Identification of 3,6-di-O-acetyl-1,2,4-O-orthoacetyl-α-d- glucopyranose as a direct evidence for the 4-O-acyl group participation in glycosylation

Article abstract of DOI:10.1039/c1cc11680k

The formation of 3,6-di-O-acetyl-1,2,4-O-orthoacetyl-α-d- glucopyranose was observed in the gold(i)-catalyzed glycosidation of peracetyl glucopyranosyl ortho-hexynylbenzoate; experiments with substrates bearing deuterium labeled 2-O-acetyl or 4-O-acetyl groups indicated that the orthoacetate was derived from the 4-O-acetyl group, which provided a direct evidence for the remote participation of the 4-O-acyl group in glycosylation.

Full text of DOI:10.1039/c1cc11680k

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COMMUNICATION
Identification of 3,6-di-O-acetyl-1,2,4-O-orthoacetyl-a-D-glucopyranose
as a direct evidence for the 4-O-acyl group participation in
glycosylationwz
Yuyong Ma, Gaoyan Lian, Yao Li and Biao Yu*
Received 24th March 2011, Accepted 9th May 2011
DOI: 10.1039/c1cc11680k
The formation of 3,6-di-O-acetyl-1,2,4-O-orthoacetyl-a-D-
glucopyranose was observed in the gold(I)-catalyzed glycosidation
of peracetyl glucopyranosyl ortho-hexynylbenzoate; experi-
ments with substrates bearing deuterium labeled 2-O-acetyl or
4-O-acetyl groups indicated that the orthoacetate was derived
from the 4-O-acetyl group, which provided a direct evidence for
the remote participation of the 4-O-acyl group in glycosylation.
Ph3PAuNTf2, CH2Cl2, 4 A MS, rt, 3 h),7 more than ten
products were discerned on TLC. The normal b-glucoside 4
was isolated in 31% yield. The 2-OH glucoside 6 in a a/b
mixture of 4.9 : 1 (H-1a: 4.89 ppm, d, J = 4.4 Hz; H-1b:
4.34 ppm, d, J = 7.6 Hz) was isolated in 13% yield, which
was supposedly derived from 1,2-orthoacetate 3.8 Another
product, i.e., the 2-OH acetate 8 (in B2% yield) was also
known to be derived from 1,2-orthoacetate 3,8 while trace
amount of 3 did still remain. Inseparable disaccharides, via
coupling with the resulting alcohols (e.g., 6 and 8), were
detected by MS analysis.8 Lactol 7 (13%) was produced
during workup. Unexpected was that 1,2,4-orthoacetate 5
(H-1: 5.79 ppm, d, J = 4.8 Hz; orthoacetyl methyl group:
1.66 ppm for 1H and 118.3 ppm for 13C) was identified
as another major product (12%). Similar treatment with
peracetyl b-D-galactopyranosyl or -mannopyranosyl ortho-
hexynylbenzoate led to the corresponding 1,2-orthoester and
1,2-trans-glycoside cleanly.y8,9
a-D-Glucopyranose 1,2,4-orthoesters have been prepared
via intramolecular trans-orthoesterification of a-D-glucopyranose
1,2-orthoesters which bear a free 4-OH.10 These derivatives
(e.g., 3,6-di-O-benzyl-a-D-glucopyranose 1,2,4-orthopivalate)
could undergo cationic ring-opening polymerization to
provide cellulose derivatives.11 In the present case, two pathways
were possible for the formation of 1,2,4-orthoacetate 5
(Scheme 2). Pathway I involved neighboring group participation
Neighboring group participation from the 2-O-acyl group of
glycosyl donors is of paramount importance in making the
1,2-trans-glycosidic linkages.1 Participation from the remote
acyl groups of glycosyl donors might also contribute to the
stereochemical outcomes of glycosylations. Thus, partici-
pation of the 4-O-acyl group in donors has been accounted
for the
a
selective formation of galactopyranosides2
and fucopyranosides3 and the b selective formation of
mannopyranosides.4 However, results against the participation
of the 4-O-acyl group have also been reported.5 Trapping
experiments of a bridging dioxocarbenium ion intermediate to
support the putative 4-O-acyl group participation in glycosy-
lation have not yet been successful.6
Recently, we developed
a new glycosylation method
employing glycosyl ortho-alkynylbenzoates as donors and a
gold(I) complex as catalyst.7a The wide substrate scope and
versatility of this new method have been showcased in the
synthesis of a number of the complex glycoconjugates.7
However, our original attempts with peracetyl glucopyranosyl
ortho-hexynylbenzoate as the donor met with no success,
which led to complex mixtures. Understanding this exception
requires characterization of the complex products. To
facilitate characterization of the products, pure b anomer 1
and easily identifiable 4-penten-1-ol (2) were selected as
coupling partners (Scheme 1). Under the typical glycosylation
conditions for glycosyl ortho-alkynylbenzoates (0.1 equiv.
State Key Laboratory of Bioorganic and Natural Products Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 345 Lingling Road, Shanghai 200032, China.
E-mail: byu@mail.sioc.ac.cn; Fax: (0086)-21-64166128
w This article is part of the ‘Glycochemistry and glycobiology’ web-
theme issue for ChemComm.
z Electronic supplementary information (ESI) available: Experimental
details, characterization data, and NMR spectra. See DOI: 10.1039/
c1cc11680k
Scheme 1 Glycosylation of 4-penten-1-ol (2) with peracetyl b-D-
glucopyranosyl ortho-hexynylbenzoate 1. Yields are based on donor 1.
c
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Chem. Commun., 2011, 47, 7515–7517 7515

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group in a glycosylation reaction. The present evidence has
been obtained only on one glucose donor, nevertheless,
participation of the 4-O-acyl group from a galactose-type of
donor (where the 4-O-acyl group is favorably axial) or a
mannose-type of donor (where the 4-O-acyl group is
equatorial as in the glucose but trans to the 2-O-group) should
be easier than from a glucose donor.2–4 Thus, the remote
participation of the 4-O-acyl group does possible in certain
glycosidic coupling reactions.
We thank the financial support from the National Natural
Science Foundation of China (20932009 and 20621062) and the
Ministry of Science and Technology of China (2010CB529706).
Notes and references
y 3,6-Di-O-acetyl-1,2,4-O-orthoacetyl-a-D-glucopyranose (5). To
a
mixture of peracetyl glucopyranosyl ortho-hexynylbenzoate 1 (128 mg,
0.24 mmol), 4-penten-1-ol 2 (20 mL, 0.20 mmol), and 4 AMS (200 mg)
in dry CH2Cl2 (10 mL) was added a solution of PPh3AuNTf2 in
CH2Cl2 (0.05 N, 0.4 mL). After being stirred at rt for 3 h, the mixture
was filtered through a pad of Celite. The filtrate was concentrated.
The residue was subjected to careful separation on silica gel
column chromatography. Compound 510b (8 mg, 12%) was isolated
Scheme 2 Possible reaction pathways for the formation of 1,2,4-
orthoacetate 5.
from the 2-O-acetyl group to form dioxolenium B as a key
intermediate, which would lead to the well known reaction
pathways to give 1,2-orthoester 3 and b-glycoside 4.8 Possibly,
the C4-O in a boat conformer C might attack the 1,2-dioxo-
lenium, resulting in the formation of 1,2,4-orthoacetate 5 with
expulsion of CH3CO+ which could be captured by the alcohols
to form the acyl transfer products.8 Alternatively, remote
participation from the 4-O-acetyl group led to 1,4-dioxolenium
D, which could be attacked by C2-O to give 1,2,4-orthoacetate
5 with departure of CH3CO+.
(petroleum ether–EtOAc, 5 : 1; Rf 0.21) as
a colorless syrup:
[a]2D5 = 27.9 (c 0.6, CHCl3); 1H NMR (400 MHz, CDCl3) d 5.80
(d, J = 4.8 Hz, 1 H), 5.20 (d, J = 4.6 Hz, 1 H), 4.64 (t, J = 6.9 Hz, 1 H),
4.51 (m, 1 H), 4.31 (dd, J = 6.9, 11.3 Hz, 1 H), 4.21 (m, 2 H), 2.13
(s, 3 H), 2.10 (s, 3 H), 1.66 (s, 3 H); 13C NMR (100 MHz, CDCl3)
d 169.5, 168.4, 118.3, 96.5, 73.8, 71.1, 69.3, 63.8, 62.6, 19.8, 19.7, 19.0.
ESI-MS (m/z) 288.9 [M + H+]; HRMS (ESI) m/z calcd C12H16O8Na
[M + Na]+ 311.0737, found 311.0735.
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To discriminate these two plausible reaction pathways, we
managed to prepare substrates 9 and 10 which bear a deuterium
labeled 2-O-acetyl or 4-O-acetyl group, respectively.9 Treat-
ment of the 2-O-trideuteriumacetate 9 with alcohol 2 under the
aforementioned glycosylation conditions led to 1,2,4-ortho-
acetate
5 (12%), without detection of the 1,2,4-ortho-
trideuteriumacetate counterpart 11 (Fig. 1). This result indicated
clearly that the resulting orthoacetate in 5 was fully derived
from the 4-O-acetyl group in the donor but not from the
2-O-acetyl group. Supportively, an experiment under similar
conditions with 4-O-trideuteriumacetate donor 10 led to the
1,2,4-orthotrideuteriumacetate 11 (11%) without detection of
1,2,4-orthoacetate 5. These evidences demonstrated unambiguously
that the formation of 1,2,4-orthoacetate 5 was proceeded
through pathway II, in that a remote participation from the
4-O-acetyl group was effected even in the presence of the
neighboring 2-O-acetyl group.
4 For examples, see: C. de Meo, M. N. Kamat and
A. V. Demchenko, Eur. J. Org. Chem., 2005, 706.
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Soc., 2009, 131, 17705.
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In conclusion, here we have provided the first direct experi-
mental evidence for the remote participation of the 4-O-acyl
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9 See Supporting Information for detailsz.
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N. K. Kochetkov, A. D. Naumov and I. V. Obruchnikov, Carbohydr.
Res., 1971, 16, 497; (b) L. V. Backinowsky, N. E. Byramova,
Fig. 1 Discrimination of the two plausible pathways with substrates
(9 and 10) bearing 2-O- or 4-O-trideuteriumacetyl group.
c
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c
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Chem. Commun., 2011, 47, 7515–7517 7517