103, 811 – 891.
[2] For the use of sulfoxide ligands in metal-centered catalysis, see
also: a) B. R. James, R. S. McMillan, Can. J. Chem. 1977, 55,
3927 – 3932, b) H. Grennberg, A. Gogoll, J. E. Bäckvall, J. Org.
Chem. 1991, 56, 5808 – 5811; c) N. Khiar, I. Fernµndez, F.
Alcudia, Tetrahedron Lett. 1993, 34, 123 – 126, d) M. C. Carreæo,
J. L. G. Ruano, M. C. Maestro, L. M. M. Cabrejas, Tetrahedron:
Asymmetry 1993, 4, 727 – 734; e) M. Ordoæez, V. Guerrero-
de la Rosa, V. Labastida, J. M. Llera, Tetrahedron: Asymmetry
In summary, the process of sulfoxide turnover in covalent
catalysis has been achieved through the development of a
versatile glycosylation reaction that employs a simple, com-
mercially available, nonmetallic catalyst for anomeric hy-
droxy activation and subsequent coupling. The sulfoxide
catalyst functions uniquely in three capacities, first as an O
5876
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2003, 42, 5874 –5877