Catalytic glycosylation with rhodium(III)-triphos catalysts

Article abstract of DOI:10.1055/s-2003-40337

The formation of glycosides in high yield from 1-hydroxy sugars using catalytic amounts (0.5molpercent) of Rh(III)Cl₃(triphos) (1a) or [Rh(III)(MeCN)₃(triphos)](TfO)₃ (1b) is described. High stereocontrol at the anomeric c

Full text of DOI:10.1055/s-2003-40337

LETTER
1303
Catalytic Glycosylation with Rhodium(III)-Triphos Catalysts
Catalytic
G
lycosy
e
lation with
a
Rhodium(
t
III)-Tr
i
r
phosCat
i
alysts ce Wagner,a Michael Heneghan,b Gerhard Schnabel,c Beat Ernst*a
a
Institute of Molecular Pharmacy, Pharmacenter, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland
E-mail: beat.ernst@unibas.ch
b
c
Present address: Ciba Speciality Chemicals, 4002 Basel, Switzerland
Present address: Bayer CropScience GmbH, Industriepark Hoechst, 65926 Frankfurt, Germany
Received 27 March 2003
In memory of Professor Raymond Urgel Lemieux. We dedicate this paper to Ray Lemieux in recognition of his pathbraking contributions
to the carbohydrate area.
OBn
OBn
Abstract: The formation of glycosides in high yield from 1-hy-
droxy sugars using catalytic amounts (0.5mol%) of
Rh(III)Cl3(triphos) (1a) or [Rh(III)(MeCN)3(triphos)](TfO)3 (1b) is
described. High stereocontrol at the anomeric center is achieved by
neighboring group participation. In addition, an application of this
new glycosylation procedure for the synthesis of a derivative of the
oviposition-deterring pheromone of the cherry fruit fly Rhagoletis
cerasi is presented.
O
O
0.5 mol% 1a or 1b
BnO
BnO
BnO
BnO
OH
OBn
OBn
OBn
2
4
A: 1 equiv HC(OBn)3,
A: CH2Cl2, r.t.
84% (α:β = 62:38)
87% (α:β = 64:36)
B: 1 equiv BnOH, CH2Cl2,
B: Soxhlet (4Å MS),
B: reflux, 23 h
Key words: catalytic glycosylation, Rh(III)triphos catalysts, 1-hy-
droxy sugars, O-glycosides, oviposition-deterring pheromone
(OTf)3
Me
Me
Numerous methods for the formation of the biologically
important O-glycosidic linkage1 have been developed
since the classical Koenigs–Knorr2 and Fischer3 glyco-
sylation procedures. Comprehensive reviews of glyco-
sylation methodologies have recently been published.4
The development of efficient glycosylation procedures
is, however, still a most challenging topic in organic syn-
thesis.
PPh2
RhIII
Cl
PPh2
Cl
Cl
NCCH3
NCCH3
Ph2P
Ph2P
Ph2P
RhIII
Ph2P
NCCH3
1a
1b
Scheme 1 Catalytic glycosylation with 1-hydroxy sugars.
A glycosidic bond is generally constructed with a glycosyl
donor, which contains a particular leaving group. Direct
formation of a glycosidic bond from a 1-hydroxy sugar
has obvious advantages, since the reaction step for the in-
troduction of an activating group is not required and the
hydrolysis of the donor, which is a major side reaction in
glycosylation reactions, can be avoided in principal. Sur-
prisingly, rather little has been reported on dehydrative
glycosylation.5 In this communication we present a novel
catalytic glycosylation procedure starting from hemiace-
tals using Rh(III)-complexes of the terdentate triphos
ligand: Rh(III)Cl3(triphos) (1a) and [Rh(III)(MeCN)3-
(triphos)](TfO)3 (1b).
Venanzi et al.6 demonstrated the acetalization of ketones
and aldehydes using an alcohol, the corresponding trialkyl
orthoformate as a desiccant and a catalytic amount of
Rh(III) complex 1a or 1b. When we applied these condi-
tions to tetra-O-benzyl-D-glucopyranose (2), an a/b-mix-
ture of the corresponding benzyl glycosides (4) was
formed in high yield within minutes (see Scheme 1,
condition A).
To avoid the disadvantage of the preparation of the ortho-
formate with three equivalents of the respective glycosyl
acceptor, a modified procedure was developed. For the re-
moval of the water formed in the glycosylation reaction,
the reaction flask was equipped with a Soxhlet extractor
containing activated molecular sieves (4 Å). Under these
conditions for the azeotropic removal of water, an excel-
lent yield of the corresponding glycoside was obtained
with both catalysts 1a and 1b (see Scheme 1, condition B).
To study the scope of this catalytic glycosylation proce-
dure, various alcohols and glycosyl donors have been in-
vestigated (see Table 1). Using 2 as glycosyl donor,
primary (entries 1 and 2) and secondary alcohols (entry 3)
or phenols (entry 4) gave good to excellent yields. In ad-
dition, glycosylation of the 6-hydroxyl group of methyl
2,3,4-tri-O-benzyl-a-D-glucopyranoside (11) yielded
81% of the corresponding disaccharide (entry 5). Accept-
able yields were obtained with the corresponding galac-
tose donor 13 (entry 6), whereas the glycosylation of the
cellobiose derivative 15 gave the glycoside 16 only in
moderate yield (entry 7).
Synlett 2003, No. 9, Print: 11 07 2003.
Art Id.1437-2096,E;2003,0,09,1303,1306,ftx,en;S03603ST.pdf.
© Georg Thieme Verlag Stuttgart · New York

1304
Beatrice Wagner et al.
LETTER
Table 1 Glycosylation with 0.5 mol% Rh(III)-Catalyst 1b in Refluxing CH2Cl2 with Azeotropic Removal of Water
Entry
1
Glycosyl donors
Glycosyl acceptors
Reaction time
23 h
Prod. Yield a:b
4
87%
64:36
3
5
27
2
3
4
20 h
17 h
23 h
6
8
94%
67%
64%
59:41
66:34
64:36
3b-cholestanol
7
10
9
5
6
27 h
21 h
12
14
81%
71%
74:26
60:40
118
5
137
7
5
20 h
16a
46%
50:50
159
1710
1911
8
9
5
5
96 h
21 h
18b
20
29%
53%
67:33
>2:98
10
11
11
5
16 h
16 h
21
23
41%
96%
>2:98
>2:98
2212
12
13
14
16 h
16 h
26 h
25
92%
75%
78%
>2:98
>2:98
>2:98
24
11
26
28c
2713
a 30% glycosyl donor could be reisolated. b The major side reaction is the decomposition of 18; no product was formed within 96 h using 1.5
mol% TfOH. c Only the b(1-6)-disaccharide was formed.
Synlett 2003, No. 9, 1303–1306 ISSN 1234-567-89 © Thieme Stuttgart · New York

LETTER
Catalytic Glycosylation with Rhodium(III)-Triphos Catalysts
1305
In all these examples, a/b-mixtures corresponding to the steps,15 the backbone of the pheromone derivative was
thermodynamic ratio were obtained. When the reaction of synthesized by a Grignard reaction. After benzylation of
entry 2 was carried out in the presence of one equivalent the hydroxyl group in C-8 followed by removal of the ter-
of the 6b-anomer, the thermodynamic control could clear- minal silyl protection (Æ24), the Rh(III)-catalyzed glyco-
ly be demonstrated (see Scheme 2). The product ratio 6a/ sylation yielded the corresponding glucoside 2517 in
b was again 59:41, whereas a kinetic control would have excellent chemical yield and stereoselectivity. Oxidative
yielded an a/b-ratio of 30:70.
cleavage of the PMP ether followed by Jones oxidation at
C-1 gave the carboxylic acid 35 in 69% overall yield. The
activated ester of 35, obtained with N-hydroxysuccinim-
ide and DCC, was transformed into the taurin amide. In a
final step, all benzyl protective groups were removed by
hydrogenolysis yielding 15-demethyl-ODP 30.18
OBn
O
BnO
BnO
OH
PMPO(CH2)8OH (5),
OBn
OBn
O
CH2Cl2, Soxhlet (4Å MS),
reflux, 23 h
2 (1 equiv)
+
BnO
BnO
The presented results clearly demonstrate the synthetic
potential of this new catalytic glycosylation procedure
leading to glycosides with excellent yields and stereo-
selectivity. The rather long reaction time is a consequence
of the inefficient removal of water formed in the glyco-
sylation. We are therefore currently investigating more
efficient reaction conditions, which would allow a signi-
ficant reduction of the reaction time.
OBn
O
1b (0.5 mol%)
O(CH2)8OPMPm
OBn
BnO
O(CH2)8OPMP
6 (95%, α:β = 59:41)
BnO
OBn
6β (1 equiv)
Scheme 2 Thermodynamic vs. kinetic control.
To achieve stereocontrol in respect to the anomeric center,
neighboring group assistance proved to be necessary.
Since the reaction time with fully acylated glycosyl do-
nors (e.g. 17) was enormously elongated and did not give
the expected stereocontrol (entry 8), donors selectively
acylated at the 2-position were used. With 2-O-acetyl-
3,4,6-tri-O-benzyl-D-glucopranose (19) and 2-O-benzoyl-
3,4,6-tri-O-benzyl-glucopyranose (22) excellent yields as
well as b-stereocontrol were realized (entries 9–14).
General Procedure
To a 50 mL round-bottom flask equipped with a Soxhlet extractor
containing activated 4 Å molecular sieves glycosyl donor (2 mmol),
glycosyl acceptor (2 mmol), rhodium(III)-catalyst 1a or 1b (0.5
mol%) and solvent (CH2Cl2, 1,2-dichloroethane, chloroform, ben-
zene, toluene) were added. The reaction mixture was heated to re-
flux and followed by TLC. When the reaction was shown to be
complete, the reaction mixture was filtered through a short pad of
silica gel and the solvent was removed in vacuo. The residue was
then chromatographed on silica gel.
According to mechanistic studies for the Rh(III)-cata-
lyzed acetalization reaction,6 it appears that two free cis
coordination sites are required in the catalyst precursor.
Applied to the glycosylation procedure, both substrates,
hemiacetal and alcohol, can then be coordinated adjacent
to each other to the metal center before coupling. The
strong trans-effect of the facial chelating tripodal phos-
phine activates all three cis-positions equivalently. Thus,
catalyst activity can be attributed to the Lewis acidity of
the complex cation and to its ability to act as a template for
the simultaneous activation of the hemiacetal and the al-
cohol. However, e.g. the catalyst 1b could also react with
alcohols by b-H abstraction and formation of
[Rh(III)H(MeCN)2(triphos)]2+ leading to the liberation of
a proton. To clarify a possible contribution by acid catal-
ysis, the glycosylation reaction of entry 8 was conducted
in the presence of 1.5 mol% TfOH. However, under these
reaction conditions, the formation of 18 could not be ob-
served within 96 h.
Acknowledgement
RhIIICl3(triphos) and [RhIII(MeCN)3(triphos)](TfO)3 were supplied
by the research group of late Prof. Dr. L. M. Venanzi, Laboratory of
Inorganic Chemistry, ETH Zürich, Switzerland.
References
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Rhagoletis cerasi14 (Scheme 3). We have shown15 that
the natural pheromone 29 is a diastereomeric mixture in
respect to the stereocenter at C-8. In addition, we could
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Synlett 2003, No. 9, 1303–1306 ISSN 1234-567-89 © Thieme Stuttgart · New York

1306
Beatrice Wagner et al.
LETTER
a,b
HO (CH2)7
31
OH
TBDMSO (CH2)7
Cl
OBn
(CH2)7
24
32
c,d,e
HO (CH2)7
O
OMe
HOOC(CH3)6COOH
MeO
O
(CH2)7
CHO
33
34
OBn
O
BnO
OBn
OBn
BnO
OBn
OBn
(CH2)6COOH
BzO
OH
O
O
BnO
BnO
BnO
BnO
O
g,h
O
22
(CH2)7
(CH2)7OPMP
(CH2)7
f
OBz
OBz
25
35
OH
OH
8
H
N
O
HO
HO
i,j,k
O
SO3Na
15
OH
O
8RS,15-demethyl-ODP (30)
OH
OH
8
H
N
O
HO
HO
O
15
SO3Na
OH
CH3
O
8RS,15R-ODP (29)
Scheme 3 a) TBDMSCl, imidazole, CH2Cl2, r.t. (82%); b) Me2C=CClNMe2,19 CH2Cl2, 0 °C to r.t. (88%); c) Mg, THF, r.t. to 80 °C
(61%); d) BnBr, NaH, DMF, 60 °C (72%); e) Bu4NF, THF, r.t., 1 h (91%); f) 0.5 mol% [Rh(III)(MeCN)3(triphos)](TfO)3, 1 equiv 22, CH2Cl2,
16 h (92%, b:a >98:2); g) CAN, CH3CN/H2O, r.t., 1 h (90%); h) CrO3, H2SO4, acetone, 0 °C, 2 h (84%); i) N-hydroxysuccinimide, DCC, DME,
r.t., 20 h (92%); j) H2NCH2CH2SO3Na, MeOH, r.t., 5 h (88%); k) H2, Pd/C (10%), MeOH, r.t., 24 h (78%).
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Synlett 2003, No. 9, 1303–1306 ISSN 1234-567-89 © Thieme Stuttgart · New York