Improved version of the Fischer-Zach synthesis of glycals: Vitamin B-12 catalyzed reductive elimination of glycosyl bromides

Full text of DOI:10.1021/jo981952e

1424
J . Org. Chem. 1999, 64, 1424-1425
Sch em e 1. F isch er -Za ch Syn th esis of Tr ia cetyl
Im p r oved Ver sion of th e F isch er -Za ch
Glu ca l
Syn th esis of Glyca ls: Vita m in B-12
Ca ta lyzed Red u ctive Elim in a tion of
Glycosyl Br om id es
Christopher L. Forbes and Richard W. Franck *
Department of Chemistry, Hunter College,
New York, New York 10021-5024
Received September 28, 1998
Glycals are unsaturated sugars with a double bond
located between C1 and C2. These compounds have a
long history of use as building blocks in carbohydrate
chemistry, and if anything, their importance has in-
creased, particularly because of their effectiveness as
glycosyl donors.1,2 The first synthesis of glycals was
reported by Fischer and Zach, in which 1-bromo-tet-
racetylglucose was reduced with Zn dust in acetic acid.3
(Scheme 1).
Sch em e 2. B-12 Ca ta lytic Cycle (Ad a p ted fr om
Sch effold ) for th e Syn th esis of Tr ia cetyl Glu ca l
This historic experiment served as the basis for the
modern method described in Methods in Carbohydrate
Chemistry and recently updated by Koreeda.4 A minor
but annoying technical problem in all versions of the
Fischer-Zach method is that extensive washing with
sodium bicarbonate is required during workup to neu-
tralize the acetic acid from the reaction medium. The one
flaw in the method is that it fails in the furanoid glycal
series where the acidic conditions lead to furan deriva-
tives. However, Ireland showed that a Na-naphthalene
anion radical reduction served to make furanoid glycals
readily available.5 Over the years, other reducing systems
have been used to prepare glycals from 1-bromopyranose
materials.6 By and large, these new methods offer the
advantage of avoiding the acidic conditions of the Fis-
cher-Zach procedure. However, none have as yet been
widely adopted in place of the original Zn dust method,
probably because of a perception that the advantages to
be gained are outweighed by problems of special reagent
preparation or manipulation. We wish to describe a
modified version of the Fischer-Zach method of forming
glycals from glycosyl bromides, which is done in neutral
media and therefore avoids the multiple bicarbonate
washes for removal of acetic acid, the reaction medium
of the original procedure The modification is one de-
scribed by Scheffold in which vitamin B-12 is used as a
catalyst for reductive eliminations.7 The best precedent
for our purposes was the use of B-12 with Zn dust to
cleave chloroethyl-O protecting groups.7c The vitamin is
a source of cobalt(III), which is reduced to Co(I). The
Co(I) is assumed to insert into the C-halogen bond,
which is fragmented by further reduction. In fact, a
mixture of zinc dust and ammonium chloride can be used
to carry out the Co(III)-Co(I) transformation. Because
the insertion-elimination step reoxidizes the B-12 back
to Co(III), only a catalytic amount of vitamin B-12 is
necessary for the reaction. (Scheme 2).
(1) Danishefsky, S. J .; Bilodeau, M. T. Angew. Chem., Int. Ed. Engl.
1996, 35, 1380-1419. A recent review of glycal chemistry, with
particular emphasis on applications of glycosyl transfer in which
glycals are the donors, including extensive contributions of the
Danishefsky group.
(2) Marzabadi, C. H.; Dios, A.; Geer, A.; Franck, R. W. J . Org. Chem.
1998, 63, 6673-6679. An article that includes a survey of cycloaddition
reactions of glycals.
Thus, application of the Scheffold protocol, which uses
methanol as solvent and ammonium chloride as a buffer
along with Zn dust as a reductant, serves admirably in
the Fischer-Zach synthesis. The necessary control was
run to show that without the vitamin B-12 the Zn dust/
methanol combination gave glycal in poor yield. The
modification fails with furanoid glycals (as does the
original method). Table 1 lists the 1-bromosugar starting
materials and yields of glycals formed. Because there is
(3) Fischer, E.; Zach, K. Sitzungsber. Kl. Preuss. Akad. Wiss. 1913,
27, 311-317.
(4) . (a) Roth, W.; Pigman, W. Methods in Carbohydrate Chemistry
Whistler, R. L., Wolfrom, M. L., Eds.; Academic Press: New York, 1963;
Vol. 2, p 405-408. (b) Shafizadeh, F. Methods in Carbohydrate
Chemistry; Whistler, R. L., Wolfrom, M. L., Eds., Academic Press: New
York, 1963; Vol. 2, p 409-410. (c) Shull, B. K.; Wu, Z.; Koreeda, M. J .
Carbohydr. Chem. 1996, 15, 955-964.
(5) Ireland, R. E.; Thaisrivongs, S.; Vanier, N.; Wilcox, C. S. J . Org.
Chem. 1980, 45, 48-61.
(6) (a) DePouilly, P.; Chenede, A.; Mallet, J .-M.; Sinay, P. Bull. Soc.
Chim. Fr. 1993, 130, 256-265; SmI2. (b) Cavallaro, C. L.; Schwartz,
J . J . Org. Chem. 1995, 60, 7056; (Cp2TiCl)2; this article includes a
survey of reductive elimination methods. (c) Spencer, R. P.; Schwartz,
J . Tetrahedron Lett. 1996, 37, 4357-4360; (Cp2TiCl)2. (d) Furstner,
A.; Weidmann, H. J . Org. Chem. 1989, 54, 2307-2311; K-graphite.
Prof. Furstner, Max Planck Institut, Mulheim-Ruhr, <fuerstner@
mpi-muelheim.mpg.de> has compiled an exhaustive listing of glycal
syntheses via reductive elimination (personal communication from the
author).
(7) (a) Scheffold, R.; Rytz, G.; Walder, L. Modern Synthetic Methods;
Scheffold, R., Salle, O., Eds.; Verlag: Frankfurt, 1983; Vol. 3, 355-
440. (b) Scheffold, R.; Abrecht, S.; Orlinski, R.; Ruf, H.-R.; Stamoula,
P.; Tinembart, O.; Walder, L.; Weymuth, C. Pure Appl. Chem. 1987,
59, 363-372. (c) Scheffold, R.; Amble, E. Angew. Chem., Int. Ed. Engl.
1980, 19, 629-630. (d) Zhou, D.-L.; Walder, P.; Scheffold, R.; Walder,
L. Helv. Chim. Acta 1992, 75 995-1011.
10.1021/jo981952e CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/26/1999

Notes
J . Org. Chem., Vol. 64, No. 4, 1999 1425
Ta ble 1. Rea cta n ts, P r od u cts, a n d Yield s in th e Vita m in B-12 Ca ta lyzed Elim in a tion
reactant glycosyl bromide
glycal
yielda,b
tetraacetyl-1-bromo-D-glucose
tetraacetyl-1-bromo-D-galactose
triacetyl-1-bromo-L-rhamnose
tetraacetyl-1-bromo-D-mannose
triacetyl-D-glucal
triacetyl-D-galactal
diacetyl-L-rhamnal
triacetyl-D-glucal
94% (60-70%) [98%]
93% (66%) [58%]
45% [71%]
95%
a
b
The yields in parenthesis are reported in the Methods in Carbohydrate Chemistry procedure (ref 4b). The yields in brackets are
reported in the Koreeda procedure (ref 4c).
crude product was dissolved in water (30 mL) and extracted with
chloroform (1 × 60 mL and 3 × 30 mL). All of the organic
extracts were combined, dried over magnesium sulfate, concen-
trated via rotary evaporator, and dried under vacuum, at which
time a white solid appeared. The NMR of the product was
identical to that of a commercial sample of pure tri-O-acetyl
glucal. The product was obtained in 94% yield (0.708 g, 2.60
mmol). This procedure was repeated to make tri-O-acetyl
galactal in 93% yield; the NMR of the galactal also was identical
to that of a commercial sample.
no difference in yield between the glucose and mannose
examples, we conclude that stereoelectronic effects in this
series are negligble.
In conclusion, we believe that the Scheffold B-12
modification for Zn dust reductions can be profitably used
in almost any case where Zn dust is used in reductive
eliminations.
Exp er im en ta l Section
P r ep a r a tion of 6-Deoxy-3,4 d i-O-Acetoxy-L-Glu ca l (L-
Rh a m n a l). Vitamin B-12 (82.4 mg, 0.06 mmol) was dissolved
in 20 mL of dry methanol under inert conditions, followed by
the addition of zinc dust (7.89 g, 120.7 mmol) and ammonium
chloride (6.48 g, 121.1 mmol). The solution was allowed to stir
for 30 min, during which time it took on a deep red-purple color.
6-Deoxy-2,3,4-tri-O-acetyl-L-glucosyl bromide (2.0327 g, 6.0 mmol)
was then dissolved separately in 25 mL of dry methanol and
added to the original reaction flask. The resulting mixture
became a yellow-orange color. After 5 min, the contents of the
reaction flask were washed through Celite (using methanol) and
concentrated under reduced pressure. The reddish solid residue
was then dissolved in water (70 mL) and extracted three times
with chloroform (70 mL each). The organic layers were collected,
dried over magnesium sulfate, and concentrated under reduced
pressure. The resulting yellow runny oil was chromatographed
on silica gel first pretreated with triethylamine 1% v/v in
petroleum ether/ EtOAc 8:1 as a column rinsing solvent and then
eluted with petroleum ether/EtOAc 8:1. The isolated product was
a pure yellow oil (560 mg, 45%), identical by NMR with a
commercial sample.
The zinc used required successive washings with 1 N HCl,
water, and methanol for activation. It was then dried in vacuo
for at least 1 h.
Tetra-O-acetyl-D-glucopyranosyl bromide was purchased from
Sigma Chemicals and was used to prepare tri-O-acetyl glucal.
The other 1-bromosugars were obtained by means of the classical
HBr procedure, which in our hands gave better yields than the
alternate TMSBr method. The glycal products were identified
by direct comparison with authentic samples.
P r ep a r a tion of Tr i-O-Acetyl Glu ca l. A solution of vitamin
B-12 (36.7 mg, 0.027 mmol) in 10 mL of anhydrous methanol
was purged with N2 for 30 min in a three-necked 50-mL round-
bottom flask fitted with a stir bar. Then, the zinc (2.06 g, 31.5
mmol) and ammonium chloride (1.68 g, 31.5 mmol) were added
to the solution, which was stirred for 45 min. Afterward, tetra-
O-acetyl-D-glucopyranosyl bromide (1.07 g, 2.60 mmol) was
dissolved in 5 mL of anhydrous methanol and added to the
reaction flask. Immediately after addition of the bromide, the
dark red solution changed to reddish-yellow in color and then
back to the dark red in about 30 s. A TLC was taken after 5
min, which showed that the reaction had gone to completion (Rf
) 0.41 in 5:1 petroleum ether/ethyl acetate). The solution was
then filtered through a pad of Celite to remove the zinc, and
the Celite was rinsed with methanol to ensure that all of the
solution was retrieved. The methanol solution was then concen-
trated via rotary evaporator and vacuum dried to give the crude
white and red solid crude product. To isolate pure product, the
Ack n ow led gm en t. This research was supported by
NIH grants GM 51216 and RR 03037 (RCMI) and PSC-
CUNY funds.
J O981952E