Electrochemical glycosylation in the presence of a catalytic chemical mediator

Article abstract of DOI:10.1002/poc.1388

Electrochemical glycosylation of thioglycoside donors proceeds efficiently in an undivided cell in the presence of a catalytic amount of the chemical mediator (4-bromophenyl) ammoniumyl hexachloroantimonate (BAHA). In comparison with electrochemical glyco

Full text of DOI:10.1002/poc.1388

Research Article
Received: 23 January 2008,
Revised: 7 April 2008,
Accepted: 7 April 2008,
Published online in Wiley InterScience: 2008
(www.interscience.wiley.com) DOI 10.1002/poc.1388
Electrochemical glycosylation in the presence
of a catalytic chemical mediator
a
b
a
*
Ludovic Drouin , Richard G. Compton and Antony J. Fairbanks
Electrochemical glycosylation of thioglycoside donors proceeds efficiently in an undivided cell in the presence of a
catalytic amount of the chemical mediator (4-bromophenyl) ammoniumyl hexachloroantimonate (BAHA). In com-
parison with electrochemical glycosylation alone, the use of a catalytic amount of BAHA greatly increases the rate of
reaction, reduces the potential required and inhibits ester-protecting group migrations. Copyright ß 2008 John Wiley
& Sons, Ltd.
Supplementary electronic material for this paper is available in Wiley InterScience at http://www.mrw.interscience.wiley.com/
suppmat/0894-3230/suppmat/
Keywords: glycosylation; oligosaccharides; electrochemistry; oxidation; catalysis
toxic and/or expensive. In the context of oligosaccharide synthesis,
INTRODUCTION
electrochemically mediated glycosylation has over the recent
years been successively investigated by Noyori,[30] Sinay¨ and
Amatore,[31–33] Lubineau,[34–36] Yoshida,[37–39] ourselves[40,41] and
Torii.[42] These extensive studies have in many cases facilitated the
synthesis of di- and oligosaccharides without recourse to the use of
toxic, expensive or sensitive activators. However recent investi-
The fundamental importance of oligosaccharides in a plethora of
vital biological processes is now extremely well recognised.[1,2]
Consequentially, oligosaccharides have attracted the attention of
synthetic chemists, not only for use as biological tools and
probes, but also as challenging targets for total synthesis, the
complexities of which have necessitated the development of
significant new synthetic methodologies.
gations into electrochemical glycosylation of
a variety of
aryl-substituted thio-mannosides[43] revealed the strong tendency
for ester-protecting groups to migrate from the glycosyl donor to
the glycosyl acceptor under the reaction conditions. Consequently
yields of glycosylation were markedly decreased when ester-
protected glycosyl donors were used, and it was also observed that
reactions were particularly sluggish in most of these cases. These
general findings contrast disfavourably with the ready and high
yielding glycosylation of thioglycosides by chemical activation
methods, which in particular are not plagued by donor-protecting
groups limitations.
Central to the synthesis of any oligosaccharide are the
glycosylation reactions by which the constituent monosacchar-
ide building blocks are assembled into the highly complex
oligosaccharide architecture. Extremely notable developments in
the field of glycosylation over the past century have led to the
establishment of useful and relatively robust methodologies[3]
particularly with respect to the variety of anomeric leaving
groups and activation methods available, ranging from the classic
Koenigs–Knorr reaction[4] to the Schmidt trichloroacetimidate
approach.[5] Other recent developments have focussed on the
improvement of the speed of assembly of complex structures
from monosaccharide building blocks, for example by reactivity
tuning[6–14] or programmable solid phase synthesis,[15–18] whilst
others have attempted to improve the stereo control of
glycosylation for the formation of ‘difficult’ anomeric lin-
kages.[19–29] However, despite these impressive developments
no one particular method of glycosylation appears to be
universally superior to the others, or even applicable in all
situations. The net result is that the development of new methods
for the formation of the glycosidic bond still remains an
interesting challenge, particularly in terms of development of
new ‘green chemistry’ techniques that avoid the use of toxic and
expensive reagents, and which facilitate the rapid and
straightforward assembly of glycoside building blocs into
oligosaccharide structures in a regio- and stereoselective fashion.
In particular circumstances electrochemically mediated synthesis
can represent an attractive and more environmentally benign
synthetic technique which may display marked advantages,
particularly where the traditional chemical reagents required are
During the course of their investigations into electrochemical
glycosylation, Sinay¨ and Amatore[44,45] and latterly Pinto[46] reported
the activation of thioglycosides by the use of stoichiometric
quantities of the salt tris-(4-bromophenyl) ammoniumyl hexachlor-
oantimonate 1 (BAHA, Fig. 1). Although efficient, the use of at least a
stoichiometric amount of this hazardous antimony-based activator
was required in order to achieve successful glycosylation,
unfortunately representing little significant advance over alternative
*
Correspondence to: A. J. Fairbanks, Department of Chemistry, Chemistry
Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1
3TA, UK.
E-mail: antony.fairbanks@chem.ox.ac.uk
a
L. Drouin, A. J. Fairbanks
Department of Chemistry, Chemistry Research Laboratory, University of
Oxford, Mansfield Road, Oxford, UK
b
R. G. Compton
Department of Chemistry, Physical and Theoretical Chemistry Laboratory,
University of Oxford, UK
J. Phys. Org. Chem. 2008, 21 516–522
Copyright ß 2008 John Wiley & Sons, Ltd.

ELECTROCHEMICAL GLYCOSYLATION
Figure 1. Catalysis of electrochemical glycosylation of a thioaryl glycoside donor in the presence of a sub-stoichiometric quantity of BAHA 1
toxic stoichiometric activators of thioglycosides. However in one
publication Sinay¨ and Amatore referred to the possible use of
catalytic quantities of BAHA in conjunction with electrochemical
regeneration of the radical cation in situ; they suggested that such a
process might be used for the synthesis of disaccharides, although
further details were not provided.[44] In fact both Steckhan and
coworkers[47,48] had already described the similar use of catalytic
quantities of electrochemical mediators both for the low potential
anodic decarboxylation of carboxylates and for the electrochemical
removal of 1,3-dithiane-protecting groups. However, since the initial
suggestion from Sinay¨ and Amatore there have been no further
reports in this area. An investigation into whether the more general
advantages of electrochemistry as a means of activation of thiogly-
cosides could in fact be combined with the use of a catalytic
quantity of BAHA was therefore considered worthwhile. Such an
approach may allow one to ‘have the best of both worlds’ in so far as
avoiding the need for stoichiometric chemical activator, whilst in
addition possibly avoiding some of the more general limitations of
electrochemical glycosylation, particularly in terms of donor-
protecting group identity, and speed and efficacy of glycosylation.
Fourier Transform spectrophotometer. Mass spectra were
recorded on VG Micromass 30F, ZAB 1F, Masslab 20–250,
Micromass Platform 1 APCI or Trio-1 GCMS (DB-5 column)
spectrometers, using desorption chemical ionisation (NH3 DCI),
electron impact (EI), electron spray ionisation (ESI), chemical
ionisation (NH3 CI), atmospheric pressure chemical ionisation
(APCI) and fast atom bombardment (FAB) techniques as stated.
Optical rotations were measured on
a Perkin-Elmer 241
polarimeter with a path length of 1 dm. Concentrations are
given in g/100 ml. Microanalyses were performed by the
microanalytical services of the Inorganic Chemistry Laboratory,
Oxford. Thin layer chromatography (t.l.c.) was carried out on
Merck glass backed sheets, pre-coated with 60F254 silica. Plates
were developed using 0.2% w/v cerium (IV) sulfate and 5%
ammonium molybdate in 2 M sulfuric acid. Flash chromato-
graphy was carried out using Sorbsil C60 40/60 silica. Solvents
and available reagents were dried and purified before use
according to standard procedures.
General procedure for electrochemical glycosylation with/
without mediator
EXPERIMENTAL
Electrochemical glycosylation was achieved using a conventional
three-electrode potentiostatic system by means of a working
electrode (Pt), an auxiliary electrode (Pt) (dimensions of both,
25 mm ꢀ 25 mm ꢀ 0.198 mm) and a pseudo-reference electrode
(Ag). The cell volume was 25 ml. Under an atmosphere of argon,
donor (ꢁ70–150 mg, 1.0 equiv.), acceptor (ꢁ30–70 mg, 1.2
General
Melting points were recorded on a Kofler hot block. Proton
nuclear magnetic resonance (dH) spectra were recorded on Varian
Gemini 200 (200 MHz), Bruker AC 200 (200 MHz), Bruker DPX 400
(400 MHz), Bruker AV 400 (400 MHz) or Bruker AMX 500 (500 MHz)
spectrometers. Carbon nuclear magnetic resonance (dC) spectra
were recorded on a Bruker DPX 400 (100.6 MHz) or a Bruker AMX
500 (125.75 MHz) spectrometer. Multiplicities were assigned
using APTor DEPTsequence. All chemical shifts are quoted on the
d-scale. Infrared spectra were recorded on a Perkin-Elmer 150
˚
equiv.), n-Bu4NClO4 (ꢁ650 mg) and 3 A molecular sieves were
suspended in anhydrous acetonitrile (20 ml), and the reaction
mixture was stirred at 25 8C for 30 min. For reactions in the
presence of mediator, the required quantity of (4-BrC6H4)3NSbCl6
(ꢁ10 mg, 0.1 equiv.) was then added. Electrolysis was carried out
at the stated potential (þ1.5 to þ2.2 V) until the required charge
J. Phys. Org. Chem. 2008, 21 516–522
Copyright ß 2008 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/poc

L. DROUIN, R. G. COMPTON AND A. J. FAIRBANKS
was reached (typically 2.5 F molꢂ1). The mixture was then filtered
through Celite1, concentrated under reduced pressure, and the
residue was dissolved in diethyl ether. Any remaining solid was
removed by filtration through Celite1, and the filtrate was
concentrated in vacuo. The residue was purified by flash column
chromatography on silica (petroleum ether/ethyl acetate, 9:1) to
afford the desired disaccharide.
(CH2), 69.9 (CH2), 70.5 (CH), 70.8 (CH), 71.0 (CH2), 71.6 (CH), 72.5
(CH), 73.5 (CH), 74.7 (CH2), 75.1 (CH2), 75.8 (CH), 77.2 (CH2), 81.8
(CH), 96.4 (C-1a), 102.4 (C-1b), 108.7 (Cq), 109.5 (Cq), 127.6
(4 ꢀ ArCH), 127.9 (2 ꢀ ArCH), 128.0 (4 ꢀ ArCH),128.1 (4 ꢀ ArCH),
128.3 (4 ꢀ ArCH), 128.7 (2 ꢀ ArCH) 138.1 (ArC), 138.4 (ArC), 138.6
(ArC); m/z (ESIþ) 800.57 ([M þ NH4]þ, 70%), 841.57 ([M þ
CH3CN þ NH4]þ, 100%), 1624.47 ([2M þ CH3CN þ NH4]þ, 2%).
General procedure for glycosylation mediated by
stoichiometric (4-BrC6H4)3NSbCl6 (BAHA) alone
6-O-(3,4,6-Tri-O-benzyl-2-O-pivaloyl-a,b-D-mannopyranosyl)-
(1 ! 6)-1,2:3,4-di-O-isopropylidene-a-D-galactopyranoside 4b
Under an atmosphere of argon, donor (ꢁ30–90 mg, 1.0 equiv.),
4-Methoxyphenyl 3,4,6-tri-O-benzyl-2-pivaloyl-1-thio-a-D-manno-
pyranoside 2b (93 mg, 0.14mmol), 1,2:3,4-diacetone-a-D-galacto-
pyranoside 3 (44 mg, 0.17 mmol), n-Bu4NClO4 (575mg, 0.70 mmol),
acetonitrile (15 ml), 1.5 V, 17 C (3h), gave disaccharide 4b (66 mg,
60%, a:b, 76:24); 4ba: 76%; yellowish oil; t.l.c. (petroleum ether/
˚
acceptor (ꢁ20–50 mg, 1.2 equiv.) and 3 A molecular sieves were
suspended in anhydrous acetonitrile (10 ml) and the reaction
mixture was stirred at room temperature for 30 min prior to
addition of (4-BrC6H4)3NSbCl6 (ꢁ120–340 mg, 1.2–3.0 equiv.).
After the reaction was complete as monitored by t.l.c. (90–150
min), the mixture was filtered and then concentrated under
reduced pressure. The residue was purified by flash column
chromatography on silica (petroleum ether/ethyl acetate; 9:1) to
afford the desired disaccharide.
20
ethyl acetate, 7:3) Rf 0.8; ½aꢃD -6 (c, 1.2 in CHCl3); nmax (film) 1732 (s,
nC O), 1371 (s, nC—O) cmꢂ1; dH (500 MHz, CDCl3) 1.21 (3 ꢀ 3H, s,
—
—
(CH3)3C), 1.33 (3H, s, CH3), 1.35 (3H, s, CH3), 1.43 (3H, s, CH3), 1.52 (3H,
s, CH3), 3.72 (1H, dd, J5a,6a 6.5Hz, J
m, H-6b), 3.80 (1H, dd, J5;6 a 6.5Hz, J6a;6 a
(1H, m, H-60b), 3.83–3.87 (1H, m, H-5b), 3.91 (1H, at, J3b,4b 9.5 Hz,
J4b,5b 9.5 Hz, H-4b), 3.95 (1H, dat, J4a,5a 1.5 Hz, J5a,6a 6.5Hz, J5a;6 a
0
6a;6 a 10.5 Hz, H-6a), 3.72–3.74 (1H,
0
0
10.5 Hz, H-60a), 3.78–3.82
0
6-O-(2,3,4,6-Tetra-O-benzyl-a, b-D-mannopyranosyl)-(1 ! 6)-
1,2:3,4-di-O-isopropylidene-a-D-galactopyranoside 4a
6.5 Hz, H-5a), 3.99 (1H, dd, J2b,3b 3.0 Hz, J3b,4b 9.5Hz, H-3b), 4.22 (1H,
dd, J3a,4a 8.0 Hz, J4a,5a 1.5Hz, H-4a), 4.31 (1H, dd, J1a,2a 5.0Hz, J2a,3a
2.5 Hz, H-2a), 4.49 (1H, d, J 11.0 Hz, CH2Bn), 4.50 (1H, d, J
11.0 Hz, CH2Bn), 4.51 (1H, d, J 13.0 Hz, CH2Bn), 4.60 (1H, dd, J2a,3a
2.5 Hz, J3a,4a 8.0 Hz, H-3a), 4.68 (1H, d, J 12.0 Hz, CH2Bn), 4.69 (1H, d, J
11.0 Hz, CH2Bn), 4.82 (1H, d, J 11.0 Hz, CH2Bn), 4.88 (1H, d, J1b,2b
2.0 Hz, H-1b), 5.40 (1H, dd, J1b,2b 2.0 Hz, J2b,3b 3.0 Hz, H-2b), 5.51 (1H,
d, J1a,2a 5.0 Hz, H-1a), 7.15–7.36 (15 ꢀ 1H, m, 15 ꢀ ArH); dC (126MHz,
CDCl3) 24.5 (CH3), 24.9, (CH3), 25.0 (CH3), 26.1 (CH3), 27.1 ((CH3)3C),
38.9 (CqPiv), 65.8 (C-5a), 65.9 (C-6), 68.1 (C-2b), 68.8 (C-6), 70.6 (C-3a),
70.7 (C-2a), 70.8 (C-4a), 71,4 (CH2Bn), 71.5 (C-5b), 73.1 (CH2Bn), 74.1
(C-4b), 75.1 (CH2Bn), 78.3 (C-3b), 96.3 (C-1a), 97.8 (C-1b), 108.6 (Cq),
109.3 (Cq), 107.4 (ArCH), 127.4 (2 ꢀ ArCH), 127.6 (ArCH), 127.9
4-Methoxyphenyl 2,3,4,6-tetra-O-benzyl-1-thio-a-D-mannopy-
ranoside 2a (112 mg, 0.17 mmol), 1,2:3,4-diacetone-a-D-galac-
topyranoside 3 (44 mg, 0.17 mmol) and n-Bu4NClO4 (700 mg,
2.05 mmol), anhydrous acetonitrile (24 ml), þ 1.5 V, 40 C (5 h) gave
disaccharide 4a (118 mg, 89%, a:b, 73:27); 4aa: 73%; yellowish oil;
22
t.l.c. (petroleum ether/ethyl acetate, 7:3) Rf 0.6; ½aꢃD -48 (c, 1.7 in
20
CHCl3) (lit.,[49,50] ½aꢃ -2.6 (c, 2.3 in CHCl3)); dH (400 MHz, CDCl3)
1.34 (2 ꢀ 3H, s, 2 ꢀDCH3), 1.45 (3H, s, CH3), 1.52 (3H, s, CH3), 3.71
(1H, dd, J 10.5 Hz, J 6.5 Hz, CH), 3.75 (1H, dd, J 4.5 Hz, J 12.5 Hz, CH),
3.78–3.88 (5 ꢀ 1H, m, 5 H), 3.92 (1H, dd, J 9.5 Hz, J 3.0 Hz, CH), 3.98
(1H, dat, J 5.5 Hz, J 7.0 Hz, CH), 4.17 (1H, dd, J 1.5 Hz, J 8.0 Hz, H-2b),
4.33 (1H, dd, J 2.5 Hz, J 5.0 Hz, H-2a), 4.51–4.79 (8H, m,), 4.88 (1H,
dd, J 10.5 Hz, CH2Bn), 5.04 (1H, d, J 1.5 Hz, H-1b), 5.54 (1H, d, J
5.0 Hz, H-1a), 7.10–7.42 (20 ꢀ 1H, m, 20 ꢀ ArH); dC (100 MHz,
CDCl3) 24.6 (CH3), 24.9 (CH3), 26.0 (CH3), 26.2 (CH3), 65.3 (CH), 65.4
(CH2), 69.3 (CH2), 70.8 (CH), 70.9 (CH), 71.1 (CH), 72.3 (CH), 72.3
(CH2), 72.5 (CH2), 73.5 (CH2), 74.7 (CH), 75.0 (CH), 75.3 (CH2), 80.2
(CH), 96.5 (C-1a), 97.4 (C-1b), 108.8 (Cq), 109.5 (Cq), 127.6 (CH),
127.7 (ArCH), 127.7 (ArCH), 127.8 (ArCH), 127.8 (4 ꢀ ArCH), 128.0
(4 ꢀ ArCH), 128.2 (4 ꢀ ArCH), 128.5 (4 ꢀ ArCH), 138.5 (ArC), 138.6
(ArC), 138.7 (ArC), 138.8 (ArC); m/z (ESIþ) 800.44 ([M þ NH4]þ,
100%), 841.49 ([M þ CH3CN þ NH4]þ, 92%), 1583.64 ([2M þ
NH4]þ, 10%), 1624.04 ([2M þ CH3CN þ NH4]þ, 3%); 4ab: 27%;
(2 ꢀ ArCH), 128.1 (2 ꢀ ArCH), 128.2 (2 ꢀ ArCH), 128.2 (2 ꢀ ArCH),
—
—
128.3 (2 ꢀ ArCH), 138.3, 138.3, 138.4 (ArC), 138.4 (ArCH), 177.6 (C
O); (HRMS (ESIþ) Calcd. For C44H56NaO12 (M þ Naþ) 799.3664.
Found 799.3662); 4bb: 24%; colourless oil; t.l.c. (petroleum ether/
20
ethyl acetate, 7:3) Rf 0.5; ½aꢃD -39 (c, 0.2 in CHCl3); dH (400MHz,
CDCl3) 1.24 (3 ꢀ 3H, s, (CH3)3C), 1.29 (3H, s, CH3), 1.32 (3H, s, CH3),
1.42 (3H, s, CH3), 1.52 (3H, s, CH3), 3.46 (1H, dat, J4b,5b 3.5Hz, J5b,6b
0
3.5 Hz, J5b;6b 9.5 Hz, H-5b), 3.65 (1H, dd, J2b,3b 3.0 Hz, J3b,4b 9.5 Hz,
H-3b), 3.69 (1H, dd, J5a,6a 10.5 Hz, J6a;6a0 4.0Hz, H-6a), 3.74–3.79
(3 ꢀ 1H, m, H-6b, H-60b, H-60a), 3.97 (1H, ddd, J4a,5a 1.5Hz, J5a,6a
10.5 Hz, J5a;6a0 4.0Hz, H-5a), 4.02 (1H, dd, J3b,4b 9.5Hz, J4b,5b 3.5 Hz,
H-4b), 4.20 (1H, dd, J3a,4a 8.0 Hz, J4a,5a 1.5 Hz, H-4a), 4.28 (1H, dd, J1a,2a
5.0 Hz, J2a,3a 2.5 Hz, H-2a), 4.46 (1H, d, J 11.5 Hz, CH2Bn), 4.50 (1H, d, J
10.5 Hz, CH2Bn), 4.55 (1H, d, J 12.0 Hz, CH2Bn), 4.56 (1H, dd, J2a,3a
2.5 Hz, J3a,4a 8.0 Hz, H-3a), 4.63 (1H, brs, H-1b), 4.68 (1H, d, J
12.0 Hz, CH2Bn), 4.74 (1H, d, J 11.5 Hz, CH2Bn), 4.83 (1H, d, J
11.0 Hz, CH2Bn), 5.50 (1H, d, J1a,2a 5.0 Hz, H-1a), 5.61 (1H, d, J2b,3b
3.0 Hz, H-2b), 7.10–7.40 (15ꢀ 1H, m, 15 ꢀ ArH); dC (100 MHz, CDCl3)
24.3 (CH3), 25.0 (CH3), 25.9 (CH3), 26.0 (CH3), 27.2 ((CH3)3C), 39.0
(CqPiv), 67.5 (C-2b), 67.8 (CH), 68.8 (C-6), 69.0 (C-6), 70.5 (C-3a), 70.6
(C-2a), 70.9 (CH2Bn), 71.2 (C-4a), 73.2 (CH2Bn), 74.2 (CH), 75.1
(CH2Bn), 75.4 (CH), 80.3 (C-3b), 96.2 (C-1a), 99.3 (C-1b), 108.7 (Cq),
109.2 (Cq), 127.4 (ArCH), 127.6 (2 ꢀ ArCH), 127.6 (ArCH), 127.6
23
yellowish oil; t.l.c. (petroleum ether/ethyl acetate, 7:3) Rf 0.4; ½aꢃD
20
-52 (c, 0.6 in CHCl3) (lit.,[49,50] ½aꢃD -72.6 (c, 2.7 in CHCl3)); dH
(400 MHz, CDCl3) 1.33 (3H, s, CH3), 1.34 (3H, s, CH3), 1.45 (3H,
s, CH3), 1.48 (3H, s, CH3), 3.44 (1H, ddd, J 2.5 Hz, J 5.0 Hz, J 9.5 Hz,
CH), 3.47 (1H, dd, J 3.0 Hz, J 9.5 Hz, CH), 3.62 (1H, dd, J 8.5 Hz, J
11.0 Hz, CH), 3.76–3.81 (2 ꢀ 1H, m, 2 ꢀ CH), 3.90 (1H, at, J 9.5 Hz,
CH), 4.01 (1H, d, J 3.0 Hz, CH), 4.10 (1H, dat, J 2.0 Hz, J 2.0 Hz, J
8.5 Hz, CH), 4.22 (1H, dd, J 2.0 Hz, J 6.0 Hz, CH), 4.23–4.25 (1H, m,
CH), 4.33 (1H, d, J 12.0 Hz, CH2Bn), 4.34 (1H, dd, J 2.5 Hz, J 5.0 Hz,
H-2a), 4.43–4.63 (4H, m, 3H CH2Bn, CH), 4.46 (1H, d, J 2.0 Hz, H-1b),
4.60 (1H, dd, J 10.0 Hz, CH2Bn), 4.90 (1H, d, J 10.5 Hz, CH2Bn), 4.93
(1H, d, J 12.5 Hz, CH2Bn), 5.02 (1H, d, J 12.5 Hz, CH2Bn), 5.60 (1H, d,
J 5.0 Hz, H-1a), 7.14–7.52 (20 ꢀ 1H, m, 20 ꢀ ArH); dC (100 MHz,
CDCl3) 24.4 (CH3), 25.1 (CH3), 25.9 (CH3), 26.0 (CH3), 68.0 (CH), 69.5
(ArCH), 128.0 (2 ꢀ ArCH), 128.1 (2 ꢀ ArCH), 128.2 (2 ꢀ ArCH), 128.2
—
(2 ꢀ ArCH), 128.3 (2 ꢀ ArCH), 176.6 (C O), 137.9 (ArC), 138.5
—
(2 ꢀ ArC).
www.interscience.wiley.com/journal/poc
Copyright ß 2008 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2008, 21 516–522

ELECTROCHEMICAL GLYCOSYLATION
6-O-(3,4,6-Tri-O-benzoyl-2-O-benzyl-a,b-D-mannopyranosyl)-
(1 ! 6)-1,2:3,4-di-O-isopropylidene-a-D-galactopyranoside 4c
1.92 mmol), acetonitrile (20 ml), 2.2 V, 39 C, gave disaccharide
4d (59 mg, 49%, a:b, 80:20); 4d a: 80%; colourless oil; t.l.c.
19
(petroleum ether/ethyl acetate, 7:3) Rf 0.4; ½aꢃD -61 (c, 0.3 in
4-Methoxyphenyl 3,4,6-tri-O-benzoyl-2-O-benzyl-1-thio-a-D-
mannopyranoside 2c (123 mg, 0.17 mmol), 1,2:3,4-diacetone-a-D-
galactopyranoside 3 (65 mg, 0.25 mmol), n-Bu4NClO4 (685 mg,
2.00 mmol), acetonitrile (20 ml), 2.2 V, 156 C, gave disaccharide 4c
(59 mg, 41%, a:b, 86:14); 4c a: 86%; yellow oil; t.l.c. (petroleum
—
CHCl3); nmax(film) 3010 (w, nCHAr), 2988 (w, nCH), 1728 (s, nC O),
—
1601, 1595, 1500, 1452 (m, nC CAr), 1263, 1060 (s, nCO) cmꢂ1; dH
—
—
(500 MHz, CDCl3) 1.36 (6H, s, 2 ꢀ CH3), 1.43 (3H, s, CH3), 1.63 (3H,
s, CH3), 3.89 (1H, dd, J5a,6a 6.5 Hz, J6a;6 a 11.0 Hz, H-6a), 3.97 (1H, dd,
0
J5a;6 a
6.5 Hz, J5a;6 a
H-4a), 4.35 (1H, dd, J1a,2a 5.0 Hz, J2a,3a 2.5 Hz, H-3a), 4.50 (1H, dd,
J5b,6b 3.0 Hz, J6b;6 b 12.0 Hz, H-6b), 4.59 (1H, brdat, J4b,5b 10.0 Hz,
J5b,6b 3.0 Hz, J5b;6 b 3.0 Hz, H-5b), 4.67 (1H, dd, J2a,3a 2.0 Hz, J3a,4a
8.0 Hz, H-3a), 4.69 (1H, dd, J5b;6 b 3.0 Hz, J6b;6 b
12.0 Hz, H-60b), 5.16
0
6.5 Hz, J6a;6 a
0
11.0 Hz, H-60a), 4.12 (1H, dat, J4a,5a 2.0 Hz, J5a,6a
6.5 Hz, H-5a), 4.34 (1H, dd, J3a,4a 8.0 Hz, J4a,5a 2.0 Hz,
ether/ethyl acetate, 7:3) Rf 0.5; ½aꢃ24 -14 (c, 0.9 in CHCl3); nmax (film)
D
3020 (w, nCHAr), 2934 (w, nCH), 1725 (s, nC O), 1601, 1598, 1500,
0
—
—
-1
—
1452 (m, nC CAr), 1270, 1069 (s, nCO), 711 (m, dCH) cm ; d
—
H
0
(500 MHz, CDCl3) 1.34 (6H, s, 2 ꢀ CH3), 1.44 (3H, s, CH3), 1.58 (3H,
s, CH3), 3.81 (1H, dd, J5a,6a 6.5 Hz, J6a;6 a 10.5 Hz, H-6a), 3.94 (1H, dd,
J5a;6 a 6.5 Hz, J6a;6 a
10.5 Hz, H-60a), 4.07 (1H, dat, J4a,5a 1.5 Hz, J5a,6a
0
0
0
0
0
0
(1H, d, J1b,2b 2.0 Hz, H-1b), 5.57 (1H, d, J1a,2a 5.0 Hz, H-1a), 5.74 (1H,
dd, J1b,2b 2.0 Hz, J2b,3b 3.0 Hz, H-2b), 5.91 (1H, dd, J2b,3b 3.0 Hz, J3b,4b
10.0 Hz, H-3b), 6.14 (1H, at, J3b,4b 10.0 Hz, H-4b), 7.25–7.28 (2 ꢀ 1H,
m, 2 ꢀ ArH), 7.33–7.45 (7 ꢀ 1H, m, 7 ꢀ ArH), 7.48–7.53 (1H, m,
ArH), 7.55–7.62 (2 ꢀ 1H, m, 2 ꢀ ArH), 7.84 (2 ꢀ 1H, dd, J 8.5 Hz, J
1.5 Hz, 2 ꢀ ArH), 7.96 (2 ꢀ 1H, dd, J 8.5 Hz, J 1.5 Hz, 2 ꢀ ArH), 8.06
(2 ꢀ 1H, dd, J 8.5 Hz, J 1.5 Hz, 2 ꢀ ArH), 8.12 (2 ꢀ 1H, dd, J 8.5 Hz, J
1.5 Hz, 2 ꢀ ArH); dC (126 MHz, CDCl3) 24.6 (CH3), 25.1 (CH3), 26.1
(CH3), 26.4 (CH3), 63.0 (C-6b), 66.8 (C-5a), 67.0 (C-4b), 67.7 (C-6a),
69.0 (C-5b), 70.4 (C-3b), 70.5 (C-2b), 70.8 (C-3a), 71.0, 71.1 (C-2a,
C-4a), 96.5 (C-1a), 98.0 (C-1b), 108.9 (Cq), 109.6 (Cq), 128.4
(2 ꢀ ArCH), 128.5 (2 ꢀ ArCH), 128.6 (2 ꢀ ArCH), 128.7 (2 ꢀ ArCH),
129.2 (ArC), 129.3 (ArC), 129.5 (ArC), 129.8 (2 ꢀ ArCH), 129.9
(2 ꢀ ArCH), 129.9 (2 ꢀ ArCH), 130.0 (2 ꢀ ArCH), 130.1 (ArC), 133.1
0
6.5 Hz, J5a;6 a 6.5 Hz, H-5a), 4.13 (1H, dd, J1b,2b 1.5 Hz, J2b,3b 3.0 Hz,
H-2b), 4.26 (1H, dd, J3a,4a 8.0 Hz, J4a,5a 1.5 Hz, H-4a), 4.34 (1H, dd,
J1a,2a 5.0 Hz, J2a,3a 2.5 Hz, H-2a), 4.45 (1H, dd, J4b,5b 10.0 Hz, J5b,6b
0
0
5.0 Hz, J5b;6 b 2.5 Hz, H-5b), 4.48 (1H, dd, J5b,6b 5.0 Hz, J6b;6 b 12.0 Hz,
H-6b), 4.57 (1H, dd, J5b;6 b 2.5 Hz, J6b;6 b
0
0
12.0 Hz, H-60b), 4.64 (1H,
dd, J2a,3a 2.5 Hz, J3a,4a 8.0 Hz, H-3a), 4.65 (1H, d, J 12.0 Hz, CH2Bn),
4.69 (1H, d, J 12.0 Hz, CH2Bn), 5.11 (1H, d, J1b,2b 1.5 Hz, H-1b), 5.55
(1H, d, J1a,2a 5.0 Hz, H-1a), 5.69 (1H, dd, J2b,3b 3.0 Hz, J3b,4b 10.0 Hz,
H-3b), 6.06 (1H, at, J3b,4b 10.0 Hz, J4b,5b 10.0 Hz, H-4b), 7.15–7.38
(11 ꢀ 1H, m, 11 ꢀ ArH), 7.45–7.53 (3 ꢀ 1H, m, 3 ꢀ ArH), 7.92–8.10
(6 ꢀ 1H, m, 6 ꢀ ArH); dC (126 MHz, CDCl3) 24.7 (CH3), 25.1 (CH3),
26.1 (CH3), 26.2 (CH3), 63.6 (C-6b), 66.2 (C-5a), 66.7 (C-6a), 67.4
(C-4b), 69.1 (C-5b), 70.7 (C-2a), 70.8 (C-3a), 71.1 (C-4a), 72.4 (C-3b),
73.1 (CH2Bn), 75.7 (C-2b), 96.5 (C-1a), 97.9 (C-1b), 108.8 (Cq), 109.5
(Cq), 127.6, 128.4, 128.5, 129.9 (16 ꢀ ArCH), 127.7 (ArCH), 29.4
(ArC), 129.5 (ArC), 130.0 (ArC), 132.9 (ArCH), 133.3 (2 ꢀ 1ArCH),
—
(ArCH), 133.3 (ArCH), 133.5 (ArCH), 133.6 (ArCH), 165.5 (C O),
—
þ
—
—
—
165.5 (C O), 165.6 (C O), 166.4 (C O); (HRMS (ESI ) Calcd.
—
—
—
For C46H50NO15 (M þ NHþ4 ) 856.3175. Found 856.3167).
—
—
—
—
137.8 (ArC), 165.5 (C O), 165.9 (C O), 166.4 (C O); (HRMS
—
—
(ESIþ) Calcd. For C46H52NO14 (M þ NHþ4 ) 842.3382. Found
842.3422); 4cb: 14 %; colourless oil; t.l.c. (petroleum ether/
24
ethyl acetate, 7:3) Rf 0.4; ½aꢃD -7 (c, 0.2 in CHCl3); dH (500 MHz,
RESULTS AND DISCUSSION
CDCl3) 1.33 (6H, s, 2 ꢀ CH3), 1.42 (3H, s, CH3), 1.55 (3H, s, CH3), 3.75
(1H, dd, J5a,6a 6.5 Hz, J6a;6 a 10.5 Hz, H-6a), 3.89 (1H, dd, J5a;6 a
0
0
The general concept underlying the potential use of a catalytic
quantity as a chemical mediator for electrochemical glycosylation
of a thioglycoside is outlined in Fig. 1. Cyclic voltammetry of
BAHA in acetonitrile at 50 mVꢄsꢂ1 previously revealed[51] an
electrochemically reversible couple with a formal oxidation
potential of þ0.78 V. Therefore at applied potentials above þ0.8 V
fast oxidation of the reduced form of the mediator would occur at
the anode to provide the BAHA radical cation in situ. Oxidation of
the thioglycoside by the BAHA radical cation could then occur,
probably more rapidly than direct oxidation of the thioglycoside
at the anode, allowing catalysis of thioglycoside oxidation.
Subsequent fragmentation would provide an intermediate
glycosyl cation, which would then undergo glycosylation with
the glycosyl acceptor R’OH. The consequential formation of the
reduced form of the mediator during oxidation of the thioglyco-
side would complete the cycle; the catalytic mediator could then
be rapidly electrochemically re-oxidised in order to promote
further glycosylation sequences (Fig. 1).
Electrochemical glycosylation of the thiophenyl mannoside
donors 2a–2d was undertaken in the presence of diacetone
galactose 3 as a glycosyl acceptor (Scheme 1). A second series of
electrochemical glycosylation reactions was also performed in
which a catalytic amount (0.1 equivalents) of BAHA was added to
the mixtures of donors and acceptor as a chemical mediator
before the external potential was applied. Finally, for the purpose
of comparison, glycosylation of the donors 2a–2d and acceptor 3
was also performed simply by using an excess of BAHA in the
6.5 Hz, J6a;6 a
H-2b), 4.02 (1H, dat, J4a,5a 2.0 Hz, J5a,6a 6.5 Hz, J5a;6 a
4.09 (1H, ddd, J4b,5b 10.0 Hz, J5b,6b 2.0 Hz, J5b;6 b 4.0 Hz, H-5b), 4.23
(1H, dd, J3a,4a 8.0 Hz, J4a,5a 2.0 Hz, H-4a), 4.25 (1H, at, J3b,4b 10.0 Hz,
4b,5b 10.0 Hz, H-4b), 4.32 (1H, dd, J1a,2a 5.0 Hz, J2a,3a 2.5 Hz, H-2a),
4.58 (1H, dd, J5b,6b 2.0 Hz, J6b;6 b 12.0 Hz, H-6b), 4.62 (1H, dd, J2a,3a
2.5 Hz, J3a,4a 8.0 Hz, H-3a), 4.63 (1H, d, J 12.0 Hz, CH2Bn), 4.68 (1H, d,
0
10.5 Hz, H-60a), 4.00 (1H, dd, J1b,2b 1.5 Hz, J2b,3b 3.5 Hz,
6.5 Hz, H-5a),
0
0
J
0
0
J 12.0 Hz, CH2Bn), 4.79 (1H, dd, J5b,6b 4.0 Hz, J6b;6 b 12.0 Hz, H-6b),
5.05 (1H, d, J1b,2b 1.5 Hz, H-1b), 5.43 (1H, dd, J2b,3b 3.5 Hz, J3b,4b
10.0 Hz, H-3b), 5.53 (1H, d, J1a,2a 5.0 Hz, H-1a), 7.16–7.31 (5 ꢀ 1H,
m, 5 ꢀ ArH), 7.36–7.47 (6 ꢀ 1H, m, 6 ꢀ ArH), 7.53–7.61 (3 ꢀ 1H, m,
3 ꢀ ArH), 8.01–8.11 (6 ꢀ H, m, 6 ꢀ ArH); dC (126 MHz, CDCl3) 24.7
(CH3), 25.1 (CH3), 26.1 (CH3), 26.3 (CH3), 64.1 (C-6b), 66.2 (C-5a),
66.2 (C-4b), 66.4 (C-6a), 70.7 (C-2a), 70.8 (C-3a), 71.1 (C-4a), 71.6
(C-5b), 73.1 (CH2Bn), 74.7 (C-3b), 76.2 (C-2b), 96.5 (C-1a), 97.8
(C-1b), 108.9 (Cq), 109.5 (Cq), 127.6, 128.4, 128.5, 128.6, 130.0
(16 ꢀ ArCH), 127.8 (ArCH), 129.7 (2 ꢀ ArC), 130.0 (ArC), 133.2
—
(ArCH), 133.4 (2 ꢀ ArCH), 138.0 (ArC), 166.9 (C O), 167.2
—
—
(2 ꢀ C O).
—
6-O-(2,3,4,6-Tetra-O-benzoyl-a,b-D-mannopyranosyl)-(1 ! 6)-
1,2:3,4-di-O-isopropylidene-a-D-galactopyranoside 4d
4-Methoxyphenyl 2,3,4,6-tetra-O-benzoyl-1-thio-a-D-mannopy-
ranoside 2d (104 mg, 0.14 mmol), 1,2:3,4-diacetone-a-D-galacto-
pyranoside
3 (48 mg, 0.18 mmol), n-Bu4NClO4 (658 mg,
J. Phys. Org. Chem. 2008, 21 516–522
Copyright ß 2008 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/poc

L. DROUIN, R. G. COMPTON AND A. J. FAIRBANKS
Scheme 1. Glycosylation reactions of donors 2a–d with diacetone galactose 3
absence of any applied external potential. The results of these
three series of glycosylation reactions are reported in Table 1.
Direct electrolysis of benzylated donor 2a at þ1.5 V for 5 h in
the presence of DAG 3 afforded the disaccharide 4a in 89% yield
as a diastereomeric mixture of anomers (a:b, 73:27) (Table 1, entry
1(i)). Alternatively when the electrolysis was undertaken at the
higher potential of þ2.2 V for 15 h, the disaccharide 4a was
formed in 80% yield, again as a diastereomeric mixture (a:b,
73:27) (Table 1, entry 1(ii)). Interestingly when the electroglyco-
sylation was performed at þ1.5 V in the presence of a catalytic
amount of BAHA (0.1 equiv.), the disaccharide 4a was formed in
87% yield, but with a much shorter reaction time (30 min),
indicating that the presence of the mediator had significantly
increased the reaction rate. On this issue a referee suggested that
the rate of reaction is in fact determined by the current, and not
the other way around. Since these reactions are performed at
constant potential, the flow of current and the rate of reaction are
indeed linked; it is our view that it is the rate of reaction which is
accelerated by the addition of the BAHA, which then has the
corresponding effect that the required charge is passed over a
shorter period of time; that is the increased rate of reaction
increases the current, and not the other way around. When the
glycosylation was performed simply using a significant excess of
BAHA (3.0 equiv.) the reaction was complete after 90 min, but 4a
was only produced in 64% yield, again as a diastereomeric
mixture (a:b, 53:47). However, when this reaction was repeated in
the presence of supporting electrolyte (n-Bu4NClO4, 1M),
glycosylation occurred more efficiently giving the disaccharide
4a in 95% yield and with an improved diastereomeric ratio (a:b,
73:27), suggesting a significant influence of the electrolyte salt on
the diastereoselectivity of the glycosylation reaction.
Since it has been widely demonstrated that ester-protecting
groups on the glycosyl donor can be problematic for electro-
chemical glycosylation purposes, attention then turned to the
use of a variety of ester-protected donors. In this respect
optimum results had previously been obtained by the use of
2-O-Piv protected donors, such as 2b, and thioglycoside 2b was
therefore selected as the next donor for comparative purposes.
Direct electrolysis of 2b at þ1.5 V for 4 h led to the formation of
the expected disaccharide 4b in 60% yield, as a diastereomeric
mixture (a:b, 76:24) (Table 1, entry 2(i)). When the electrolysis
was repeated at þ2.2 V for 15 h the disaccharide 4b was
obtained in 55% yield (a:b, 82:18) (Table 1, entry 2(ii)).
Contrastingly electrolysis of the donor 2b in the presence of
a catalytic amount of BAHA (0.1 equiv.) at þ1.5 V gave the
desired disaccharide 4b in 53% yield only after 45 min, again as
a diastereomeric mixture (a:b, 9:1) (Table 1, entry 2). Finally
the use of an excess of BAHA alone (1.7 equiv.) afforded the
Table 1. Glycosylation reactions of thioaryl glycosyl donors 2a–d with diacetone galactose 3 mediated by electrochemical means
alone, by electrochemical activation in the presence of catalytic BAHA, and by chemical activation with an excess of BAHA
Electrochemical activation
alone [potential, (time)%
yield, anomeric ratio]
Electrochemical activation mediated
by catalytic BAHA [potential, (time)%
yield, anomeric ratio]
Chemical activation with
stoichiometric BAHA [(time),%
yield, anomeric ratio]
Entry
1
Donor
2a
(i) þ1.5 V (5 h) 4a 89%
(a:b, 73:27)
þ1.5 V (0.5 h) 4a 87%
(a:b, 73:27)
(1.5 h)
4a 64%
(a:b, 53:47)a
4a 95%
(a:b, 73:27)b
(2.5 h) 4b 96%
(a:b, 88:12)a
(ii) þ2.2 V (15 h) 4a 80%
(a:b, 73:27)
2
2b
(i) þ1.5 V (4 h) 4b 60%
(a:b, 76:24)
þ1.5 V (0.75 h) 4b 53%
(a:b, 9:1)
(ii) þ2.2 V (15 h) 4b 55%
(a:b, 82:18)
3
4
2c
þ2.2 V (15 h) 4c 41%
(a:b, 86:14) 5 30%
þ2.2 V (15 h) 4d 49%
(a:b, 4:1) 5 30%
þ1.5 V (0.75 h) 4c 60%
(a:b, >20:1)
(2 h) 4c 68%
(a:b, >20:1)a
(1.5 h) 4d 59%
(a:b, 87:13)a
2d
þ1.5 V (0.9 h) 4d 49%
(a:b, >20:1)
a Chemical activation with BAHA performed in the absence of any electrolyte.
b Chemical activation with BAHA performed in the presence of 1 M n-Bu4NClO4.
www.interscience.wiley.com/journal/poc
Copyright ß 2008 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2008, 21 516–522

ELECTROCHEMICAL GLYCOSYLATION
desired disaccharide 4b in 96% yield (a:b, 88:12) after 2.5 h
(Table 1, entry 2).
we have demonstrated the potential advantages of the use of a
catalytic quantity of BAHA as a mediator for the electrochemical
activation of a series of aryl thiomannosides. On comparison, the
desired disaccharides were obtained in generally improved
yields, and in all cases more rapidly and at lower potentials than
that obtained by the use of electrochemical activation alone.
Additionally electrochemical glycosylation mediated by BAHA
was not accompanied by the migration of benzoyl-protecting
groups from donor to acceptor as was invariably the case for
electrochemical glycosylation alone. It may be expected that the
use of a catalytic chemical mediator is amenable to, and may
present advantages for, the electrochemical oxidation of a variety
of sulfur-containing substrates or other, more generally any
oxidisable species. However, despite the incremental advantages
demonstrated herein, BAHA itself remains a toxic and hazardous
material. The search therefore will now broaden to investigate the
potential of other less toxic chemical mediators to facilitate
electrochemical glycosylation and other electrochemical trans-
formations.
Ester-protecting group lability and tendency to migrate to the
acceptor hydroxyl during electrochemical glycosylation is not
limited to ester protection of the 2-position of the glycosyl donor.
Investigation of glycosylation of 2-O benzyl donor protected
donor 2c bearing benzoate protection of the hydroxyls at
positions 3-, 4- and 6- was undertaken next. Direct electrolysis of
2c at þ2.2 V produced the desired disaccharide 4c in 41% yield, as
a diastereomeric mixture (a:b, 86:14). However in addition to
glycosylation, transesterification also occurred and the 6-benzoyl
protected acceptor 5 was produced in 30% yield (Table 1, entry
3).[43] Notable also was the fact that glycosylation was particularly
sluggish at þ1.5 V, and the significant over-potential of þ2.2 V
was required to make the reaction go to completion. However,
pleasingly, the use of the catalytic amount of the mediator BAHA
improved the electrochemical glycosylation process. In this case
the desired disaccharide 4c was obtained in 60% yield as
predominantly a single anomer (a:b, >20:1) after only 45 min
at the lower oxidation potential of þ1.5 V (Table 1, entry 3).
Moreover, importantly no migration of benzoyl-protecting
groups occurred, and thus compound 5 was not observed. In
this instance chemical activation using BAHA (1.5 equiv.) as a
stoichiometric oxidant afforded 4c in 68% yield, again effectively
as a single anomer (a:b, >20:1) after 2 h (Table 1, entry 3).
Finally investigations turned to the use of the per-benzoylated
thioglycoside donor 2d. Electrolysis of donor 2d in the presence
of 3 could only be achieved at the higher potential of þ2.2 V, and
afforded the corresponding disaccharide 4d in 49% yield (a:b,
4:1), along with the trans-esterification product 5 (30% yield)
(Table 1, entry 4). Electrochemical activation in the presence of a
catalytic amount of BAHA (0.1 equiv.), at the lower potential of
þ1.5 V, furnished the desired disaccharide 4d in a similar yield of
49% (a:b, >20:1) after 0.9 h (Table 1, entry 4); notably although
the yield of disaccharide product was similar to electrochemical
glycosylation alone, once again the benzoylated acceptor 5 was
not observed. Finally it was noted that chemical glycosylation
using stoichiometric BAHA (1.2 equiv.) gave a slightly better yield
of disaccharide 4d (59%, a:b, 87:13) after 1.5 h (Table 1, entry 4).
Overall these results taken together indicate that not only is
the use of a catalytic quantity of BAHA beneficial to the
electrochemical glycosylation reaction in terms of rate and
efficiency, but also in particular that the use of catalytic BAHA
stops trans-esterification of the glycosyl acceptor when glycosyl
donors bearing labile ester-protecting groups are used. Although
electrochemical activation in the presence of catalytic BAHA is
not always superior in terms of product yield to the use of excess
BAHA alone, the advantages of the use of this material in catalytic
form, not least of which are cost and impact by the reduction in
the use of toxic antimony salts, are significant.
Acknowledgements
We gratefully acknowledge financial support from the EPSRC
(Project studentship GR/T24692/01 to L. D.).
REFERENCES
[1] A. Varki, Glycobiology 1993, 3, 97–130.
[2] R. A. Dwek, Chem. Rev. 1996, 96, 683–720.
[3] B. G. Davis, J. Chem. Soc., Perkin Trans. 1 2000, 2137–2160.
[4] W. Koenigs, E. Knorr, Ber. Dtsch. Chem. Ges. 1901, 34, 957–981.
[5] R. R. Schmidt, Angew. Chem., Int. Ed. Engl. 1986, 25, 212–235.
[6] D. R. Mootoo, P. Kondrasson, U. Udodong, B. Fraser-Reid, J. Am. Chem.
Soc. 1988, 110, 5583–5584.
[7] P. Grice, S. V. Ley, J. Pietruszka, H. W. M. Priepke, E. P. E. Walter, Synlett
1995, 781–784.
[8] M. K. Cheung, N. L. Douglas, B. Hinzen, S. V. Ley, X. Pannecoucke,
Synlett 1997, 257–260.
[9] P. Grice, S. V. Ley, J. Petruszka, H. M. I. Osborn, H. W. M. Piepke, S.
Warrinder, Chem. Eur. J. 1997, 3, 431–440.
[10] L. Green, B. Hinzen, S. J. Ince, P. Langer, S. V. Ley, S. L. Warriner, Synlett
1998, 440–442.
[11] N. L. Douglas, S. V. Ley, U. Lu¨cking, S. L. Warriner, J. Chem. Soc., Perkin
Trans. 1 1998, 51–65.
[12] Z. Zhang, I. R. Ollmann, X.-S. Ye, R. Wischnat, T. Baasov, C.-H. Wong,
J. Am. Chem. Soc. 1999, 121, 734–753.
[13] X.-S. Ye, C.-H. Wong, J. Org. Chem. 2000, 65, 2410–2431.
[14] F. Burkhart, Z. Zhang, S. Wacowich-Sgarbi, C.-H. Wong, Angew. Chem.
Int. Ed. 2001, 40, 1274–1277.
[15] Z. Zhang, I. R. Ollmann, X.-S. Ye, R. Wischnat, T. Baasov, C.-H. Wong,
J. Am. Chem. Soc. 1999, 121, 734–753.
[16] O. J. Plante, E. R. Palmacci, P. H. Seeberger, Science 2001, 291,
1523–1527.
[17] P. H. Seeberger, Chem. Comm. 2003, 1115–1121.
[18] P. H. Seeberger, W.-C. Haase, Chem. Rev. 2000, 100, 4349–4393.
[19] K. Chayajarus, D. J. Chambers, M. J. Chugthai, A. J. Fairbanks, Org. Lett.
2004, 6, 3797–3800.
CONCLUSIONS
[20] A. J. Fairbanks, Synlett, 2003, 1945–1958.
[21] S. C. Ennis, A. J. Fairbanks, R. J. Tennant-Eyles, H. S. Yeates, Synlett
1999, 1387–1390.
[22] K.-H. Jung, M. Mu¨ller, R. R. Schmidt, Chem. Rev. 2000, 100, 4423–4442.
[23] F. Barresi, O. Hindsgaul, J. Am. Chem. Soc. 1991, 113, 9377–9379.
[24] F. Barresi, O. Hindsgaul, Synlett 1992, 759–760.
[25] F. Barresi, O. Hindsgaul, Can. J. Chem. 1994, 72, 1447–1465.
[26] G. Stork, J. J. La Clair, J. Am. Chem. Soc. 1996, 118, 247–248.
[27] G. Stork, G. Kim, J. Am. Chem. Soc. 1992, 114, 1087–1088.
[28] Y. Ito, T. Ogawa, Angew. Chem. Int. Ed. Engl. 1994, 33, 1765–1767.
Although ‘direct’ electrochemically mediated glycosylation has
been demonstrated as a feasible synthetic technique, its
widespread applicability, particularly for the assembly of complex
oligosaccharides, remains undemonstrated. Limitations of the
methodology in comparison with more conventional chemical
glycosylation are the lengthier reaction times required, the low
yields of disaccharide often produced, and, in particular, the
problems associated with use of ester-protecting groups. Herein
J. Phys. Org. Chem. 2008, 21 516–522
Copyright ß 2008 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/poc

L. DROUIN, R. G. COMPTON AND A. J. FAIRBANKS
[29] M. Lergenmuller, T. Nukada, K. Kuramochi, A. Dan, T. Ogawa, Y. Ito, Eur.
J. Org. Chem. 1999, 1367–1376.
[30] R. Noyori, I. Kurimoto, J. Org. Chem. 1986, 51, 4320–4322.
[31] C. Amatore, A. Jutand, J.-M. Mallet, G. Meyer, P. Sinay, J. Chem. Soc.,
Chem. Commun. 1990, 718–719.
[32] J.-M. Mallet, G. Meyer, F. Yvelin, A. Jutand, C. Amatore, P. Sinay¨,
Carbohydr. Res. 1993, 244, 237–246.
[33] C. Amatore, A. Jutand, G. Meyer, P. Bourhis, F. Machetto, J.-M. Mallet, P.
Sinay¨, C. Tabeur, Y.-M. Zhang, J. Appl. Electrochem. 1994, 24, 725–729.
[34] G. Balavoine, A. Gref, J.-C. Fischer, A. Lubineau, Tetrahedron Lett. 1990,
31, 5761–5764.
[35] G. Balavoine, S. Berteina, A. Gref, J.-C. Fischer, A. Lubineau,
J. Carbohydr. Res. 1995, 14, 1217–1236.
[36] G. Balavoine, S. Berteina, A. Gref, J.-C. Fischer, A. Lubineau,
J. Carbohydr. Res. 1995, 14, 1237–1249.
[37] S. Yamago, K. Kokubo, O. Hara, S. Masuda, J.-I. Yoshida, J. Org. Chem.
2002, 67, 8584–8592.
[40] R. R. France, R. G. Compton, B. G. Davis, A. J. Fairbanks, N. V. Rees, J. D.
Wadhawan, Org. Biomol. Chem. 2004, 2, 2195–2202.
[41] R. R. France, N. V. Rees, J. D. Wadhawan, A. J. Fairbanks, R. G. Compton,
Org. Biomol. Chem. 2004, 2, 2188–2194.
[42] N. Tanaka, F. Ohnishi, D. Uchihata, S. Torii, J. Nokami, Tetrahedron Lett.
2007, 48, 7383–7387.
[43] L. Drouin, R. G. Compton, N. Fietkau, A. J. Fairbanks, Synlett 2007,
2711–2717.
[44] See reference 27 in A. Marra, J.-M. Mallet, C. Amatore, P. Sinay¨, Synlett
1990, 572–574.
[45] Y.-M. Zhang, J.-M. Mallet, P. Sinay¨, Carbohydr. Res. 1992, 236,
73–88.
[46] B. S. Mehta, B. M. Pinto, Carbohydr. Res. 1998, 310, 43–51.
[47] W. Schmidt, E. Steckhan, J. Electroanal. Chem. 1978, 89, 215–220.
[48] M. Platen, E. Steckhan, Tetrahedron Lett. 1980, 21, 511–514.
[49] G. Singh, H. Vankayalapati, Tetrahedron: Asymmetry 2000, 11,
125–138.
[38] S. Suzuki, K. Matsumoto, K. Kawamura, S. Suga, J.-I. Yoshida, Org. Lett.
2004, 6, 3755–3758.
[50] T. Yamanoi, Kazumi, N. H. Takeyama, K. Yanagihara, T. Inazu, Bull.
Chem. Soc. Jpn. 1994, 67, 1359–1366.
[39] T. Nokami, A. Shibuya, H. Tsuyama, S. Suga, A. A. Bowers, D. Crich, J.-I.
Yoshida, J. Am. Chem. Soc. 2007, 129, 10922–10928.
[51] A. J. Wain, I. Streeter, M. Thompson, N. Fietkau, L. Drouin, A. J.
Fairbanks, R. G. Compton, J. Phys. Chem. B 2006, 110, 2681–2691.
www.interscience.wiley.com/journal/poc
Copyright ß 2008 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2008, 21 516–522