Gold-catalyzed synthesis of α-D-glucosides using an o-ethynylphenyl β-D-1-thioglucoside donor

Article abstract of DOI:10.1016/j.carres.2018.10.010

A gold-catalyzed glucosylation method using an o-ethynylphenyl β-D-1-thioglucoside as donor is described. The reaction proceeds in a mostly S_N2 pathway. A series of α-D-glucosides are obtained in good yields and with up to 19:1 α-selectivity.

Full text of DOI:10.1016/j.carres.2018.10.010

Accepted Manuscript
Gold-catalyzed synthesis of 1,2-cis glucosides using an o-ethynylphenyl thioglucoside
donor
Zhitong Zheng, Liming Zhang
PII:
S0008-6215(18)30580-9
https://doi.org/10.1016/j.carres.2018.10.010
CAR 7620
DOI:
Reference:
To appear in: Carbohydrate Research
Received Date: 7 October 2018
Revised Date: 25 October 2018
Accepted Date: 25 October 2018
Please cite this article as: Z. Zheng, L. Zhang, Gold-catalyzed synthesis of 1,2-cis glucosides using
an o-ethynylphenyl thioglucoside donor, Carbohydrate Research (2018), doi: https://doi.org/10.1016/
j.carres.2018.10.010.
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ACCEPTED MANUSCRIPT

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Gold-Catalyzed Synthesis of 1,2-cis Glucosides Using an o-
Ethynylphenyl Thioglucoside Donor
Zhitong Zhenga, and Liming Zhanga,*
aDepartment of Chemistry and Biochemistry, University of California, Santa Barbara
Santa Barbara, CA 93117, United States
Keywords:
Glycosylation; 1,2-cis glucosidic bond; o-ethynylphenyl thioglucoside; gold catalysis; SN2
pathway
Abstract:
A glucosylation method featuring gold catalysis-activated o-ethynylphenyl thioglucosides as
donors is described. With donor design and condition optimization, the reaction proceeds in a
mostly SN2 pathway. A series of 1,2-cis glucosides are obtained in good yields and with up to
19:1 α-selectivity.
1. Introduction
Stereoselective construction of 1,2-cis glycosidic bonds remains challenging despite recent
advances.[1, 2] Glycosylation reactions often involve oxocarbenium intermediates, which
frequently result in the formation of anomeric mixtures of low to moderate selectivities (Scheme
1a). Previous achievements in selective construction of 1,2-cis glycosidic bond entail employing
donor directing groups,[3-9] harnessing different reactivities of equilibrating donor anomers,[10-
12] or exploiting conformational preferences of the reactive intermediates to minimize the
formation of undesirable anomers (Scheme 1b).[13-16] Notwithstanding, these methods still rely
on specific structural features of the donor molecule and, therefore, often fall short in generality.
An arguably more general approach to stereoselective glycosylation and in particular to the
formation of 1,2-cis glycosides is to engineer a SN2-type process solely based on the leaving
* Corresponding author. Tel.: +1 805-893-7392. Email: zhang@chem.ucsb.edu.

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group and regardless of the remaining donor structure. As such, the stereochemistry of the newly
formed glycosidic bond would in theory only depend on the anomeric configuration of a donor
molecule (Scheme 1a).[2] SN2 or “SN2-like” reactions has been realized between
deprotonated/anionic acceptors and glycosyl halide[17, 18] or sulfonate[19-25] donors and via a
macrocyclic bisthiourea-catalyzed cooperative activation strategy,[26] but much advance in this
area is still desired. We attempted to develop activation strategies to generate anomeric leaving
groups that would permit SN2-type glycosylations. Herein, we report our preliminary results on a
gold-catalyzed synthesis of 1,2-glucosides using o-ethynylphenyl thioglucodis donors.
Scheme 1. Glycosylation reactions and selected approaches to forming 1,2-cis glycosidic bonds.
Gold catalysis has been increasingly applied in glycoside synthesis for the past decade.[27-37] In
2012, Yu et al reported the use of o-alkynylphenyl thioglycoside as donor in a gold(I)-catalyzed
glycosylation reaction. In this chemistry, the cationic and acidic Au(I) complex promotes the
cyclization of the sulfur atom to the C-C triple bond, which results in the formation of a
benzothiophenium intermediate. This reactive species is then susceptible to nucleophilic attack
by acceptors (Scheme 2a).[38] However, the reaction suffers from low stereoselectivity and
moderate yields due to side reactions and mostly proceeds through an oxocarbenium
intermediate. We reasoned that modifying this system might render this type of activation

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suitable for SN2-type glycosylation and hence could circumvent those drawbacks (Scheme 2b).
Firstly, we proposed to replace the donor benzyl protecting groups with more electron-
withdrawing 4-chlorobenzyl groups (PCB),[39] aiming to inductively discourage the formation
of oxocarbenium intermediate B. Secondly, we would employ (2-ethynylphenyl)thio group,
which differs from Yu’s version by the absence of alkyne terminus substituent, as the latent
leaving group to 1) decrease the steric hindrance around the sulfur in the activated donor A,
which should discourage the expulsion of the benzothiophene, and 2) ensure a faster gold-
catalyzed cyclization reaction. Finally, we reasoned that a less acidic IPrAu+ catalyst would
further stabilize the sulfonium intermediate A and favor the SN2 pathway.
Scheme 2. Redesigning o-Alkynylphenyl thioglycoside donors.
2. Results and Discussion
Based on this design, we synthesized anomerically pure o-ethynylphenyl thioglucosides 1 and 2
and performed a series of initial studies with n-hexanol as the acceptor (Table 1). To our delight,
glycoconjugate 3a’ was obtained in an encouraging α/β ratio of 7:1 when the substrate 1 bearing
benzyl protecting groups was employed as donor. Lowering the reaction temperature to -20 °C
improved the ratio to 13:1. Eventually, the donor 2 bearing 4-chlorobenzyl groups gave an
excellent 19:1 ratio at -20 °C, confirming the value of employing inductive destabilization of the
oxocarbenium intermediate to improve the reaction’s SN2 charateristics. Later, we were glad to
find that lowering the catalyst loading to 5% does not change the reaction outcome. Following
-
these encouraging results, a quick screening of counterion indicated that NTf2 gave the best

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result. Notably, little selectivity was observed with OTf- (Table 1, entry 5), which is in
accordance with the previously reported counterion effect of OTf-.[40, 41]
Table 1. Reaction condition optimization
PGO
PGO
PGO
PGO
PGO
IPrAuCl, 5Å MS
O
O
nC6H13OH
(3 equiv.)
S
+
PGO
DCM, temperature
PGO
PGO
OnC6H13
PG = Bn
1
PG = Bn
3a'
PCB 3a
PCB 2
IPrAuCl
loading
Halide
Yield and
Entry Donor
abstractor
(5 mol %)
AgNTf2
Temperature
b
Selectivity (
α/β)
10 mol%
10 mol%
10 mol%
5 mol%
5 mol%
5 mol%
5 mol%
1
2
3
4
5
6
7
rt
60%, 7/1
1
1
2
2
2
2
2
AgNTf2
AgNTf2
AgNTf2
AgOTf
-20 °C
-20 °C
-20 °C
-20 °C
-20 °C
-20 °C
66%, 13/1
83%. 19/1
84%, 19/1
80%, 0.8/1
90%, 15/1
65%, 16/1
AgSbF6
NaBARF
Concentration: 0.05M. Reaction was stirred in a cooling bath for 6 hours before being quenched by nBu4NCl.
a
b
Combined yield and anomeric ratio determined by NMR with internal references.
With optimal conditions in hand, we investigated the scope of this gold-catalyzed glucosylation
reaction. Like n-hexanol, benzyl alcohol was converted to the corresponding benzyl glucoside 3b
in excellent yield and selectivity. When secondary and tertiary alcohols were used, a slight drop
in yield and selectivity was observed (Table 2, 3c, 3d, and 3e), most likely due to the increased
steric hindrance that hampers the SN2 attack. A moderate 66% yield and 10:1 selectivity was
obtained with benzoic acid as nucleophile (Table 2, 3f). Cholesterol was also successfully
converted to the corresponding glycoconjugate 3g in moderate yield and a 5:1 α/β selectivity.
Finally, the galactose-derived acceptor with a free 6-OH group reacted smoothly under the
optimal conditions, yielding the disaccharides 3h in 68% yield and a decent anomeric selectivity.
Table 2. Scope study of the glycosylation method
Product
R group
Bn
Yield Selectivity (
80% 19/1
α/β)
3b

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72%
74%
15/1
16/1
3c
3d
tBu
Bz
73%
66%
15/1
10/1
3e
3f
63%
68%
5/1
3g
3h
12/1
a Reactions were stirred in cooling bath for 10 hours. All yields are combined isolated yield. Anomeric ratio
was determined by NMR.
The scope studies reveal that the nucleophilicity and the steric hindrance of an acceptor, as
expected, affect the reaction outcome. As a general trend, a less nucleophilic and sterically more
hindered acceptor tends to give a lower yield and a poorer selectivity. We hypothesized that as
the reaction proceeds, the benzothiophene byproduct accumulated in the reaction mixture may in
turn react with the activated donor A, resulting in racemization of the donor (Scheme 3a).
Additionally, the benzothiophene may coordinate to the cationic gold(I) catalyst and therefore
slow the reaction, as corroborated by the reaction shown in Scheme 3b. Additionally, the side
product D generated from a formal [1,3] shift[38] of the intermediate A could be detected in
almost all cases (Scheme 3c), which accounts for the moderate yields in some of the challenging
cases.

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Scheme 3. Involvement of benzothiophene byproduct in the reaction
3. Conclusions
In summary, we have developed an improved gold catalysis for the construction of 1,2-cis
glucosidic bonds using o-ethynylphenyl thioglucoside donors. The method improves upon the
previously reported approach and realizes largely SN2 glucosylation. Good to excellent level of
α-seletivities can be realized. The employment of 4-chlorobenzyl group instead of the typical
benzyl group as sugar OH protecting group permits enhanced levels of SN2 due to inductive
destabilization of the SN1 oxocarbenium intermediate.
4. Acknowledgements
This work was supported by the NIH Glycoscience Common Fund program (1U01GM125289).
The research reported here made use of a 400 MHz NMR instrument funded by NIH
S10OD012077 and the shared facilities of the UCSB MRSEC (NSF DMR 1720256).
5. Experimental
General

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Ethyl acetate (ACS grade), hexanes (ACS grade), dichloromethane (ACS grade) were purchased
from Fisher Scientific and used without further purification. ACS grade 1,2-dichloroethane were
purchased from Acros Organics and used directly. Commercially available reagents were used
without further purification. Reactions were monitored by thin layer chromatography (TLC)
using Silicycle precoated silica gel plates. Flash column chromatography was performed over
Silicycle silica gel (230-400 mesh). 1H NMR and 13C NMR spectra were recorded on a Varian
400 MHz spectrometer, a Varian 500 MHz Unity plus spectrometer, and a Varian 600 MHz
Unity plus spectrometer, using residue solvent peaks as internal standards (CDCl3, 1H: 7.26 ppm;
13C: 77.00 ppm). Infrared spectra were recorded with a Perkin Elmer FT-IR spectrum 2000
spectrometer and are reported in reciprocal centimeter (cm-1). Mass spectra were recorded with
Waters (Micromass) LCT premier #1, using electrospray method and TOF detector.
Preparation of 2,3,4,6-tetra-O-(4-chlorobenzyl)-D-glucopyranose (SI-1)
To a cooled (0 °C) mixture of 1-methyl-D-glucopyranose (1.94 g, 10 mmol), TBAI (369 mg, 1
mmol), and DMF (25 mL) was added NaH (60% in mineral oil, 2 g, 5 equiv.). The mixture was
then stirred vigorously for 20 min, and 4-chlorobenzyl chloride (8 g, 5 equiv.) was added in
small portions. The reaction was warmed up to room temperature gradually, heated at 60 °C for
12 hours, and quenched by careful addition of saturated NH4Cl solution at 0 °C. The crude
product was extracted by DCM, washed with water and brine, and concentrated under vacuum.

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To the crude product of the first step was added HOAc (50 mL) and HCl (6M, 10 mL), and the
mixture was stirred at 100 °C until TLC showed complete transformation of the starting material.
The reaction was concentrated under vacuum, dissolved by DCM, washed with saturated
NaHCO3, and dried with MgSO4. Upon removal of DCM under vacuum, the crude product was
purified by silica gel column chromatography to give the product as a colorless oil (4.1 g, 61%,
mixture of both anomers). 1H NMR (400 MHz, CDCl3) δ 7.35 – 6.96 (m, 16H), 5.24 (d, J = 3.5
Hz, 0.7H, α-anomer), 4.93 – 4.36 (m, 8.3H), 4.01 (ddd, J = 10.1, 4.1, 2.1 Hz, 0.7H, α-anomer),
3.92 (t, J = 9.3 Hz, 0.7H, α-anomer), 3.68 – 3.46 (m, 4.3H), 3.34 (dd, J = 9.0, 7.7 Hz, 0.3H, β-
anomer). 13C NMR (126 MHz, CDCl3) δ 136.99, 136.81, 136.69, 136.49, 136.16, 133.88, 133.69,
133.63, 133.54, 133.44, 129.34, 129.26, 129.23, 128.93, 128.92, 128.84, 128.81, 128.70, 128.64,
128.59, 128.55, 128.54, 97.52, 91.07, 84.31, 82.91, 81.49, 80.03, 77.68, 74.71, 74.68, 74.54,
74.04, 73.75, 72.74, 72.69, 72.33, 70.17, 68.84, 68.58. HRMS (ESI+, C34H32Cl4O6Na):
calculated 699.0851, 701.0827, 703.0806, found 699.0848, 701.0836, 703.0839.
Preparation of Glucopyranosyl Chlorides (SI-2 and SI-3)
5 mmol of corresponding D-glucopyranose and 10 mmol of oxalyl chloride was mixed in DCM
(20 mL) at room temperature, and 3 drops of DMF was added into the solution. Gas evolution
was ovserved immediately, and the reaction was stirred at room temperature for 2 hours. The
reaction was then concentrated under vacuum and purified with silica gel column
chromatography to give the corresponding glucopyranosyl chlorides as colorless oil.
2,3,4,6-tetra-O-benzyl-D-glucopyranosyl chloride (SI-2)

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Prepared in 70% yield from 2,3,4,6-tetra-O-benzyl-D-glucopyranose. Its NMR data is in
accordance with those reported by Takeo et al.[32]
2,3,4,6-tetra-O-(4-chlorobenzyl)-D-glucopyranosyl chloride (SI-3)
Prepared in 59% yield from SI-1. 1H NMR (500 MHz, CDCl3) δ 7.33 – 7.03 (m, 14H), 6.12 (d, J
= 3.7 Hz, 1H), 4.88 (d, J = 11.3 Hz, 1H), 4.74 (dd, J = 11.3, 4.5 Hz, 2H), 4.70 – 4.59 (m, 2H),
4.55 (d, J = 12.2 Hz, 1H), 4.46 (d, J = 11.3 Hz, 1H), 4.42 (d, J = 12.3 Hz, 1H), 4.11 – 4.04 (m,
1H), 3.99 (t, J = 9.2 Hz, 1H), 3.76 – 3.61 (m, 4H). 13C NMR (126 MHz, CDCl3) δ 136.83,
136.35, 136.08, 135.79, 134.00, 133.71, 133.63, 133.54, 129.28, 129.27, 129.23, 129.22, 129.03,
128.84, 128.77, 128.64, 128.60, 128.60, 93.02, 81.16, 79.90, 76.33, 74.83, 74.23, 73.28, 72.71,
71.98, 67.76. . HRMS (ESI+, C34H31Cl5O5Na): calculated 717.0512, 719.0487, 721.0464,
found 717.0659, 719.0513, 721.0464.
Preparation of Glycosyl Donors (1 and 2)

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2-Bromo-1-(trimethylsilylethynyl)benzene was synthesized quantitatively according to method
reported by Ohno group.[35] A solution of 2-bromo-1-(trimethylsilylethynyl)benzene (860 mg,
3.4 mmol) in THF (10 mL) was cooled to -78 °C, and tBuLi (1.7 M in hexanes, 4 mL, 6.8 mmol)
was added dropwise. The solution was stirred at -78 °C for another 30 minutes, and sulfur (109
mg, 3.4 mmol) was added in one portion at -78 °C. The reaction was then kept at 0 °C for 1 hour
and cooled down again to -78 °C before a solution of corresponding glucopyranosyl chloride
(SI-2 or SI-3, 2.5 mmol) in THF (5 mL) was added in one portion. The reaction was then
warmed up to room temperature and stirred for 10 hours or until complete consumption of the
glucopyranosyl chloride. The mixture was quenched by water, concentrated under vacuum,
dissolved in a mixture of methanol and DCM (1:1, 10 mL in total), added K2CO3 (200 mg), and
stirred for 2 hours. Upon completion, the mixture was partitioned in DCM and water, extracted
by additional DCM, dried with MgSO4, and concentrated under vacuum. Column
chromatography with silica gel gave the desired product 1 and 2.
1
Prepared in 72% overall yield from SI-2. 1H NMR (400 MHz, CDCl3) δ 7.76 – 7.66 (m, 1H),
7.54 – 7.48 (m, 1H), 7.48 – 7.42 (m, 2H), 7.40 – 7.28 (m, 16H), 7.27 – 7.21 (m, 2H), 7.20 – 7.14
(m, 2H), 5.03 – 4.93 (m, 2H), 4.92 – 4.81 (m, 3H), 4.80 – 4.73 (m, 1H), 4.67 – 4.52 (m, 3H),
3.88 – 3.56 (m, 6H), 3.40 (s, 1H). 13C NMR (101 MHz, CDCl3) δ 138.36, 138.20, 138.11, 137.95,
137.84, 133.26, 129.71, 129.44, 128.59, 128.48, 128.46, 128.34, 127.96, 127.91, 127.86, 127.82,
127.75, 127.68, 127.57, 126.26, 122.61, 86.69, 86.30, 83.34, 83.31, 81.37, 80.97, 79.10, 77.75,

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75.89, 75.64, 75.10, 73.42, 69.02. HRMS (ESI+, C42H40O5SNa): calculated 679.2494, 680.2527,
found 679.2479, 680.2546.
2
Prepared in 60% overall yield from SI-3. 1H NMR (500 MHz, CDCl3) δ 7.64 – 7.59 (m, 1H),
7.52 – 7.47 (m, 1H), 7.30 – 7.21 (m, 12H), 7.21 – 7.17 (m, 2H), 7.15 (d, J = 8.3 Hz, 2H), 7.07 (d,
J = 8.4 Hz, 2H), 4.91 (d, J = 10.4 Hz, 1H), 4.84 – 4.68 (m, 4H), 4.62 (d, J = 10.4 Hz, 1H), 4.57 –
4.51 (m, 2H), 4.46 (d, J = 12.1 Hz, 1H), 3.73 (dd, J = 10.9, 1.9 Hz, 1H), 3.69 – 3.48 (m, 5H),
3.36 (s, 1H). 13C NMR (126 MHz, CDCl3) δ 137.70, 136.71, 136.56, 136.34, 136.22, 133.72,
133.66, 133.53, 133.45, 133.41, 129.71, 129.38, 128.97, 128.96, 128.92, 128.75, 128.61, 128.60,
128.56, 128.51, 128.49, 126.51, 122.84, 86.51, 86.28, 83.36, 81.30, 80.94, 79.01, 77.68, 74.82,
74.67, 74.09, 72.67, 68.86. HRMS (ESI+, C42H36Cl4O5SNa): calculated 815.0935, 817.0914,
819.0894, found 815.0918, 817.0886, 819.0870.
General Procedure for Glycosylation Reaction

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To a vial equipped with screw cap (with septum) was added corresponding glycosyl acceptor (3
equiv.), IPrAuCl (5 mol %), additive (5 mol %), 5Å molecular sieve (10 mg per 0.5 mmol donor),
and dry DCM (0.5 mL per 0.5 mmol donor). The mixture was stirred at room temperature for 15
minutes and was cooled down to -20 °C before a cold solution of glycosyl donor in DCM (0.5
mL per 0.5 mmol donor) was added with syringe. The reaction was stirred at -20 °C until
completion. The reaction mixture was then concentrated under vacuum and purified by silica gel
column chromatography. Anomeric ratio was determined by 1H NMR.
3a
Prepared in 84% yield. α-anomer: 1H NMR (500 MHz, CDCl3) δ 7.29 – 7.21 (m, 12H), 7.19 (d, J
= 8.4 Hz, 2H), 7.01 (d, J = 8.3 Hz, 2H), 4.88 (d, J = 11.3 Hz, 1H), 4.78 (d, J = 3.6 Hz, 1H), 4.73
– 4.53 (m, 5H), 4.44 – 4.37 (m, 2H), 3.92 (t, J = 9.2 Hz, 1H), 3.74 (ddd, J = 10.0, 3.6, 2.0 Hz,
1H), 3.70 – 3.53 (m, 4H), 3.49 (dd, J = 9.6, 3.6 Hz, 1H), 3.41 (dt, J = 9.8, 6.7 Hz, 1H), 1.66 –
1.58 (m, 2H), 1.39 – 1.22 (m, 6H), 0.89 (t, J = 6.7 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ
137.26, 136.67, 136.61, 136.34, 133.67, 133.55, 133.49, 133.32, 129.18, 129.14, 128.91, 128.82,
128.58, 128.54, 128.53, 128.50, 96.61, 81.90, 80.19, 77.71, 74.64, 74.06, 72.68, 72.09, 70.01,
68.51, 68.33, 31.61, 29.35, 25.82, 22.59, 14.04. HRMS (ESI+, C40H44Cl4O6Na): calculated
783.1790, 785.1768, 787.1749, found 783.1800, 785.1765, 787.1760. β-anomer: 1H NMR (400
MHz, CDCl3) δ 7.31 – 7.20 (m, 12H), 7.13 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.4 Hz, 2H), 4.89 (d,
J = 11.4 Hz, 1H), 4.81 (d, J = 11.4 Hz, 1H), 4.72 – 4.55 (m, 4H), 4.51 – 4.42 (m, 2H), 4.35 (d, J
= 7.8 Hz, 1H), 3.93 (dt, J = 9.5, 6.5 Hz, 1H), 3.73 – 3.60 (m, 2H), 3.60 – 3.46 (m, 3H), 3.45 –
3.33 (m, 2H), 1.72 – 1.56 (m, 2H), 1.45 – 1.18 (m, 6H), 0.91 – 0.84 (m, 3H). 13C NMR (126
MHz, CDCl3) δ 136.96, 136.91, 136.57, 136.49, 133.56, 133.45, 133.37, 129.31, 129.03, 128.92,
128.84, 128.54, 128.52, 128.50, 128.49, 103.58, 84.48, 82.02, 77.84, 74.70, 74.63, 74.02, 73.74,

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72.69, 70.18, 68.84, 31.61, 29.72, 25.83, 22.59, 14.02. HRMS (ESI+, C40H44Cl4O6Na):
calculated 783.1790, 785.1768, 787.1749, found 783.1815, 785.1765, 787.1738.
3b
Prepared in 83% yield. 1H NMR (500 MHz, CDCl3) δ 7.43 – 7.31 (m, 5H), 7.30 – 7.18 (m, 12H),
7.15 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.2 Hz, 2H), 4.93 – 4.84 (m, 2H), 4.71 (dd, J = 11.6, 3.0 Hz,
3H), 4.61 – 4.52 (m, 3H), 4.48 (d, J = 12.1 Hz, 1H), 4.44 – 4.38 (m, 2H), 3.98 (t, J = 9.3 Hz, 1H),
3.79 (ddd, J = 10.0, 3.5, 2.0 Hz, 1H), 3.66 (dd, J = 10.6, 3.5 Hz, 1H), 3.61 – 3.53 (m, 2H), 3.50
(dd, J = 9.6, 3.6 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 137.15, 136.88, 136.53, 136.41, 136.25,
133.57, 133.55, 133.46, 133.33, 129.17, 129.13, 128.94, 128.80, 128.54, 128.52, 128.44, 128.41,
128.00, 95.19, 81.90, 79.84, 77.54, 74.71, 74.07, 72.65, 72.01, 70.23, 69.12, 68.25. HRMS (ESI+,
C41H38Cl4O6Na): calculated 789.1320, 791.1299, 793.1281, found 789.1318, 791.1260, 793.1290.
3c
iPr
O
O
O
O
Cl
Cl
O
O
Cl
Cl
Prepared in 72% yield. 1H NMR (500 MHz, CDCl3) δ 7.29 – 7.20 (m, 12H), 7.16 (d, J = 8.2 Hz,
2H), 7.01 (d, J = 8.4 Hz, 2H), 5.02 (d, J = 3.6 Hz, 1H), 4.86 (d, J = 11.4 Hz, 1H), 4.73 – 4.68 (m,

ACCEPTED MANUSCRIPT
2H), 4.65 – 4.56 (m, 3H), 4.39 (dd, J = 11.7, 7.7 Hz, 2H), 3.99 – 3.90 (m, 2H), 3.70 (dd, J = 10.5,
3.7 Hz, 1H), 3.61 – 3.52 (m, 2H), 3.48 (dd, J = 9.7, 3.5 Hz, 1H), 3.33 (td, J = 10.6, 4.3 Hz, 1H),
2.36 (pd, J = 6.9, 2.4 Hz, 1H), 2.16 – 2.08 (m, 1H), 1.66 – 1.58 (m, 2H), 1.41 – 1.22 (m, 3H),
1.08 – 0.90 (m, 2H), 0.85 (t, J = 6.4 Hz, 6H), 0.69 (d, J = 6.9 Hz, 3H). 13C NMR (126 MHz,
CDCl3) δ 137.21, 136.68, 136.64, 136.41, 133.52, 133.47, 133.35, 133.30, 129.15, 128.91,
128.80, 128.72, 128.52, 128.48, 128.44, 98.44, 81.72, 81.49, 80.61, 78.01, 75.27, 74.50, 74.05,
72.67, 72.19, 70.21, 68.64, 48.71, 43.04, 34.22, 31.70, 24.68, 22.98, 22.28, 21.07, 16.09. HRMS
(ESI+, C44H50Cl4O6Na): calculated 837.2259, 839.2239, 841.2222, found 837.2247, 839.2239,
841.2240.
3d
Prepared in 76% yield. 1H NMR (500 MHz, cdcl3) δ 7.30 – 7.21 (m, 12H), 7.18 (d, J = 8.4 Hz,
2H), 7.02 (d, J = 8.4 Hz, 2H), 4.94 (d, J = 3.6 Hz, 1H), 4.87 (d, J = 11.4 Hz, 1H), 4.71 (dd, J =
11.3, 1.8 Hz, 2H), 4.66 – 4.53 (m, 3H), 4.40 (d, J = 11.9 Hz, 2H), 3.94 (t, J = 9.3 Hz, 1H), 3.85
(ddd, J = 10.1, 3.6, 2.0 Hz, 1H), 3.80 (ddd, J = 10.0, 3.6, 1.8 Hz, 1H), 3.71 (dd, J = 10.5, 3.5 Hz,
1H), 3.62 – 3.54 (m, 2H), 3.49 (dd, J = 9.6, 3.6 Hz, 1H), 2.18 (dddd, J = 13.3, 9.9, 4.8, 3.2 Hz,
1H), 2.09 (ddd, J = 15.1, 10.0, 4.4 Hz, 1H), 1.71 (td, J = 11.2, 10.4, 6.1 Hz, 1H), 1.62 (t, J = 4.5
Hz, 1H), 1.27 – 1.20 (m, 3H), 1.11 (dd, J = 13.4, 3.4 Hz, 1H), 0.89 (s, 3H), 0.85 (s, 6H). 13C
NMR (126 MHz, CDCl3) δ 137.30, 136.74, 136.56, 136.41, 133.57, 133.52, 133.44, 133.28,
129.14, 129.00, 128.92, 128.91, 128.57, 128.53, 128.51, 128.49, 98.38, 85.68, 81.79, 80.51,
77.84, 74.55, 74.21, 72.67, 71.70, 70.45, 68.55, 49.64, 47.42, 45.08, 36.92, 28.32, 26.73, 19.69,
18.80, 13.92. HRMS (ESI+, C44H48Cl4O6Na): calculated 835.2103, 837.2082, 839.2065, found
835.2119, 837.2073, 839.2104.

ACCEPTED MANUSCRIPT
3e
Prepared in 73% yield. 1H NMR (500 MHz, CDCl3) δ 7.30 – 7.21 (m, 12H), 7.18 (d, J = 8.3 Hz,
2H), 7.01 (d, J = 8.3 Hz, 2H), 5.15 (d, J = 3.6 Hz, 1H), 4.87 (d, J = 11.4 Hz, 1H), 4.70 (dd, J =
11.3, 2.2 Hz, 2H), 4.64 – 4.57 (m, 3H), 4.39 (dd, J = 11.6, 5.2 Hz, 2H), 3.96 – 3.90 (m, 2H), 3.70
(dd, J = 10.5, 3.4 Hz, 1H), 3.62 – 3.53 (m, 2H), 3.47 (dd, J = 9.7, 3.6 Hz, 1H), 1.26 (s, 9H). 13C
NMR (126 MHz, CDCl3) δ 137.34, 136.67, 136.62, 136.41, 133.60, 133.50, 133.27, 129.34,
129.22, 129.14, 129.03, 128.86, 128.84, 128.69, 128.60, 128.57, 128.54, 128.51, 128.50, 128.34,
91.20, 86.41, 81.89, 80.11, 78.04, 75.41, 74.52, 74.10, 72.67, 72.02, 69.59, 68.62, 28.62. HRMS
(ESI+, C38H40Cl4O6Na): calculated 755.1476, 757.1454, 759.1435, found 755.1470, 757.1459,
759.1436.
3f
Prepared in 73% yield. 1H NMR (500 MHz, CDCl3) δ 8.07 – 8.04 (m, 2H), 7.64 – 7.59 (m, 1H),
7.51 – 7.46 (m, 2H), 7.30 – 7.18 (m, 14H), 7.04 (d, J = 8.4 Hz, 2H), 6.61 (d, J = 3.4 Hz, 1H),
4.88 (d, J = 11.3 Hz, 1H), 4.78 – 4.68 (m, 3H), 4.57 (d, J = 12.0 Hz, 2H), 4.48 (d, J = 11.1 Hz,

ACCEPTED MANUSCRIPT
1H), 4.42 (d, J = 12.4 Hz, 1H), 4.02 – 3.92 (m, 2H), 3.78 – 3.69 (m, 4H), 3.62 (dd, J = 10.9, 2.0
Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 164.83, 136.89, 135.95, 133.77, 133.75, 133.64, 133.59,
133.48, 129.91, 129.30, 129.21, 129.06, 128.95, 128.83, 128.64, 128.61, 128.59, 128.58, 128.57,
128.56, 90.36, 81.53, 79.10, 74.69, 74.45, 73.07, 72.81, 72.18, 68.08, 29.70. HRMS (ESI+,
C41H36Cl4O7Na): calculated 803.1113, 805.1091, 807.1074, found 803.1118, 805.1094, 807.1047.
3g
O
O
O
O
O
H
Cl
Cl
H
H
O
H
Cl
Cl
Prepared in 63% yield. 1H NMR (500 MHz, CDCl3) δ 7.32 – 7.17 (m, 14H), 7.02 (d, J = 8.4 Hz,
2H), 5.26 (dd, J = 5.0, 2.4 Hz, 1H), 4.97 (d, J = 3.7 Hz, 1H), 4.89 (d, J = 11.4 Hz, 1H), 4.74 –
4.67 (m, 2H), 4.66 – 4.54 (m, 3H), 4.43 – 4.34 (m, 2H), 3.93 (t, J = 9.3 Hz, 1H), 3.85 (ddd, J =
10.2, 3.7, 2.1 Hz, 1H), 3.69 (dd, J = 10.6, 3.7 Hz, 1H), 3.60 (dd, J = 10.6, 2.1 Hz, 1H), 3.55 (dd, J
= 10.1, 8.9 Hz, 1H), 3.51 – 3.42 (m, 2H), 2.47 – 2.34 (m, 1H), 2.27 (ddd, J = 13.4, 5.0, 2.1 Hz,
1H), 1.99 (ddt, J = 30.4, 12.8, 3.5 Hz, 2H), 1.91 – 1.79 (m, 3H), 1.63 – 1.02 (m, 18H), 1.03 –
0.78 (m, 15H), 0.68 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 140.64, 137.30, 136.59, 136.58,
136.36, 133.72, 133.51, 133.32, 129.28, 129.15, 128.87, 128.86, 128.60, 128.54, 128.53, 128.51,
121.89, 94.51, 81.93, 79.99, 77.85, 74.64, 74.11, 72.65, 71.99, 70.02, 68.64, 56.77, 56.18, 50.14,
42.34, 39.93, 39.78, 39.52, 37.09, 36.77, 36.20, 35.78, 31.92, 31.89, 29.69, 28.22, 28.01, 27.64,
24.29, 23.83, 22.80, 22.55, 21.07, 19.37, 18.72, 11.86. HRMS (ESI+, C61H76Cl4O6Na):
calculated 1067.4293, 1069.4280, 1070.4304, found 1067.4281, 1069.4283, 1070.4281.
3h

ACCEPTED MANUSCRIPT
Prepared in 63% yield. 1H NMR (500 MHz, CDCl3) δ 7.29 – 7.21 (m, 12H), 7.17 (d, J = 8.2 Hz,
2H), 7.01 (d, J = 8.2 Hz, 2H), 5.52 (d, J = 5.0 Hz, 1H), 4.99 (d, J = 3.6 Hz, 1H), 4.86 (d, J = 11.4
Hz, 1H), 4.72 – 4.66 (m, 3H), 4.62 – 4.54 (m, 3H), 4.40 (dd, J = 11.8, 3.2 Hz, 2H), 4.35 – 4.28
(m, 2H), 4.03 (td, J = 6.8, 1.8 Hz, 1H), 3.92 (t, J = 9.3 Hz, 1H), 3.84 – 3.77 (m, 2H), 3.74 – 3.67
(m, 2H), 3.63 – 3.56 (m, 2H), 3.54 – 3.49 (m, 1H), 1.52 (s, 3H), 1.44 (s, 3H), 1.33 (s, 3H), 1.30
(s, 3H). 13C NMR (126 MHz, CDCl3) δ 137.26, 136.68, 136.36, 133.53, 133.43, 133.30, 129.18,
129.04, 128.92, 128.77, 128.54, 128.50, 128.48, 109.30, 108.59, 81.72, 79.84, 77.50, 74.61,
73.94, 72.66, 71.40, 70.92, 70.67, 70.58, 70.09, 68.36, 66.24, 65.64, 26.14, 26.06, 24.92, 24.66.
HRMS (ESI+, C46H50Cl4O11Na): calculated 941.2005, 943.1985, 945.1970, found 941.2009,
943.1934, 945.1954.
Compound D
Found in all reactions. NMR spectra closely resembles similar compound reported by Yu
group.[38] 1H NMR (500 MHz, CDCl3) δ 7.83 (d, 1H), 7.73 (d, 1H), 7.40 – 7.27 (m, 9H), 7.17 (d,
J = 8.4 Hz, 2H), 7.12 – 7.04 (m, 4H), 6.87 – 6.82 (m, 2H), 4.86 – 4.77 (m, 2H), 4.74 (d, J = 11.1
Hz, 1H), 4.68 – 4.57 (m, 4H), 4.53 (d, J = 12.4 Hz, 1H), 4.41 (d, J = 10.9 Hz, 1H), 4.08 (d, J =

ACCEPTED MANUSCRIPT
10.8 Hz, 1H), 3.81 – 3.70 (m, 4H), 3.62 – 3.54 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 142.22,
139.63, 139.07, 136.85, 136.74, 136.45, 135.93, 133.64, 133.53, 133.46, 133.38, 129.35, 129.03,
129.02, 128.92, 128.80, 128.69, 128.61, 128.60, 128.55, 128.51, 128.34, 128.24, 124.52, 124.44,
123.57, 122.88, 122.51, 86.41, 83.69, 79.61, 78.09, 77.98, 74.68, 74.22, 74.18, 72.79, 68.73.
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°
°
°
Gold-catalyzed glucosylation reaction using an o-ethynylphenyl thioglucoside donor
Mostly SN2 with good nucleophilic alcohols
p-Chlorobenzyl used as protecting group to retard SN1 process
Let this/here be light
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