Electrochemical formation of glycals in THF

Article abstract of DOI:10.1016/S0040-4039(01)01544-1

A new method is presented to produce unsaturated sugars from glycosyl bromides. This work offers a simplification of existing electrochemical approaches to these types of species and is amenable to scale up for large-scale production. In addition, this work is intended to provide a means of employing electrochemistry that can be duplicated in most organic chemistry laboratories using readily available glassware and equipment.

Full text of DOI:10.1016/S0040-4039(01)01544-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7371–7374
Electrochemical formation of glycals in THF
J. D. Parrish and R. Daniel Little*
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, USA
Received 1 August 2001; accepted 22 August 2001
Abstract—A new method is presented to produce unsaturated sugars from glycosyl bromides. This work offers a simplification of
existing electrochemical approaches to these types of species and is amenable to scale up for large-scale production. In addition,
this work is intended to provide a means of employing electrochemistry that can be duplicated in most organic chemistry
laboratories using readily available glassware and equipment. © 2001 Elsevier Science Ltd. All rights reserved.
Glycals are versatile and useful intermediates in organic
synthesis. They have been employed in natural product
form elimination and substitution products (3 and 4).
Our initial investigations, conducted in a divided electro-
chemical cell, led us to conclude that we could limit these
unwanted side-reactions by increasing the current density
(and thus limiting the reaction time) of the reduction. We
realized that the utilization of undivided cells would not
only allow us to reach the high currents desired, but also
greatly simplify the reaction conditions.
1
2
synthesis, C-glycoside formation and oligosaccharide
3
preparation. Traditionally these unsaturated sugars
have been prepared via the reduction of glycosyl halides
4
by various metallic or organometallic reagents. Electro-
chemistry has also been utilized, but the procedure
required the use of a mercury cathode, a divided electro-
5
chemical cell, and acidic conditions. We sought to
develop a convenient and general set of conditions that
would avoid the use of mercury, and could be employed
by electrochemists and non-electrochemists alike. In this
letter we report the achievement of these objectives by
utilizing controlled current electrolysis.
Though electrochemical oxidations are commonly per-
formed in single cells, electrochemical reductions under
these conditions are less common. However, the recent
6
development of sacrificial anodes has greatly increased
the practicality of undivided cells for constant current
reductions. By using a reticulated vitreous carbon
7
We initially investigated the reduction of acetobromoglu-
cose (1) to tri-(O)-acetyl glucal (2) as a model reaction.
As depicted in Scheme 1, a concern is the ability of
transient acetate (produced as the reaction progresses) to
(RVC) cathode and a consumable zinc anode under
constant current conditions we were able to achieve the
rapid (reactions typically last less than 20 min) conver-
sion of 1 to glycal 2 in excellent yield (Scheme 2). We
AcO
AcO
AcO
AcO
AcO
AcO
AcO
AcO
acetate-promoted
elimination
1. reduction
O
O
O
AcO
2. elimination
AcO
AcO
Br
1
2
3
substitution
by acetate
AcO
AcO
O
OAc
AcO
AcO
4
Scheme 1. Reactivity patterns of glycosyl bromides.
*
Corresponding author. Tel.: +1-805-893-3693; fax: +1-805-893-4120; e-mail: little@chem.ucbs.edu
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01544-1

7
372
J. D. Parrish, R. D. Little / Tetrahedron Letters 42 (2001) 7371–7374
2 e-
O
have since applied these conditions to a variety of other
O
substrates and the results are shown in Table 1. The
yields vary from fair to excellent. Note that this method
is also applicable to compounds possessing acid-sensi-
tive protecting groups (entry 9), which are incompatible
with the classical Fischer–Zach zinc/acetic acid method
of glycosyl halide reduction. In addition, these condi-
tions appear to be tolerant of potentially sensitive pro-
tecting groups such as benzyl ethers (entry 10) which
LiClO /THF
4
AcO
Br
RVC cathode, zinc anode
Controlled current electrolyisis in undivided cell
8
Scheme 2. Electrochemical reduction of glycosyl bromides.
See Fig. 1 and Table 1.
Table 1. Electrochemical formation of glycals from glycosyl bromides
yield (%)a
glycosyl halide
Entry
product
AcO
O
AcO
AcO
AcO
1
2
O
90
AcO
AcO
AcO
Br
OAc
AcO
AcO
AcO
AcO
O
O
AcO
AcO
84
74
Br
BzO
BzO
O
BzO
BzO
3
4
O
BzO
BzO
BzO
Br
AcO
AcO
OAc
O
AcO
AcO
OAc
O
48
AcO
Br
OAc
O
H C
3
H C
3
5
6
AcO
AcO
O
O
AcO
AcO
42
44
Br
AcO
AcO
AcO
AcO
O
AcO
Br
AcO
AcO
AcO
Br
AcO
O
AcO
O
AcO
AcO
O
7
8
AcO
O
57
68
AcO
O
OAc
O
OAc
OAc AcO
Br
AcO
AcO
AcO
AcO
AcO
AcO
O
O
O
OAc
AcO
AcO
O
O
OAc
O
AcO
OAc
OAc
O
O
O
O
O
9
1
O
5
5
AcO
AcO
AcO
Br
BnO
AcO
AcO
BnO
O
O
0
AcO
AcO
47
AcO
Br
aIsolated yield after column chromatography.

J. D. Parrish, R. D. Little / Tetrahedron Letters 42 (2001) 7371–7374
7373
Figure 1. Electrochemical cell employed in preparative electrolysis.
9
can be cleaved using reductive electrochemistry.
typical experimental setup is illustrated in Fig. 1.
A
mL). The combined organic extracts were washed with
brine (30 mL), dried (MgSO ), filtered and concen-
4
trated. The crude material was purified by flash column
chromatography on silica gel using ether/pentane solu-
tions as eluant. All products had NMR spectra in
The reaction likely involves direct reduction of the
carbonꢀbromine bond at the cathode followed by rapid
elimination of the neighboring acetate group to provide
the glycal. However, we cannot rule out the possible
role of highly activated zinc (formed at the cathode
surface due to oxidation of the zinc anode followed by
reduction of the resulting zinc salts at the cathode)
produced as the reaction proceeds. There also exists the
possibility of the zinc salts participating as Lewis acidic
species to activate the carbonꢀbromine bond towards
cleavage. We intend to pursue further investigations
into these possibilities.
8b,10b
agreement with previously published data.
Acknowledgements
We thank the UCSB Committee on Research for their
support of our program in electrochemistry. J.D.P. also
wishes to acknowledge the John H. Tokuyama fellow-
ship for support.
In conclusion, we have developed a simplified electro-
chemical approach to glycals employing constant cur-
rent electrochemistry conducted in a single cell using a
consumable zinc anode. This approach allows for the
use of inexpensive and readily available materials to
quickly produce large amounts of unsaturated sugars.
This method also avoids the use of acidic conditions or
large amounts of organometallic reagents.
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