On the generality of the superarmament of glycosyl donors

Article abstract of DOI:10.1039/c7ob02966g

It was established that 2-O-benzoyl-3,4,6-tri-O-benzyl protected β-SEt, β-SPh and β-SBox glucosyl donors are not superarmed when using the NIS/TfOH promoter system, but instead have a similar reactivity as their classically armed tetra-O-benzyl protected glucosyl counterparts. The β-SBox 2-O-benzoyl-3,4,6-tri-O-benzyl glucosyl donor, however, was found to be superarmed under DMTST activation. Our studies have shown that the increased reactivity of the β-SBox 2-O-benzoyl-3,4,6-tri-O-benzyl glucosyl donor with DMTST activation could be a unique case, and that the high reactivity of glucosyl donors with the 2-O-benzoyl-3,4,6-tri-O-benzyl protection pattern is not general as earlier suggested.

Full text of DOI:10.1039/c7ob02966g

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On the Generality of Superarmament of Glycosyl Donors
Lulu Teressa Poulsen, Mads Heuckendorff and Henrik H. Jensen*
Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus C, Denmark,
hhj@chem.au.dk
Abstract It was established that 2-O-benzoyl-3,4,6-tri-O-benzyl protected 1-SEt, 1-SPh and 1-SBox
glucosyl donors are not superarmed when using the NIS/TfOH promoter system, but instead have a
similar reactivity as the classically armed tetra-O-benzyl protected glucosyl counterparts. The 1-SBox 2-
O-benzoyl-3,4,6-tri-O-benzyl glucosyl donor, however, was found to be superarmed under DMTST
activation. Our studies have shown that the increased reactivity of the 1-SBox 2-O-benzoyl-3,4,6-tri-O-
benzyl glucosyl donor with DMTST activation could be a unique case, and that high reactivity for
glucosyl donors with the 2-O-benzoyl-3,4,6-tri-O-benzyl protection pattern is not general as earlier
suggested.
1

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Introduction
1
Despite the long history of glycosylation chemistry, modern approaches are still highly empirical and no general
2,3
approach for glycosylation has been established. Each glycosidic linkage to be formed can become a unique task of
4
optimizing e.g. glycosyl donor-type, protection group pattern, promoter system, acceptor, solvent and temperature.
Chemoselective activation, reactivity tuning and reactivity measurements of glycosyl donors are ongoing topics in
5
carbohydrate chemistry. The continued interest in glycosyl donor reactivity is a result of the well-established benefit
of chemoselective glycosyl donor activation, which has been demonstrated in seminal papers from research groups led
6
7
by Fraser-Reid, Ley and Wong8a respectively using either O-pentenyl, seleno- or thioglycosides as donors. Their
important contributions have both demonstrated basic chemical behavior of the glycosylation reaction, and shown
how this fundamental understanding can be of great benefit for improving the effectiveness of assembling complex
oligosaccharide structures. Specifically, Wong and co-workers have impressively measured reactivity values of
8
several hundred glycosyl donors and demonstrated a continuum of reactivity. We have recently further expanded
upon this continuum by fine-tuning the reactivity of glycosyl donors by varying the para-substituent of benzyl ethers
9
(OMe, H, Cl, CN).
The first chemoselective activation was performed by Fraser-Reid and co-workers using O-pentenyl glucosides in a
celebrated paper where also the terms armed and disarmed glycosyl donors were coined.6 The terms refers to the ease
with which the donors were activated, which correlates to their reactivity towards the promoter and their subsequent
oxacarbenium ion formation. Later, also the term superarmed and super disarmed donors have been used in the
10
literature.12 There has not been given a strict definition of superarmament, but we here suggest the following, which
is accordance with initial results by Fraser-Reed and co-workers:
A given aldopyranosyl donor with fixed anomeric stereochemistry is said to be armed if it is perbenzylated. An
aldopyranosyl donor is termed disarmed if it is i) peracylated; ii) has 1,2-trans stereochemistry;11 and iii) an armed
donor of identical stereochemistry and anomeric leaving group can be activated chemoselectively over a mono-
deacylated analogue of the donor in question and lead to a successful glycosylation reaction in reasonable yield
between the two fragments.
Accordingly, a aldopyranosyl donor is said to be superarmed if it can be chemoselectively activated over a mono-
debenzylated armed donor of identical stereochemistry and anomeric leaving group and lead to a successful
glycosylation reaction between the two fragments where a benzyl ether protecting group has been removed from the
armed donor.
The definition given above does not allow for use of the term superarmed for donors that are just more reactive than
an armed donor or the use of the term disarmed for donor less reactive than and armed donor. The reactivity
difference has to be large enough to allow for chemoselective activation and glycosylation. Based on earlier results by
Wong8 and us9 we believe that a relative reactivity value varying a factor of at least seven-fold is required to allow for
a successful glycosylation reaction.
Glycosyl donors that fall into the category of being superarmed have previously been reported by Bols and co-
12
workers, who forced thioglycosides into an axial rich conformation by installing bulky silyl protecting groups.
13
These conformationally superarmed donors were the first to open up for a new unexplored area of reactivity. Later,
Demchenko presented the electronically superarmed glycosyl donor possessing a 2-O-benzoyl substituent trans to a S-
14,15,16,17,18
benzoxaloyl (SBox) leaving group, capable of carrying out anchimeric assistance upon activation.
The
2

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concept of electronically superarming, defined as being more reactive, was expanded and claimed to be general for
glycosyl donors of the O-pentenyl, S-ethyl, S-phenyl, S-tolyl and S-thiazolinyl type using different promoter
19
systems.
In a collaborative effort, Demchenko and Bols have recently combined the chemical features that induces
conformational and electronical superarmament, giving highly reactive and stereoselective donors, but a 2-O-
benzoylated b-1-SPh donor failed to be more reactive under NIS/TfOH activation than the analogous 2-O-benzylated
20,21
donor.
In addition, work by Wong and co-workers has questioned if the electronically superarmed donor reported
22
by Demchenko and co-workers was even more reactive than a traditionally benzylated, armed donor.
Given the opposing results mentioned above and also results from our own work with the catalytically activated o-
23
methoxybenzoate functionalized glycosyl donor, we decided to investigate the electronically superarmed donor
system in greater detail. Here, we describe our recent investigations into the generality of superarmament of
thioglycoside based glycosyl donors.
Competition Experiments and Discussion
We set out to study three (SPh, SEt, SBox) different sets of glucosyl donors (
Figure 1). In each set a traditionally armed tetra-O-benzylated donor (1, 3 or 5) was to compete with a donor
possessing the electronical superarming protecting group pattern with a 2-O-benzoyl group (2, 4 or 6).
Figure 1.
24
Prior to the competition experiments, all donors were tested under NIS/TfOH promoted glycosylation conditions
using
L-menthol as acceptor. All donors (1-6) activated easily and gave good and reproducible yields (81-94%).
Subsequently, glycosyl donor reactivity was evaluated in competition experiments within each set of donors (
Figure 1). These were performed by mixing the competing donors in a 1.0:1.0 ratio and checking this by 13C-NMR
25
spectroscopy. The mixture was then dissolved and mixed with the acceptor (L-menthol, 5 equiv. or 1 equiv.) and the
promoter (always 10 mol% TfOH and NIS in either 1 equiv. or 5-6 equiv., respectively to the equiv. of acceptor).
After ended reaction and work-up, a new 13C-NMR spectrum was recorded of the crude reaction mixture and the
anomeric signals of the unreacted donors were integrated and compared. The consumption of a donor is hereby a
3

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direct result of its reactivity. The smallest integral value after ended reaction consequently results for the most reactive
donor. Thus, the smaller the value, the more reactive the donor. All competition experiments were conducted several
times and the results were found to be highly reproducible.
Thiophenyl functionalized donors 1 and 2 were competed under five different sets of conditions (Table 1). In Entry
1, the promoter NIS was the limiting factor, while Entry 2 describes the result where the acceptor was the limiting
factor. Since more of donor 2 is left unreacted after ended reaction under both sets of conditions, donor 1, being tetra-
O-benzylated having an armed protecting group pattern, is clearly the most reactive of the two. This demonstrates that
the presence of a 2-O-benzoyl group does not generally lead to a more reactive donor, let alone donor superarmament.
Performing the competition experiments as described under Entry 2, but at a higher, isothermal temperature (0 °C,
Entry 3), did not change the outcome. Next, DMTST was investigated as promoter both in absence (Entry 4) and
presence of the sterically hindered base 2,4,6-tri-tertbutylpyrimidine (TTBP) (Entry 5). In the former case, the
reactivity had now turned to become slightly higher for the 2-O-benzoyl protected donor (2), while the classically
armed donor (1) was more reactive in the presence of TTBP. We do not characterize the slightly higher reactivity of
donor 2 over 1 under DMTST activation as being at the level of superarmed. Lastly, the relative reactivity of the
corresponding SEt donors (3 and 4) were investigated (Entry 6). The competition experiment resulted in the same
finding as for SPh donors 1 and 2, with the classically armed donor (3) being more reactive than the 2-O-benzoylated
counterpart (4).
Table 1. Competition experiments with thioglucoside glycosyl donors
Entry
Promoter system
Acceptor
5 eq.
Temperature/
time
RRc
1:2
1
2
3
4
NIS (1 eq.),
TfOH (0.1 eq. a)
-78 to 0 °C/
4 h
1 : 1.9
1 : 2.4
1 : 2.3
1 : 0.9
NIS (5 eq.),
TfOH (0.1 eq.a)
1 eq.
-78 to 0 °C/
4 h
NIS (5 eq.),
TfOH (0.1 eq. a)
1 eq.
0 °C/
2 h
DMTST (6 eq.)
1 eq.
0 °C/
2 h
4

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5
DMTST (6 eq.)
1 eq.
5 eq.
0 °C/
1 : 1.4
TTBP (1 eq.)
2 h
6b
NIS (1 eq.),
TfOH (0.1 eq. a)
-78 to 0 °C/
4 h
1 : 2
aWith respect to the amount of donor. bCorresponding SEt donors 3 and 4 were competed against one another. cRR:
reactivity ratio, (donor 1)/(donor 2)a and (donor 3)/(donor 4)b. Ratio refers to the ratio of unreacted donors after
glycosylation.
A similar series of competition experiments were conducted with the SBox donors 5 and 6 (Table 2). Activation by
NIS/TfOH (Entry 1) demonstrated a different behavior for the SBox donors compared to the SPh and SEt donors, in
that the 2-O-benzoyl analogue of the former donor type is more reactive than the tetra-O-benzylated counterparts.
Again, the established relative reactivity factor of approximately two does not justify donor 6 being superarmed under
NIS/TfOH activation.
Table 2. Competition Experiments with SBox Donors.
Entry Promoter system
Temperature/
time
RRb
5:6
1
2
3
4
NIS (4 eq.), TfOH
(40 %a)
0 °C to rt/
2.5 h
1: 0.55
DMTST (6 eq.)
0 °C/
2 h
1: 0.1
DMTST (6 eq.)
TTBP (1 eq.)
0 °C/
4 h
No
reaction
TfOH (20 %a)
0 °C to rt/
2.5 h
1: 0.7
5

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5
6
MeOTf (6 eq.)
0 °C to rt/
1 h
1: 0.5
1:2.5
Cu(OTf)2 (6 eq.)
rt/
3 h
b
aWith respect to the amount of each donor. Acceptor:
L
-menthol (1 eq.). RR: reactivity ratio, (donor 5)/(donor 6).
Ratio refers to the ratio of unreacted donors after glycosylation.
26
Activation by DMTST of donor 5 and 6 (Entry 2) fully confirms previous reports by Demchenko and co-workers
established in their first article on the topic of electronically superarmed donors.14 The large reactivity difference
under DMTST activation being approximately a factor of 10 is expected to merit a classification as superarmed.
Chemoselective activation has indeed also been shown by Demchenko and co-workers under this type of activation.14
The intriguing difference in reactivity of SBox donors induced by DMTST activation compared to NIS/TfOH
activation, led to several speculations into the difference between the two thiophilic promoter systems, which
previously has not been thoroughly investigated. Under NIS/TfOH promoted glycosylations with thioglycoside
glycosyl donors, NIS is activated by a catalytic amount of TfOH (10 mol%), which remains constant during the
reaction since the excess acceptor proton ends up on the nitrogen atom forming the neutral succinimide. In the case of
DMTST activation, however, there is no acid present from the beginning of the glycosylation, but excess protons from
the acceptor alcohol accumulates as TfOH as the glycosylation proceeds. We therefore speculated whether this
increasing amount of acid present under DMTST activation of SBox donors, somehow could be important for the
mode of activation of the SBox donors. This donor type could in principle be activated either on the S atom, the more
27
remote N atom or a dynamic combination of the two modes of activation along the course of the reaction..
To a first approximation, according to the hardÞsoft acidÞbase (HSAB) principle, the sulfur atom in SBox is a soft
Lewis base and should be activated by soft Lewis acids such as iodonium ions and DMTST. Activation could also
occur at the harder nitrogen atom of SBox by protonation. One could speculate whether activation at the SBox‘ sulfur
atom would be more inductively influenced by the electron withdrawing effect of the 2-O-benzoyl, compared to
activation at the more remote nitrogen atom, resulting in a lower rate for thiophilic activation on S compared to N-H+
activation.
28
To explore the acid dependence of SBox activation by DMTST the acid scavenger TTBP was added to the
reaction mixture. While addition of TTBP to the DMTST promoted reaction of SPh donors (1 and 2) did not have a
pronounced effect (Entry 5, Table 1), activation of SBox in presence of TTBP did not occur at all (Entry 3, Table 2),
demonstrating the importance of TfOH for SBox activation. Next, SBox activation with only TfOH was investigated
(Entry 4), resulting in a reactivity difference mirroring that found for NIS/TfOH activation of SBox donors, but not to
the superarmed level found for DMTST activation. The similar reactivity ratios could indicatethat NIS/TfOH
activation of SBox occurs by N-protonation. Demchenko and co-workers, however, have previously studied this
reaction and found the disulfide BoxSSBox as a reaction by-product, and of this basis concluded that activation occurs
through reaction of S with I+ as generally accepted for thioglycoside activation. The BoxSSBox, however, could in
principle also be formed after TfOH activation of the SBox donor generating HSBox followed by oxidation of this by
NIS to the disulfide.27
6

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Given the possibility of the nucleofuge HSBox to undergo tautomerisation, as also discussed by Demchenko and
co-workers,27 proposing an exact mechanism for SBox activation with various promoter systems is not trivial.
Similarly, it is not clear how different modes of activation influence the degree of armament.
Lastly, to test the influence of other known activators of SBox glycosyl donors we also explored both MeOTf or
Cu(OTf)2. The former activator (MeOTf) was found to preferentially activate the 2-O-benzoyl donor 6, but not in a
degree near to what can be characterized as superarmed. The latter (Cu(OTf)2) was found to activate the tetra-O-
benzyl protected donor 5.
Conclusion
We have investigated whether the presence of a 2-O-benzoyl protecting group of a tri-O-benzylated glucosyl donor
generally leads to superarmament across different donor types (SPh, SEt and SBox) and varying promoter systems.
The overall conclusion is, that DMTST and SBox indeed offers a privileged combination of reagents in this study,
which results in a reactivity difference large enough between a traditionally armed donor and its 2-O-benzoylated
counterpart to be synthetically useful. Exchange of a 2-O-benzyl group for a 2-O-benzoyl does not generally result in
superarmament, but does alter the pattern of reactivity, which is a testament to the complexity of glycosyl donor
activation and glycosylation. A deeper level of understanding of the mechanisms behind the reaction between the
glycosyl donor and promoter could potentially lead to useful tools to make glycosylation chemistry and
oligosaccharide synthesis more efficient.
Experimental Section
General Methods
All reagents were used as purchased without further purification. Importantly, high quality
NIS was used (Chempur (004499, N-iodosuccinimide/98%+). Dry solvents were taken from
a solvent purification system. Glassware used for water-free reactions were dried for 12 h at
120 °C before use. Columns were packed with silica gel 60 (230œ400 mesh) as the stationary
phase. TLC plates were visualized by 10% H2SO4 in EtOH and heating until spots appeared.
1H-NMR and 13C-NMR spectra were recorded on a 400 MHz spectrometer with respect to 1H
resonances. Chemical shifts (K) are reported in ppm relative to the residual solvent signal.
High-resolution mass spectral (HRMS) data were obtained on an electrospray (ES) mass
spectrometer analyzing time-of-flight.
General Procedure for Glycosylations
A mixture of glycosyl donor (0.10 mmol), glycosyl acceptor (0.15 mmol), and freshly
activated molecular sieves (3 Å, 100 mg) in CH2Cl2 (2 mL) was stirred under argon for 1 h.
The solution was cooled to œ78 °C using a dry ice/acetone bath. NIS (0.11 mmol) and TfOH
(0.1 mL of a 0.1 M solution of TfOH in CH2Cl2) were added. Lumps of dry ice were removed
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from the acetone bath and the reaction was slowly allowed to reach 0 °C (approximately 3
hours). Upon completion, the solids were filtered off and the filtrate was washed with
aqueous 10% Na2S2O3 solution. The organic layer was separated, dried with MgSO4, and
concentrated in vacuo. The residue was purified by flash column chromatography on silica
gel to afford the corresponding glycoside. Anomeric ratios were measured by comparison of
1
integral intensities of the anomeric protons and anomeric carbons from H-NMR and 13C-
NMR spectra of crude reaction mixtures.
Competition Experiments
General Procedure for Competition Experiments with the NIS/TfOH Promoter System
13
The two glycosyl donors (0.10 mmol each) were dissolved in CDCl3. A C NMR spectrum
was recorded and the ratios of the donors were checked to be 1.0:1.0 by comparing peak
intensities from similar carbon atoms. The solvent was evaporated and (-)- -menthol
L
(0.5 mmol) and anhydrous CH2Cl2 (2 mL) were added. The mixture was stirred with freshly
activated molecular sieves (3 Å, 100 mg) for 1 h under inert atmosphere. The solution was
cooled to -78 °C and NIS (0.10 mmol) and TfOH (0.1 mL of a 0.1 M solution of TfOH in
CH2Cl2) were added. Lumps of dry ice were removed from the acetone bath and the reaction
mixture was slowly allowed to reach 0 °C over approximately 4 h. At 0 °C the solids were
filtered off and the filtrate was washed with aqueous Na2S2O3 (10 % in H2O). The organic
phase was dried over Na2SO4, filtered and concentrated in vacuo. The crude mixture was
dissolved in CDCl3 and a 13C NMR spectrum was recorded. The unreacted donor ratios were
measured by comparison of integral intensities of the anomeric carbons from the 13C NMR
spectra of the crude reaction mixtures.
Preparation of DMTST solution8
DMSTS was prepared by combining dimethyldisulfide (0.34 mL, 3.0 mmol) and MeOTf
(0.26 mL, 3.0 mmol) in dry CH2Cl2 (1 mL). The mixture was stirred for 1 h and 0.1 mL was
extracted and added to the competition experiment.
General Procedure for Competition Experiments with the DMTST Promoter System
13
The two glycosyl donors (0.10 mmol each) were dissolved in CDCl3. A C NMR spectrum
was recorded and the ratios of the donors were checked to be 1.0:1.0. The solvent was
8

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evaporated and (-)- -menthol (0.1 mmol) and anhydrous CH2Cl2 (2 mL) were added. The
L
mixture was stirred with freshly activated molecular sieves (3 Å, 100 mg) for 1 h under inert
atmosphere. The solution was cooled to 0 °C and DMTST (0.6 mmol) was added. The
reaction mixture was allowed to stir for 2 h at 0 °C then quenched with one drop of Et3N. The
solid was filtered off and the filtrate was washed with an aqueous solution of NaOH (1 %)
and with H2O (three times). The organic phase was dried over MgSO4, filtered and
concentrated in vacuo. The crude mixture was dissolved in CDCl3 and a 13C NMR was
recorded. The product ratios were measured by comparison of integral intensities of the
anomeric carbons from the 13C NMR spectra of the crude reaction mixtures.
General Procedure for Competition Experiments with the DMTST Promoter System
and base TTBP
13
The two glycosyl donors (0.10 mmol each) were dissolved in CDCl3. A C NMR spectrum
was recorded and the ratios of the donors were checked to be 1.0:1.0. The solvent was
evaporated and (-)- -menthol (0.1 mmol) and anhydrous CH2Cl2 (2 mL) were added. The
L
mixture was stirred with freshly activated molecular sieves (3 Å, 100 mg) for 1 h under inert
atmosphere. The solution was cooled to 0 °C and TTBP (0.15 mmol) and DMTST (0.6
mmol) were added. The reaction mixture was allowed to stir for 2 h at 0 °C before quenched
by one drop of Et3N. The solid was filtered off and the filtrate was washed with an aqueous
solution of NaOH (1 %) and with H2O (three times). The organic phase was dried over
MgSO4, filtered and concentrated in vacuo. The crude mixture was dissolved in CDCl3 and a
13C NMR was recorded. The product ratios were measured by comparison of integral
intensities of the anomeric carbons from the 13C NMR spectra of the crude reaction mixtures.
General Procedure for Competition Experiments with the MeOTf Promoter System
13
The two glycosyl donors (0.10 mmol each) were dissolved in CDCl3. A C NMR spectrum
was recorded and the ratios of the donors were checked to be 1.0:1.0. The solvent was
evaporated and (-)- -menthol (0.1 mmol) and anhydrous CH2Cl2 (2 mL) were added. The
L
mixture was stirred with freshly activated molecular sieves (3 Å, 100 mg) for 1 h under inert
atmosphere. The solution was cooled to 0 °C and MeOTf (0.6 mmol) was added. The ice bath
was removed and the reaction mixture was stirred for 1 h at rt. before Et3N (0.5 mL) was
added. The solid was filtered off and the filtrate was washed with H2O (three times). The
organic phase was dried over Na2SO4, filtered and concentrated in vacuo. The crude mixture
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was dissolved in CDCl3 and a 13C NMR spectrum was recorded. The product ratios were
measured by comparison of integral intensities of the anomeric carbons from the 13C NMR
spectra of the crude reaction mixtures.
General Procedure for Competition Experiments with the TfOH Promoter System
13
The two glycosyl donors (0.10 mmol each) were dissolved in CDCl3. A C NMR spectrum
was recorded and the ratios of the donors were checked to be 1.0:1.0. The solvent was
evaporated and (-)- -menthol (0.1 mmol) and anhydrous CH2Cl2 (2 mL) were added. The
L
mixture was stirred with freshly activated molecular sieves (3 Å, 100 mg) for 1 h under inert
atmosphere. The solution was cooled to 0 °C and TfOH (0.2 mmol) was added. The ice bath
was removed and the reaction mixture was stirred for 1 h at rt. The solid was filtered off and
the filtrate was washed with sat. aq. NaHCO3 and H2O (three times). The organic phase was
dried over Na2SO4, filtered and concentrated in vacuo. The crude mixture was dissolved in
CDCl3 and a 13C NMR spectrum was recorded. The product ratios were measured by
comparison of integral intensities of the anomeric carbons from the 13C NMR spectra of the
crude reaction mixtures.
General Procedure for Competition Experiments with the Cu(OTf)2 Promoter System
13
The two glycosyl donors (0.10 mmol each) were dissolved in CDCl3. A C NMR spectrum
was recorded and the ratios of the donors were checked to be 1.0:1.0. The solvent was
evaporated and (-)- -menthol (0.1 mmol) and anhydrous CH2Cl2 (2 mL) were added. The
L
mixture was stirred with freshly activated molecular sieves (3 Å, 100 mg) for 1 h under inert
atmosphere. Cu(OTf)2 (0.60 mmol) was added the green mixture was stirred for 3 h at rt. The
solid was filtered off and the filtrate was washed with sat. aq. NaHCO3 and brine. The
organic phase was dried over MgSO4, filtered and concentrated in vacuo. The crude mixture
was dissolved in CDCl3 and a 13C NMR spectrum was recorded. The product ratios were
measured by comparison of integral intensities of the anomeric carbons from the 13C NMR
spectra of the crude reaction mixtures.
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Synthesis of Donors
Phenyl 2,3,4,6-tetra-O-benzyl-1-thio-5-D-glucopyranoside (1)
Phenyl 2,3,4,6-tetra-O-acetyl-1-thio-1- -glucopyranoside (21.8 g, 49.7 mmol, 1 equiv.) was
D
dissolved in MeOH and sodium methoxide solution (25 wt. % in MeOH) was added until a
pH-value of approximately 10 was reached. The reaction mixture was stirred for 30 h at rt,
then neutralized with DOWEX® Acidic Cation Exchanger Resin in MeOH. The resin was
filtered off by suction and the product mixture was concentrated in vacuo. The crude product
was dissolved in anhydrous DMF (60 mL) and cooled to 0 °C. NaH (60 % (w/w) dispersion
in mineral oil, 15.9 g, 397 mmol, 8 equiv.) was added and the mixture was stirred for 10 min
prior to dropwise addition of BnBr (35.5 mL, 298 mmol, 6 equiv.). The resulting mixture was
stirred for 18 h at rt then quenched by cautiously transferring the mixture into a large volume
of H2O at 0 °C. The aqueous phase was extracted with CH2Cl2 (three times) and the
combined organic phases were dried over MgSO4 and concentrated in vacuo. The residue was
purified by flash column chromatography (pentane/EtOAc 4:1) to afford the product (19.9 g,
31.4 mmol, 63 %) as a white solid. Rf 0.66 (pentane/EtOAc 5:1). [ꢀ]D295K +3.2 (c 1.0, CHCl3).
lit. +3 (CHCl3).1 Mp (uncorr.) 91.5 œ 92.5 °C. lit. 91 œ 92 °C.1 1H NMR (400 MHz, CDCl3) KH
7.57 œ 7.52 (m, 2H, ArH), 7.37 œ 7.14 (m, 23H, ArH), 4.86 (d, J 10.9 Hz, 1H, CHHPh), 4.85
(d, J 10.2 Hz, 1H, CHHPh), 4.81 (d, J 10.8 Hz, 1H, CHHPh), 4.79 (d, J 10.8 Hz, 1H,
CHHPh), 4.69 (d, J 10.3 Hz, 1H, CHHPh) 4.63 (d, J 9.8 Hz, 1H, H1), 4.57 (d, J 12.0 Hz, 1H,
CHHPh), 4.55 (d, J 10.8 Hz, 1H, CHHPh), 4.50 (d, J 12.0 Hz, 1H, CHHPh) 3.75 (dd, J 9.8
Hz, 1H, H6a), 3.72 œ 3.64 (m, 2H, H6b, H3/H4), 3.61 (t, J 9.2 Hz, 1H, H3/H4) 3.50 œ 3.44
(m, 1H, H5), 3.47 (dd, J 9.5 Hz, 8.6 Hz, 1H, H2). 13C NMR (100 MHz, CDCl3) KC 138.4
(ArC), 138.3 (ArC), 138.0 (ArC), 133.8 (ArC), 132.0 œ 127.5 (ArCH), 87.5 (C1), 86.8
(C3/C4), 80.6 (C2/C5), 79.1 (C2/C5), 77.8 (C4/C3), 75.9 (CH2Ph), 75.5 (CH2Ph), 75.1
(CH2Ph), 73.5 (CH2Ph), 69.0 (C6). HRMS (ES): calcd. for C40H40O5SNa+ 655.2494; found
655.2488. Spectral values were in accordance with previously reported data.2
Phenyl 2-O-benzoyl-3,4,6-tri-O-benzyl-1-thio-5-D-glucoyranoside (2)
Phenyl 3,4,6-tri-O-benzyl-1-thio-1-D-glucoyranoside (100 mg, 0.18 mmol, 1 equiv.) was
dissolved in anhydrous CH2Cl2 (3 mL) and DMAP (9 mg, 0.09 mmol, 0.5 equiv.), Et3N (0.13
mL, 0.92 mmol, 5 equiv.) and BzCl (0.08 mL, 0.74 mmol, 4 equiv.) were added. The mixture
was stirred at rt for 18 h. To quench excess BzCl the mixture was stirred with DMAPA3 (0.
09 mL, 0.74 mmol, 4 equiv.) for 10 min. The reaction mixture was washed with aq. 1M HCl
11

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(x3), sat. aq. NaHCO3 and brine. The organic phase was dried over MgSO4, filtered and
concentrated in vacuo. The resulting residue was purified by flash column chromatography
(pentane/EtOAc 10:1) yielding the product (86 mg, 0.14 mmol, 74%) as a white solid. Rf 0.35
295K
(pentane/EtOAc 5:1). [ꢀ]D
+28.2 (c 1.0, CHCl3), lit. +21.7 (c 1.1, CHCl3).3 Mp (uncorr.)
1
128.4 œ 129.1 °C. H NMR (400 MHz, CDCl3) KH 8.09 œ 8.03 (m, 2H, ArH), 7.63 œ 7.09 (m,
23H, ArH), 5.30 (t, J 9.5 Hz, 1H, H2), 4.82 (dd, J 10.8 Hz, J 10.8 Hz, 2H, CHHPh, CHHPh),
4.75 (d, J 11.0 Hz, 1H, H1), 4.67 œ 4.56 (m, 4H, 2xCH2Ph), 3.86 (t, J 9.3 Hz, 1H, H3), 3.85 œ
13
3.77 (m, 2H, H6a, H6b), 3.76 (t, J 8.8 Hz, 1H, H4), 3.67 œ 3.60 (m, 1H, H5). C NMR (101
MHz, CDCl3) KC 165.2 (C=O) 138.2 (ArC), 137.9 (ArC), 137.6 (ArC), 137.2 (ArC), 133.2 œ
127.6 (ArCH), 86.2 (C1), 84.3 (C3), 79.5 (C5), 77.8 (C4), 75.4 (CH2Ph), 75.1 (CH2Ph), 73.4
(CH2Ph), 72.4 (C2), 68.9 (C6). HRMS (ES): calcd. for C40H38O6S [M+Na+] 669.2281; found
669.2288. Spectral values were in accordance with previously reported data.4
KSBox salt
K2CO3 (5.0 g, 1 equiv.) was added to a stirred solution of HSBox (4.55 g, 1 equiv.) in
anhydrous acetone. The mixture was refluxed for at 60 °C for 3 h. The acetone was
evaporated off and the KSBox salt (8.9 g) was dried overnight under reduced pressure.
Benzoxazolyl 2,3,4,6-tetra-O-benzyl-1-thio-5-D-glucopyranoside (5)
Phenyl 2,3,4,6-tetra-O-benzyl-1-thio-1-D-glucopyranoside (1.57 g, 2.48 mmol, 1 equiv.) was
stirred with freshly activated molecular sieves (3 Å, 1.50 g) in anhydrous CH2Cl2 (25 mL) for
1 h under inert atmosphere prior to addition of a freshly prepared solution of Br2 in CH2Cl2
(25.2 mL of a 0.118 M solution, 2.98 mmol, 1.2 equiv.). The orange mixture was stirred for 5
min at rt. The solid was filtered off and the filtrate was concentrated in vacuo. The crude
glucosyl bromide was dissolved in anhydrous acetone (20 mL) and KSBox salt (1.18 g, 6.20
mmol, 2.5 equiv.) and 18-crown-6 ether (72 mg, 0.27 mmol, 0.11 equiv.) were added under
inert atmosphere. The reaction mixture was stirred for 16 h at rt. Upon completion, the solid
was filtered off and washed with CH2Cl2. The filtrate was washed with an 1% NaOH aq.
solution and H2O (three times). The organic phase was dried over Na2SO4, filtered and
concentrated in vacuo. The residue was purified by flash column chromatography
(toluene/EtOAc 50:1) to afford the product (419 mg, 0.62 mmol, 25 %) as a slightly yellow
295K
solid. Rf (EtOAc/pentane 4:1) 0.41. [ꢀ]D
+6.6 (c 1.0, CHCl3), lit. +0.89 (c 1.0, CHCl3)4.
o
Mp (uncorr.) 95.9 œ 96.5 oC, lit. 96 œ 97 C.6 1H NMR (400 MHz, CDCl3) KH 7.84 œ 7.80 (m,
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1H, ArH), 7.61 œ 7.34 (m, 23H, ArH), 5.73 (d, J 9.4 Hz, 1H, H1), 5.15 (d, J 11.0 Hz, 1H,
CHHPh), 5.12 (d, J 10.9 Hz, 1H, CHHPh), 5.09 (d, J 10.5 Hz, 1H, CHHPh), 5.07 (d, J 10.5
Hz, 1H, CHHPh) 5.05 (d, J 10.5 Hz, 1H, CHHPh), 4.83 (d, J 10.9 Hz, 1H, CHHPh), 4.78 (d,
J 12.0 Hz, 1H, CHHPh), 4.65 (d, J 12.0 Hz, 1H, CHHPh), 4.07 œ 3.94 (m, 5H, H2, H3, H4,
H6S, H61), 3.93 œ 3.85 (m, 1H, H5). 13C NMR (101 MHz, CDCl3) KC 161.5 (C=N), 151.7
(ArC-O), 141.7 (ArC-N), 138.2 (ArC), 137.9 (ArC), 137.9 (ArC), 137.4 (ArC), 128.4 œ 127.5
(ArCH), 124.3 (ArCH), 124.2 (ArCH), 118.9 (ArCH), 109.9 (ArCH), 86.5, 84.7 (C1), 80.5,
79.6, 77.3, 75.7 (CH2Ph), 75.4 (CH2Ph), 74.9 (CH2Ph), 73.3 (CH2Ph), 68.3 (C6). HRMS
(ES): calcd. for C41H39NO6SNa+ 696.2390; found 696.2399. Spectral values were in
accordance with previously reported data.5
Benzoxazolyl 2-O-benzoyl-3,4,6-tri-O-benzyl-1-thio-5-D-glucopyranoside (6)
Phenyl 2-O-benzoyl-3,4,6-tri-O-benzyl-1-thio-1-D-glucoyranoside (700 mg, 1.08 mmol, 1
equiv.) was stirred with freshly activated molecular sieves (3 Å, 500 mg) in anhydrous
CH2Cl2 (15 mL) for 1 h under inert atmosphere prior to addition of a freshly prepared
solution of Br2 in CH2Cl2 (9.1 mL of a 0.118 M solution, 2.98 mmol, 1.2 equiv.). The
reaction mixture was stirred for 5 min at rt. The solid was filtered off and the filtrate was
concentrated in vacuo. The crude glucosyl bromide 16 was dissolved in anhydrous acetone
(20 mL) and KSBox salt (1.18 g, 6.20 mmol, 2.5 equiv.) and 18-crown-6 ether (72 mg, 0.27
mmol, 0.11 equiv.) were added under inert atmosphere. The reaction mixture was stirred for
16 h at rt. Upon completion, the solid was filtered off and washed with CH2Cl2. The filtrate
was washed with an 1% NaOH aq. solution and H2O (three times). The organic phase was
dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash
column chromatography (pentane/EtOAc 10:1) to afford the product (586 mg, 0.85 mmol,
79%) as a white solid. Rf (EtOAc/pentane 4:1) 0.30. [ꢀ]D295K +66.8 (c 1.0, CHCl3), lit. +106.7
o
(c 1, CHCl3).6 Mp (uncorr.) 96.2 œ 98.0 °C, lit. 96 œ 97 C.6 1H NMR (400 MHz, CDCl3) KH
8.12 (d, J 7.4 Hz, 2H, ArH), 7.72 (d, J 7.6 Hz, 1H, ArH), 7.61 (t, J 7.4 Hz, 1H, ArH), 7.51 œ
7.25 (m, 20H, ArH), 5.95 (d, J 10.3 Hz, 1H, H1), 5.68 (dd, J 10.1 Hz, 9.0 Hz, 1H, H2), 4.99
(d, J 10.9 Hz, 1H, CHHPh), 4.93 (d, J 11.1 Hz, 1H, CHHPh), 4.85 (d, J 11.1 Hz, 1H
CHHPh), 4.76 (d, J 10.9 Hz, 1H, CHHPh), 4.75 (d, J 12.0 Hz, 2H, CHHPh), 4.62 (d, J
12.0 Hz, 1H, CHHPh), 4.14 (t, J 8.8 Hz, 1H, H3), 4.07 (t, J 9.1 Hz, 1H, H4), 3.98 œ 3.90 (m,
3H, H5, H6S, H61). 13C NMR (101 MHz, CDCl3) KC 165.4 (C=O), 162.0 (C=N), 152.0 (ArC-
O), 141.7 (ArC-N), 138.1 (ArC), 137.7 (ArC), 133.5 (ArC), 130.0 (ArCH), 129.3 (ArC),
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128.6 - 127.8 (ArCH), 124.5 (ArCH), 124.4 (ArCH), 118.9 (ArCH), 110.2 (ArCH), 84.0
(H1), 84.0 (H3), 80.2 (H5), 77.5 (H4), 75.5 (CH2Ph), 75.2 (CH2Ph), 73.6 (CH2Ph), 72.5 (H2),
68.5 (H6). HRMS (ES): calcd. for C41H37NO7SNa+ 710.2183; found 710.2190. Spectral
values were in accordance with previously reported data.6
L-Menthyl 2,3,4,6-tetra-O-benzyl-8-D-glucopyranoside (78)
295K
Appearance: Colorless oil. Rf 0.38 (pentane/EtOAc, 5:1). [ꢀ]D
+31 (c 1.0, CHCl3), lit.
+31.3 (c 1.1, CHCl3). 7 1H NMR (400 MHz, CDCl3) KH 7.37 - 7.23 (m, 18H, ArH), 7.15 -
7.11 (m, 2H, ArH), 5.02 (d, J 3.6 Hz, 1H, H1), 4.98 (d, J 10.9 Hz, 1H, CHHPh), 4.84 (d, J
10.7 Hz, 1H, CHHPh), 4.82 (d, J 10.9 Hz, 1H, CHHPh), 4.72 (d, J 11.8 Hz, 1H, CHHPh),
4.68 (d, J 12.3 Hz, 1H, CHHPh), 4.64 (d, J 12.3 Hz, 1H, CHHPh), 4.47 (d, J 12.1 Hz, 1H,
CHHPh), 4.45 (d, J 10.7 Hz, 1H, CHHPh), 4.02 (t, J 9.5 Hz, H3), 4.00 œ 3.93 (m, 1H, H5),
3.75 (dd, J 10.5, 3.7 Hz, 1H, H6S), 3.64 (t, J 9.4 Hz, 1H, H4), 3.64 (dd, J 10.5, 1.6 Hz, 1H,
H61), 3.55 (dd, J 19.8, 3.6 Hz, 1H, H2), 3.35 (dt, J 10.6, 4.3 Hz, 1H, OCH), 2.42 (dsep, J 6.9,
1.9 Hz, 1H, CH(CH3)2), 2.16 œ 2.08 (m, 1H), 1.65 - 1.57 (m, 2H), 1.40 œ 1.25 (m, 2H), 1.08 œ
0.75 (m, 3H), 0.86 (d, J 6.4 Hz, 3H, CH3), 0.83 (d, J 7.1 Hz, 3H, CH3), 0.71 (d, J 6.9 Hz, 3H,
CH3). 13C NMR (101 MHz, CDCl3) KC 138.9 (ArC), 138.4 (ArC), 138.3 (ArC), 138.0 (ArC),
128.5 - 127.5 (ArCH), 98.6 (C1), 82.0 (C3), 81.0 (OCH), 80.5 (C2), 78.1 (C4), 75.5 (CH2Ph),
75.1 (CH2Ph), 73.5 (CH2Ph), 73.2 (CH2Ph), 70.3 (C5), 68.6 (C6), 48.8, 43.1 (CH2), 34.3
(CH2), 31.7, 24.6 (CH(CH3)2), 22.9 (CH2), 22.3 (CH3), 21.1 (CH3), 16.1 (CH3). HRMS (ES):
+
Calcd. for C44H54O6NH4 696.4259; found 696.4273. Spectral values were in accordance
with previously reported data. 7
L-Menthyl 2,3,4,6-tetra-O-benzyl-5-D-glucopyranoside (75)
Appearance: White solid. Rf 0.47 (pentane/EtOAc, 5:1). [ꢀ]D295K -16 (c 1.0, CHCl3), lit. -17.2
(c 1.05, CHCl3).8 1H NMR (400 MHz, CDCl3) KH 7.57 œ 7.53 (m, 1H, ArH), 7.43 œ 7.23 (m,
19H, ArH), 5.01 (d, J 10.6 Hz, 1H, CHHPh), 4.98 (d, J 10.8 Hz, 1H, CHHPh), 4.88 (d, J 10.8
Hz, 1H, CHHPh), 4.85 (d, J 11.0 Hz, 1H, CHHPh), 4.74 (d, J 10.9 Hz, 1H, CHHPh), 4.67 (d,
J 12.0 Hz, 1H, CHHPh), 4.64 (d, J 10.4 Hz, 1H, CHHPh), 4.60 (d, J 12.2 Hz, 1H, CHHPh),
4.53 (d, J 7.8 Hz, 1H, H1), 3.75 (d, J 3.2 Hz, 2H, H6S, H61), 3.70 (t, J 8.5 Hz, H3/H4), 3.65
(t, J 9.0 Hz, H4/H3), 3.56 (td, J 10.7, 4.2 Hz, 1H, OCH), 3.50 œ 3.44 (m, 1H, H5), 3.47 (t, J
8.2 Hz, 1H, H2), 2.46 œ 2.35 (m, 1H, CH(CH3)2), 2.20 (d, J 12.1 Hz, 1H), 1.72 (m, 2H), 1.46
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œ 1.28 (m, 2H), 1.11 œ 0.92 (m, 3H), 0.98 (d, J 7.1 Hz, 3H, CH3), 0.96 (d, J 6.6 Hz, 3H, CH3),
0.88 (d, J 6.9 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) KC 138.9 (ArC), 138.6 (ArC),
138.4 (ArC), 138.3 (ArC), 129.1 œ 127.2 (ArCH), 100.8 (C1), 85.0 (C3/C4), 82.3 (C5/C2),
78.0 (C4/C3), 77.8 (OCH), 75.7 (CH2Ph), 75.1 (CH2Ph), 74.9 (CH2Ph), 74.9 (C2/C5), 73.7
(CH2Ph), 69.4 (C6), 48.2, 41.0 (CH2), 34.5 (CH2), 31.5, 25.3 (CH(CH3)2), 23.3 (CH2), 22.3
(CH3), 21.2 (CH3), 16.0 (CH3). Spectral values were in accordance with previously reported
data.8
L-Menthyl 3,4,6-tri-O-benzyl-2-O-benzoyl-5-D-glucopyranoside (8)
295K
Appearance: White solid. Rf 0.50 (pentane/EtOAc, 4:1). [ꢀ]D
-17 (c 1.0, CHCl3). Mp
1
(uncorr.) 68.0 œ 70.0 °C. H NMR (400 MHz, CDCl3) KH 7.95 -7.92 (m, 2H, ArH), 7.51 œ
7.39 (m, 1H, ArH), 7.34 (t, J 7.7 Hz, 2H, ArH), 7.28 œ 7.13 (m, 10H, ArH), 7.09 œ 7.01 (m,
5H, ArH), 5.14 (t, J 8.5 Hz, 1H, H2), 4.76 (d, J 10.6 Hz, 1H, CHHPh), 4.66 (d, J 11.0 Hz,
1H, CHHPh), 4.58 (d, J 10.6 Hz, 1H, CHHPh), 4.56 (d, J 12.1 Hz, 1H, CHHPh), 4.55 (d, J
10.8 Hz, 1H, CHHPh), 4.49 (d, J 12.5 Hz, 1H, CHHPh), 4.48 (d, J 8.3 Hz, 1H, H1), 3.72 (t, J
9.0 Hz, 1H, H3), 3.70 œ 3.62 (m, 3H, H4, H6S, H61), 3.47 œ 3.40 (m, 1H, H5), 3.31 (td, J
10.8, 4.1 Hz, 1H, OCH), 2.23 (dsep, J 6.9, 2.5 Hz, 1H, CH(CH3)2), 1.82 œ 1.75 (m, 1H), 1.52
œ 1.41 (m, 2H), 1.24 œ 1.11 (m, 2H), 1.10 - 1.00 (m, 1H), 0.89 - 0.78 (m, 1H), 0.77 (d, J 7.1
Hz, 3H, CH3), 0.69 (d, J 6.8 Hz, 3H, CH3), 0.64 (d, J 6.6 Hz, 3H, CH3), 0.60 - 0.47 (m, 1H).
13C NMR (101 MHz, CDCl3) KC 165.3 (C=O), 138.5 (ArC), 138.2 (ArC), 138.1 (ArC), 133.0
(ArCH), 130.4 (ArC), 129.9 (ArCH), 129.2 (ArCH), 128.6 - 127.3 (ArCH), 99.3 (C1), 83.1
(C3), 78.8 (OCH), 78.3 (C4), 75.4 (C5), 75.2 (CH2Ph), 74.9 (CH2Ph), 74.2 (C2), 73.9
(CH2Ph), 69.3 (C6), 47.5, 41.1 (CH2), 34.3 (CH2), 31.4, 25.1, 23.1 (CH(CH3)2), 22.2 (CH3),
+
21.1 (CH3), 15.9 (CH3). HRMS (ES) Calcd. for C44H52O7NH4 710.4071 found; 710.4062.
Associated content
Supporting Information
The Supporting Information is available free of charge on the publications website:
Glycosylation results under a non-competitive setting and 1H and 13C spectra of compounds.
AUTHOR INFORMATION
Corresponding Author
15

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*Email: hhj@chem.au.dk
ACKNOWLEDGMENT
We are grateful for financial support from The Villum Foundation (VKR023110).
REFERENCES
1 Fischer, E. Berichte der Dtsch. Chem. Gesellschaft 1893, 26, 2400-2412.
2 Zhu, X.; Schmidt, R. R. Angew. Chem. Int. Ed. 2009, 48, 1900-1934.
3 Christensen, H. M.; Oscarson, S.; Jensen, H. H. Carbohydr. Res. 2015, 408, 51-95.
4 Wang, L.-X.; Davis, B. G. Chem. Sci. 2013, 4, 3381-3394.
5
a) Gervay-Hague, J. Acc. Chem. Res. 2016, 49, 35-47. b) Fraser-Reid, B.; López, J. C. Top. Curr. Chem. 2011, 301, 1-29. c)
Codée, J. D. C.; Litjens, R. E. J. N.; van den Bos, L. J.; Overkleeft, H. S.; van der Marel, G. a. Chem. Soc. Rev. 2005, 34, 769-782.
6 Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid, B. J. Am. Chem. Soc. 1988, 110, 5583-5584.
7 Douglas, N. L.; Ley, S. V.; Lücking, U.; Warriner, S. L. J. Chem. Soc. Perkin Trans. 1. 1998, 51-66.
8
a) Zhang, Z.; Ollmann, I. R.; Ye, X.-S.; Wischnat, R.; Baasov, T.; Wong, C.-H. J. Am. Chem. Soc. 1999, 121, 734-753. b)
Koeller, K. M.; Wong, C. H. Chem. Rev. 2000, 100, 4465-4494. c) Lee, J.-C.; Greenberg, W. a; Wong, C.-H. Nat. Protoc. 2006, 1,
3143-3152.
9 Heuckendorff, M.; Poulsen, L. T.; Jensen, H. H. J. Org. Chem. 2016, 81, 4988-5006.
10 The term superdisarmed (ref 17) will not be defined here since it has been used in contexts where anomeric stereochemistry of
the disarmed and so-called superdisarmed is not identical.
11 Aldopyranosyl donors with a 1,2-cis relationship may be super disarmed, see ref. 17.
12
a) Pedersen, C. M.; Nordstrøm, L. U.; Bols, M. J. Am. Chem. Soc. 2007, 129, 9222-9235. b) Jensen, H. H.; Bols, M. Acc.
Chem. Res. 2006, 39, 259-265. c) Jensen, H. H.; Pedersen, C. M.; Bols, M. Chem. Eur. J. 2007, 13, 7576-7582.
13 a) Heuckendorff, M.; Pedersen, C. M.; Bols, M. Chem. Eur. J. 2010, 16, 13982-13994. b) Heuckendorff, M.; Pedersen, C. M.;
Bols, M. J. Org. Chem. 2012, 77, 5559-5568. c) Heuckendorff, M.; Pedersen, C. M.; Bols, M. J. Org. Chem. 2013, 78, 7234-7248.
14
a) Mydock, L. K.; Demchenko, A. V. Org. Lett. 2008, 10, 2103-2106. b) Mydock, L. K.; Demchenko, A. V. Org. Lett. 2008,
10, 2107-2110.
15 Demchenko, A. V; Malysheva, N. N.; De Meo, C. Org. Lett. 2003, 5, 455-458.
16 Definition of anchimeric assistance see http://goldbook.iupac.org/N04100.html (visited 5.1.2018)
17 Crich, D.; Li, M. Org. Lett. 2007, 9, 4115-4118.
18 Conformationally superarmed donors are more reactive than electronically superarmed donors.
19
a) Premathilake, H. D.; Mydock, L. K.; Demchenko, A. V. J. Org. Chem. 2010, 75, 1095-1100. b) Premathilake, H. D.;
Demchenko, A. V. Top. Curr. Chem. 2011, 301, 189-221.
20 Heuckendorff, M.; Premathilake, H. D.; Pornsuriyasak, P.; Madsen, A. Ø.; Pedersen, C. M.; Bols, M.; Demchenko, A. V. Org.
Lett. 2013, 4526-4528.
21 See supporting information of reference 14
22 Hsu, Y.; Lu, X.-A.; Zulueta, M. M. L.; Tsai, C.-M.; Lin, K.-I.; Hung, S.-C.; Wong, C.-H. J. Am. Chem. Soc. 2012, 134, 4549-
4552.
23 S. K. Kristensen, S. Salamone, M. R. Rasmussen, M. H. S. Marqvorsen, H. H. Jensen , Eur. J. Org. Chem. 2016, 5365-5376.
24 Veeneman, G. H.; van Leeuwen, S. H.; van Boom, J. H. Tetrahedron Lett. 1990, 31, 1331-1334.
25
13C NMR spectroscopic integration is a valid method for obtaining product ratios of diastereomeric pairs, see: Otte, D. A. L.;
Borchmann, D. E.; Lin, C.; Weck, M.; Woerpel, K. A. Org. Lett. 2014, 16, 1566-1569.
26 Fügedi, P.; Garegg, P. J. Carbohydr. Res. 1986, 149, C9-C12.
27 Kamat, M. N.; Rath, N. P.; Demchenko, A. V. J. Org. Chem. 2007, 72, 6938-6946.
28
Protonated TTBP is a strong acid with a pKa of 1.0, but much weaker than triflic acid. See Van der Pas, H.C.; Koudijs, A.,
Recl. Trav. Chim. Pays-Bas, 1978, 97, 159-161.
16