Environmentally benign synthesis of sugar orthoesters promoted by anhydrous sodium acetate and ultrasound

Article abstract of DOI:10.1002/cjoc.201100385

A convenient and alternative procedure for the synthesis of sugar orthoesters from glycosyl bromides with anhydrous sodium acetate as base under ultrasound irradiation is described. Various sugar and sugar-sugar orthoesters were prepared in 70%-91% isolat

Full text of DOI:10.1002/cjoc.201100385

FULL PAPER
DOI: 10.1002/cjoc.201100385
Environmentally Benign Synthesis of Sugar Orthoesters Pro-
moted by Anhydrous Sodium Acetate and Ultrasound
Zhao, Jinzhong*,a(赵晋忠)
Wei, Shanqiaob(魏善巧)
Shao, Huawub(邵华武)
Yue, Aiqina(岳爱琴)
a Shanxi Agricultural University, Taigu, Shanxi, 030801, China
b Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences,
Chengdu, Sichuan 610041, China
A convenient and alternative procedure for the synthesis of sugar orthoesters from glycosyl bromides with an-
hydrous sodium acetate as base under ultrasound irradiation is described. Various sugar and sugar-sugar orthoesters
were prepared in 70%—91% isolated yields.
Keywords ultrasound, sodium acetate, sugar orthoesters, glycosyl bromide, carbohydrates
Introduction
sodium acetate as base under ultrasound irradiation to
achieve the highly efficient tranformation of glycosyl
bromides into corresponding 1,2-orthoesters in acetoni-
trile at room temperature (Scheme 1). Notably, this
procedure is particularly efficient for the synthesis of
sugar-sugar orthoesters.
Sugar 1,2-orthoesters are useful synthetic intermedi-
ates in carbohydrate chemistry,[1,2] since they can be
readily converted into corresponding 1,2-trans-gly-
cosides by the action of protonic or Lewis acids.[3,4]
Sugar 1,2-orthoesters show remarkable glycosidation
properties, particularly in oligosaccharide synthesis, and
they can also react with various aglycons or rearrange to
provide O-glycosides,[5] glycosyl phosphate[6] and oli-
gosaccharides.[7] The preparation of sugar 1,2-ortho-
esters is based on the anomerization of glycosyl bro-
mides and the formation of acyloxonium ion, using
ammonium salt,[8] silver triflate[3a,9] and other promoters
in the presense of an organic base.[10] Among these
methods, the reaction of glycosyl bromide with alcohol
promoted by tetrabutylammonium bromide in the pres-
ence of 2,6-lutidine is one of the most popular ap-
proaches. As a consequent it has been widely investi-
gated and modified.[11,12] However, the published meth-
ods for sugar 1,2-orthoester synthesis present some
drawbacks such as the requirement for an expensive,
foul-smelling, toxic, and environmentally harmful or-
ganic base, which motivate the development of a con-
venient alternative procedure for the preparation of
sugar 1,2-orthoesters. Ultrasound irradiation, which
minimizes waste production and use of hazardous re-
agents by enhancing the rate, yield, and selectivity of
chemical transformations, has emerged as an environ-
mentally benign technology to take the place of tradi-
tional agitation in recent years.[13]
Scheme 1 Sugar orthoester synthesis promoted by sodium ace-
tate and ultrasound
R1
R1
2
O
NaOAc, MeCN, R OH,
O
RO
RO
RO
RO
US (40 Hz, 600 W), r.t.
O
OR
O
Br
OR2
1
R
=CH , OAc, OBz, OMs, OTs
3
R = Ac(Bz)
2
R
= OCH , OCH CH , OCH CH=CH , PhCH OH,
,
CH
OH C
C
3
2
3
2
2
2
2
O
O
O
O
O
OCH3
BnO
BnO
O
,
O
OBn
O
Experimental
General methods
Sonochemical reactions were carried out in a com-
mercially available ultrasound cleaning bath (40 kHz,
600 W) equipped with an automatic thermally regulated
heating/cooling circulation system. Reactions were
monitored by thin layer chromatography using silica gel
Herein, we wish to report a convenient alternative
synthesis of 1,2-orthoesters, which involves the use of
*
E-mail: zhaojz@sxau.edu.cn; Fax: 0086-0354-6286959
Received September 23, 2011; accepted October 14, 2011; published online February 29, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201100385 or from the author.
Chin. J. Chem. 2012, 30, 627—633
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627

Zhao et al.
FULL PAPER
HSGF254 plates. Flash chromatography was performed
4.16 (m, 1H), 4.25 (dd, J ＝ 4.7, 11.8 Hz, 1H),
4.62—4.54 (m, 3H), 5.14—5.15 (m, 1H), 5.30 (dd, J＝
9.5, 9.7 Hz, 1H), 5.50 (m, 1H), 7.26—7.31 (m, 5H).
Sugar orthoester 9 White solid, m.p. 128—129
1
using silica gel HG/T2354-92. H NMR and 13C NMR
(600 and 150 MHz, respectively) spectra were recorded
1
in CDCl3. H NMR chemical shifts are reported in δ
1
relative to tetramethylsilane (TMS), with the solvent
resonance employed as the internal standard (CDCl3, δ
＝7.26). Data are reported as follows: chemical shift,
multiplicity (s＝singlet, d＝doublet, t＝triplet, m＝
multiplet), integration, and coupling constants (Hz). 13C
NMR chemical shifts are reported from tetramethylsi-
lane (TMS) with the solvent resonance as the internal
standard (CDCl3, δ＝77.0). ESI-HRMS spectra were
recorded on a BioTOF Q instrument. Optical rotations
were examined on a Perkin Elmer-341 digital polarime-
ter. D-Glucose, D-mannose, D-galactose and
L-rhamnose were commercially available and used
without further purification.
℃; [α]2D5 －2.5 (c 0.2, EtOAc); H NMR (CDCl3) δ:
1.73 (s, 3H), 2.08 (s, 3H), 2.12 (s, 3H), 3.05 (s, 3H),
3.28 (s, 3H), 3.77—3.80 (m, 1H), 4.28 (dd, J＝2.7, 11.1
Hz, 1H), 4.30 (dd, J＝5.5, 11.1 Hz, 1H), 4.63 (dd, J＝
3.1, 3.1 Hz, 1H), 5.17 (dd, J＝3.8, 10.0 Hz, 1H), 5.25
(dd, J＝9.4, 9.8 Hz, 1H), 5.51 (d, J＝2.5 Hz, 1H); 13C
NMR (CDCl3) δ: 20.6, 20.7, 24.0, 37.7, 50.1, 65.5, 67.2,
70.2, 71.6, 76.2, 97.5, 124.3, 169.6, 170.3;
HR-EMSIMS calcd for C14H22NaO11S [M ＋ Na]
421.0775, found 421.0772.
Sugar orthoester 10 Syrup, [α]2D5 ＋30.5 (c 0.2,
EtOAc); 1H NMR (CDCl3) δ: 1.59 (s, 3H), 2.03 (s, 3H),
2.10 (s, 3H), 2.45 (s, 3H), 3.24 (s, 3H), 3.70—3.73 (m,
1H), 4.07—4.13 (m, 2H), 4.56 (dd, J＝2.9, 3.7 Hz, 1H),
5.11 (dd, J＝3.8, 9.8 Hz, 1H), 5.16 (dd, J＝9.2, 9.6 Hz,
1H), 5.41 (d, J＝2.7 Hz, 1H), 7.34 (d, J＝7.9 Hz, 2H),
7.78 (d, J＝8.3 Hz, 2H); 13C NMR (CDCl3) δ: 20.6,
20.7, 21.6, 24.0, 50.0, 65.9, 67.9, 70.2, 71.3, 76.3, 97.4,
124.3, 128.1, 129.8, 132.5, 145.0, 169.5, 170.3;
HR-EMSIMS calcd for C20H26NaO11S [M ＋ Na]
497.1088, found 497.1081.
General
procedure
for
the
synthesis
of
1,2-orthoesters
The glycopyranosyl bromide (1 mmol) was dis-
solved in dry acetonitrile (5 mL), then alcohol (10
mmol), tertabutylammonium bromide (1 mmol), sodium
acetate (2 mmol), and molecular sieves 4 Å (600 mg)
were added. The reaction mixture was processed under
ultrasound irradiation. TLC was used to monitor for
completion of reaction. The solvent was evaporated to
dryness, and the residue was purified by silica gel col-
umn chromatrography.
Sugar orthoester 11 White solid, m.p. 145—146
1
[α]2D5
1 (c 0.2, EtOAc); H NMR (CDCl ) δ:
℃;
－
3
1.18 (t, J 7.0 Hz, 3H), 1.73 (s, 3H), 2.08 (s, 3H), 2.12
＝
(s, 3H), 3.05 (s, 3H), 3.59 3.50 (m, 2H), 3.77 3.79
—
—
(m, 1H), 4.28 (dd, J 2.7, 11.0 Hz, 1H), 4.33 (dd, J
＝
＝
General procedure for the synthesis of sugar-sugar
orthoesters
5.5, 11.1 Hz, 1H), 4.61 (dd, J 3.1, 3.5 Hz, 1H), 5.17
＝
(dd, J 3.9, 9.9 Hz, 1H), 5.25 (dd, J 9.5, 9.7 Hz, 1H),
＝
＝
5.49 (d, J 2.5 Hz, 1H); 13C NMR (CDCl3) δ: 15.1,
The glycosyl acceptor (1 mmol) and glycopyranosyl
bromide (2 mmol) were dissolved in dry acetonitrile (5
mL), then alcohol (10 mmol), tertabutylammonium
bromide (1 mmol), sodium acetate (2 mmol), and mo-
lecular sieves 4 Å (600 mg) were added. The reaction
mixture was processed under ultrasound irradiation.
TLC was used to monitor for completion of reaction.
The solvent was evaporated to dryness, and the residue
was purified by silica gel column chromatrography.
Sugar orthoester 2 White power, m.p. 107—108
℃; [α]2D5 －24 (c 0.2, EtOAc); 1H NMR (CDCl3) δ:
1.74 (s, 3H), 2.05 (s, 3H), 2.07 (s, 3H), 2.12 (s, 3H),
3.28 (s, 3H), 3.67—3.69 (m, 1H), 4.14 (dd, J＝1.9, 11.7
Hz, 1H), 4.24 (dd, J＝5.0, 12.2 Hz, 1H), 4.61 (dd, J＝
2.9, 3.5 Hz, 1H), 5.15 (dd, J＝4.0, 10.0 Hz, 1H), 5.30
(dd, 1H, J＝9.7, 9.8 Hz), 5.49 (d, J＝2.5 Hz, 1H).
Sugar orthoester 7 Syrup, [α]2D5 －11 (c 0.2,
EtOAc); 1H NMR (CDCl3) δ: 1.77 (s, 3H), 2.05 (s, 3H),
2.07 (s, 3H), 2.11 (s, 3H), 3.67—3.69 (m, 1H), 4.00—
4.05 (m, 2H), 4.13—4.15 (m, 1H), 4.23 (dd, J＝4.7,
12.2 Hz, 1H), 4.60 (m, 1H), 5.13—5.15 (m, 2H), 5.24—
5.28 (m, 2H), 5.48 (d, J＝2.5 Hz, 1H), 5.84—5.91 (m,
1H).
＝
20.6, 20.7, 24.3, 37.7, 58.4, 65.6, 67.3, 70.2, 71.6, 76.0,
97.5, 124.0, 169.6, 170.3; HR-EMSIMS calcd for
C H NaO S [M Na] 435.0932, found 435.0936.
＋
15 24
11
Sugar orthoester 12 White solid, m.p. 127—129
1
℃; [α]2D5 ＋11 (c 0.1, EtOAc); H NMR (CDCl3) δ:
1.75 (s, 3H), 2.08 (s, 3H), 2.12 (s, 3H), 3.05 (s, 3H),
3.78—3.79 (m, 1H), 4.06—4.00 (m, 2H), 4.28 (dd, J＝
3.0, 11.3 Hz, 1H), 4.33 (dd, J＝5.6, 11.3 Hz, 1H), 4.62
(dd, J ＝ 3.1, 3.8 Hz, 1H), 5.18—5.14 (m, 2H),
5.27—5.24 (m, 2H), 5.51 (d, J＝2.8 Hz, 1H), 5.84—
5.90 (m, 1H); 13C NMR (CDCl3) δ: 20.6, 20.7, 24.4,
37.7, 64.0, 65.5, 67.3, 70.1, 71.7, 76.0, 97.6, 116.8,
124.1, 133.9, 169.6, 170.2; HR-EMSIMS calcd for
C16H24NaO11S [M＋Na] 447.0932, found 447.0925.
Sugar orthoester 13 Syrup, [α]2D5 ＋23 (c 0.2,
EtOAc); 1H NMR (CDCl3) δ: 1.63 (s, 3H), 2.03 (s, 3H),
2.10 (s, 3H), 2.37 (dd, J＝2.3, 2.3 Hz, 1H), 2.45 (s, 3H),
3.72—3.79 (m, 1H), 4.15—4.07 (m, 4H), 4.15 (d, J＝
1.8 Hz, 2H), 4.62 (dd, J＝3.2, 3.3 Hz, 1H), 5.18—5.11
(m, 2H), 5.43 (d, J＝2.8 Hz, 1H), 7.34 (d, J＝8.0 Hz,
2H), 7.78 (d, J＝8.2 Hz, 2H); 13C NMR (CDCl3) δ: 14.2,
20.6, 20.7, 21.6, 24.0, 51.0, 65.7, 68.0, 69.9, 71.6, 73.7,
76.0, 79.4, 97.5, 123.9, 128.1, 129.8, 130.0, 132.5,
145.1, 169.5, 170.2; HR-EMSIMS calcd for
C22H26NaO11S [M＋Na] 521.1088, found 521.1065.
Sugar orthoester 8 Syrup, [α]2D5 －3 (c 0.2,
EtOAc); 1H NMR (CDCl3) δ: 1.82 (s, 3H), 2.05 (s, 3H),
2.07 (s, 3H), 2.09 (s, 3H), 3.68—3.70 (m, 1H), 4.14—
628
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 627—633

Environmentally Benign Synthesis of Sugar Orthoesters
Sugar orthoester 14 White solid, m.p. 130—132
84.6, 97.4, 104.6, 124.2, 127.6, 127.7, 127.8, 127.9,
128.0, 128.1, 128.4, 128.5, 138.3, 138.5, 138.6, 169.4,
170.3, 170.6; HR-EMSIMS calcd for C42H50NaO15 [M
＋Na] 817.3042, found 817.3018.
1
℃; [α]2D5 ＋1 (c 0.2, EtOAc); H NMR (CDCl3) δ:
1.77 (s, 3H), 2.08 (s, 3H), 2.12 (s, 3H), 2.38 (dd, J＝1.9,
1.9 Hz, 1H), 3.05 (s, 3H), 3.79—3.81 (m, 1H), 4.18 (d,
J＝2.1 Hz, 2H), 4.29 (dd, J＝2.8, 11.2 Hz, 1H), 4.33
(dd, J＝5.6, 11.5 Hz, 1H), 4.68 (dd, J＝3.2, 3.2 Hz, 1H),
5.18 (dd, J＝4.0, 10.0 Hz, 1H), 5.25 (dd, J＝9.4, 9.7 Hz,
1H), 5.53 (d, J＝2.9 Hz, 1H); 13C NMR (CDCl3) δ: 20.7,
24.0, 37.7, 51.1, 65.4, 67.2, 69.9, 71.8, 73.7, 76.0, 79.4,
97.6, 123.9, 169.6, 170.2; HR-EMSIMS calcd for
C16H22NaO11S [M＋Na] 445.0775, found 445.0783.
Sugar orthoester 15 White solid, m.p. 141—142
Sugar-sugar orthoester 24 Syrup, [α]2D5 －18.5
(c 0.2, EtOAc); 1H NMR ( (CD3)2CO) δ: 1.30 (s, 3H),
1.31 (s, 3H), 1.37 (s, 3H), 1.45 (s, 3H), 1.67 (s, 3H),
2.01 ( s, 3H), 2.05 (s, 6H), 3.52 (dd, J＝6.5, 9.7 Hz, 1H),
3.67 (dd, J＝6.3, 9.7 Hz, 1H), 3.86—3.87 (m, 1H), 3.98
—4.00 (m, 1H), 4.15 (d, J＝4.4 Hz, 2H), 4.25 (dd, J＝
1.8, 7.9 Hz, 1H), 4.32 (dd, J＝2.4, 5.2 Hz, 1H), 4.45 (m,
1H), 4.60 (dd, J＝2.4, 7.9 Hz, 1H), 4.86 (dd, J＝2.0, 9.5
Hz, 1H), 5.13 (dd, J＝2.8, 2.8 Hz, 1H), 5.44 (d, J＝4.9
Hz, 1H), 5.72 (d, J＝5.3 Hz, 1H).
1
℃; [α]2D5 ＋10 (c 0.2, EtOAc); H NMR (CDCl3) δ:
1.81 (s, 3H), 2.08 (s, 3H), 2.10 (s, 3H), 3.05 (s, 3H),
3.78—3.81 (m, 1H), 4.35—4.28 (m, 2H), 4.64—4.54
(m, 3H), 5.16 (dd, J＝3.9, 9.9 Hz, 1H), 5.26 (dd, J＝9.5,
9.7 Hz, 1H), 5.52 (d, J＝2.7 Hz, 1H), 7.37—7.26 (m,
5H); 13C NMR (CDCl3) δ: 20.7, 24.4, 37.7, 65.0, 65.5,
67.3, 70.0, 71.7, 76.0, 97.6, 124.2, 127.0, 127.5, 127.7,
128.4, 128.6, 137.4, 169.6, 170.2; HR-EMSIMS calcd
for C20H26NaO11S [M＋Na] 497.1088, found 497.1079.
Sugar orthoester 16 White solid, m.p. 150—152
Sugar-sugar orthoester 25 Syrup, [α]2D5 ＋9.5 (c
0.2, EtOAc); 1H NMR (600 MHz, (CD3)2CO) δ: 1.30 (s,
3H), 1.31 (s, 3H), 1.37 (s, 3H), 1.46 (s, 3H), 1.63 (s, 3H),
2.13—2.01 (m, 9H), 3.55 (m, 1H), 3.67—3.69 (m, 1H),
3.90 (dd, J＝4.9, 6.7 Hz, 1H), 4.04 (dd, J＝7.2, 14.1 Hz,
1H), 4.10 (dd, J＝5.5, 11.3 Hz, 1H), 4.18 (dd, J＝7.2,
11.5 Hz, 1H), 4.26—4.28 (m, 1H), 4.43—4.40 (m, 2H),
4.61 (dd, J＝2.2, 7.8 Hz, 1H), 5.07 (dd, J＝3.5, 6.4 Hz,
1H), 5.40 (dd, J＝2.5, 2.9 Hz, 1H), 5.45 (dd, J＝4.9 Hz,
1H), 5.87 (d, J＝4.9 Hz, 1H).
1
℃; [α]2D5 －129 (c 0.7, EtOAc); H NMR (CDCl3) δ:
3.23 (s, 3H), 4.14—4.09 (m, 1H), 4.35 (dd, J＝4.7, 12.1
Hz, 1H), 4.51 (dd, J＝3.1, 11.9 Hz, 1H), 5.08 (dd, J＝
3.3, 3.7 Hz, 1H), 5.66 (dd, J＝4.1, 10.0 Hz, 1H), 5.80 (d,
J ＝ 2.9 Hz, 1H), 5.88 (dd, J ＝ 9.5, 9.6 Hz, 1H),
7.30—7.26 (m, 3H), 7.42—7.32 (m, 6H), 7.53—7.47
(m, 3H), 7.71—7.69 (m, 2H), 7.90—7.89 (m, 4H), 8.01
(d, J＝7.6 Hz, 2H).
Sugar-sugar orthoester 26 Syrup, [α]2D5 －34.3
(c 0.3, EtOAc); 1H NMR ((CD3)2CO) δ: 1.16 (d, J＝6.2
Hz, 3H), 1.30 (s, 3H), 1.31 (s, 3H), 1.36 (s, 3H), 1.47 (s,
3H), 1.66 (s, 3H), 2.03 (s, 6H), 3.56 (dd, J＝6.7, 9.8 Hz,
1H), 3.64 (dd, J＝5.6, 10.1 Hz, 1H), 3.68—3.70 (m,
1H), 3.89—4.03 (m, 1H), 4.23 (dd, J＝1.4, 7.9 Hz, 1H),
4.32 (dd, J＝2.2, 4.9 Hz, 1H), 4.60 (dd, J＝2.0, 7.9 Hz,
1H), 4.65 (dd, J＝2.4, 4.0 Hz, 1H), 4.97 (dd, J＝9.7, 9.8
Hz, 1H), 5.20 (dd, J＝4.0, 10.0 Hz, 1H), 5.44 (d, J＝5.0
Hz, 1H), 5.61 (d, J＝2.2 Hz, 1H); 13C NMR (CDCl3) δ:
16.9, 19.8, 23.8, 24.3, 24.8, 25.5, 61.4, 66.9, 70.5, 70.7,
71.0, 77.3, 96.3, 97.3, 108.1, 108.7, 123.8, 169.5, 169.6;
HR-EMSIMS calcd for C24H36NaO13 [M ＋ Na]
555.2048, found 555.2037.
Sugar orthoester 17 Syrup, [α]2D5 ＋20 (c 0.4,
1
EtOAc); H NMR (CDCl3) δ: 1.23 (d, J＝6.2 Hz, 3H),
1.73 (s, 3H), 2.06 (s, 3H), 2.12 (s, 3H), 3.27 (s, 3H),
3.49—3.52 (m, 1H), 4.59 (dd, J＝2.3, 3.9 Hz, 1H),
5.03—5.08 (m, 2H), 5.41 (d, J＝2.3 Hz, 1H).
Sugar-sugar orthoester 22 White solid, m.p. 121
1
—123 ℃; [α]2D5 －27.7 (c 0.3, EtOAc); H NMR
(CDCl3) δ: 1.32 (s, 3H), 1.33 (s, 3H), 1.42 (s, 3H), 1.53
(s, 3H), 1.76 (s, 3H), 2.04 (s, 3H), 2.06 (s, 3H), 2.11 (s,
3H), 3.60 (dd, J＝6.2, 9.2 Hz, 1H), 3.74—3.69 (m, 2H),
3.91 (dd, J＝5.5, 6.1 Hz, 1H), 4.15 (dd, J＝2.8, 11.9 Hz,
1H), 4.24—4.22 (m, 2H), 4.29 (dd, J＝2.4, 5.1 Hz, 1H),
4.58 (dd, J＝2.4, 7.9 Hz, 1H), 4.62 (dd, J＝3.1, 3.5 Hz,
1H), 5.18 (dd, J＝4.1, 10.0 Hz, 1H), 5.28 (dd, J＝9.4,
9.8 Hz, 1H), 5.50 (m, 2H).
Results and Discussion
First, peracetylated mannopyranosyl bromide (1)
was chosen to investigate the sonochemical effects and
catalytic effects of inorganic base on the synthesis of
1,2-orthoester (2) at room temperature (Scheme 2). This
reaction was carried out in an ultrasound cleaning bath
(40 kHz, 600 W) equipped with an automatic thermally
regulated heating/cooling circulation system.
Sugar-sugar orthoester 23 Syrup, [α]2D5 ＋10 (c
1
0.3, EtOAc); H NMR (CDCl3) δ: 1.74 (s, 3H), 2.00 (s,
3H), 2.04 (s, 3H), 2.07 (s, 3H), 3.41—3.42 (m, 2H),
3.51 (d, J＝9.2 Hz, 1H), 3.55 (s, 3H), 3.68—3.60 (m,
3H), 3.75 (d, J＝8.8 Hz, 1H), 4.14 (dd, J＝2.6, 12.2 Hz,
1H), 4.23 (dd, J＝5.1, 12.3 Hz, 1H), 4.28 (d, J＝7.8 Hz,
1H), 4.48 (dd, J＝2.9, 3.3 Hz, 1H), 4.62 (d, J＝10.9 Hz,
1H), 4.69 (d, J＝11.0 Hz, 1H), 4.77 (d, J＝11.0 Hz, 1H),
4.82 (d, J＝11.0 Hz, 1H), 4.90 (dd, J＝7.8, 10.9 Hz,
2H), 5.12 (dd, J＝3.9, 9.8 Hz, 1H), 5.27 (dd, J＝9.6, 9.6
Hz, 1H), 5.39 (d, J＝2.5 Hz, 1H), 7.34—7.26 (m, 15H);
13C NMR (CDCl3) δ: 20.6, 20.7, 24.4, 57.0, 61.8, 62.5,
65.7, 70.3, 71.5, 73.8, 74.7, 74.9, 75.6, 76.4, 77.7, 82.3,
Scheme 2 Synthesis of orthoester (2) from acetylated mannosyl
bromide (1)
OMe
OAc
OAc
OAc
O
O
NaOAc, MeCN
O
O
AcO
AcO
AcO
AcO
US (40 Hz, 600 W), r.t.
Br
2
1
Chin. J. Chem. 2012, 30, 627—633
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
629

Zhao et al.
FULL PAPER
Table 1 Optimization of reaction conditions for the synthesis of
According to the data shown in Table 1 (Entry 3), the
NaOAc and acetonitrile combination produced the best
yield of 89%.
2a
Timea
Isolated yielda
(stir.b)/%
Entry Base/mmol Solvent
(stir.b)/h
Given that 2 was readily obtained from 1 using
NaOAc in acetonitrile under ultrasound irradiation, the
synthesis of all the 1,2-orthoesters shown in Scheme 1
and Table 2 was explored under the same conditions. In
the beginning, mannopyranosyl bromide was treated
with allyl alcohol and propynol; a high yield of the cor-
responding 1,2-orthoesters was obtained (Table 1, En-
tries 1, 2). On the basis of this result, we treated the
6-O-mesyl and 6-O-tosyl mannopyranosyl bromides
with various alcohols such as methanol, ethanol, allyl
alcohol, propynol, and benzylalcohol. The correspond-
ing orthoesters were obtained in 70%—88% yields (Ta-
ble 1, Entries 3—11). Among these orthoesters,
6-O-tosyl and 6-O-mesyl could be easily substituted by
other groups, thereby expanding the library of sugar
orthoesters. Furthermore, the generality of the synthesis
of benzyolated mannosyl methyl orthoester 16 and ac-
etylated rhamnosyl orthoester 17 under the same condi-
tions was investigated. Excellent yield was obtained for
orthoester 16 (Table 2, Entriy 10), whereas, only a
modest yield was obtained for the acetylated rhamnosyl
orthoesters (Table 2, Entry 11).
1
2
3
4
5
6
7
8
KF
CH2Cl2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
6 (14)
76 (70)
81 (78)
89 (82)
79
KF
4 (10)
NaOAc
Na2CO3
K2CO3
NaHCO3
Na2SO3
Na2HPO4
3 (10)
3
3
3
3
3
75
83
60
67
a Under ultrasound irradiation at room temperature. b Using mag-
netic stirrer under slient conditions.
Compound 1 was treated with potassium fluoride[11a]
in acetonitrile and dichloromethane under ultrasound
irradiation and high-speed magnetic stirring (Table 1,
Entries 1, 2). A high yield of 2 was obtained in acetoni-
trile, and the reaction time was significantly reduced
under ultrasound irradiation. To optimize the method,
NaOAc, Na2CO3, K2CO3, NaHCO3, Na2SO3, and
Na2HPO4 were used as bases, and afforded the target
compounds under ultrasound irradiation in not bad yield.
Table 2 Synthesis of various substituted 1,2-orthoesters from pyranosyl bromide
Entry
1
Glycosyl bromide
Acceptor
Product
Timea (stir.b)/hIsolated yielda (stir.b)/%
O
OAc
OAc
OAc
O
O
O
O
AcO
AcO
CH2＝CHCH2OH
4 (13)
4 (15)
3 (10)
3
80 (68)
73 (65)
88 (80)
80
AcO
AcO
Br
7
1
O
OAc
OAc
OAc
O
O
O
O
AcO
2
3
4
5
CH2OH
AcO
AcO
AcO
Br
Br
Br
Br
1
8
OMs
OCH3
O
OMs
OAc
O
O
O
AcO
AcO
AcO
AcO
CH3OH
3
9
OCH3
O
OTs
OTs
OAc
O
O
O
AcO
AcO
AcO
AcO
CH3OH
4
10
OMs
OMs
OCH2CH3
O
OAc
O
O
O
AcO
AcO
AcO
AcO
CH3CH2OH
3
83
3
11
630
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 627—633

Environmentally Benign Synthesis of Sugar Orthoesters
Continued
Entry
6
Glycosyl bromide
Acceptor
Product
Timea (stir.b)/h Isolated yielda (stir.b)/%
O
OMs
OAc
OMs
O
O
O
O
AcO
CH2＝CHCH2OH
4
77
AcO
AcO
AcO
3
Br
Br
Br
12
O
O
OTs
OTs
OAc
O
O
O
AcO
AcO
HC C CH2OH
HC C CH2OH
CH2OH
7
4
78
AcO
AcO
4
13
O
OMs
OMs
OAc
O
O
O
AcO
AcO
O
8
4
70
AcO
AcO
3
14
O
OMs
OMs
OAc
O
O
O
O
AcO
AcO
9
AcO
AcO
6 (15)
76 (69)
3
Br
15
Ph
OBz
OBz
OMe
O
OBz
O
O
O
BzO
BzO
BzO
BzO
10
CH3OH
4
91
5
Br
Br
16
O
AcO
O
O
AcO
AcO
11
CH3OH
3 (12)
75 (66)
O
AcO
OCH3
OAc
17
6
a Under ultrasound irradiation at room temperature. b Using magnetic stirrer under slient conditions.
Table 3 Synthesis of sugar-sugar orthoesters from glycosyl bromidesa
Entry Glycosyl bromide
Acceptor
Product
Timea (stir.b)/h Isolated yielda (stir.b)/%
O
O
O
OH
OAc
OAc
O
O
O
O
OAc
O
AcO
AcO
O
1
6 (18)
90 (83)
O
O
O
O
AcO
AcO
O
O
Br
1
20
22
H3CO
O
OBn
OH
OAc
OAc
O
O
O
BnO
BnO
AcO
AcO
OAc
OCH3
2
6 (15)
85 (80)
OBn
OBn
O
O
O
OBn
AcO
AcO
1
Br
21
23
Chin. J. Chem. 2012, 30, 627—633
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
631

Zhao et al.
FULL PAPER
Continued
Entry Glycosyl bromide
Acceptor
Product
Timea (stir.b)/h Isolated yielda (stir.b)/%
OAc
O
AcO
AcO
O
OH
O
OAc
O
O
O
O
O
AcO
AcO
3
6
81
O
O
O
OAc
O
Br
18
20
O
O
O
24
OAc
AcO
OAc
O
O
OH
O
OAc
OAc
O
O
O
O
4
6 (15)
82 (78)
O
AcO
O
O
O
OAc
19
O
Br
O
20
O
O
25
O
AcO
O
O
OH
O
AcO
O
Br
O
O
O
O
AcO
5
6 (15)
76 (72)
O
O
AcO
O
OAc
O
6
20
O
O
26
a Under ultrasound irradiation at room temperature. b Using magnetic stirrer under slient conditions.
The generality of the reaction for synthesis of
sugar-sugar orthoesters was also studied. Sugar-sugar
orthoesters are extremely important intermediates for
oligosaccharide synthesis, which is typically performed
by the reaction of a glycosyl bromide donor with a gly-
cosyl acceptor with only one free hydroxyl group in the
presence of an organic base.[3a] Hence, 1 and 20 were
treated with NaOAc in acetonitrile under ultrasound.
The reaction was completed at room temperature, and
an excellent yield of sugar-sugar orthoester 22 was ob-
tained (Table 3, Entry 1). Subsequently, sugar-sugar
orthoesters 23, 24, 25 and 26 were obtained in
76%—85% yields (Table 3, Entries 2—5).
Conclusions
In summary, ultrasound irradiation improved the
yield of sugar orthoesters and reduced the reaction time
significantly. The presented method involves the using
of environmentally friendly anhydrous sodium acetate
as base, and convenient operations. All of these factors
make it an attractive alternative procedure for the syn-
thesis of sugar 1,2-orthoesters, especially for the syn-
thesis of sugar-sugar 1,2-orthoesters.
Acknowledgement
The authors are grateful for financial support from
the Project of Science and Technology of Shanxi Prov-
ince (No. 20100311069) and the Scientific Research
Foundation of Shanxi Agricultural University (No.
XB2009013).
Scheme 3 Synthesis of sugar-sugar orthoester
R1
HO
O
NaOAc, MeCN
AcO
AcO
O
+
US (40 Hz, 600 W), r.t.
OAc
Br
R1
R
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