Cooperative catalysis in glycosidation reactions with o-glycosyl trichloroacetimidates as glycosyl donors

Article abstract of DOI:10.1002/anie.201302158

Thiourea mediates cooperative glycosidation through hydrogen bonding. N,N′-Diarylthiourea as cocatalyst enforces an S_N2-type acid-catalyzed glycosidation even at room temperature (see scheme; Bn=benzyl). From O-(α-glycosyl) trichloroacetimidates as glycosyl donors and various acceptors, β-glycosides are preferentially or exclusively obtained.

Full text of DOI:10.1002/anie.201302158

Angewandte
Chemie
DOI: 10.1002/anie.201302158
Glycosidation
Cooperative Catalysis in Glycosidation Reactions with O-Glycosyl
Trichloroacetimidates as Glycosyl Donors**
Yiqun Geng, Amit Kumar, Hassan M. Faidallah, Hassan A. Albar, Ibrahim A. Mhkalid, and
Richard R. Schmidt*
Table 1: Reactions of donor 1a and acceptor 2a in the presence of
different catalysts 3 and cocatalyst 4.[a]
Thioureas form strong hydrogen bonds with such anions as
chloride, cyanide, and carboxylates and also with neutral
compounds containing groups properly aligned to accept two
hydrogen bonds, thus leading to coordination complexes.[1,2]
This observation was very successfully employed in organo-
catalysis and, with chiral thiourea derivatives, in asymmetric
synthesis.[3,4] It was found that thioureas are able to catalyze
acetal formation from aldehydes and alcohols in the presence
of orthoesters as condensing agent[5] and also from highly
reactive a-halogen ethers and alcohols.[6] Recently, this
approach to the synthesis of acetals was extended by Galan
and co-workers[7] to the addition of alcohols to glycals,
providing a specific class of glycosides, namely 2-deoxyglyco-
sides. However, not even the quite acidic N,N’-bis[3,5-bis-
(trifluoromethyl)phenyl]thiourea (Table 1, 4) with a pKa of
8.5[8] is expected to activate such highly reactive glycosyl
donors as the O-glycosyl trichloroacetimidates under stan-
dard conditions. Generally, acids with a lower pKa value (ꢀ 5)
are required; commonly, catalytic amounts of TMSOTf or
BF3·OEt2 are used.[9]
Entry Catalyst (3a–g)
Cocatalyst Reaction
b/a ratio[b]
4
time
(yield[c])
1[d]
2[d]
3
4
5
PhCO2H (3a)
3a
–
PhCOCO2H (3b)
3b
CH3COCO2H (3c)
p-MeOC6H4COCO2H
À
+
+
À
+
+
+
24 h
4 h
48 h
18 h
5 h
1:1 (<5%)[e]
8:1
No reaction[f]
6bb (5%)
> 20:1[g]
5:1
6
7
48 h
10 h
> 20:1[g]
(3d)
8
p-NO2C6H4COCO2H
+
50 min
> 20:1[g]
(3e)
9
10
11
(PhO)2PO2H (3 f)
3 f
(p-NO2C6H4O)2PO2H
(3g)
À
+
À
48 h
3 h
48 h
1:1 (30%)
> 20:1[g]
3:2 (80%)
In work by the Schreiner group,[10] the Jacobsen group,[11]
and others,[12] cooperativity between Brønsted acids and
hydrogen-bonding cocatalysts, as for instance thiourea deriv-
atives, was observed in organocatalysis that was also success-
fully applied to asymmetric synthesis.[10a] Therefore, the study
of cooperative phenomena with thiourea cocatalysts in glyco-
side bond formation with O-glycosyl trichloroacetimidates as
efficient glycosyl donors[9] is of great promise. As these
donors, which are different from most other commonly used
glycosyl donors,[9] are accessible to activation with catalytic
amounts of an acid, they are ideally suited for such studies.
Obviously, it is hoped that not only the reaction rate and the
product yield but also the anomeric selectivity will be
governed by the interaction of a thiourea cocatalyst with
12
3g
+
40 min
>20:1[g] (90%)
[a] General procedure: 1a (1.0 equiv), 2a (1.2 equiv), and 4 (5 mol%)
were dissolved in CH2Cl2 and then the catalyst 3a–g (5 mol%) was
added at room temperature. After completion of the reaction (if not
otherwise indicated, ꢁ90% formation of 5a), the reaction mixture was
1
worked up. [b] Determined by H NMR spectroscopy. [c] Determined
after purification by flash silica gel chromatography. [d] 15 mol% of
catalyst 3a and 4 were employed to increase the reaction rate. [e] About
5% of b-d-glucopyranosyl benzoate 6ab was formed. [f] Under reflux
after 48 h, about 40% 5aa,b was obtained; b/a ratio=4:1. [g] Detection
limit of the minor isomer.
[*] Dr. Y. Geng, Dr. A. Kumar, Prof. Dr. R. R. Schmidt
Fachbereich Chemie, Universitꢀt Konstanz, Fach 725
78457 Konstanz (Germany)
the substrates (glycosyl donor and acceptor) and the catalyst.
As compound 4 has proven to be very successful in previous
thiourea-based studies,[2,5b,8,13–15] this achiral compound was
selected for our work. Thus in these first studies, the anomeric
selectivity will be determined essentially by the chirality of
the glycosyl donor and, in the absence of directing groups,
essentially by the configuration of the anomeric center.
For the basic studies, a-d-glucopyranosyl trichloroaceti-
midate 1a[9,16] was selected as donor, isopropanol (2a) as
acceptor, and benzoic acid (3a, pKa = 4.2)[10b] as catalyst. As
previously observed,[9,16] 3a led with 1a to slow formation of
b-d-glucopyranosyl benzoate 6ab until 3a was consumed;
E-mail: richard.schmidt@uni-konstanz.de
Prof. Dr. H. M. Faidallah, Prof. Dr. H. A. Albar, Dr. I. A. Mhkalid,
Prof. Dr. R. R. Schmidt
Chemistry Department, Faculty of Science
King Abdulaziz University, Jeddah 21589 (Saudi Arabia)
[**] The authors acknowledge the generous support of this work by the
University of Konstanz. This paper was also funded by the Deanship
of Scientific Research (DSR), King Abdulaziz University under grant
No. 26-3-1432/HiCi. The authors therefore acknowledge technical
and financial support of KAU.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201302158.
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only a minor amount of a 1:1 anomeric ratio of glycosides
5aa,b was obtained (Table 1, entry 1). However, when
cocatalyst 4 was added (entry 2), the result was totally
different: in much shorter reaction time, exclusive formation
of glycoside 5a in an 8:1 b/a ratio was observed; thus, a strong
influence of thiourea 4 on reaction rate, yield, and stereose-
lectivity became evident. As expected, the cocatalyst 4 alone
did not catalyze the glycosidation at room temperature
(entry 3). To attain faster reaction rates, the more acidic
phenylglyoxylic acid (3b, pKa = 2.1)[10b] was investigated
(entries 4, 5). In the absence of 4, the catalyst 3b was
consumed, leading to glycosyl carboxylate 6bb; however, in
the presence of cocatalyst 4, fast and practically exclusive
formation of 5ab was observed. Also the studies with pyruvic
acid (3c) and aryl glyoxylic acids 3d and 3e (entries 6–8)
showed that with increasing acidity of the Brønsted acid
catalyst, the reaction rate increases without losing the high b-
selectivity. Therefore, we turned our attention to phosphorous
acids as catalysts (entries 9–12), which are also known to react
with 1a directly to b-d-glucopyranosyl phosphates 7b.[17] In
the presence of 2a as acceptor and with 3 f and 3g as catalyst,
essentially a,b-mixtures of 5aa,b were formed in slow
reactions (entries 9, 11). However, when cocatalyst 4 was
added, the b-anomeric glucoside 5ab was obtained practically
exclusively in fast reactions (entries 10, 12). This result is
independent of the addition procedure of the reagents: that is,
addition of catalyst 3g to a mixture of 1a, 2a, and 4 (normal
procedure; see Table 1) or addition of donor 1a to a mixture
of 2a, 3g, and 4 (inverse procedure)[9b,c,18] led to the same
result.
(entries 4–6). However, owing to a very fast reaction at
temperatures as low as À788C, no major reaction rate
difference was observed for complete formation of product
5a. Overall, in the presence of the strong catalyst TMSOTf,
the cooperativity effect is less dramatic than found for the
Brønsted acids in Table 1.
Studies with other acceptors were based on the highly
promising results with 3g as catalyst and 4 as cocatalyst
(Table 1, entry 12). Thus, reaction of 1a with allyl alcohol (2b)
led practically exclusively to allyl b-d-glucopyranoside 5bb
(Table 3,[19] entry 1). Other primary alcohols, such as 4-
Table 3: Reaction of donor 1a with acceptors 2a–k in the presence of 3g
as catalyst and 4 as cocatalyst.[a]
Entry ROH
Reaction
time
Product Yield [%][b] b/
a ratio[c]
1
2
3
15 min
30 min
10 min
5bb
93
91
95
>20:1[d]
10:1
5ca,b
5db
>20:1[d]
4
5
6
7
1.5 h
5ea,b
5 fa,b
5ga,b
5ab
85
87
83
90
5:1
7:1
30 min
10 min
40 min
4:1
As about 1 mol% of TMSOTf is generally used as catalyst
for the activation of O-glycosyl trichloroacetimidate donors,[9]
corresponding comparison studies were also performed with
this catalyst (Table 2). Reaction of donor 1a and acceptor 2a
with TMSOTf as catalyst showed the known strong depend-
ence of the a,b-selectivity on the reaction temperature
(entries 1–3).[9] This result is explained by acid-catalyzed
activation of the donor leading to temperature-dependent
ion-pair formation, thus favoring an SN2-type reaction at low
temperature and SN1-type at high temperature.[9] Addition of
cocatalyst 4 to these reactions obviously leads to a competing
reaction course that further increases the b-selectivity
>20:1[d]
8
4 h
1 h
5ha,b 88
6:1
4:1
9[e]
5ia,b
87
10[e]
11[e]
2 h
5ja,b
5ka,b
82
78
5:1
6:1
3.5 h
[a] General procedure: 1a (1.0 equiv), 2 (1.2 equiv), and 4 (5 mol%)
were dissolved in CH2Cl2 and then 3g (5 mol%) was added. After
completion of the reaction by TLC detection, the reaction mixture was
worked up. [b] Determined after purification by flash silica gel chroma-
tography. [c] Determined by 1H NMR spectroscopy. [d] Detection limit of
the minor isomer. [e] CH3CN was used as the solvent.
Table 2: Reaction of donor 1a with isopropanol (2a) as acceptor in the
presence of TMSOTf as catalyst and 4 as cocatalyst at different
temperatures.[a]
Entry
Addition
Reaction
Reaction
5aa,b
of 4
temperature [8C]
time [min]
b/a ratio
1
2
3
4
5
6
À
À
À
+
+
+
0
À40
À78
0
5
10
30
5
10
30
1:1
5:1
12:1
pentenol (2c) and propargyl alcohol (2d), also gave gluco-
sides 5cb and 5db, respectively, preferentially or exclusively
(entries 2, 3). With decreasing nucleophilicity of the acceptor
hydroxy group (through steric and/or inductive effects), as in
acceptors 2e–g and 2h, the reaction rate and the high
preference for b-product formation decreased and different
from isopropanol 2a as acceptor (entry 7), the a-anomer
could also be detected (entries 4–6 and 8; formation of 5e–
ga,b and 5ha,b). A particularly interesting case is sterically
1.3:1
11:1
À40
À78
> 20:1[b]
[a] General procedure: 1a (1.0 equiv), 2a (1.2 equiv), and 4 (5 mol%)
were dissolved in CH2Cl2 and then TMSOTf (1 mol%) was added. After
completion of the reaction, yielding ꢁ90% of 5aa,b, the reaction
1
mixture was worked up and the product ratio determined by H NMR
spectroscopy. [b] Detection limit of the minor isomer.
2
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demanding (+)-menthol (2i). With 3g as catalyst and 4 as
cocatalyst, a 4:1 ratio in favor of the b-isomer 5ib was
obtained (entry 9) when the reaction was carried out in
acetonitrile as solvent, which allowed a rate increase. Studies
with two additional carbohydrate acceptors (2j and 2k,
entries 10 and 11), again using acetonitrile as solvent, showed
that also the b-(1-6)- and b-(1-3)-connected disaccharides
(5jb and 5k,b respectively) can be successfully obtained as
major products with this method.
4 to the reaction mixture containing 2a and 3g leads to an
increase in reaction rate under formation of b-products 11ab
and 13ab, respectively (entries 7 and 8). Thus, the cooperative
effect of 4 in these glycosidations is also supported.
As a universal cooperative catalysis phenomenon had
been observed in the catalytic glycosidations with different O-
glycosyl trichloroacetimidates while using 3g as catalyst and 4
as cocatalyst, further efforts were focused on the reaction
mechanism. As previous observations do not rule out that
glycosyl carboxylates 6 or glycosyl phosphates 7, respectively,
could be the decisive intermediates in these glycosidations
(results in Table 1), 1a was transformed with 3g into glycosyl
phosphate 7gb (Scheme 1). However, attempted reaction of
Other glycosyl donors were also investigated (Table 4).[19]
Studies with a-d-galactosyl trichloroacetimidate 8a[9b] were of
particular interest, as this glycosyl donor generally provides
Table 4: Reactions of donor 8a, 10a and 12a with different acceptors in
the presence of 3g as catalyst and 4 as cocatalyst.[a]
Entry Donor ROH Reaction time Product Yield [%][b] b/a ratio[c]
1
2
3
4
8a 2b
8a 2d
8a 2 f
8a 2a
8a 2i
8a 2j
10a 2a
12a 2a
30 min
20 min
1.5 h
3 h
2 h
3.5 h
5 h
9ba,b
9db
91
93
87
89
86
81
95
88
12:1
>20:1[d]
9:1
9 fa,b
9aa,b
9ia,b
9ja,b
11ab
13ab
Scheme 1. Control experiments using 7gb in the glycosydations with
2a.
7:1
4:1
5:1
5[e]
6[e]
7
>20:1[d]
>20:1[d]
7gb with acceptor 2a did not lead to glycoside 5a; when 3g
(5 mol%) was added to this reaction mixture, only 30% of
a 1:1-mixture of 5aa,b was obtained after 14 h (Scheme 1,
(1)). Addition of cocatalyst 4 (5 mol%) to this reaction
mixture of 7gb, 2a, and 3g increased the reaction rate, and
practically complete transformation to 5aa,b was observed
after 1 h; however, the anomeric ratio was still 1:1 (Scheme 1,
(2)). Therefore, glycosyl phosphate 7gb is not the decisive
intermediate in these glycosidations.
8
22 h
[a] General procedure: 8a or 10a or 12a (1.0 equiv), 2 (1.2 equiv), and 4
(5 mol%) were dissolved in CH2Cl2 and was then added at room
temperature 3g (5 mol%). After completion of the reaction by TLC
detection, the reaction mixture was worked up. [b] Determined after
purification by flash silica gel chromatography. [c] Determined by
1H NMR spectroscopy. [d] Detection limit of the minor isomer.
[e] CH3CN was used as the solvent.
1H NMR spectroscopy studies with mixtures of the
cocatalyst 4 and donor 1a or acceptor 2a,[20] respectively,
showed, in addition to the expected shifts of the -NH and -OH
signals, shifts of the proton signals, for instance, of the
bis(trifluoromethyl)phenyl residues. These shifts are also
visible for mixtures of 1a + 2a + 4. However, owing to low
solubility, almost no effect was observed for 1:1 mixtures of
3g + 4 and also for 3g + 2a. However, addition of 2a to
a mixture of 3g (10 mol%) + 4 (10 mol%) led to immediate
dissolution and to increased shifts of the aryl protons of 4.
From these results, the following conclusions can be
drawn:
- The thiourea 4 is decisive for the reaction rate increase and
the b-selectivity.
- Glycosyl carboxylates or phosphates, respectively, are not
decisive intermediates.
- Glycosyl cations, as generally discussed in the TMSOTf
catalyzed activation of O-glycosyl trichloroacetimidates,
are not the decisive intermediates in the reaction course
mediated by thiourea 4.
- Fast complex formation between acceptor 2a, catalyst 3g,
and cocatalyst 4 seems to precede interaction with donor 1a
and the following product formation.
more a-product than glycosyl donor 1a under the same
reaction conditions. However, allyl alcohol (2b) and 4-
methoxybenzyl alcohol (2 f) as acceptors preferentially led
to the b-anomers 9bb and 9 fb, respectively, in the presence of
3g as catalyst and 4 as cocatalyst (entries 1, 3); with propargyl
alcohol (2d), the b-anomer 9db was formed practically
exclusively (entry 2). Isopropanol (2a), as a very reactive
secondary alcohol, showed still a strong preference for the b-
anomer 9ab (entry 4) and even sterically demanding
(+)-menthol (2i) furnished a 4:1 mixture of 9ia,b (entry 5).
With 6-O-unprotected glycosyl acceptor, the b-disaccharide
9jb was obtained preferentially (entry 6). Therefore, there is
also a strong effect of cocatalyst 4 on the glycosidation rate,
yield, and a/b selectivity with galactosyl donor 8a. Studies
with glycosyl donors having anchimerically assisting groups in
2-positions, such as 2,3-di-O-benzoyl-4,6-O-benzylidene pro-
tected glucosyl donor 10a[19] and 2,3,4-tri-O-benzoyl pro-
tected xylosyl donor 12a,[19] showed that addition of thiourea
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- This complex has steric constraints, and thus the thiourea 4
cocatalyst effect decreases with increasing steric bulk of the
acceptor.
[1] a) P. J. Smith, M. V. Reddington, C. S. Wilcox, Tetrahedron Lett.
1992, 33, 6085 – 6088; b) E. Fan, S. A. Vanarman, S. Kincaid,
A. D. Hamilton, J. Am. Chem. Soc. 1993, 115, 369 – 370; c) J. S.
Albert, A. D. Hamilton, Tetrahedron Lett. 1993, 34, 7363 – 7366.
[2] For a recent review see: Z. Zhang, P. R. Schreiner, Chem. Soc.
Rev. 2009, 38, 1187 – 1198.
[3] For reviews see: a) P. R. Schreiner, Chem. Soc. Rev. 2003, 32,
289 – 296; b) Y. Takemoto, Org. Biomol. Chem. 2005, 3, 4299 –
4306; c) S. J. Connon, Chem. Eur. J. 2006, 12, 5418 – 5427;
d) M. S. Taylor, E. N. Jacobsen, Angew. Chem. 2006, 118, 1550 –
1573; Angew. Chem. Int. Ed. 2006, 45, 1520 – 1543; e) A. G.
Doyle, E. N. Jacobsen, Chem. Rev. 2007, 107, 5713 – 5743.
[4] For recent reviews on asymmetric synthesis employing chiral
thioureas as organocatalysts, see: a) M. Mahlau, B. List, Angew.
Chem. 2013, 125, 540 – 556; Angew. Chem. Int. Ed. 2013, 52, 518 –
533; b) K. Brak, E. N. Jacobsen, Angew. Chem. 2013, 125, 558 –
588; Angew. Chem. Int. Ed. 2013, 52, 534 – 561.
These conclusions support a reaction course as proposed
in Scheme 2. The thiourea 4 effects, together with catalyst 3g
and acceptor 2a, the hydrogen-bond-mediated formation of
a complex.[21] Upon interaction with donor 1a, this complex
[5] a) M. Kotke, P. R. Schreiner, Tetrahedron 2006, 62, 434 – 439;
b) M. Kotke, P. R. Schreiner, Synthesis 2007, 779 – 790.
[6] S. E. Reisman, A. G. Doyle, E. N. Jacobsen, J. Am. Chem. Soc.
2008, 130, 7198 – 7199.
[7] E. I. Balmond, D. M. Coe, M. C. Galan, E. M. McGarrigle,
Angew. Chem. 2012, 124, 9286 – 9289; Angew. Chem. Int. Ed.
2012, 51, 9152 – 9155.
[8] G. Jakab, C. Tancon, Z. Zhang, K. M. Lippert, P. R. Schreiner,
Org. Lett. 2012, 14, 1724 – 1727.
Scheme 2. Proposed reaction course.
[9] For reviews, see: a) R. R. Schmidt, Angew. Chem. 1986, 98, 213 –
236; Angew. Chem. Int. Ed. Engl. 1986, 25, 212 – 235; b) R. R.
Schmidt, W. Kinzy, Adv. Carbohydr. Chem. Biochem. 1994, 50,
21 – 123; c) X. Zhu, R. R. Schmidt, Angew. Chem. 2009, 121,
1932 – 1967; Angew. Chem. Int. Ed. 2009, 48, 1900 – 1934.
[10] a) T. Weil, M. Kotke, C. M. Kleiner, P. R. Schreiner, Org. Lett.
2008, 10, 1513 – 1516; b) Z. Zhang, K. M. Lippert, H. Hausmann,
M. Kotke, P. R. Schreiner, J. Org. Chem. 2011, 76, 9764 – 9776.
[11] R. S. Klausen, E. N. Jacobsen, Org. Lett. 2009, 11, 887 – 890.
[12] D. Uraguchi, Y. Ueki, T. Ooi, Science 2009, 326, 120 – 123.
[13] P. R. Schreiner, A. Wittkopp, Org. Lett. 2002, 4, 217 – 220.
[14] X.-S. Wang, C.-W. Zheng, S. L. Zhao, Z. Chai, G. Zhao, G.-S.
Yang, Tetrahedron: Asymmetry 2008, 19, 2699 – 2704.
[15] X. Li, H. Deng, S. Luo, J.-P. Cheng, Eur. J. Org. Chem. 2008,
4350 – 4356.
generates activation complex A, leading to proton transfer to
the leaving group in an intramolecular reaction and concom-
itant proton release from the acceptor, thus facilitating an
acid-base catalyzed SN2-type glycoside bond formation.[22]
Thus, thiourea 4 functions as a relay for proton transfer as,
for instance, often found for the imidazole residue in the
active site of hydrolases. Competing reaction courses, leading
for example to a-product formation via directed attack at the
trichloroacetimidate favoring an SN1-type reaction course (or
reaction between donor and catalyst), are only effective in the
presence of less reactive acceptors.
In summary, thiourea 4 as cocatalyst exhibits a cooperative
behavior that has a strong effect on the reaction rate, yield,
and the selectivity of glycosidations. This compound enables
hydrogen-bond-mediated complex formation between O-
glycosyl trichloroacetimidate donors, acceptors, and acid
catalysts; acid–base-catalyzed SN2-type glycoside bond for-
mation is facilitated even at room temperature and in the
absence of anchimeric assistance. This finding is of great
practical usefulness and of great promise for further studies to
finally completely control anomeric selectivity even at
ambient temperature.
[16] R. R. Schmidt, J. Michel, Angew. Chem. 1980, 92, 763 – 764;
Angew. Chem. Int. Ed. Engl. 1980, 19, 731 – 732.
[17] a) R. R. Schmidt, M. Stumpp, J. Michel, Tetrahedron Lett. 1982,
23, 405 – 408; b) R. R. Schmidt, M. Stumpp, Liebigs Ann. Chem.
1984, 680 – 691.
[18] R. R. Schmidt, A. Toepfer, Tetrahedron Lett. 1991, 32, 3353 –
3356.
[19] Compounds 5a–5e, 5g–5k, 9a, 9b, 9d, 9i, 9j, 10a, and 12a have
been previously prepared. For references and physical data, also
of 5 f, 9 f, 11ab, and 13ab, see the Supporting Information.
1
[20] For the H NMR studies of the interaction of cocatalyst 4 with
donor 1a, acceptor 2a, or catalyst 3g, see the Supporting
Information.
Received: March 14, 2013
[21] The authors are grateful to one of the reviewers, who drew our
attention to the importance of the hydrogen-bond-mediated
interaction between the catalyst (3g) and cocatalyst (4).
[22] For cases of acid–base catalysis in glycosidations, see: a) A.
Kumar, V. Kumar, R. T. Dere, R. R. Schmidt, Org. Lett. 2011, 13,
3612 – 3615; b) A. Kumar, Y. Geng, R. R. Schmidt, Adv. Synth.
Catal. 2012, 354, 1489 – 1499; c) A. Kumar, R. R. Schmidt, Eur. J.
Org. Chem. 2012, 2715 – 2719.
Revised: May 14, 2013
Published online: && &&, &&&&
Keywords: acid–base catalysis · cooperativity · glycosylation ·
.
organocatalysis · thiourea
4
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Communications
Glycosidation
Y. Geng, A. Kumar, H. M. Faidallah,
H. A. Albar, I. A. Mhkalid,
R. R. Schmidt*
&&&& — &&&&
Cooperative Catalysis in Glycosidation
Reactions with O-Glycosyl
Trichloroacetimidates as Glycosyl Donors
Thiourea mediates cooperative glycosi-
dation through hydrogen bonding. N,N’-
Diarylthiourea as cocatalyst enforces an
SN2-type acid-catalyzed glycosidation
even at room temperature (see scheme;
Bn=benzyl). From O-(a-glycosyl) tri-
chloroacetimidates as glycosyl donors
and various acceptors, b-glycosides are
preferentially or exclusively obtained.
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