TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7257–7259
ZnCl2-catalyzed Ferrier reaction; synthesis of 2,3-unsaturated
1-O-glucopyranosides of allylic, benzylic and tertiary alcoholsꢀ
B. K. Bettadaiah and P. Srinivas*
Central Food Technological Research Institute, Mysore 570013, India
Received 15 June 2003; revised 18 July 2003; accepted 5 August 2003
Abstract—Tertiary, allylic and benzylic alcohols react with 3,4,6-tri-O-acetyl-D-glucal in dichloromethane at 25°C in the presence
of ZnCl2 to afford the corresponding 2,3-unsaturated-1-O-glucopyranoside acetates in 65–91% yields, with selective formation of
the a-anomer.
© 2003 Elsevier Ltd. All rights reserved.
2-Deoxyglycoside derivatives of a wide range of com-
pounds have been shown to be of immense biological
importance.1 A simple route to their preparation consti-
tutes addition to 2,3-unsaturated glycopyranosides.
These, in turn, can be prepared from the reaction of
In a typical reaction, 3,4,6-tri-O-acetyl-D-glucal (5
mmol) was dissolved in anhydrous CH2Cl2 (10 ml), to
which catalyst (10 mol%) was added, followed by addi-
tion of the substrate (5 mmol). After completion of
reaction, the syrupy crude product, obtained after usual
work-up, was subjected to column chromatography
with 10% EtOAc in pet. ether (60–80°C) as eluent. The
pure products, containing mixtures of a and b isomers
alcohols with 3,4,6-tri-O-acetyl-D-glycal in the presence
of Lewis acid catalysts. Substitution occurs along with
an allylic rearrangement, which is generally referred to
as Ferrier rearrangement.2 A variety of catalysts are
employed in this reaction viz., BF3·OEt2,3 SnCl4,4
FeCl3,5 InCl3,6 InBr3,7 Yb(OTf)3,8 Sc(OTf)3,9 montmo-
1
were characterized by H, 13C and elemental analysis.
In the first instance, the reaction of
D-glucal with
rillonite K-10,10 LiBF4 and BiCl3.12 Interestingly, zinc
11
p-menth-1-en-4-ol, an aroma chemical (Table 1, 1g),
was studied using various catalysts such as PTS, BF3,
BBr3, ZnI2, SnCl4. In these cases, dehydration of the
alcohol and dimerization of glucal17 were predominant.
However, in the presence of zinc chloride (10 mol%),
these side reactions were considerably reduced and the
glucoside was formed as the major product. Of the
chloride has been tried as a catalyst along with hydro-
chloric acid in the reaction of D-glucal with p-nitrophe-
nol in refluxing dioxan. However, formation of the
glycoside was not observed.13 Our earlier studies have
revealed that the reaction of SN1-active (allylic, benzylic
and tertiary) halides with a variety of nucleophiles
(-OH, -OCOCH3, -SCN, -SCOCH3, and -N3), as their
zinc salts afforded high yields of substitution prod-
ucts.14 Also, O- and S-glucosides of several simple,
long chain as well as terpenic alcohols, phenols and
sterols have been synthesized from the reaction of
a-glucopyranosyl bromide with the corresponding zinc
salts.15,16 In the present investigation, we examined the
efficacy of zinc chloride as a catalyst in the preparation
of 2,3-unsaturated glucopyranoside acetates of tertiary,
benzylic and allylic alcohols, especially of monoterpene
and isoprenyl alcohols, under Ferrier rearrangement
conditions.
several
solvents
employed,
the
reaction
in
dichloromethane was rapid and the 2,3-unsaturated-1-
O-glucopyranoside diacetate was obtained in good
yield. The reaction of D-glucal with a selected group of
monoterpenic and alkyl/aryl substituted alcohols
together with the yields of the glucoside acetates
obtained are summarized in Table 1 and Scheme 1.
Product yields were better with benzylic alcohols than
with allylic and tertiary alcohols. The anomeric ratios
suggest selective axial approach by the nucleophile
leading to the preferred formation of the a-isomers.
The specific rotation of the products indicated that the
allylic rearrangement in the aglycon did not occur
which would have resulted in racemization of the agly-
con, especially with regard to the monoterpenyl deriva-
tives (entries 1a, 1b, 1f and 1g). In the case of the
tertiary substrates, suppression of the competitive elimi-
ꢀ Supplementary data associated with this article can be found at
doi:10.1016/S0040-4039(03)01885-9
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01885-9