Sodium hydride/hexamethylphosphoric triamide: a new and
efficient reagent towards the synthesis of protected
1,2- and 5,6-enopyranosides
Khalid Mohammed Khan,*a Shahnaz Perveen,b Syed Tasadaque Ali Shah,a
Mohammed Saleh Shekhania and Wolfgang Voelter*c
L e t t e r
a HEJ Research Institute of Chemistry, International Center for Chemical Sciences,
University of Karachi, Karachi-75270, Pakistan
b PCSIR L aboratories Complex O† University Road Karachi, Karachi-75280, Pakistan
c Abteilung fur Physikalische Biochemie des Physiologisch-chemischen Instituts der Universitat
T ubingen, Hoppe-Seyler Strae 4, D-72076 T ubingen, Germany.
E-mail: wolfgang.voelter=uni-tuebingen.de
Received (in Montpellier, France) 18th December 2000, Accepted 25th April 2001
First published as an Advance Article on the web 13th June 2001
A new method for the elimination of hydrogen halides and p-
toluenesulfonic acid from sugar moieties using sodium hydride
(NaH) in hexamethylphosphoric triamide (HMPA) at room
temperature is reported. NaH/HMPA has several advantages
compared to NaH/DMF: elimination products are produced in
high yields even from sterically hindered starting materials, and
not only from halides, but also tosylates.
the intention of cleaving the tosyl group, but surprisingly
found that 3,4-di-O-acetyl-5,6-enoglucal was formed as an
elimination product in 90% yield (Scheme 1).
As shown in Table 1, our NaH/HMPA16 reagent gives
higher yields of elimination products compared to the report-
ed NaH/DMF procedure,6 and is also suitable for dehydro-
tosylations. Using NaH/DMF for entries 1, 7, 8 and 9 yielded
less than 5% of the elimination products; in addition a
complex mixture of non-separable side products was obtained.
To determine the general utility of this reagent, we prepared
several tosylates and halides of di†erent sugars, reacted these
with sodium hydride in HMPA and isolated the elimination
products in excellent yields (Table 1).
In conclusion, NaH in HMPA16 is a reagent which pro-
duces elimination products from halides as well as p-
toluenesulfonic acid esters in high yields. As this procedure
has several advantages it is a valuable addition to existing
methods.
Numerous stable carbohydrate derivatives with an oleÐnic
bond in their carbon skeleton are constituents of a series of
naturally occurring compounds. Besides, these unsaturated
carbohydrates represent a versatile family of chiral templates
that can be further elaborated into useful synthons.1
The introduction of double bonds in the carbohydrate
framework results in the formation of three categories of com-
pounds: alkenes, enols and enediols. Furthermore, the double
bond may be exo- or endocyclic with respect to the carbo-
hydrate ring (furanoid or pyranoid). Their various versatile
properties and syntheses are reported comprehensively in the
literature.1h3 The normal standard procedure for the synthesis
of glycals and 2-hydroxyglucals is the elimination of HBr from
acylglycosyl bromides by treatment with Zn/Cu in acetic acid,
and its improved version4 with secondary amines,2a,4,5 and,
more recently, with the dimeric Ti(III) species (Cp TiCl) 6a
Experimental
In a typical reaction, a solution of a halogenated or tosylated
sugar (1 molar equiv.) in HMPA (1 ml per mmol; if the start-
ing sugar is not soluble in HMPA, a saturated solution in
THF can be added) to a suspension of oil-free NaH (2.2 molar
equiv.) in anhydrous HMPA, (1 ml per mmol) under argon at
0 ¡C and the mixture allowed to stir at room temperature for
the time given in Table 1. Upon completion of the reaction
(TLC analysis, 12 to 24 h), quenching was performed either
with wet diethyl ether or water and the mixture Ðltered
through a pad of Celite. Aqueous work up of the Ðltrate and
silica gel chromatography a†orded pure elimination products
(Table 1).16
2
2
or using sodium hydride in DMF.6b Much attention has
been focused on the synthesis of 6-deoxyhex-5-enopyranose
derivatives, due to their unique synthetic utility, and
on their transformation to cyclohexane (cylitols) and
cyclopentane derivatives in which the ring oxygen atom
of the sugar is replaced by a methylene group.7,8 The hex-
5,6-enopyranosides, also starting materials for the synthesis
of prostaglandins,8a are accessible by treating 6-bromo-
and 6-iodo-6-deoxyhexopyranosides with NaH/DMF,6
CsF/DMF,9 AgF/pyridine,10 1,8-diazabicyclo[5.4.0]undec-7-
Representative spectroscopic data for 2
ene (DBU)/CH CN,11 NaI/BuNI/MS4A/DMSO and DBU/
3
DMSO12 or DBU/DMF.13 These methods, however, often
[a]25 \ [176¡ (CHCl , c \ 1); 1H NMR (300 MHz, CDCl ):
D
3
3
su†er from low yields or the formation of by-products.
d 6.54 (1H, dd, J \ 5.1, J \ 0.6, H-1), 5.42 (1H, dd,
1, 2
1, 3
Previously, we reported the cleavage of silyl ethers14 with
sodium hydride (NaH) in hexamethylphosphoric triamide
(HMPA) and the selectivity of this reagent towards the cleav-
age of tert-butyldiphenylsilyl ethers in the presence of tert-
butyldimethylsilyl ethers.15 In an extension of our work on
the reactivity of NaH in HMPA,16 we exposed 6-O-p-
tosylsulfonyl-3,4-di-O-acetyl-D-glucal (1) to our reagent with
Scheme 1
896
New J. Chem., 2001, 25, 896È898
DOI: 10.1039/b010196f
This journal is ( The Royal Society of Chemistry and the Centre National de la Recherche ScientiÐque 2001
Khan
