Tandem catalysis for a one-pot regioselective protection of carbohydrates: The example of glucose

Article abstract of DOI:10.1002/anie.200703437

(Chemical Equation Presented) Fine-tuning the conditions for a tandem reaction using a single catalyst in a single reaction vessel leads to carbohydrate building blocks displaying different patterns of protecting groups (see picture). This process greatly simplifies the access to oligomers, as illustrated by the rapid assembly of a trisaccharide.

Full text of DOI:10.1002/anie.200703437

Communications
DOI: 10.1002/anie.200703437
Carbohydrates
Tandem Catalysis for a One-Pot Regioselective Protection of
Carbohydrates: The Example of Glucose**
Antoine Français, Dominique Urban, and Jean-Marie Beau*
In the assembly of oligosaccharide structures from mono-
Table 1: Persilylated d-glucopyranoside 1 under reductive alkylation
conditions.[a]
saccharide building blocks, the major focus logically centers
on the challenge of developing the stereoselective formation
of glycosidic bonds.[1] Much less attention is given to elabo-
rating monomeric building blocks (glycosyl donors and
acceptors)that usually require designing a multistep sequence
of transformations that involves several protecting-group
manipulations.[1,2] Replacing these lengthy multistep
approaches by new strategies that rely on the minimal use
of separate steps would be highly attractive. In particular, the
development of one-pot, catalyzed tandem processes without
intermediate separation steps is a desirable strategy to carry
out a sustainable multistep synthesis with high efficiency.[3]
Over the past few years, our laboratory has presented
several strategic options that have drastically shortened the
synthetic route to bioactive glycoconjugates.[4] As part of this
work, we report here the successful development of a
sequential tandem Lewis acid catalysis which includes two
or more distinct steps promoted by a single catalyst in a single
reaction vessel.[5]
Entry
Cu(OTf)2
[mol%]
CH2Cl2/CH3CN
Yield [%]
2/3
1
2
3
4
0.5
0.5
0.5
1
98:2
57
32
65
44
1:7
3:2
1:3
2:3
0:100
80:20
80:20
[a] TMS=trimethylsilyl.
Acetal formation, regioselective reductive opening of
arylidene acetals or reductive etherification, and acylation are
reactions widely used on carbohydrate templates that can all
be readily catalyzed by triflate salts or trimethylsilyl triflate
(TMSOTf).[6–9] The possibility then emerges that these
reactions could be programmed in tandem.[5] This intriguing
approach would, however, require an absolute fine-tuning of
the experimental conditions that would be compatible with all
three reactions conducted in the same vessel. Particularly
crucial would be to exploit the kinetic/thermodynamic
preferences that would lead to a clean regioselective protec-
tion of sugars.[10,11]
We decided to implement a one-pot regioselective benzyl-
ation of a glucopyranoside, a procedure seen as a balanced
complement to the highly regioselective de-O-benzylation of
benzylated sugar derivatives promoted by excess amounts of
isobutylaluminum reagents[12] or oxidizing agents.[13] Results
outlined in Table 1 present our initial attempts to prepare
regioselectively 3,4-di-O-benzyl-d-glucopyranoside 2 using a
one-pot procedure from the per-O-trimethylsilylated deriva-
tive 1 as the substrate sugar for model studies.[14] When
[Cu(OTf)2] was used as the sole catalyst [Cu(OTf)2] and
“easy” conditions were maintained (08C to room temperature
with a minimum loading of catalyst), success resulted from a
subtle choice of solvent conditions (cf. entries 1 and 2,
Table 1).
This preliminary study, although not synthetically useful,
proved that the tandem process was indeed operating with a
low loading of the catalyst (0.5–1 mol%). This also indicated
that adjusting the reaction conditions for the regioselective
one-pot preparation of 3-O-benzyl-4,6-O-benzylidene-d-glu-
copyranoside 3 would be easily feasible. This was next
examined using the same substrate but with different triflate
catalysts (Table 2). With a selected set of solvent conditions,
we were pleased to discover that the addition of an excess of
benzaldehyde (3 equiv), Et3SiH (1.1 equiv), and 1 mol% of
Cu(OTf)2 in CH3CN to a solution of silylated a-methyl
glucopyranoside 1 in CH2Cl2 (final CH2Cl2/CH3CN ratio of
4:1)resulted in the clean formation of compound 3 in 78%
yield (entry 3, Table 2). Lower loadings of the catalyst
resulted in lower yields of 3 with the concurrent formation
of only the acetal 4 (47 and 18% with 0.25 and 0.5 mol% of
Cu(OTf)2, respectively, entries 1 and 2, Table 2). In constrast,
the decreased yields of 3 with higher catalyst loadings (2.5 and
5 mol%)are explained by the surprising formation of the
mono-O-benzyl derivative 5 (25 and 38%, respectively,
entries 4 and 5, Table 2). The use of the other triflate catalysts
(entries 6–9, Table 2)under the same conditions (1 mol%
catalyst in the same solvent at room temperature)was less
[*] A. Français, Dr. D. Urban, Prof. J.-M. Beau
UniversitØ Paris-Sud 11
Institut de Chimie MolØculaire et des MatØriaux associØ au CNRS
Laboratoire de Synth›se de BiomolØcules
91405 Orsay Cedex (France)
Fax: (+33)1-6985-3715
E-mail: jmbeau@icmo.u-psud.fr
[**] We thank the Minist›re de la Recherche for a PhD grant to A.F.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
8662
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2007, 46, 8662 –8665
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
Take advantage of blue reference links
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&

Angewandte
Chemie
Table 2: One-pot regioselective protection of a-methyl d-glucopyrano-
side 1.[a]
Table 3: Copper triflate catalyzed one-pot regioselective protection of
thio-d-glucopyranosides 6–9.[a]
Entry
X
Product
Yield [%][b]
1
2
3
6: b-SPh
7: b-STol
8: b-SEt[c]
10
11
80
79
53
12
19
60
12: X=b-SEt
13: X=a-SEt
12: X=b-SEt
13: X=a-SEt
4
9: a-SEt[c]
Entry
Catalyst
Mol %
Yield of 3 [%][b]
[c]
1
2
3
4
5
6
7
8
9
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
TMSOTf
Bi(OTf)3
Hf(OTf)4
VO(OTf)2
0.25
0.5
1
2.5
5
1
1
1
1
[a] General reaction conditions: 3 equiv benzaldehyde, 1.1 equiv Et3SiH,
1 mol% Cu(OTf)2 in CH2Cl2/CH3CN (4:1) at 08C, 10 min. [b] Yield after
silica gel chromatography. [c] Reaction performed at room temperature
for 2 h.
70
78
48[d]
45[e]
49[f]
36[f]
52[f]
57[f]
[g]
[a] General reaction conditions: 3 equiv benzaldehyde, 1.1 equiv Et3SiH,
x mol% M(OTf)n in CH2Cl2/CH3CN (4:1) at room temperature, 10 min.
[b] Yield of 3 after silica gel chromatography. [c] Only acetal 4 was formed
in 47% yield. [d] Ether 5 was also formed in 25% yield. [e] Ether 5 was
also formed in 38% yield. [f] Acetal 4 and ether 5 were also formed.
[g] The Bi(OTf)3/Et3SiH combination is not stable, see reference [15].
Bn=benzyl.
Scheme 1. Origin of the one-pot regioselective benzylation at posi-
tion 3 of a-methyl d-glucopyranoside 1. a) PhCHO (3 equiv), 1 mol%
Cu(OTf)2, CH2Cl2/CH3CN (4:1), room temperature, 0.5 h, 23%;
b) Et3SiH (1.1 equiv), 1 mol% Cu(OTf)2, CH2Cl2/CH3CN (4:1), room
temperature, 0.5 h; 3: 56% yield, 15: 8% yield (diol 4 also formed in
7% yield). TES=triethylsilyl.
efficient in giving 3, and both acetal 4 and ether 5 were also
obtained. Under these reaction conditions, Ba(OTf)2, Yb-
(OTf)3, and Sm(OTf)3 were inefficient, providing only the 4,6-
acetal 4 (results not shown).
sequential addition of reagents that would be active under
copper triflate catalysis. Thus further acylation proceeded in
good overall yields (69–79%)with the anhydrides, either at
room temperature (Ac2O, 3 equiv)or at reflux temperature
(Bz2O and Piv2O, 4 equiv)to provide the corresponding fully
protected carbohydrates 16–21 (Scheme 2). For example b-
thiophenyl glycoside 17 was provided as a crystalline material
in 79% yield without the need for column chromatography.
Similarly, when the same procedure was followed by the
copper triflate catalyzed regioselective ring opening of the
4,6-O-benzylidene in the presence of the BH3·THF complex,
the 3,4-di-O-benzyl derivatives 22 and 23 were obtained
highly selectively in good yields (Scheme 2). Switching from
this borane-promoted reductive opening to the silane-pro-
moted reductive cleavage in CH3CN[7d] furnished the 3,6-di-
O-benzyl-d-glucopyranoside 2 (step c, Scheme 2).[17]
The utility of these diverse one-pot syntheses of mono-
meric building blocks was highlighted in an efficient iterative
construction[18] of protected trimeric oligosaccharide 25, using
the fully protected b-selective glycosyl donor 17, acceptor 10
as the precursor of the internal unit, and acceptor 3 as the
terminating building block (Scheme 3). Phenylsulfenyl-pro-
moted assembly of 17 and 10 following the procedure of Crich
and Smith[19] provided exclusively b-dimeric glycosyl donor 24
in 70% yield (b/a > 95:5), which on further activation and
coupling with the acceptor 3 yielded with unexpected
exclusive a-selectivity a,b-triglucoside 25 (a/b > 95:5)in
66% yield.
This tandem transformation was successfully extended to
the corresponding thioglucopyranosides, representative
building blocks of a widely used class of glycosyl donors
(Table 3). With the thioaryl substrates 6 and 7, the best results
were obtained at 08C, with a tetrabutylammonium fluoride
treatment at the end of the reaction for g-scale preparations.
(entries 1 and 2, Table 3). However, reactions of the corre-
sponding thioethyl glycosides 8 and 9 produced a mixture of
anomers 12 and 13 (65–79%, total yield), as a consequence of
an acid-catalyzed anomerization (entries 3 and 4, Table 3).
In order to clarify the key regioselective benzylation at
position 3 of the tandem process the same conditions were
applied to 1 omitting the reducing Et3SiH (step a, Scheme 1).
This gave the bis-benzylidene acetal 14 as only one diaste-
reomer as shown which, after treatment with our standard
reductive procedure, provided only 3-O-benzyl derivatives 3
and 15 in 64% total yield with no detectable amounts of the
regioisomeric 2-O-benzyl derivative. This indicates that the
one-pot regioselective alkylation at position 3 most probably
arises from a regioselective reductive opening of a transient
2,3-acetal, with the other 4,6-acetal being stable under these
reaction conditions.[16]
With this one-pot procedure in hand in which all reagents
are present at the onset of the reaction, we then explored the
possibility of extending further the “tandem” process by
Angew. Chem. Int. Ed. 2007, 46, 8662 –8665
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 8663
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
Take advantage of blue reference links
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&

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
[1] H. Paulsen, Angew. Chem. 1982, 94, 184 – 201; Angew. Chem. Int.
Ed. Engl. 1982, 21, 155 – 173; R. R. Schmidt, Angew. Chem. 1986,
98, 213 – 236; Angew. Chem. Int. Ed. Engl. 1986, 25, 212 – 235;
“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.
[3] For some key reviews see: a)L. F. Tietze, Chem. Rev. 1996, 96,
115 – 136; b)S. E. Denmark, A. Thorarensen, Chem. Rev. 1996,
96, 137 – 165; c)D. E. Fogg, E. N. dos Santos, Coord. Chem. Rev.
2004, 248, 2365 – 2379; d)A. Ajamian, J. L. Gleason, Angew.
Chem. 2004, 116, 3842 – 3848; Angew. Chem. Int. Ed. 2004, 43,
3754 – 3760; e)J.-C. Wasilke, S. J. Obrey, R. T. Baker, G. C.
Bazan, Chem. Rev. 2005, 105, 1001 – 1020; f)D. Enders, C.
Grondal, M. R. M. Hüttl, Angew. Chem. 2007, 119, 1590 – 1601;
Angew. Chem. Int. Ed. 2007, 46, 1570 – 1581.
[4] a)N. Grenouillat, B. Vauzeilles, J.-J. Bono, E. Samain, J.-M.
Beau, Angew. Chem. 2004, 116, 4744 – 4746; Angew. Chem. Int.
Ed. 2004, 43, 4644 – 4646; b)S. Zameo, B. Vauzeilles, J.-M. Beau,
Angew. Chem. 2005, 117, 987 – 991; Angew. Chem. Int. Ed. 2005,
44, 965 – 969; c)A. Malapelle, Z. Abdallah, G. Doisneau, J.-M.
Beau, Angew. Chem. 2006, 118, 6162 – 6166; Angew. Chem. Int.
Ed. 2006, 45, 6016 – 6020.
[5] For some selected reports on tandem catalysis with Lewis acids
see: a)N. Giuseppone, J. Collin, Tetrahedron 2001, 57, 8989 –
8998; b)N. Jaber, M. AssiØ, J.-C. Fiaud, J. Collin, Tetrahedron
2004, 60, 3075 – 3083; c)A. Orita, Y. Nagano, K. Nakazawa, J.
Otera, Adv. Synth. Catal. 2002, 344, 548 – 555; d)H. Du, X.
Zhang, Z. Wang, K. Ding, Tetrahedron 2005, 61, 9465 – 9477.
[6] Acetal formation. TMSOTf: a)T. Tsunoda, M. Suzuki, R.
Noyori, Tetrahedron Lett. 1980, 21, 1357 – 1358; b)K. Masaaki,
H. Wataru, J. Org. Chem. 2003, 68, 3413 – 3415; Sc(NTf2)3: K.
Ishihara, Y. Karumi, M. Kubota, H. Yamamoto, Synlett 1996,
839 – 840; Bi(OTf)3: N. M. Leonard, M. C. Oswald, D. A. Frei-
berg, B. A. Nattier, R. C. Smith, R. S. Mohan, J. Org. Chem.
2002, 67, 5202 – 5205; VO(OTf)2: C.-T. Chen, S.-S. Weng, J.-Q.
Kao, C.-C. Lin, M.-D. Jan, Org. Lett. 2005, 7, 3343 – 3346.
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
8664 www.angewandte.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2007, 46, 8662 –8665
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
Take advantage of blue reference links
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&

Angewandte
Chemie
[7] Regioselective opening of arylidene acetals: Bu2BOTf: a)L.
Jiang, T.-K. Chan, Tetrahedron Lett. 1998, 39, 355 – 358; b)J. M.
Hernandez-Torres, J. Achkar, A. Wei, J. Org. Chem. 2004, 69,
7206 – 7211; VO(OTf)2: c)C.-C. Wang, S.-Y. Luo, C.-R. Shie, S.-
C. Hung, Org. Lett. 2002, 4, 847 – 849; Cu(OTf)2: d)C.-R. Shie,
Z.-H. Tzeng, S. S. Kulkarni, B.-J. Uang, C.-Y. Hsu, S.-C. Hung,
Angew. Chem. 2005, 117, 1693 – 1696; Angew. Chem. Int. Ed.
2005, 44, 1665 – 1668.
[8] Reductive etherification: TMSOTf: S. Hatakeyama, H. Mori, K.
Kitano, H. Yamada, M. Nishizawa, Tetrahedron Lett. 1994, 35,
4367 – 4370; Yb(OTf)3: G. V. M. Sharma, A. K. Mahalingam, J.
Org. Chem. 1999, 64, 8943 – 8944; Cu(OTf)2: W.-C. Yang, X.-A.
Lu, S. S. Kulkarni, S.-C. Hung, Tetrahedron Lett. 2003, 44, 7837 –
7840.
[9] Acylation: TMSOTf: P. A. Procopiou, S. P. D. Baugh, S. S. Flack,
G. G. A. Inglis, Chem. Commun. 1996, 2625 – 2626; Bi(OTf)3: A.
Orita, C. Tanahashi, A. Kakuda„ J. Otera, Angew. Chem. 2000,
112, 2999 – 3001; Angew. Chem. Int. Ed. 2000, 39, 2877 – 2879;
Ce(OTf)3: G. Bartoli, R. Dalpozzo, A. de Nino, L. Maiuolo, M.
Nardi, A. Procopio, A. Tagarelli, Green Chem. 2004, 6, 191 – 192;
Sc(OTf)3: J.-C. Lee, C.-A. Tai, S.-C. Hung, Tetrahedron Lett.
2002, 43, 851 – 865; Cu(OTf)2: C.-A. Tai, S. S. Kulkarni, S.-C.
Hung, J. Org. Chem. 2003, 68, 8719 – 8722; In(OTf)3: K. K.
Chauhan, C. G. Frost, I. Love, D. Waite, Synlett 1999, 1743 –
1745; Li(OTf): B. Karimi, J. Maleki, J. Org. Chem. 2003, 68,
4951 – 4954.
[10] After this work was completed, a publication appeared reporting
a very similar study: C.-C. Wang, J.-C. Lee, S.-Y. Luo, S. S.
Kulkarni, Y.-W. Huang, C.-C. Lee, K.-L. Chang, S.-C. Hung,
Nature 2007, 446, 896 – 899; Our work was previously reported at
the Fifth Meeting of Organic Chemistry for Young Researchers,
March 14, 2007, Saclay, France, Abstract CO 03 (http://www.rco-
idf.net/).
[12] T. Lecourt, A. J. Pearce, A. Herault, M. Sollogoub, P. Sinaþ,
Chem. Eur. J. 2004, 10, 2960 – 2971, and previous work.
[13] J. Madsen, C. Viuf, M. Bols, Chem. Eur. J. 2000, 6, 1140 – 1146,
and references therein.
[14] The use of the unprotected carbohydrates was not successful,
partly as a consequence of their very low solubility. The per-O-
TMS derivatives were prepared in quantitative yields from the
corresponding glycopyranosides (TMSCl, pyridine, room tem-
perature)and were used without purification.
[15] The Bi(OTf)3/Et3SiH combination is not stable and probably
generates elemental bismuth and triethylsilyl triflate/triflic acid
as the acid catalysts, in analogy with the BiBr3/Et3SiH combi-
nation: J. S. Bajwa, X. Jiang, J. Slade, K. Prasad. O. Repic, T. J.
Blacklock, Tetrahedron Lett. 2002, 43, 6709 – 6713; P. A. Evans, J.
Cui, S. J. Gharpure, Org. Lett. 2003, 5, 3883 – 3885.
[16] This too most likely explains the results obtained by Hung in
using TMSOTf[10] and shows that the attribution of this
regioselective benzylation “to the higher nucleophilicity of the
3-oxygen atom” as previously stated[10] probably represents a
minor contribution. For a related (noncatalytic)regioselective
reductive opening of a cyclic 2,3-acetal of glucopyranoside see
H. Takahashi, H. Mitsuzuka, K. Nishiyama, S. Ikegami, Synthesis
2006, 1415 – 1418.
[17] The yield of compound 2 was moderated by the formation of
2,3,4-tri-O-benzyl-d-glucopyranoside derivative (15% yield)
resulting from further reductive benzylation at position 2 with
residual benzaldehyde.
[18] For a recent account on iterative glycosylation approaches see:
Y. Wang, X.-S. Ye, L.-H. Zhang, Org. Biomol. Chem. 2007, 5,
2189 – 2200, and references therein.
[19] D. Crich, M. Smith, J. Am. Chem. Soc. 2001, 123, 9015 – 9020.
[20] E. Bousquet, M. Khitri, L. Lay, F. Nicotra, L. Panza, G. Russo,
Carbohydr. Res. 1998, 311, 171 – 181.
[11] For a sequential one-pot strategy for making per-O-acetylated
acetals see B. Mukhopadhyay, Tetrahedron Lett. 2006, 47, 4337 –
4341.
Angew. Chem. Int. Ed. 2007, 46, 8662 –8665
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 8665
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
Take advantage of blue reference links
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&