Tetranuclear zinc cluster: A dual purpose catalyst for per-: O -acetylation and de- O -acetylation of carbohydrates

Article abstract of DOI:10.1039/c6ra12050d

The trifluoroacetic acid adduct of tetranuclear zinc cluster Zn₄(OCOCF₃)₆O catalysis in per-O-acetylation and de-O-acetylation of carbohydrates at 70 °C can be tuned by adjusting the reaction medium. Per-O-acetylation of hexopyranoses with a near stoichiometric amount of acetic anhydride in toluene resulted in the exclusive formation of pyranosyl products as an anomeric mixture, whereas de-O-acetylation of acetates occurred in methanol in high yields. In the latter, methanol acts as both nucleophile and solvent, and the reaction conditions were compatible to acid- and base-sensitive groups and amino acid derivatives.

Full text of DOI:10.1039/c6ra12050d

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Tetranuclear zinc cluster: a dual purpose catalyst
for per-O-acetylation and de-O-acetylation of
carbohydrates†‡
Cite this: RSC Adv., 2016, 6, 58749
Ting-Wei Lin,§ Avijit K. Adak,§ Hong-Jyune Lin, Anindya Das, Wei-Chen Hsiao,
*
Ting-Chun Kuan and Chun-Cheng Lin
The trifluoroacetic acid adduct of tetranuclear zinc cluster Zn4(OCOCF3)6O catalysis in per-O-acetylation
and de-O-acetylation of carbohydrates at 70 ꢀC can be tuned by adjusting the reaction medium. Per-O-
acetylation of hexopyranoses with a near stoichiometric amount of acetic anhydride in toluene resulted
in the exclusive formation of pyranosyl products as an anomeric mixture, whereas de-O-acetylation of
acetates occurred in methanol in high yields. In the latter, methanol acts as both nucleophile and
solvent, and the reaction conditions were compatible to acid- and base-sensitive groups and amino acid
derivatives.
Received 9th May 2016
Accepted 4th June 2016
DOI: 10.1039/c6ra12050d
www.rsc.org/advances
iodine7 are also used as catalysts in the per-O-acetylation of
carbohydrates. Other reagents that catalyze O-acetylation of
Introduction
carbohydrates using acetic anhydride include Lewis acids, for
instance Ce(OTf)2,8 ZnCl2,9 FeCl3,10 V(O) (OTf)2,11 Sc(OTf)3,12
Cu(OTf)2,13 Zn(ClO4)2$6H2O,14 Cu(ClO4)2$6H2O;15 Brønsted
acids such as HClO4,16 H2SO4,17 sulfamic acid,18 and meth-
anesulfonic acid;19 heterogeneous catalysts such as montmo-
rillonite K-10,20 H-beta zeolite,21 molecular sieves,22 ionic
liquid,23 enzyme catalysts such as lipases,24 and others such as
deep eutectic solvent,25 and sulfonic acid-functionalized nano
g-Al2O3.26 Although these methods are effective for per-O-acet-
ylation of carbohydrates, the use of excess acetic anhydride as
solvent causes tedious work up in the neutralization step.
Additionally, only a few of these have been used in large-scale
Hydroxyl functionality is ubiquitous in natural products and,
consequently, requires the introduction of O-acetate as a mask
for hydroxyl groups and subsequent deprotection steps.1 In the
context of carbohydrate chemistry, O-acetyl groups not only
serve as protecting groups, but also as modulators of reactivity
in glycosylation. Per-O-acetylated carbohydrates are inexpensive
and invaluable substrates for the preparation of various bio-
logically relevant oligosaccharides, glycoconjugates, and
natural products.2 In addition, per-O-acetylation is routinely
employed for characterization and identication of carbohy-
drate structures. As a consequence, an overwhelming number of
O-acetylation and de-O-acetylation methods have been devel-
oped for widespread use in organic and natural product
synthesis, as well as industrial processes.3 The standard O-
acetylation reaction is typically carried out using either acetyl
chloride or acetic anhydride as the acetylating reagent. The
latter is perhaps the most extensively used reagent, and usually
requires a catalyst to achieve a reasonable reaction rate. For per-
O-acetylation of carbohydrates, pyridine is the most commonly
used solvent/catalyst, although it is known to have unpleasant
odors and acute toxicity.4 Certain derivatives of pyridine such as
4-(N,N-dimethylamino)pyridine (DMAP) and 4-(1-pyrrolidino)
pyridine also catalyze the acetylation reaction, in some
instances 104-times faster than pyridine.5 Sodium acetate6 and
synthesis
of
carbohydrate
building
blocks
and
intermediates.10,13,19
In this context, previously we introduced LiClO4 as a mild
catalyst in combination with a stoichiometric amount of acetic
anhydride for per-O-acetylation of saccharides under solvent-
free conditions, scalable and applicable to multi-gram
synthesis.27 For preparative purposes, later we carried out
synthesis of per-O-acetylated saccharides on a multi-gram scale
using catalytic LiClO4, involving only a simple work-up and
neutralization with saturated aqueous NaHCO3 solution to give
products.28
Here, we report the rst use of a m-oxo-tetranuclear zinc
cluster triuoroacetic acid adduct Zn4(OCOCF3)6O$(CF3COOH)n
(1)29e as a dual catalyst for per-O-acetylation of saccharides using
near-stoichiometric acetic anhydride in toluene, and de-O-
acetylation of saccharides when methanol is used as a solvent
and nucleophile. The Zn4(OCOCF3)6O catalyst has been
employed in a number of synthetic applications, including the
acylation of alcohols and deacylation of acetates and
Department of Chemistry, National Tsing Hua University, Hsinchu-300, Taiwan.
E-mail: cclin66@mx.nthu.edu.tw; Fax: +886 3 5711082; Tel: +886 3 5753147
† In memory of Dr Chang-Ching Lin.
‡ Electronic supplementary information (ESI) available: Copies of NMR (1H and
13C) spectra of all new compounds. See DOI: 10.1039/c6ra12050d
§ Authors have equal contribution.
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benzoates.29,30 To our knowledge, this is the rst use of 1 for per-
O-acetylation and de-O-acetylation of carbohydrates, consider-
ably expanding the application scope of Zn cluster catalysis in
carbohydrate chemistry.
Table 1 Per-O-acetylation of carbohydrates using a tetranuclear Zn
cluster 1
In the seminal work of Ohshima and Mashima,29,30 tetranu-
clear Zn cluster was utilized as a robust multimetallic catalyst
that enables acylation of alcohols in the presence of amines.
The selective transesterication of hydroxyl groups in the
presence of primary and secondary amines might explain the
extremely high oxophilicity of this Zn catalysis. Despite this
high chemoselectivity in O-acylation reaction of the amino
alcohols and transesterication of amino acid ester derivatives,
the only monosaccharide tested30b has largely been limited to
acetylation of the C6 primary hydroxyl group. Therefore more
studies are needed to understand the substrate scope of this
catalysis. Furthermore, catalyst 1 might be susceptible to other
classes of (bio)molecules using different acylation reagents
such as acetic anhydride. To address this, we investigated
enhanced enzyme-like selectivity of 1 for O-acetylation and de-
O-acetylation of hydroxyl groups to structurally more diverse
polyhydroxylated compounds such as carbohydrates and also
amino acid derivatives.
Crude
Entry Substrate
1
Product
yielda (%) (a/b)
99
98
98
97
—
2
3
4
0.7/1
0.9/1
1/2.2
5
96
98
—
—
We were pleased to see that exposure of methyl-a-D-gluco-
pyranoside (2) to a near-stoichiometric amount of acetic anhy-
dride (1.1 mol eq. per OH group of sugar) in the presence of
tetranuclear Zn catalyst 1 (1.25 mol% per OH group of sugar)
6
ꢀ
and at 70 C for 12 h (indicated by the disappearance of 2 on
TLC) did indeed provide the fully acetylated methyl-a-D-gluco-
pyranoside (10)31 as essentially a single component, without any
observed effect on the interglycosidic linkage and with good
yield (Table 1, entry 1, 99% yield). The product could be isolated
with minimal handling and purications; removal of volatiles
under reduced pressure was followed by passing through
a short plug of silica to remove the catalyst with a purity of more
than 97%, as indicated by 1H NMR spectroscopy. Further
examination with a disaccharide, D-lactose (3), under identical
conditions as described above also revealed the desired product
in a yield of 98% (Table 1, entry 2). The excellent yields and
efficiencies exhibited by the catalyst 1 prompted us to select
these conditions for further exploration.
7b
99
99
0.6/1
1/0.9
8c
a
Yield of crude product with purity higher than 97% according to 1H
b
NMR spectroscopy. A mixture of D-galactopyranosyl pentaacetates
and D-galactofuranosyl pentaacetates with the ratio 1 : 1. A mixture
of
c
D-mannopyranosyl
pentaacetates
and
D-mannofuranosyl
pentaacetates with the ratio 10 : 1.
Next, the scope for O-acetylation of hydroxyl groups in other
saccharides was examined (Table 1). D-Glucose (4) and N-acetyl- analyses. However, per-O-acetylation of hexoses with “galac-
D-glucosamine (5) provided a comparable yield of correspond- tosyl” and “mannosyl” congurations produced a mixture of
ing acetylated product in 98% (entry 3) and 97% (entry 4), pyranosyl forms together with undesired D-galactofuranosyl
respectively. Moreover, acid labile groups such as iso- pentaacetates (pyranosyl/furanosyl ¼ 1/1, entry 7) and D-man-
propylidene survived the present conditions (entry 5). As nofuranosyl pentaacetates (pyranosyl/furanosyl ¼ 10/1, entry 8),
a representative example of a complex carbohydrate, N-ace- as inspected by the 1H NMR spectra of the crude products.33 In
tylneuraminic acid methylester (7), a polyfunctional ulosonic short, we demonstrate the application of tetranuclear Zn cata-
acid of ve hydroxyl groups with different reactivities, was lyst 1 in per-O-acetylation of saccharides.
acylated to 15 in which the hydroxyl at C-2 position remained
A diverse and representative scope of saccharides is well
unaffected (entry 6), in accord with previous reports.27 tolerated by this catalysis (Table 2) inclusive of anomeric azide
Compound 15 is a valuable precursor for the synthesis of sialyl (entry 1, 96%), and an 5N,4O-carbonyl-proteced thiosialoside
phosphite donors,32 our new procedure should provide a desir- (entry 3, 95%). However, in the case of partially benzylated
able alternative. In Table 1, per-O-acetylated saccharides lactoside (19) tethered with an alkyl azide at the reducing end,
(entries 2–4) are exclusively in the pyranosyl form as an resulted in the formation of desired product (28) in a modest
anomeric mixture, and the assignment of anomeric stereo- 40% yield (entry 2). The yield of 28 was diminished presumably
chemistry was determined based on 400 MHz 1H NMR spectral due to the competing formation of a mixture of regioisomeric
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Table 2 Tetranuclear Zn cluster 1 catalyzed O-acetylation of partially
protected carbohydrates and amino acid derivatives
excellent yields (33: 98%, 34: 93%, and 35: 95%; entries 7–9),
and more importantly, neither epimerization of the a-stereo-
center nor O-alkyl transesterication of carbamates was
noticed. In addition, the catalytic system is susceptible to acid-
sensitive groups such as benzyl and allyl ester, and Boc pro-
tecting group.
Entry Substrate
1
Product
Yielda (%)
96
Conversely, because of its efficiency and irreversible nature,
de-O-acetylation of acetates in carbohydrates still relies heavily
on classical basic or acidic hydrolysis, such as those that involve
1
NaOMe (Zemplen deacylation), K2CO3,34 N2H4,35 DBU,36 and
´
Brønsted acids like HCl.37 Recently, oxometallic species was
employed at elevated temperature to facilitate deacylation of
monosaccharides.38 Aqueous or pure alcohol is the preferred
solvent in such de-O-acetylation reactions, and almost pure
products could be obtained by a careful neutralization of the
catalysts, usually by exposing to acid/base or acidic/basic resins
followed by evaporation of the volatiles. These reaction proto-
cols are useful; however, exposure to acid or base may have
detrimental effects on substrates such as elimination and epi-
merization, and functional groups sensitive to acid or base may
not be fully compatible. Therefore, a milder and neutral cata-
lytic de-O-acetylation method which no longer requires such
neutralization steps is highly desirable. In view of the trans-
esterication of acetates using 1, we hypothesized that meth-
anolysis of saccharides catalyzed by Zn cluster 1 could be
performed, as 1 retained its catalytic activity even in the pres-
ence of excess amounts of alcohol.30
2
3
40b
95
4
5
6
92
97
94
An initial evaluation of the proposed catalytic de-O-acetyla-
tion was conducted with 27 in the presence of 1.25 mol% (per
OAc group of sugar) of 1, and transesterication was completed
within 12 h (indicated by the disappearance of 27 on TLC) under
reuxing methanol (0.6 M) (Table 3, entry 1). More importantly,
because methylacetate is the only co-product formed in this
7
8
98
93
1
process, pure (by H NMR) compound 18 could be obtained in
9
95
a 91% isolated yield (entry 1) simply by evaporation and ltra-
tion through a short-pad of silica gel. De-O-acetylation of other
important substrates under these conditions was then attemp-
ted and the results are shown in Table 3. The developed de-O-
acetylation protocol can be conducted very easily and safely; the
transesterication proceeded simply by heating the acetates in
commercial methanol in the presence of a catalytic amount of 1.
Thioglycosides (entries 2–5) with an N-Troc protection at C-2
(entries 2–3), and an N-benzyl-2,3-trans oxazolidinone (entry 4)
are capable of deacylation by this catalytic protocol with
consistently very good to excellent yields of products (89–98%).
Implementation of a selenophenyl galactoside 38 with an azido
group at C-2 (entry 6) proved sluggish (20 h) and needs 5 mol%
catalyst to give a reasonably good yield of 87%. Protected
serine–glucoside 39 can be similarly unmasked to triol 23 with
the transesterication of allyl ester in a yield of 74% (entry 7).
Removal of O-acetates in L-serine derivatives 33–35 readily
provided corresponding products almost quantitatively (entries
8–10). While deacetylation of L-serine derivatives caused
a transesterication of the benzyl (entry 8) and allyl ester
(entries 9–10), respectively, neither epimerization of a-stereo-
center nor O-alkyl transesterication of carbamates was
observed.
a
Yield of crude product with purity higher than 97% according to 1H
b
NMR spectroscopy. Yields aer 30 h under the loading of 5 mol% 1.
Partial O-acetylated derivative (32%) was also formed.
mono-O-acetylated derivative (32%). The addition of more than
1.25 mol% of 1 and a prolonged reaction time (30 h) did not
alter the outcome of the reaction. Amino sugars which occur
abundantly in natural oligosaccharides with varied substitu-
tions at C-2 and anomeric position are successful in acylation
reaction (entries 4–6). Extension of this protocol to N-tri-
chloroethoxycarbonyl (Troc) protected thioglycosides 21–22
furnished fully protected thioglycosides 30 (entry 4) and 31
(entry 5) in excellent yields (92–97%). Moreover, a serine-derived
glucoside (23) produced fully-protected serine glucoside 32 also
in a respectable yield of 94% (entry 6), demonstrating the
potential of Zn catalysis in glycoprotein synthesis. Finally, to
examine the mildness of the acylation conditions, we also
conducted O-acetylation of L-serine derivatives 24–25 (N-Fmoc)
and 26 (N-Boc). As before, O-acetylation again accomplished
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Table 3 Tetranuclear Zn cluster 1 catalyzed de-O-acetylation of Table 4 Methanolysis of carbohydrates using catalytic tetranuclear Zn
carbohydrates and amino acid derivatives in methanol
cluster 1
Yielda (%)
91
Entry
1
Substrate
Product
Yielda (%)
Entry
1
Substrate
Product
97
2
3
4
5
6
98
91
89
95
87b
2
3
98
95
4
96
5
6
98
96
7
74
7
99
99
8
9
99
99
8
a
Refers to isolated yield.
10
99
a
b
Refers to isolated yield. Aer 20 h. Reaction started with 2.5 mol%
(per OAc) of 1; aer 12 h, another 2.5 mol% of 1 was employed.
Conclusions
In summary, we have demonstrated that tetranuclear Zn cluster
Zn4(OCOCF3)6O$(CF3COOH)n is an extremely effective dual
purpose catalyst for per-O-acetylation and de-O-acetylation of
carbohydrates. This method required only a near stoichiometric
amount of acetic anhydride (1.1 mol equiv. per OH group of
sugar) for O-acetylation of saccharides. The de-O-acetylation
process can be performed very easily and safely; simply by
heating the acetates in commercial grade methanol in the
presence of catalytic amount of 1 (1.25 mol% per OH group of
sugar). Overall, employing the tetranuclear Zn cluster as catalyst
minimizes reagent use, workup, and purications. We antici-
pate that this method of protection/deprotection strategy to
prepare commonly used building blocks would nd applica-
tions in oligosaccharide synthesis.
We next examined the substrate generality of the Zn cluster-
catalyzed de-O-acetylation under reuxed methanol conditions
(Table 4). The reaction protocol is straightforward and is
susceptible to de-O-acetylation of a variety of saccharides. As
revealed in Table 4, selectively protected hexo-furanose (entries
1 and 4), galacto- (entries 2 and 7), gluco- (entries 3, 5, and 6)
and manno- (entry 8) pyranose derivatives can be efficiently
unmasked in good to nearly quantitative yields (95–99%).
Importantly, TBDMS, phthalimido (Phth), and acid sensitive
groups such as isopropylidene (entries 1–4), trityl (entry 6), and
benzylidene (entries 7–8) are tolerated in these reaction condi-
tions without loss in reaction efficiencies.
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1H, J ¼ 11.0 Hz), 4.84 (dd, 1H, J ¼ 10.2, 3.4 Hz), 4.75–4.69 (m,
3H), 4.58 (d, 1H, J ¼ 4.3 Hz), 4.56 (d, 1H, J ¼ 4.3 Hz), 4.49 (d, 1H,
J ¼ 7.9 Hz), 4.45 (d, 1H, J ¼ 12.2 Hz), 4.39 (d, 1H, J ¼ 12.2 Hz),
4.35 (d, 1H, J ¼ 7.9 Hz), 4.18 (d, 1H, J ¼ 12.2 Hz), 4.00–3.89 (m,
2H), 3.76 (dd, 1H, J ¼ 10.8, 3.8 Hz), 3.68 (d, 1H, J ¼ 10.2 Hz),
3.56–3.48 (m, 4H), 3.39 (t, 1H, J ¼ 8.4 Hz), 3.35–3.31 (m, 1H),
3.29–3.27 (m, 2H), 3.21 (t, 2H, J ¼ 7.0 Hz), 1.97 (s, 3H), 1.93 (s,
3H), 1.68–1.63 (m, 2H), 1.59–1.53 (m, 2H), 1.45–1.32 (m, 4H);
13C NMR (100 MHz, CDCl3) d 170.0, 169.9, 138.9, 138.6, 138.2,
137.9, 137.8, 128.3 (ꢁ2), 128.26 (ꢁ2), 128.2 (ꢁ2), 128.16 (ꢁ2),
127.93 (ꢁ2), 127.90 (ꢁ2), 127.8 (ꢁ2), 127.76 (ꢁ2), 127.7 (ꢁ4),
127.6, 127.5, 127.4 (ꢁ2), 127.2, 103.5, 102.3, 82.6, 81.6, 76.4,
75.2, 74.8 (ꢁ2), 73.1 (ꢁ2), 72.8, 71.4, 69.6, 67.9, 67.8, 66.7, 51.2
(ꢁ2), 50.6, 29.5, 28.7, 26.4, 25.6, 20.6, 20.5; HRMS (ESI) m/z calcd
for C57H67N3NaO13 [M + Na]+ 1024.4572, found 1024.4567.
Experimental section
General methods
The catalyst, tetranuclear Zn cluster triuoroacetic acid adduct
Zn4(OCOCF3)6O$(CF3COOH)n (1) (Strem Chemicals Inc., USA.,
Cat. no. 30-4050) was obtained from commercial source and
used as receiveꢀd. All reactions were performed in oven-dried
glassware (120 C) under a nitrogen atmosphere unless other-
wise specied. All solvents were dried and distilled by standard
techniques. 1H and 13C NMR spectra were recorded on a Bruker
AV-400 spectrometer operating at 400 MHz for 1H and 100 MHz
for 13C, respectively. Chemical shis (d) are reported in ppm
and referenced to the solvent used (CDCl3, d 7.24 and 77.23;
CD3OD, d 3.31 and 49.0), with coupling constants (J) reported in
Hz. High-resolution mass spectra were recorded using electro-
spray ionization mode with a time-of-ight detector. Thin-layer
chromatography (TLC) analysis was monitored with 0.25 mm
pre-coated plates (G60F254) and detected by UV absorption at
254 nm or by staining with p-anisaldehyde–sulfuric acid at
150 ꢀC. Silica gel 60 (E. Merck) was employed for all ash-
chromatography separations.
1
Fmoc–Ser(OAc)–OAll (34). H NMR (400 MHz, CDCl3) d 7.75
(d, 2H, J ¼ 7.2 Hz), d 7.59 (d, 2H, J ¼ 7.2 Hz), d 7.39 (t, 2H, J ¼ 7.6
Hz), d 7.30 (t, 2H, J ¼ 7.6 Hz), d 5.94–5.84 (m, 1H), d 5.60 (d, 1H, J
¼ 7.6 Hz), d 5.33 (d, 1H, J ¼ 17.2 Hz), d 5.25 (dd, 1H, J ¼ 10.4, 1.2
Hz), 4.67–4.63 (3H, m), 4.49 (dd, 1H, J ¼ 11.2, 4 Hz), 4.41 (d, 2H,
J ¼ 6.9 Hz), 4.37 (dd, 1H, J ¼ 5.6, 3.4 Hz), 4.22 (t, 1H, J ¼ 6.9 Hz),
2.05 (s, 3H); 13C NMR (100 MHz, CDCl3) d 170.4, 169.2, 155.7,
143.8, 143.7, 141.3, 131.2, 127.7 (ꢁ2), 127.1 (ꢁ2), 125.0, 120.0,
119.1, 67.3, 66.5, 64.0, 53.4, 47.1; HRMS (ESI) m/z calcd for
General procedure for per-O-acetylation
A sealed tube was charged with sugar (0.51 mmol), acetic
anhydride (1.1 eq. per OH), catalyst 1 (1.25 mol% per OH), and
toluene (0.9 mL). The ask was heated at 70 ꢀC for 12 h under an
atmosphere of nitrogen. The volatiles were removed under
reduced pressure, and the reaction mixture was passed through
a short plug of silica gel to afford expected products in good to
excellent yields (Tables 1 and 2).
C
23H23NO6Na [M + Na]+ 432.1423, found 432.1414.
Boc–Ser(OAc)–OAll (35). H NMR (400 MHz, CDCl3) d 5.93–
1
5.83 (m, 1H), 5.31 (d, 1H, J ¼ 17.6 Hz), 5.25 (d, 1H, J ¼ 10.4 Hz),
4.68–4.61 (m, 2H), 4.58–4.56 (m, 2H), 4.45 (dd, 1H, J ¼ 11.2, 3.6
Hz), 4.31 (dd, 1H, J ¼ 11.2, 3.6 Hz), 2.03 (s, 3H), 1.43 (s, 9H); 13
C
NMR (100 MHz, CDCl3) d 170.4, 169.5, 155.1, 131.3, 118.9, 80.2,
66.2, 64.2, 52.9, 28.2 (ꢁ3), 20.6; HRMS (ESI) m/z calcd for
C
13H21NO6Na [M + Na]+ 310.1267, found 310.1273.
General procedure for de-O-acetylation
A mixture of 1 (1.25 mol% per OAc of sugar) and appropriate
substrates (Tables 2 andꢀ3) (0.51 mmol) in methanol (1.6 mL)
was heated at reux (70 C, bath temperature) for 12 h under
nitrogen. Aer removing volatiles under reduced pressure, the
crude product was passed through a short plug of silica gel to
provide desired products in moderate to excellent yields (Tables
3 and 4).
Acknowledgements
We thank the National Tsing Hua University, Ministry of
Education, and the Ministry of Science and Technology, Taiwan
for nancial support of this work.
N-(Fluorenylmethoxycarbonyl)-N-(2,2,2-trichloroethoxy-
carbonyl-2-amino-2-deoxy)-b-D-glucopyranosyl-L-serine methyl
ester (23). 1H NMR (400 MHz, CD3OD) d 7.80 (d, 2H, J ¼ 7.4 Hz),
7.69 (dd, 2H, J ¼ 7.4, 3.9 Hz), 7.40 (t, 2H, J ¼ 7.4 Hz), 7.33 (t dd,
2H, J ¼ 7.4, 2.4, 1.2 Hz), 4.8–4.7 (m, 2H), 4.56 (s, 1H), 4.5–4.4 (m,
3H), 4.27–4.21 (m, 2H), 4.19 (dd, 1H, J ¼ 10.8, 5.3 Hz), 3.90–3.85
(m, 2H), 3.74 (s, 3H), 3.68 (dd, 2H, J ¼ 11.9, 5.5 Hz), 3.49–3.44
(m, 1H), 3.40–3.34 (m, 1H), 3.28–3.25 (m, 1H); 13C NMR (100
MHz, CD3OD) d 172.3, 158.4, 157.2, 145.2, 145.1, 142.5 (ꢁ2),
128.8 (ꢁ2), 128.3 (ꢁ2), 126.4, 126.3, 121.0 (ꢁ2), 102.9, 97.0, 78.0,
75.7, 75.5, 72.0, 69.8, 68.3, 62.7, 59.0, 55.8, 53.1, 48.3; HRMS
(ESI) m/z calcd for C28H30N2O11Cl3 [M ꢂ H]ꢂ 675.0915, found
675.0923.
Notes and references
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Organic Synthesis, Wiley, New York, 4th edn, 2006; (b)
P. J. Kocienski, Protecting Groups, Thieme, New York, 1994.
2 J. K. Baskin, Chem. Rev., 2000, 100, 4265–4266.
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Res. Dev., 2005, 9, 253–258; (b) J. S. Carey, D. Laffan,
C. Thomsom and M. T. Williams, Org. Biomol. Chem., 2006,
4, 2337–2347.
4 B. Yu, J. Xie, S. Deng and Y. J. Hui, J. Am. Chem. Soc., 1999,
121, 12196–12197.
¨
¨
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