Dehydrative glycosidations of 2-deoxysugar derivatives catalyzed by an arylboronic ester

Article abstract of DOI:10.1016/j.carres.2018.10.002

An N-methylpyridinium-4-boronic ester acts as a catalyst for dehydrative glycosidations of 2-deoxy sugar-derived hemiacetals. The catalytic protocol is tolerant of functionalized acceptors, including alcohols bearing isopropylidene ketal, tert-butyl carbamate or benzyl carbamate groups. The results demonstrate that organoboron-catalyzed substitution reactions of alcohols, which have previously been conducted on π-activated (benzylic, allylic or propargylic) substrates, can also be used to achieve C–O bond formation from carbohydrate-derived hemiacetals.

Full text of DOI:10.1016/j.carres.2018.10.002

Accepted Manuscript
Dehydrative glycosidations of 2-deoxysugar derivatives catalyzed by an arylboronic
ester
Sanjay Manhas, Mark S. Taylor
PII:
S0008-6215(18)30457-9
10.1016/j.carres.2018.10.002
CAR 7612
DOI:
Reference:
To appear in: Carbohydrate Research
Received Date: 1 August 2018
Revised Date: 11 October 2018
Accepted Date: 11 October 2018
Please cite this article as: S. Manhas, M.S. Taylor, Dehydrative glycosidations of 2-deoxysugar
derivatives catalyzed by an arylboronic ester, Carbohydrate Research (2018), doi: https://
doi.org/10.1016/j.carres.2018.10.002.
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ACCEPTED MANUSCRIPT
Dehydrative Glycosidations of 2-Deoxysugar Derivatives Catalyzed by an Arylboronic
Ester
Sanjay Manhas and Mark S. Taylor*
Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON M5S 3H6
Canada
*Corresponding author. Tel. (+1)-416-946-0571.
E-mail address: mtaylor@chem.utoronto.ca
ORCID: 0000-0003-3424-4380
Abstract
An N-methylpyridinium-4-boronic ester acts as a catalyst for dehydrative glycosidations of 2-
deoxy sugar-derived hemiacetals. The catalytic protocol is tolerant of functionalized acceptors,
including alcohols bearing isopropylidene ketal, tert-butyl carbamate or benzyl carbamate groups.
The results demonstrate that organoboron-catalyzed substitution reactions of alcohols, which
have previously been conducted on π-activated (benzylic, allylic or propargylic) substrates, can
also be used to achieve C–O bond formation from carbohydrate-derived hemiacetals.
Graphical abstract
Keywords:
Boronic acid
Catalysis
2-Deoxyglycoside
Glycosidation

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1.
Introduction
The formation of an O-glycosidic bond generally involves the displacement of a leaving group
from the anomeric position of a carbohydrate-based electrophile (the glycosyl donor) by a
compound bearing a nucleophilic hydroxyl group (the glycosyl acceptor). Much of the
development of efficient chemical glycosylation methods has been centered around the
identification of leaving groups (often in conjunction with electrophilic activating reagents) that
provide advantages from such standpoints as reactivity, stereo- and/or regioselectivity, functional
group tolerance and operational simplicity. Broadly employed classes of glycosyl donors include
halides, trichloroacetimidates, sulfoxides, thioglycosides, glycal epoxides and pentenyl
glycosides; their properties and applications have been summarized in review articles and
monographs.1,2,3,4,5,6
The prospect of achieving a dehydrative glycosidation by formal nucleophilic displacement of
hydroxide at the anomeric position has attracted sustained interest. The Fischer glycosidation
stands as the prototype of such a process, wherein a C(1)-hemiacetal is activated by strong
Brønsted acid catalyst through the presumed intermediacy of its acyclic hydroxy aldehyde
tautomer.7 Although limitations of the method can be identified – including its incompatibility
with certain acid-labile functional groups and glycosidic linkages, and its reversible nature under
most commonly employed reaction conditions – the Fischer glycosidation continues to be
employed extensively, aided by the development of new protocols and catalysts.8,9,10 Over the
years, several other methods for dehydrative glycosidation have been developed, involving in situ
formation of such intermediates as glycosyl sulfonates, halides, imidates, oxophosphonium salts,
isoureas, oxotitanium complexes and oxosulfonium triflates.11,12 A common feature of these
methods is the requirement for a stoichiometric quantity of dehydrating reagent.

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Catalytic protocols (other than the classic Fischer glycosylation) for activation of 1-
hydroxyglycosyl donors are relatively uncommon: Lewis acids that have been successfully
employed in such catalytic, dehydrative glycosidations are Yb(OTf)3/ methoxyacetic acid,13
combinations of hexamethyldisiloxane with Sn(OTf)2, Yb(OTf)3, Ln(OTf)3 or SnCl2,14 silver(I)
perchlorate with diphenyltin sulfide or Lawesson’s reagent,15 and triphenylmethyl tetraarylborate
salts.16,17 Dehydrative glycosidations using amphiphilic sulfonic acids as catalysts in aqueous
solution have also been developed.18 Herein we report that electron-deficient boronic acids serve
as catalysts for dehydrative glycosylations of C(1)-hemiacetals derived from 2-deoxysugars.
Generation of activated glycosyl donors from 1-hydroxysugars appears to represent a new
application of the reversible carbohydrate–boronic acid interactions that have been shown to be
useful for protections, separations and chemical sensing of sugars.19,20,21
In previous work we have demonstrated that borinic acids (R2BOH) activate the equatorial
hydroxyl groups of carbohydrate-derived cis-1,2-diol motifs towards reactions with acyl, alkyl,
sulfonyl and glycosyl halide electrophiles. The proposed mechanism, which has been supported
by kinetic studies and computational modeling involves a tetracoordinate borinate ester as an
activated nucleophile. We have also employed boronic acids as protecting groups and activating
agents for carbohydrate derivatives.22,23,24,25,26 The proposal that coordination of hydroxyl groups
by organoboron compounds could trigger electrophilic, rather than nucleophilic, reactivity of
carbohydrates draws on observations reported by the groups of McCubbin and Hall. Electron-
deficient fluoroaryl-, pyridinium- or ferrocenium-based boronic acids or boronic esters were
shown to activate ionizable (benzylic, allylic and propargylic) alcohols towards Friedel–Crafts
reactions,27,28,29,30,31 1,3-transpositions,32 carbo- and heterocyclizations33 and other nucleophilic

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substitution reactions.34,35 Experimental evidence consistent with the organoboron-promoted
generation of carbocation intermediates was presented for certain catalyst/substrate combinations.
We sought to determine whether this mode of reactivity could be extended to the generation of
glycosyl donors by coordination of boronic acids or esters to the 1-OH group of carbohydrate
substrates (Scheme 1).36 Given that the majority of alcohol substrates that have been employed in
organoboron-catalyzed substitutions bear one or more carbocation-stabilizing groups, it was
unclear whether 1-hydroxycarbohydrates would be viable candidates for catalysis.37,38 We
selected C(1)-hemiacetals of 2-deoxysugars as test substrates because the lack of an electron-
withdrawing oxygen substituent at C(2) facilitates the generation of oxocarbenium ions. This
same feature contributes to the poor stability profiles of conventional 2-deoxyglycosyl donors,
and has served as motivation for the development of dehydrative glycosylations for this class of
compounds.39,40,41,42,43,44
Scheme 1. Boronic acid-catalyzed substitution reactions of π-activated (e.g., allylic, benzylic)
alcohols, and envisioned extension to anomeric hemiacetals.
2.
Results and Discussion
2.1. Catalyst optimization
The boronic acids and esters depicted in Figure 1 were evaluated as catalysts for the coupling of
hemiacetal 2a and isopropanol in 1,2-dichloroethane (DCE) at 100 °C in sealed vials. The results
are summarized in Table 1. Whereas phenylboronic acid (1a) displayed low activity,

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perfluorinated 1b catalyzed the formation of 3a in 55% yield as a mixture of anomers. Using the
more Lewis acidic catechol esters in place of the free boronic acids resulted in increased activity
(catalysts 1c–1f). Esters of N-methylpyridinium-4-boronic acid33,45 (1g–1i) provided the highest
glycosidation yields of the catalysts examined. When pyridinium-based catecholboronic ester 1i
was used as the catalyst, side product 4 was detected in the 1H NMR spectrum of the unpurified
reaction mixture. The particularly high Lewis acidity of 1i may have been responsible for the
formation of 4 by elimination and Ferrier rearrangement.46 Neopentyl glycol ester 1h was
selected as the optimal catalyst based on the data from Table 1.
Figure 1. Structures of organoboron catalysts evaluated as catalysts for glycosidation of 2a.
Table 1
Glycosidation of hemiacetal 2a with catalysts 1a–1i.

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Entry Catalyst Conversion of 2aa Yield of 3aa
1
2
3
4
5
6
7
8
9
10%
65%
10%
55%
50%
60%
60%
50%
90%
90%
85%b
1a
1b
1c
1d
1e
1f
50%
70%
60%
70%
100%
100%
100%
1g
1h
1i
a Conversion, yield and α:β ratio were determined by 1H NMR spectroscopy using a quantitative
internal standard. b Signals corresponding to side product 4 were evident in the 1H NMR
spectrum of the unpurified reaction mixture.
The organoboron-catalyzed protocol was applied to a range of glycosyl donors and acceptors
(Scheme 2). In a preparative experiment, compound 3a was isolated in 88% yield as a mixture of
anomers after purification by chromatography on silica gel. In general, good yields were obtained
for couplings of aliphatic alcohols (methanol, n-butanol, isopropanol and cyclohexanol) with
benzyl-protected hemiacetals 2a and 2b. The ratios of anomers were in agreement with those
obtained using other catalytic protocols for dehydrative glycosidation,14,17 and would be
consistent with thermodynamic control under these conditions. In keeping with this hypothesis,

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treatment of cyclohexyl glycoside 3b with isopropanol (10 equiv) in the presence of catalyst 1h
under the optimized conditions resulted in transglycosylation, generating a 5:1 mixture of
products 3a and 3b (Scheme 3). This observation indicates that glycosylation of 2a is indeed
reversible under the conditions developed in this study. A decrease in reactivity relative to 2a was
observed for the glycosidation of acetyl-protected hemiacetal 2c, as expected based on the
disarming effect of the ester protective groups.47 2,6-Dideoxyglycosides (3h, 3i) were also
prepared using catalyst 1h. In contrast, 2,3,4,6-tetra-O-benzylgalactopyranose 2f did not undergo
glycosidation under these conditions, presumably due to the destabilizing effect of the 2-alkoxy
substituent on species having oxocarbenium character.
The boronic ester-catalyzed dehydrative glycosidations were extended to more complex acceptor
alcohols (5a–5f). For these reactions, three equivalents of the glycosyl acceptor (rather than ten,
as was the case for the aliphatic alcohols) were employed. Isopropylidene ketals, as well as
benzyl and tert-butyl carbamate (Cbz and Boc) groups, were tolerated under the catalytic
conditions. The reactions of protected amino alcohols 5c–5e were significantly more α-selective
than those of the other glycosyl acceptors. Several other methods for the synthesis of α-2-
deoxyglycosides derived from protected amino alcohols have been reported
previously.48,49,50,51,52,53,54,55 A rationale for the higher stereoselectivity observed using 5c–5e
under the conditions of the present study is not readily apparent. To probe the possibility of a
specific interaction between the organoboron catalyst and the amino alcohol acceptor, the effect
of 5e on the 11B NMR spectrum of 1h was evaluated. No appreciable change in the 11B NMR
chemical shift of 1h was observed upon addition of 5e, suggesting that the two compounds do not
interact in a way that significantly alters the coordination environment at boron.
Scheme 2. Dehydrative glycosidations catalyzed by boronic ester 1h.a

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a Isolated yields after purification by silica gel chromatography without separation of anomers.
The conditions used for the synthesis of each product (Conditions A or B) are denoted in
parentheses after the yield and α:β ratio.
Scheme 3. Evidence for reversible glycosidation under the optimized conditions using catalyst
1h.

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3.
Conclusions
In conclusion, we have identified a boronic ester that serves as a catalyst for dehydrative
glycosidations of 2-deoxysugar-derived hemiacetals. A range of 2-deoxy- and 2,6-
dideoxyglycosides, derived from functionalized acceptors such as partially protected
carbohydrates and amino alcohol derivatives as well as simple aliphatic alcohols, can be
synthesized using the organoboron-catalyzed protocol. Unlike the majority of previously reported
catalysts for such dehydrative glycosidations, the organoboron catalysts allow for considerable
tuning of steric and electronic properties, as well as the potential for incorporation of other
catalytically reactive functional groups.56,57,58,59 In general, the method provides modest levels of
selectivity for the formation of α-glycosides. In the case of carbamate-protected amino alcohol
acceptors, the reactions display a significantly higher preference for formation of the α-glycoside
products.
The results indicate that organoboron catalysis of direct substitution reactions of alcohols can be
extended from π-activated substrates (the focus of previous research efforts in this area) to
anomeric hemiacetals. While the results presented here constitute a first step in this direction,
significant challenges remain. The relatively high reaction temperature (100 °C) and catalyst
loading (20 mol %), along with the failure to achieve glycosidation of the fully oxygenated
galactopyranosyl donor 2f, indicate that the activity of the optimal boronic ester identified in this
study is somewhat modest: it appears that glycosyl hemiacetals are at the threshold of the level of
reactivity needed for activation by boronic acids and their derivatives. Further evaluations of such

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substrates may be of interest as part of the ongoing effort to develop more active organoboron
catalysts for direct substitution reactions of alcohols.34,35,60
4.
Experimental
4.1. General Methods
All reactions were carried out under an argon atmosphere, unless specifically indicated. Stainless
steel needles and gas-tight syringes were used to transfer air- and moisture-sensitive liquids.
Flash chromatography was performed using neutral silica gel (Silicycle). Analytical thin layer
chromatography (TLC) was carried out using aluminium-backed silica gel 60 F254 plates (EMD)
and visualized using short-wave UV light or KMnO4 stain with appropriate heating. 1,2-
Dichloroethane was obtained from sure-seal 1L bottle (Sigma-Aldrich), under a balloon of argon.
Distilled water was obtained from an in-house supply. All other reagents and solvents were
purchased from Sigma Aldrich, Caledon, Carbosynth or Alfa Aesar and used without further
purification. Nuclear magnetic resonance (NMR) solvents were purchased from Cambridge
Isotope Laboratories. High resolution mass spectrometry (HRMS) was by direct analysis in real
time in positive ion mode (DART+) on a JEOL AccuTOF JMS-T1000LC.
Note regarding 1H NMR spectral data for compounds isolated as mixtures of anomers. Signals
from the 1H NMR spectrum corresponding to the major anomer are reported first (including those
overlapping with signals from the minor anomer), followed by well-resolved signals
corresponding to the minor anomer. The integrations were normalized to a well-resolved signal
corresponding to a single hydrogen from the major anomer, and the integrals for signals
corresponding to the minor anomer are reported relative to this normalized value for the major

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anomer. For peaks resulting from overlapping signals from the major and minor anomers, the
total integration is reported. These overlapping signals thus give integrals that are higher than the
expected number of corresponding hydrogens arising from the major anomer.
4.2. Catalyst 1h
4-Pyridineboronic acid (1 mmol, 122.9 mg) and neopentyl glycol (1 mmol, 104.15 mg) were
transferred to a long screw-cap vial. Toluene (4 mL) was added and the reaction was heated at
100 °C overnight. The resulting mixture was concentrated in vacuo and water was removed by
azeotrope with fresh toluene three times. To this crude product iodomethane (5 mmol, 311 µL)
and acetonitrile (4 mL) were added and heated at reflux (85 °C) overnight. After rotary
evaporation in a fume hood (an operation that removes excess iodomethane), the residue was
1
purified by trituration with hexanes to afford 1h as a yellow powder in quantitative yield. H
NMR (400 MHz, CDCl3): δ 9.18 (d, J = 6.1 Hz, 2H), 8.28 (d, J = 6.1 Hz, 2H), 4.72 (s, 3H), 3.83
13
11
(s, 4H), 1.04 (s, 6H). C NMR: 125 MHz, CDCl3): δ 144.2, 132.2, 72.8, 49.5, 32.0, 21.8. B
NMR (128 MHz, CDCl3): δ 25.5. HRMS (ESI+) Calculated for C11H17BNO2 [M+]: 205.1383,
found: 205.1381.
4.3. General procedure for glycosidation reactions
Glycosyl donor (0.2 mmol, 1 equiv.), glycosyl acceptor (0.6–2.0 mmol, 3–10 equiv.), and catalyst
(0.04 mmol, 0.2 equiv.), were transferred to a 2-dram vial containing a magnetic stir bar.
Anhydrous 1,2-dichloroethane (1 mL, 0.2 M) was added to the vial, and purged with a stream of
argon, and then quickly capped and sealed with Teflon™ tape. The reaction was heated at 100 °C
for 16–48 hours and monitored by TLC. The crude reaction mixture was concentrated and
purified by silica gel chromatography.

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4.4. Isopropyl 3,4,6-tri-O-benzyl-2-deoxy-
D
-galactopyranoside (3a, 5:1 α:β)
The reaction was conducted on a 0.2 mmol scale according to the general procedure (4.3) with 10
equivalents of isopropanol, from 3,4,6-tri-O-benzyl-2-deoxy-D-galactopyranose (86.9 mg). The
reaction time was 16 hours. Purification was by flash chromatography on silica gel
(pentanes/EtOAc, 95:5 → 90:10) The title compound was obtained as a colorless oil. Combined
yield (3a) = 83.8 mg, 0.176 mmol, 88%. The α:β ratio was determined to be 5:1 based on the
relative integrations of the signals at 5.10 ppm (α) and 3.47 ppm (β). Spectral data were
consistent with previous reports.61 1H NMR (400 MHz, CDCl3) Signals corresponding to
α
anomer: δ 7.39–7.21 (m, 18H), 5.13–5.06 (br d, J = 3.2 Hz, 1H, H-1α), 4.97–4.89 (d, J = 11.7 Hz,
1H), 4.69–4.57 (m, 4H), 4.54–4.41 (m, 3H), 4.05–3.92 (m, 3H), 3.92–3.84 (septet, J = 6.2 Hz, 1H,
CH-isopropyl), 3.66–3.52 (m, 3H), 2.31–2.19 (m, 1H), 1.98–1.90 (m, 1H), 1.18 (d, J = 6.3 Hz,
3H, CH3-isopropyl), 1.13 (d, J = 6.3 Hz, 3H, CH3-isopropyl) Representative signals
corresponding to
β anomer: 3.84–3.80 (m, 0.2H), 3.80–3.76 (m, 0.4H), 3.46 (m, 0.2H), 2.11 (m,
0.2H), 2.01 (m, 0.2H), 1.23 (d, J = 6.2 Hz, 0.6H, CH3-isopropyl). 13C NMR (126 MHz, CDCl3)
(anomeric mixture) δ 139.1, 139.0, 138.8, 138.7, 138.3, 138.3, 128.6, 128.6, 128.5, 128.5, 128.5,
128.4, 128.3, 128.3, 128.3, 128.1, 128.0, 127.9, 127.9, 127.8, 127.8, 127.7, 127.6, 127.6, 127.6,
127.5, 127.4, 97.3, 95.7, 75.2, 75.0, 74.4, 74.2, 73.7, 73.6, 73.6, 73.3, 73.2, 70.6, 70.6, 70.3, 70.2,
69.9, 69.7, 69.1, 68.4, 31.8, 30.5, 23.5, 21.5. HRMS (DART+): calculated for C30H40NO5
[M+NH4]+: 494.2907, found: 494.2907.
4.5. Cyclohexyl 3,4,6-tri-O-benzyl-2-deoxy-D-galactopyranoside (3b, 4:1 α:β)

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The reaction was conducted on a 0.2 mmol scale according to the general procedure (4.3) with 10
equivalents of cyclohexanol, from 3,4,6-tri-O-benzyl-2-deoxy-D-galactopyranose (86.9 mg). The
reaction time was 16 hours. Purification was by flash chromatography on silica gel
(pentanes/EtOAc, 100:0 → 80:20). The title compound was obtained as a colorless oil. Combined
yield (3b) = 86.3 mg, 0.167 mmol, 84%. The α:β ratio was determined to be 4:1 based on the
relative integrations of the signals at 5.12 ppm (α) and 2.11 ppm (β). Spectral data for the α
anomer were consistent with previous reports.53 1H NMR (400 MHz, CDCl3) Signals
corresponding to
α anomer: δ 7.43–7.20 (m, 19H), 5.16–5.11 (d, J = 3.6 Hz, 1H), 4.97–4.91 (d, J
= 11.7 Hz, 1H), 4.70–4.39 (m, 7H), 4.05–3.89 (m, 3H), 3.69–3.48 (m, 5H), 2.31–2.18 (m, 1H),
1.98–1.91 (m, 1H), 1.91–1.78 (m, 2H), 1.78–1.61 (m, 3H), 1.54–1.46 (m, 1H), 1.44–1.03 (m, 8H).
Representative signals corresponding to
β anomer: 3.82–3.80 (m, 0.25H), 3.79–3.75 (m, 0.25H),
3.48–3.43 (m, 0.25H), 2.18–2.05 (m, 0.25H), 2.04–2.00 (m, 0.25 H). 13C NMR (100 MHz,
CDCl3) δ 139.1, 138.8, 138.3, 128.5, 128.5, 128.5, 128.3, 128.2, 127.9, 127.8, 127.7, 127.6,
127.6, 127.4, 127.4, 98.3, 95.7, 75.2, 74.6, 74.4, 73.6, 73.5, 73.3, 70.6, 70.0, 69.8, 33.6, 31.9,
31.8, 25.8, 24.5, 24.3, 24.2. HRMS (DART+): calculated for C33H44NO5 [M+NH4]+: 534.3220,
found: 534.3228.
4.6. n-Butyl 3,4,6-tri-O-benzyl-2-deoxy-D-galactopyranoside (3c, 4:1 α:β)
The reaction was conducted on a 0.2 mmol scale according to the general procedure (4.3) with 10
equivalents of n-butanol, from 3,4,6-tri-O-benzyl-2-deoxy-D-galactopyranose (86.9 mg). The
reaction time was 16.5 hours. Purification was by flash chromatography on silica gel
(hexanes/diethyl ether 95:5 → 70:30). The title compound was obtained as a colorless oil.
Combined yield (3c) = 87.8 mg, 0.179 mmol, 90%. The α:β ratio was determined to be 4:1 based
1
on the relative integrations of the signals at 4.97 ppm (α) and 3.83 ppm (β). H NMR (400 MHz,

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CDCl3) Signals corresponding to
α anomer: δ 7.39–7.22 (m, 19H), 4.97 (br. d, J = 3.8, 1H), 4.93
(d, J = 11.6 Hz, 1H), 4.68–4.38 (m, 7H), 4.00–3.85 (m, 3H), 3.69–3.52 (m, 4H), 3.44–3.32 (m,
1H), 2.27–2.17 (m, 1H), 2.02–1.96 (m, 1H), 1.57–1.44 (m, 3H), 1.43–1.30 (m, 3H), 0.94–0.89 (t,
J = 7.4 Hz, 3H). Representative signals corresponding to
β anomer: 3.83 (m, 0.25H), 3.49–3.45
(ddd, J = 6.9, 5.6, 1.2 Hz, 0.25H), 2.14–2.03 (m, 0.5H). 0.92–0.89 (t, J = 7.3 Hz, 0.75H). 13C
NMR (126 MHz, CDCl3) (anomeric mixture) δ 138.9, 138.9, 138.6, 138.3, 138.1, 138.1, 128.4,
128.4, 128.4, 128.3, 128.3, 128.2, 128.2, 128.1, 127.8, 127.7, 127.7, 127.6, 127.6, 127.5, 127.4,
127.4, 127.3, 127.3, 100.4, 97.7, 74.9, 74.2, 73.5, 73.4, 73.0, 70.4, 70.1, 69.8, 69.6, 67.2, 31.6,
31.3, 19.4, 13.9. HRMS (DART+): calculated for C31H42NO5 [M+NH4]+: 508.3063, found:
508.3063.
4.7. Methyl 3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranoside (3d, 5:1 α:β)
The reaction was conducted on a 0.2 mmol scale according to the general procedure (4.3) with 10
equivalents of methanol, from 3,4,6-tri-O-benzyl-2-deoxy- -glucopyranose (86.9 mg). The
D
reaction time was 16 hours. Purification was by flash chromatography on silica gel
(hexanes/diethyl ether, 95:5 → 70:30). The title compound was obtained as a colorless oil.
Combined yield (3d) = 67.4 mg, 0.150 mmol, 75%. The α:β ratio was determined to be 5:1 based
on the relative integrations of the signals at 2.28 ppm (α) and 2.34 ppm (β). Spectral data were
consistent with previous reports.61 1H NMR (400 MHz, CDCl3) Signals corresponding to
α
anomer: δ 7.39–7.16 (m, 18H), 4.93–4.87 (d, J = 10.9 Hz, 1H), 4.87–4.83 (m, 1H), 4.73–4.47 (m,
6H), 4.04–3.89 (ddd, J = 11.5, 8.7, 5.1 Hz, 1H), 3.83–3.56 (m, 5H), 3.55–3.40 (m, 1H), 3.34–
3.27 (s, 3H), 2.31–2.25 (m, 1H), 1.79–1.68 (m, 1H). Representative signals corresponding to
β
anomer: 4.38–4.33 (dd, J = 9.7, 2.0 Hz, 0.2H), 2.37–2.31 (m, 0.2H), 1.68–1.57 (m, 0.2H). 13C
NMR (126 MHz, CDCl3) (anomeric mixture) δ 138.8, 138.7, 138.5, 138.4, 138.3, 128.6, 128.5,

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128.5, 128.4, 128.1, 128.0, 127.9, 127.8, 127.8, 127.7, 127.7, 100.9, 98.6, 79.5, 79.3, 78.3, 77.8,
75.3, 75.0, 74.9, 73.6, 71.9, 71.6, 70.8, 70.7, 69.4, 69.1, 56.7, 54.7, 36.7, 35.5. HRMS (DART+):
calculated for C28H36NO5 [M+NH4]+: 466.2594, found: 466.2599.
4.8. Isopropyl 3,4,6-tri-O-benzyl-2-deoxy-
The reaction was conducted on a 0.2 mmol scale according to general procedure (4.3) with 10
equivalents of isopropanol, from 3,4,6-tri-O-benzyl-2-deoxy- -glucopyranose (86.9 mg). The
D-glucopyranoside (3e, 5:1 α:β)
D
reaction time was 16 hours. Purification was by flash chromatography on silica gel
(hexanes/diethyl ether, 95:5 → 70:30). The title compound was obtained as a colorless oil.
Combined yield (3e) = 84.9 mg, 0.178 mmol, 89%. The α:β ratio was determined to be 5:1 based
on the relative integrations of the signals at 5.08 ppm (α) and 2.32 ppm (β). Spectral data were
consistent with previous reports.62 1H NMR (400 MHz, CDCl3) Signals corresponding to
α
anomer: δ 7.37–7.16 (m, 18H), 5.08 (m, 1H), 4.89 (d, J = 10.8 Hz, 1H), 4.73–4.43 (m, 7H),
4.08–3.95 (m, 1H), 3.94–3.84 (h, J = 6.2 Hz, 1H), 3.85–3.58 (m, 5H), 2.27–2.21 (ddd, J = 12.8,
5.1, 1.4 Hz, 1H), 1.77–1.70 (m, 1H), 1.16 (d, J = 6.2 Hz, 3H), 1.14–1.10 (d, J = 6.1 Hz, 3H).
Representative signals corresponding to
β anomer: 3.51–3.45 (m, 0.2H), 3.44–3.38 (dd, J = 5.2,
1.9 Hz, 0.2H), 2.33–2.28 (ddd, J = 12.5, 5.1, 2.0 Hz, 0.2H), 1.70–1.62 (m, 0.2H), 1.28–1.25 (d, J
= 6.1 Hz, 0.6H, CH3-isopropyl). 13C NMR (126 MHz, CDCl3) (anomeric mixture) δ 139.0,
138.7, 138.6, 138.6, 138.5, 138.3, 128.6, 128.5, 128.5, 128.5, 128.5, 128.5, 128.5, 128.2, 128.2,
128.0, 127.9, 127.8, 127.8, 127.8, 127.7, 127.7, 127.7, 127.6, 127.6, 98.0, 95.2, 79.8, 78.6, 78.4,
78.0, 75.3, 75.2, 75.1, 73.6, 73.6, 71.9, 71.5, 70.8, 69.7, 69.1, 68.3, 37.4, 36.1, 23.7, 23.5, 22.0,
21.4. HRMS (DART+): calculated for C30H36NO5 [M+NH4]+: 494.2920, found: 494.2916.
4.9. Cyclohexyl 3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranoside (3f, 3:1 α:β)

ACCEPTED MANUSCRIPT
The reaction was conducted on a 0.2 mmol scale according to the general procedure (4.3) with 10
equivalents of cyclohexanol, from 3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranose (86.9 mg). The
reaction time was 16 hours. Purification was by flash chromatography on silica gel
(hexane/diethyl ether 95:5 → 70:30). The title compound was obtained as a colorless oil.
Combined yield (3f) = 84.9 mg, 0.164 mmol, 82%. The α:β ratio was determined to be 3:1 based
on the relative integrations of the signals at 2.24 ppm (α) and 2.31 ppm (β). Spectral data were
consistent with previous reports.62 1H NMR (400 MHz, CDCl3) Signals corresponding to
α
anomer: δ 7.41–7.14 (m, 20H), 5.12 (d, J = 3.8 Hz, 1H), 4.94–4.85 (d, J = 10.8 Hz, 1H), 4.72–
4.47 (m, 8H), 4.08–3.97 (m, 1H), 3.90–3.51 (m, 7H), 2.27–2.20 (ddd, J = 12.8, 5.1, 1.4 Hz, 1H),
1.93–1.79 (m, 2H), 1.79–1.61 (m, 3H), 1.54–1.47 (m, 2H), 1.46–1.07 (m, 7H). Representative
signals corresponding to
β
anomer: 3.50–3.44 (m, 0.3H), 3.44–3.38 (ddd, J = 9.6, 5.2, 1.9 Hz,
13
0.3H), 2.35–2.28 (ddd, J = 12.5, 5.1, 1.9 Hz, 0.3H), 2.05–1.95 (m, 0.3H). C NMR (126 MHz,
CDCl3) δ 139.0, 138.7, 138.6, 138.6, 138.4, 138.3, 128.6, 128.5, 128.5, 128.4, 128.2, 128.1,
128.1, 128.0, 127.9, 127.8, 127.8, 127.7, 127.7, 127.6, 97.9, 95.2, 79.8, 78.7, 78.4, 78.0, 75.3,
75.2, 74.5, 73.6, 73.5, 73.5, 71.9, 71.4, 71.1, 70.9, 69.7, 69.2, 37.4, 36.2, 33.9, 33.6, 32.1, 31.6,
25.9, 24.4, 24.2. HRMS (DART+): calculated for C33H44NO5 [M+NH4]+: 534.3220, found:
534.3222.
4.10. Cyclohexyl 3,4,6-tri-O-acetyl-2-deoxy-
The reaction was conducted on a 0.2 mmol scale according to the general procedure (4.3) with 10
equivalents of cyclohexanol, from 3,4,6-tri-O-acetyl-2-deoxy- -galactopyranose (58.0 mg). The
D-galactopyranoside (3g, 6:1 α:β)
D
reaction time was 48 hours. Purification was by flash chromatography on silica gel
(pentanes/EtOAc, 100:0 → 80:20). The title compound was obtained as a colorless oil. Combined
yield (3g) = 52.5 mg, 0.141 mmol, 71%. The α:β ratio was determined to be 6:1 based on the

ACCEPTED MANUSCRIPT
relative integrations of the signals at 5.17 ppm (α) and 5.24 ppm (β). Spectral data for the α
anomer were consistent with previous reports. 63 1H NMR (400 MHz, CDCl3) Signals
corresponding to
α anomer: δ 5.35–5.26 (m, 2H), 5.18–5.14 (m, 1H), 4.27–4.03 (m, 3H), 3.59–
3.50 (m, 1H), 2.14 – 2.11 (s, 3H), 2.11–2.05 (m, 2H), 2.04 (s, 3H), 1.97 (s, 3H), 1.91–1.78 (s,
3H), 1.78–1.68 (m, 3H), 1.68–1.47 (m, 2H), 1.46–1.11 (m, 7H). Representative signals
corresponding to
β
anomer: 5.24 (m, 0.17H), 5.03–4.95 (m, 0.17H), 4.80–4.75 (dt, J = 7.0, 1.3
13
Hz, 0.17H), 4.68–4.63 (m 0.17H), 3.80–3.75 (m, 0.2H), 3.69–3.61 (m, 0.2H), 1.99 (s, 0.5H), C
NMR (126 MHz, CDCl3) (anomeric mixture – representative signals corresponding to the β
anomer are listed) δ 170.6, 170.5, 170.2, 98.3, 95.7, 75.6, 71.0, 68.9, 67.0, 66.8, 66.6, 65.5, 62.8,
61.9, 33.7, 33.5, 32.7, 32.0, 31.7, 30.9, 25.7, 24.4, 24.1, 21.0, 20.9, 20.9. HRMS (DART+):
calculated for C18H32NO8 [M+NH4]+: 390.2128, found: 390.2133.
4.11. Cyclohexyl 3,4-di-O-benzyl-2-deoxy-
The reaction was conducted on a 0.2 mmol scale according to the general procedure (4.3) with 10
equivalents of cyclohexanol, from 3,4-di-O-benzyl-2-deoxy- -rhamnopyranose (65.7 mg). The
L-rhamnopyranoside (3h, 3:1 α:β)
L
reaction time was 19 hours. Purification was by flash chromatography on silica gel
(pentanes/diethyl ether, 100:0 → 90:10) The title compound was obtained as a colorless oil.
Combined yield (3h) = 71.3 mg, 0.174 mmol, 87 %. The α:β ratio was determined to be 3:1
based on the relative integrations of the signals at 2.25 ppm (α) and 2.30 ppm (β). Spectral data
were consistent with previous reports.64 1H NMR (400 MHz, CDCl3) Signals corresponding to
α
anomer: δ 7.39–7.26 (m, 13H), 5.02 (m, 1H), 4.98–4.93 (d, J = 10.8 Hz, 1H), 4.72–4.61 (m,
4H), 4.03–3.94 (m, 1H), 3.86–3.77 (m, 1H), 3.56–3.45 (m, 1H), 3.19–3.08 (m, 1H), 2.27–2.21
(ddd, J = 12.6, 5.1, 1.4 Hz, 1H), 1.92–1.77 (m, 2H), 1.77–1.60 (m, 4H), 1.60–1.44 (m, 2H), 1.43–

ACCEPTED MANUSCRIPT
1.12 (m, 12H). Representative signals corresponding to
β
anomer: 4.95 (d, J = 10.8 Hz, 0.3 H),
4.61–4.57 (m, 0.3H), 4.57–4.52 (dd, J = 9.8, 2.0 Hz, 0.3H), 3.68–3.57 (m, 0.6H), 3.37–3.26 (m,
13
0.3H), 2.34–2.27 (ddd, J = 12.5, 5.1, 2.0 Hz, 0.3H), 2.00–1.92 (m, 0.3H). C NMR (126 MHz,
CDCl3) (anomeric mixture) δ 138.8, 138.7, 138.6, 138.5, 128.3, 128.1, 128.0, 127.7, 127.6, 127.6,
127.5, 97.3, 94.7, 84.6, 84.6, 83.7, 79.4, 77.6, 75.3, 75.3, 74.7, 74.2, 71.7, 71.2, 67.2, 67.1, 37.7,
37.5, 36.3, 33.7, 33.7, 33.4, 33.0, 31.9, 31.5, 25.7, 24.3, 24.0, 18.2, 18.1. HRMS (DART+):
calculated for C26H38NO4 [M+NH4]+: 428.2801, found: 428.2810.
4.12. Cyclohexyl 3,4-di-O-acetyl-2-deoxy-L-rhamnopyranoside (3i, 6:1 α:β)
The reaction was conducted on a 0.2 mmol scale according to the general procedure (4.3) with 10
equivalents of cyclohexanol, from 3,4-di-O-acetyl-2-deoxy- -rhamnopyranose (46.5 mg). The
L
reaction time was 48 hours. Purification was by flash chromatography on silica gel
(pentanes/ethyl acetate, 100:0 → 90:10) The title compound was obtained as a colorless oil.
Combined yield (2.62) = 37.2 mg, 0.118 mmol, 59 %. The α:β ratio was determined to be 6:1
based on the relative integrations of the signals at 5.02 ppm (α) and 4.96 ppm (β). 1H NMR (500
MHz, CDCl3): Signals corresponding to
α anomer: δ 5.37–5.25 (ddd, J = 11.7, 9.4, 5.4 Hz, 1H),
5.02 (d, J = 3.8 Hz, 1H), 4.78–4.68 (m, 1H), , 3.98–3.88 (dq, J = 9.8, 6.3 Hz, 1H), 3.58–3.49 (m,
1H), 2.20– 2.12 (ddd, J = 12.7, 5.4, 1.3 Hz, 1H), 2.05 (s, 3H), 2.00 (s, 3H), 1.89–1.66 (m, 6H),
1.61–1.47 (m, 2H), 1.45–1.18 (m, 7H), 1.18–1.13 (d, J = 6.3 Hz, 3H). Representative signals
corresponding to
β anomer: 5.00–4.92 (ddd, J = 11.9, 9.4, 5.3 Hz, 0.17H), 4.68–4.63 (dd, J =
9.7, 2.0 Hz, 0.17H), 3.68–3.60 (m, 0.17H), 3.48–3.41 (dq, J = 9.6, 6.2 Hz, 0.17H), 2.27–2.22
(ddd, J = 12.5, 5.3, 2.0 Hz, 0.17H), 2.04 (s, 0.5H), 2.02 (s, 0.5H), 13C NMR (125 MHz, CDCl3)

ACCEPTED MANUSCRIPT
δ 170.5, 170.4, 170.4, 170.1, 97.1, 94.6, 76.8, 75.3, 74.9, 74.3, 71.0, 70.0, 69.4, 65.6, 37.1, 36.0,
33.6, 33.5, 31.9, 31.5, 25.7, 25.7, 24.3, 24.3, 24.1, 24.0, 21.1, 21.1, 21.0, 20.9, 17.8, 17.6. HRMS
(DART+): calculated for C16H30NO6 [M+NH4]+: 332.2073, found: 332.2072.
4.13
6-O-(3,4,6-Tri-O-benzyl-2-deoxy-D-galactopyranosyl)-1,2:3,4-di-O-isopropylidene-D-
galactopyranoside (3j, 3:1 α:β)
The reaction was conducted on a 0.2 mmol scale according to the general procedure (4.3) with 3
equivalents of acceptor, from 3,4,6-tri-O-benzyl-2-deoxy- -galactopyranose (86.9 mg). The
D
reaction time was 21 hours. Purification was by flash chromatography on silica gel
(pentanes/diethyl ether, 100:0 → 50:50). The title compound was obtained as a colorless oil.
Combined yield (3j) = 96.8 mg, 0.140 mmol, 70%. Spectral data were consistent with previous
reports.53,65 Note: the product was isolated as a mixture of anomers, but individual fractions of
pure α and β anomers obtained upon column chromatography were used for characterization
purposes. The α:β ratio was determined to be 3:1 based on the relative integrations of the signals
1
at 4.23 ppm (α) and 4.18 ppm (β). H NMR (500 MHz; CDCl3): δ (α anomer): 7.39–7.23 (m,
15H, CH2Ph), 5.54 (d, J = 5.0 Hz, 1H, H-1'), 5.04 (br. d, J = 3.0 Hz, 1H, H-1), 4.94 (d, J = 11.6
Hz, 1H, CH2Ph), 4.64 (d, J = 11.8 Hz, 1H, CH2Ph), 4.62–4.57 (m, 3H, H-3', CH2Ph), 4.51 (d, J =
11.8 Hz, 1H, CH2Ph), 4.44 (1H, d, J = 11.8 Hz, CH2Ph), 4.32 (dd, J = 5.0 Hz, 2.5 Hz, 1H, H-2'),
4.23 (dd, J = 8.0 Hz, 1.9 Hz, 1H, H-4'), 4.01–3.94 (m, 4H, H-3, H-4, H-5, H-5'), 3.77 (dd, J =
10.7 Hz, 6.7 Hz, 1H, H-6a), 3.69 (dd, J = 10.7 Hz, 6.4 Hz, 1H, H-6b), 3.64 (dd, J = 9.2 Hz, 7.5
Hz, 1H, H-6a'), 3.57 (dd, J = 9.2 Hz, 5.7 Hz, 1H, H-6b'), 2.24 (app td, J = 12.5 Hz, 3.7 Hz, 1H,
H-2a), 2.05 (m, 1H, H-2b), 1.53 (s, 3H, CH3), 1.44 (s, 3H, CH3), 1.35 (s, 6H, 2 x CH3). 13C
NMR (125 MHz; CDCl3): δ (α anomer): 139.0, 138.7, 138.2, 128.5, 128.3, 128.3, 127.9, 127.7,

ACCEPTED MANUSCRIPT
127.6, 127.5, 127.4, 109.4, 108.6, 97.6, 96.5, 74.8, 74.4, 73.5, 73.0, 71.2, 70.8, 70.7, 70.5, 69.9,
1
69.3, 65.9, 65.6, 31.2, 26.2, 26.1, 25.1, 24.7. H NMR (500 MHz; CDCl3): δ (β anomer): 5.54
(d, J = 5.0 Hz, 1H, H-1'), 4.92 (d, J = 11.7 Hz, 1H, CH2Ph), 4.64 (d, J = 11.7 Hz, 1H, CH2Ph),
4.62–4.52 (m, 3H, H-3', CH2Ph), 4.48 (dd, J = 9.7 Hz, 2.2 Hz, 1H, 1H, H-1), 4.46 (d, J = 11.8
Hz, 1H, CH2Ph), 4.42 (d, J = 11.8 Hz, 1H, CH2Ph), 4.29 (dd, J = 5.0 Hz, 2.4 Hz, 1H H-2'), 4.18
(dd, J = 7.9 Hz, 1.9 Hz, 1H, H-4'), 4.06 (dd, J = 11.1 Hz, 2.9 Hz, 1H, H-5'), 3.99 (m, 1H, H-6a'),
3.62–3.44 (m, 5H, H-3, H-4, H5, H-6a, H-6b), 2.18 (m, 1H, H-2a), 2.08 (m, 1H, H-2b), 1.52(s,
3H, CH3), 1.42 (s, 3H, CH3), 1.32 (s, 3H, CH3), 1.30 (s, 3H, CH3). 13C NMR (125 MHz;
CDCl3): δ (β anomer): 139.1, 138.5, 138.2, 128.6, 128.5, 128.5, 128.4, 128.2, 128.0, 127.8,
127.7, 127.5, 127.4, 109.4, 108.8, 101.1, 96.5, 74.3, 74.1, 73.6, 71.9, 71.7, 70.9, 70.6, 70.2, 69.3,
68.8, 68.1, 32.8, 30.5, 29.9, 26.2, 26.1, 25.2, 24.5. HRMS (DART+): calculated for C39H48NO10
[M+NH4]+: 694.3585, found: 694.3589.
4.14. 3-O-(3,4,6-Tri-O-benzyl-2-deoxy-D-galactopyranosyl)-1,2:5,6-di-O-isopropylidene-D-
glucofuranoside (3k, 6:1 α:β)
The reaction was conducted on a 0.2 mmol scale according to the general procedure (4.3) with 3
equivalents of diacetone glucose, from 3,4,6-tri-O-benzyl-2-deoxy- -galactopyranose (86.9 mg).
D
The reaction time was 19 hours. Purification was by flash chromatography on silica gel
(pentanes/diethyl ether, 100:0 → 80:20). The title compound was obtained as a colorless oil.
Combined yield (3k) = 72.6 mg, 0.107 mmol, 54%. The α:β ratio was determined to be 6:1 based
on the relative integrations of the signals at 5.24 ppm (α) and 5.99 ppm (β). Spectral data were
1
consistent with previous reports.53,61,65 For the following H NMR data, a mixture of an
1
alpha/beta anomer peak was used as the reference proton corresponding to 1H. H NMR (500

ACCEPTED MANUSCRIPT
MHz; CDCl3): Signals corresponding to
α
anomer: δ 7.44–7.21 (m, 18H), 5.85–5.79 (d, J = 3.6
Hz, 1H), 5.27–5.21 (m, 1H), 4.96–4.89 (d, J = 11.6 Hz, 1H), 4.69–4.65 (d, J = 3.6 Hz, 1H), 4.65–
4.36 (m, 7H), , 4.23–4.20 (d, J = 2.8 Hz, 1H), 4.20–4.13 (m, 1H), 4.12–4.02 (m, 2H), 4.00–3.76
(m, 5H), 3.76–3.65 (m, 1H), 3.65–3.45 (m, 3H), 2.27–2.19 (dd, J = 12.7, 3.8 Hz, 1H), 2.04–1.91
(dd, J = 12.7, 4.5 Hz, 1H), 1.47 (s, 3H), 1.39 (s, 3H), 1.32 (s, 4H), 1.20 (s, 3H). Representative
signals corresponding to
β anomer: 6.00–5.97 (d, J = 3.7 Hz, 0.16H), 5.04–5.00 (m, 0.16H), 4.26
(m, 0.16H). 13C NMR (126 MHz, CDCl3) (anomeric mixture) δ 139.1, 138.8, 138.6, 138.5,
138.3, 138.1, 128.6, 128.5, 128.5, 128.5, 128.4, 128.3, 128.2, 128.1, 127.9, 127.9, 127.8, 127.8,
127.8, 127.7, 127.7, 127.6, 127.6, 127.5, 127.5, 125.7, 112.3, 111.9, 109.2, 106.5, 105.4, 100.9,
100.0, 99.6, 97.7, 84.1, 83.7, 81.4, 81.0, 79.6, 79.4, 75.1, 74.6, 74.5, 74.4, 73.7, 73.6, 73.4, 73.1,
73.1, 72.9, 72.7, 71.3, 71.1, 70.6, 70.5, 70.2, 70.0, 69.8, 69.4, 67.7, 67.3, 36.8, 31.2, 30.5, 30.3,
29.8, 27.3, 27.0, 26.9, 26.7, 26.3, 25.5, 24.1, 24.1.HRMS (DART+): calculated for C39H52NO10
[M+NH4]+: 694.3585, found: 694.3567.
4.15. O-(3,4,6-Tri-O-benzyl-2-deoxy-D-galactopyranosyl)-N-[(carboxybenzyl)]-
ethanolamine (3l, >19:1 α:β)
The reaction was conducted on a 0.2 mmol scale according to the general procedure (4.3) with 3
equivalents of acceptor, from 3,4,6-tri-O-benzyl-2-deoxy- -galactopyranose (86.9 mg). The
D
reaction time was 16 hours. Purification was by flash chromatography on silica gel
(pentanes/EtOAc, 100:0 ‰ 70:30). The title compound was obtained as a colorless oil. Combined
yield (3l) = 115.5 mg, 0.189 mmol, 94%. 1H NMR (500 MHz; CDCl3): δ (α anomer) 7.38–7.23
(m, 20H, CH2Ph), 5.38 (br t, J = 5.60 Hz, 1H, NH), 5.09 (br s, 2H, CH2Ph - CBz group), 4.98 (br
d, J = 3.4 Hz, 1H, H-1), 4.92 (d, J = 11.8 Hz, 1H, CH2Ph), 4.60 (d, J = 11.8 Hz, 1H, CH2Ph),

ACCEPTED MANUSCRIPT
4.59 (br s, 2H, CH2Ph), 4.49 (d, J = 12.0 Hz, 1H, CH2Ph), 4.40 (d, J = 12.0 Hz, 1H, CH2Ph),
3.94–3.83 (m, 3H, H-3, H-6, H-6'), 3.72–3.63 (m, 1H, H-ethanolamine), 3.63–3.53 (m, 2H, H-4,
H-ethanolamine), 3.53–3.45 (m, 1H, H-5), 3.45–3.30 (m, 2H, H-ethanolamine), 2.23 (app dt, J =
12.9 Hz, 4.0 Hz, H-2ax), 1.98 (m, 1H, H-2eq) 13C NMR (125 MHz; CDCl3) δ 156.6, 138.9, 138.6,
138.0, 136.7, 128.6, 128.6, 128.5, 128.5, 128.5, 128.4, 128.3, 128.3, 128.2, 128.1, 128.0, 127.8,
127.8, 127.7, 127.7, 127.7, 127.4, 98.5 (C-1α), 74.8, 74.3, 73.6, 73.1, 70.6, 70.5, 70.4, 70.0, 67.6,
66.8, 41.2, 31.3). MS (DART+): found: 629.3. [α]D20: 21.4 (c 1.0, CHCl3)
4.16. O-(3,4,6-Tri-O-benzyl-2-deoxy-D-galactopyranosyl)-N-[(carboxybenzyl)]-L-serine
methyl ester (3m, >19:1 α:β)
The reaction was conducted on a 0.2 mmol scale according to the general procedure (4.3) with 3
equivalents of acceptor, from 3,4,6-tri-O-benzyl-2-deoxy- -galactopyranose (86.9 mg). The
D
reaction time was 18 hours. Purification was by flash chromatography on silica gel
(pentanes/diethyl ether, 100:0 → 50:50). The title compound was obtained as a colorless oil.
Combined yield (3m) = 110.9 mg, 0.166 mmol, 83%. 1H NMR (500 MHz, CDCl3): δ 7.37–7.21
(m, 20H, CH2Ph), 5.80 (d, J = 8.7 Hz, 1H, N-H), 5.11 (d, J = 12.2, 1H, CH2Ph), 5.09 (d, J = 12.2,
1H, CH2Ph), 4.92 (br. d, J = 3.5 Hz, 1H, H-1), 4.90 (d, J = 11.7 Hz, 1H, CH2Ph), 4.62–4.54 (m,
3H, CH2Ph), 4.54–4.49 (m, 1H, H-serine), 4.48 (d, J = 11.8 Hz, 1H, CH2Ph), 4.38 (d, J = 11.8
Hz, 1H, CH2Ph), 3.96 (dd, J = 10.7 Hz, 3.7 Hz, 1H, HS1), 3.90–3.79 (m, 4H, H3, H4, HS2, H6),
3.73 (s, 3H, serine ester CH3), 3.60–3.48 (m, 2H, H5, H6'), 2.19 (app td, J = 12.4 Hz, 3.9 Hz, 1H,
H2ax), 1.93 (app dd, J = 12.4 Hz, 4.5 Hz, 1H, H2eq); 13C NMR (125 MHz; CDCl3) δ 170.9,
156.2, 138.8, 138.4, 138.1, 136.3, 128.6, 128.5, 128.5, 128.3, 128.3, 128.3, 127.9, 127.7, 127.7,

ACCEPTED MANUSCRIPT
127.7, 127.5, 127.5, 99.2, 74.4, 74.4, 74.5, 72.8, 70.6, 70.6, 69.5, 68.8, 67.2, 54.6, 52.7, 31.1. MS
(DART+): found: 670.3. [α]D20: 33.8 (c 1.0, CHCl3).
4.17. O-(3,4,6-Tri-O-benzyl-2-deoxy-D-galactopyranosyl)-N-[(tert-butyloxycarbonyl)]-L-
serine methyl ester (3n, >19:1 α:β)
The reaction was conducted on a 0.2 mmol scale according to the general procedure (4.3) with 3
equivalents of diacetone glucose, from 3,4,6-tri-O-benzyl-2-deoxy- -galactopyranose (86.9 mg).
D
The reaction time was 17 hours. Purification was by flash chromatography on silica gel
(pentanes/diethyl ether, 100:0 → 80:20). The title compound was obtained as a colorless oil.
Combined yield (3n) = 70.6 mg, 0.111 mmol, 56%. Spectral data were consistent with previous
reports.53 1H NMR (400 MHz, CDCl3): δ 7.40–7.21 (m, 15H), 5.44 (d, J = 9.0 Hz, 1H, N-H),
4.96–4.87 (m, 2H), 4.69–4.37 (m, 6H), 3.96–3.78 (m, 5H), 3.72 (s, 3H), 3.57 (m, 2H), 2.25–2.15
13
(m, 1H), 1.94 (dd, J = 12.7, 4.6 Hz, 1H), 1.44 (s, 9H). C NMR (126 MHz, CDCl3) δ 171.2,
155.6, 138.9, 138.5, 138.1, 128.5, 128.5, 128.3, 127.9, 127.8, 127.7, 127.7, 127.5, 99.0, 80.2,
74.5, 74.4, 73.6, 72.8, 70.6, 70.4, 69.3, 68.7, 54.1, 52.6, 31.1, 30.5, 28.5. HRMS (ESI+):
calculated for C36H46NO9 [M+H]+: 636.3167, found: 636.3165.
4.18. Dihydrocholesteryl 3,4,6-tri-O-benzyl-2-deoxy-D-galactopyranoside (3o, 5:1 α:β)
The reaction was conducted on a 0.2 mmol scale ac cording to the general procedure (4.3) with 3
equivalents of dihydrocholesterol, from 3,4,6-tri-O-benzyl-2-deoxy- -galactopyranose (86.9 mg).
D
The reaction time was 21 hours. Purification was by flash chromatography on silica gel
(pentanes/diethyl ether, 100:0 → 80:20). The title compound was obtained as a colorless oil.
Combined yield (3o) = 129.2 mg, 0.161 mmol, 80%. The α:β ratio was determined to be 5:1
based on the relative integrations of the signals at 5.14 ppm (α) and 3.80 ppm (β). 1H NMR (500

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MHz; CDCl3): Signals corresponding to
α
anomer: δ 7.40–7.21 (m, 18H), 5.14 (m, 1H), 4.98–
4.91 (d, J = 11.6 Hz, 1H), 4.67–4.40 (m, 7H), 4.05–3.89 (m, 3H), 3.69–3.47 (m, 4H), 2.27–2.18
(td, J = 12.3, 3.8 Hz, 1H), 2.03–1.92 (m, 2H), 1.92–1.76 (m, 2H), 1.75–1.60 (m, 2H), 1.59–1.42
(m, 4H), 1.42–0.85 (m, 31H), 0.78 (s, 3H), 0.64 (s, 3H), 0.62–0.55 (m, 1H). Representative
signals corresponding to
β anomer: 4.92 (d, J = 11.5 Hz, 0.2H), 3.80 (m, 0.2H), 3.47–3.43 (m,
0.2H), 2.14–2.04 (m, 0.2H). 13C NMR (125 MHz; CDCl3): (anomeric mixture) δ 139.1, 139.1,
138.8, 138.5, 138.4, 138.3, 128.6, 128.5, 128.5, 128.5, 128.5, 128.4, 128.3, 128.2, 128.0, 127.8,
127.8, 127.7, 127.7, 127.6, 127.6, 127.6, 127.4, 127.4, 98.1 (C-1β), 95.7 (C-1α), 75.6, 75.3, 74.4,
74.3, 74.2, 73.7, 73.5, 73.4, 71.8, 71.5, 70.6, 70.3, 70.0, 69.9, 69.7, 56.6, 56.4, 54.6, 54.5, 45.1,
44.9, 42.7, 40.2, 39.7, 37.2, 37.0, 36.3, 36.1, 35.9, 35.8, 35.7, 35.7, 35.6, 34.5, 33.5, 32.3, 32.2,
31.9, 30.5, 29.9, 29.5, 29.0, 28.9, 28.4, 28.2, 27.7, 24.4, 24.0, 23.0, 22.7, 21.4, 18.8, 12.4, 12.2.
HRMS (ESI+): calculated for C54H80NO5 [M+NH4]+: 822.6031, found: 822.6040.
Acknowledgements
This research was funded by NSERC, the McLean Foundation, the Canada Foundation for
Innovation (project nos. 17545 and 19119) and the Province of Ontario.
Declarations of Interest
None
Supplementary data
Copies of 1H and 13C NMR spectra for catalyst 1h and glycosides 3a–3o. Supplementary data
related to this article can be found online at [insert link].

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Highlights:
-
a boronic ester catalyzes dehydrative glycosidations of carbohydrate-derived
hemiacetals
-
-
2-deoxy and 2,6-dideoxy donors can be activated by the boronic ester catalyst
the method is tolerant of functional groups such as isopropylidene ketals and
carbamates