Regio- and stereo-selective bromo(alkoxylation)s of (E)-α-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxymethylene) carbonyl compounds. A route to near-stereopure α-bromo α-dioxymethyl carbonyl compounds

Article abstract of DOI:10.1039/b002749i

(E)-4-Methoxymethoxy-3-methylbut-3-en-2-one 17b reacts with NBS in propan-1-ol in a highly regio- and anti-stereo-selective manner to give (3R*-,4R*)-3-bromo-4-methoxymethoxy-3-methyl-4-propoxybutan-2-one 18. Compound 10, a relative of the butenone 17b in which the methoxymethyl group is replaced by the 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl unit, undergoes an analogous bromo(propoxylation) reaction with reasonable facial selectivity to give an 86:14 mixture of (3R,4R)-3-bromo-3-methyl-4-propoxy-4-(2′,3′,4′,6′-tetra- O-acetyl-β-D-glucopyranosyloxy)butan-2-one 11c and its (3S,4S)-diastereomer 12c. The major bromo(propoxy) derivative, isolable in 57% yield by fractional crystallisation, is assigned the stereostructure 11c by single-crystal X-ray crystallographic analysis. Other primary alcohols and methanol participate in the reaction of compound 10 with NBS, leading predominantly (with selectivities ranging from 75:25 to 89:11) to bromo(alkoxy) products of type 11 which are usually separable from their diastereomers of type 12 by fractional crystallisation (in yields ranging from 41 to 64%). A model to account for the role of the 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl unit in the stereoinduction process is proposed. Related bromo(propoxylation)s are observed with the vinylogous esters 24, 25a and 25b, leading to the isolation of the major products, 28, 30a and 30b (in yields ranging from 39 to 55%), and with the vinylogous carbonates 32a, 32c, 37a and 37b, providing access to the major products 33a, 33c, 38a and 38b (in yields ranging from 52 to 73%). In the presence of trifiuoroacetic acid and ethane-1,2-diol, the bromo(propoxy) derivatives 11c, 28, 30b and 33c undergo transacetalisation to give the ethylene glycol acetals 40a, 40b, 41 and 40c with ees of 94-98%, in yields ranging from 56 to 67%. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/b002749i

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Regio- and stereo-selective bromo(alkoxylation)s of (E)-ꢀ-(2,3,4,6-
tetra-O-acetyl-ꢁ-D-glucopyranosyloxymethylene) carbonyl
compounds. A route to near-stereopure ꢀ-bromo ꢀ-dioxymethyl
carbonyl compounds†
1
M. Sum Idris, David S. Larsen, Robin G. Pritchard, Anthony Schofield, Richard J. Stoodley*
and Peter D. Tiffin
Department of Chemistry, UMIST, PO Box 88, Manchester, UK M60 1QD
Received (in Cambridge, UK) 6th April 2000, Accepted 12th May 2000
Published on the Web 26th June 2000
(E)-4-Methoxymethoxy-3-methylbut-3-en-2-one 17b reacts with NBS in propan-1-ol in a highly regio- and
anti-stereo-selective manner to give (3R*,4R*)-3-bromo-4-methoxymethoxy-3-methyl-4-propoxybutan-2-one 18.
Compound 10, a relative of the butenone 17b in which the methoxymethyl group is replaced by the 2,3,4,6-tetra-O-
acetyl-β--glucopyranosyl unit, undergoes an analogous bromo(propoxylation) reaction with reasonable facial
selectivity to give an 86:14 mixture of (3R,4R)-3-bromo-3-methyl-4-propoxy-4-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β--
glucopyranosyloxy)butan-2-one 11c and its (3S,4S)-diastereomer 12c. The major bromo(propoxy) derivative,
isolable in 57% yield by fractional crystallisation, is assigned the stereostructure 11c by single-crystal X-ray
crystallographic analysis. Other primary alcohols and methanol participate in the reaction of compound 10 with
NBS, leading predominantly (with selectivities ranging from 75:25 to 89:11) to bromo(alkoxy) products of type 11
which are usually separable from their diastereomers of type 12 by fractional crystallisation (in yields ranging from
41 to 64%). A model to account for the role of the 2,3,4,6-tetra-O-acetyl-β--glucopyranosyl unit in the
stereoinduction process is proposed.
Related bromo(propoxylation)s are observed with the vinylogous esters 24, 25a and 25b, leading to the isolation
of the major products, 28, 30a and 30b (in yields ranging from 39 to 55%), and with the vinylogous carbonates 32a,
32c, 37a and 37b, providing access to the major products 33a, 33c, 38a and 38b (in yields ranging from 52 to 73%).
In the presence of trifluoroacetic acid and ethane-1,2-diol, the bromo(propoxy) derivatives 11c, 28, 30b and 33c
undergo transacetalisation to give the ethylene glycol acetals 40a, 40b, 41 and 40c with ees of 94–98%, in yields
ranging from 56 to 67%.
The dihydro derivatives were considered to arise by addition
Introduction
of hydrogen to the olefinic units of conformers of type 4, that
were adopted for steric and stereoelectronic reasons. Delivery
of hydrogen by the catalyst (in a syn-selective manner) to the
less-hindered Re-face‡ accounted for the selectivity. This model
was based upon one developed earlier to explain the Re-face
reactivity of dienyl glucosides of type 5 in Diels–Alder
reactions.5,6
As part of a programme aimed at defining, understanding and
exploiting stereocommunication through glycosidic bonds,2
we have become interested in additions to the olefinic bonds
of α-(2,3,4,6-tetra-O-acetyl-β--glucopyranosyloxymethylene)
carbonyl compounds of type 1.3 In catalytic hydrogenations,4
dihydro adducts of type 2 have been shown to predominate over
those of type 3 (Scheme 1). Although the selectivities were
Scheme 1
modest (ranging from 67:33 to 85:15), it was usually possible
to isolate the major dihydro derivatives of type 2 in acceptable
yields (ranging from 49 to 71%) simply by fractional
crystallisation.
‡ The stereodescriptor refers to the carbon atom of the olefin bearing
the 2,3,4,6-tetra-O-acetyl-β--glucopyranosyloxy unit.
† For preliminary communication, see ref. 1.
DOI: 10.1039/b002749i
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This journal is © The Royal Society of Chemistry 2000
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In this paper, we report on the behaviour of systems of type 1
in bromo(alkoxylation)s. At the outset of our studies, very little
was known about such reactions involving achiral relatives of
our substrates.§ On the assumption that their vinyl ether char-
acter would outweigh their α,β-unsaturated carbonyl character,¶
systems of type 1 were expected to react in a regioselective
manner (the bromine atom being attached to the oxygen-free
olefinic carbon atom). If anti-stereoselectivity prevailed,
bromo(alkoxy) derivatives of type 6 were predicted to predomin-
ate over those of type 7. Conversely, if syn-stereoselectivity was
dominant, products of type 8 were anticipated in preference to
ones of type 9.
and propan-1-ol; the standard work-up followed by two crystal-
lisations gave the major material 11c in 57% yield. A simpler
work-up (in which the reaction mixture was partially concen-
trated, cooled and filtered) provided compound 11c in 52%
yield.
The reaction of the butenone 10 with NBS and butan-1-ol
gave rise to an 86:14 of the bromo(butoxy) derivatives 11d and
12d, from which the major product 11d was isolated in 41%
yield after crystallisation.
When the butenone 10 was subjected to the action of NBS
and propan-2-ol or 2-methylpropan-2-ol, the tetraacetate 13 (as
a mixture of α- and β-anomers) was the major product. In the
former reaction, there was also evidence for the presence of
≈25% of two dibromo products of type 14 (as an 80:20
Results and discussion
The butenone 104 was selected for the initial bromo(alkoxyl-
ation) studies. It reacted with NBS in methanol to give, follow-
ing a standard work-up (in which the residue, obtained after
evaporation of the alcohol, was dissolved in CH2Cl2 and the
solution was washed with aq. Na2S2O5 and then concentrated),
mainly a 75:25 mixture of bromo(methoxy) derivatives. Two
crystallisations of the mixture provided the major product in
47% yield; by processing the mother liquor, it was possible to
isolate the minor product (contaminated with ≈5% of the major
adduct) in ≈10% yield. There was little doubt that the products
possessed the expected regiostructures; thus, the methine
hydrogen atoms at position 4 resonated as singlets at δ 4.95 (for
the major adduct) and δ 5.03, in accord with their acetal dis-
position. On the basis of subsequent evidence, the major
material was assigned the stereostructure 11a and the minor
one the stereostructure 12a, indicative of anti-stereoselective
additions (Scheme 2).
mixture) on the basis of the presence of singlets at δ 6.35 and
6.50 (attributed to the 4-H methine signals of the minor
and major dibromides).
To determine the effect of α-substitution, benzyl alcohol,
2-methylpropan-1-ol and 2,2-dimethylpropan-1-ol were exam-
ined in the reaction of the butenone 10 with NBS. Benzyl
alcohol provided an 89:11 mixture of the bromo(benzyloxy)
derivatives 11e and 12e, from which compound 11e was isolated
in 43% yield after crystallisation. 2-Methylpropan-1-ol gave an
88:12 mixture of the bromo(methylpropoxy) products 11f and
12f; fractional crystallisation of the mixture led to the isolation
of compound 11f in 55% yield. Mainly three products arose in
the reaction with 2,2-dimethylpropan-1-ol, considered to be a
76:10:14 mixture of compounds 11g, 12g and 14 by 1H NMR
spectroscopy; fractional crystallisation gave a 91:9 mixture of
compounds 11g and 14.
From the foregoing results, it is clear that methanol and a
range of primary alcohols participate in the reaction of the
butenone 10 with NBS. Major and minor bromo(alkoxy)
derivatives of types 11 and 12 emerge in ratios ranging from
75:25 to 89:11; the major products of type 11 can be isolated
by fractional crystallisation in yields ranging from 41 to 64%.
The major product obtained from the reaction of the buten-
one 10 with NBS and propan-1-ol was assigned the stereostruc-
ture 11c on the basis of a single-crystal X-ray crystallographic
analysis. Its molecular structure, together with its crystallo-
graphic labelling, is shown in Fig. 1.|| The stereostructures 11a,b
and 11d–g were inferred by analogy and supported by similar-
ities in the 1H NMR spectra of the compounds. Thus, the
methyl ketone signals appeared in the δ 2.20–2.32 region for
compounds 11a–g; by contrast the corresponding signals for
their diastereomers 12a–g were shifted downfield by 0.05–0.13
ppm.
Although there was no doubt that compounds 11a–g were
the major products of the bromo(alkoxylation)s of the butenone
10, the structures of the minor products were not unequivocally
defined. As indicated in Scheme 3, if the oxonium ion 15 were
to intervene, then the minor products could possess the stereo-
structures 16a–g. To shed light on this situation, the behaviour
of compound 17b (prepared in 35% yield after chromatography
by the action of ClCH2OMe on the salt 17a6 in MeCN) in the
bromo(propoxylation) was examined. The formation of a single
Scheme 2
With a view to improving the selectivity and/or the isolated
yield of the major bromo(alkoxy) derivative, the reaction of
the butenone 10 with NBS and other alcohols was examined
(Scheme 2).
The use of ethanol led to the isolation of an 80:20 mixture of
the bromo(ethoxy) derivatives 11b and 12b after the standard
work-up; two crystallisations provided compound 11b in 38%
yield. A more efficient route to compound 11b became available
when it was discovered that the material was relatively insoluble
in the reaction mixture; a simple filtration of the cooled mixture
then afforded compound 11b in 64% yield.
An 86:14 mixture of the bromo(propoxy) products 11c and
12c was produced in the reaction of the butenone 10 with NBS
§ A sub-structure search in STN International and Beilstein Crossfire of
the unit A shown below failed to provide any relevant references.
¶ A referee has asked for the basis of this assumption. It rests on the
knowledge that the reactivity of alkenes towards electrophiles is
increased by electron-donating substituents and decreased by electron-
withdrawing substituents. Electrophiles, therefore, would be expected to
be more responsive to electron-rich character than to electron-deficient
character.
|| In compound 11c, the torsional angles involving O(5Ј)–C(1Ј)–O(1Ј)–
C(4), C(1Ј)–O(1Ј)–C(4)–O(4) and O(1Ј)–C(4)–O(4)–C(6) are Ϫ76.2,
ϩ121.2 and Ϫ86.7Њ. For two other crystal structures of glycosidic
acyclic acetals, see ref. 10.
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Earlier, we had observed5 that dienes of the type 5 (R3 = H)
showed poorer Re-face selectivity in Diels–Alder reactions than
related dienes of type 5 (R3 = Me). It was of interest therefore
to compare the selectivity of the butenone 217 with that of its
relative 10 in the bromo(alkoxylation)s.
The reactions of the butenone 21 with NBS in ethanol,
propan-1-ol and benzyl alcohol were examined (Scheme 5). The
Scheme 5
first reaction afforded a 71:29 mixture of the bromo(ethoxy)
derivatives 22a and 23a, the second a 72:28 mixture of the
bromo(propoxy) products 22b and 23b, and the third an 80:20
mixture of the bromo(benzyloxy) derivatives 22c and 23c. In
each case, the product was contaminated with a significant
amount (10–25%) of the tetraacetate 13, necessitating a
chromatographic purification. However, fractional crystallis-
ation of the purified products failed to provide the major
bromo(alkoxy) material free of the minor one. The stereo-
structures of compounds 22a–c and 23a–c were not rigorously
established but were assigned by analogy with the results
observed for the butenone 10. It is worth noting, however, that
the methyl ketone signals appeared at higher field in the
major bromo(alkoxy) products [as was observed in the case of
the major bromo(alkoxy) derivatives 11a–g derived from 10].
Clearly, the bromo(alkoxylation)s of the butenone 21 were less
Re-face selective than those of its relative 10.
Fig. 1 Molecular structure of compound 11c.
Scheme 3
The bromo(propoxylation) reaction could be extended to the
pentenone 246 and compounds 25a4 and 25b.4 Thus, the acyclic
bromo(propoxy) derivative, isolated in 57% yield after chrom-
atography and assigned the structure rac-18, implied that the
addition displayed high anti-stereoselectivity. It is likely, there-
fore, that the minor products formed in the bromo(alkoxyl-
ation)s of the butenone 10 possess the stereostructures 12a–g,
rather than the stereostructures 16a–g, and that they arise
by SN2-like ring openings of the cyclic bromonium ion 20.
Correspondingly, the major bromo(alkoxylation) products are
deemed to arise from the cyclic bromonium ion 19 by similar
pathways (Scheme 4). It is worth noting that the preferred
vinylogous ester 24 [prepared from the salt 268 and the aceto-
bromoglucose 279 in much improved yield (44% versus 6%) by
using a mixture of Me2CO and water (in place of Me2SO) as the
reaction medium**] gave rise to the bromo(propoxy) derivatives
28 and 29 (Scheme 6) in the ratio 87:13; compound 28 was
Scheme 6
isolated in 51% yield after the standard work-up and crystallis-
ation (the yield was increased to 55% by simply cooling the
reaction mixture, filtering off the product and effecting its
recrystallisation). The reactions involving the methylenecyclo-
pentanone 25a and the methylenecyclohexanone 25b (Scheme
7) afforded 87:13 mixtures of the bromo(propoxy) adducts
30a/31a and 30b/31b; following crystallisation, compound 30a
was isolated in 52% yield and compound 30b in 39% yield.
As Schemes 8 and 9 illustrate, vinylogous carbonates also
underwent the bromo(propoxylation). Thus, the propenoate
Scheme 4
bromonium ion 19 is that resulting from a selective addition to
the Re-face of the olefinic bond of compound 10 and consistent
with the involvement of a reactive conformation akin to 4
(R1 = R2 = Me).
** Earlier, a similar modification was shown to result in an improvement
in the yield of the butenone 10 (see ref. 4).
J. Chem. Soc., Perkin Trans. 1, 2000, 2195–2204
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In a similar manner, the bromo(propoxy) derivatives 28, 30b
and 33c were transformed into the acetals 40b (58% yield; 94%
ee), 41 (56% yield; 96% ee) and 40c (67% yield; 98% ee).
Scheme 7
The aforecited results are of interest in the following respects.
In showing that vinylogous esters/carbonates of type 1 undergo
highly regioselective bromo(alkoxylation)s in an anti-stereo-
selective manner, they illuminate new reactivity of these syn-
thetically versatile systems. They reveal that the model used to
explain the facial reactivity of systems of type 1 in hydrogen-
ations also accounts for their behaviour in bromo(alkoxyl-
ation)s. They extend the role of the 2,3,4,6-tetra-O-acetyl-β--
glucopyranosyl unit as a cheap and practical auxiliary. Finally,
compounds 11c, 28, 30a,b, 33c, 38a,b, 40a–c and 41 are
representatives of a new class of 1,2,3-trifunctional chirons and
the present technology is capable of making them available in
gram quantities. Their clusters of reactive functionality render
the compounds of considerable potential in stereoselective
synthesis.
Scheme 8
Scheme 9
Experimental
Light petroleum refers to that fraction boiling in the range 35–
60 ЊC. NBS was recrystallised from ten times its weight of
water, dried in vacuo (over P2O5) and stored in the dark.
The progress of reactions was monitored by TLC, using
Merck plastic or aluminium sheets coated with silica gel
(60 F254); chromatograms were initially examined under UV
light (Mineralight UVG2-58) and then visualised with a
p-anisaldehyde stain [plates were sprayed with p-MeOC6H4-
CHO–conc. H2SO4–EtOH (1:4:95) and heated]. Column
chromatography was effected, under positive pressure from a
compressed-air line, with Crossfield Sorbsil C60 flash silica.
HPLC analyses were carried out with a Chiralpak AD column
(25 × 0.46 cm) employing either a Kontron system [420 pump
and 742 UV detector (set at 215 nm)] fitted with a Rheodyne
7125 injector or a Shimadzu system (LC-10AT pump, SPD-
10AV UV/vis detector, SIL-10AD autoinjector and SCL-10A
controller).
32a4 furnished an 85:15 mixture of the bromo(propoxy) deriv-
atives 33a and 34a; crystallisation of the mixture provided
compound 33a in 52% yield. A 78:22 mixture of the bromo-
(propoxy) derivatives 33b and 34b was produced in the reaction
involving the propenoate 32b [prepared (73% yield after crystal-
lisation) by Wittig condensation of the formyl ester 356 with the
phosphorane 36], from which compound 33b was isolated in
18% yield after chromatography and crystallisation. Again, it is
worth noting that replacement of the 2-methyl group by a
hydrogen atom results in a poorer Re-face selectivity. Whilst
the propenoate 32c4 showed a selectivity identical to that of
its relative 32a, it was possible to isolate the major bromo-
(propoxy) derivative 33c in a much better yield (73% after crys-
tallisation). The cyclic vinylogous carbonates 37a4 and 37b4
underwent reaction with NBS in propan-1-ol to give similar
ratios of products, the former reaction affording an 85:15 mix-
ture of the bromo(propoxy) derivatives 38a and 39a and the
latter a 90:10 mixture of compounds 38b and 39b. Following
crystallisation, compound 38a was isolated in 54% yield and
compound 38b in 66% yield.
To summarise, a range of acyclic and cyclic vinylogous esters/
carbonates of type 1 react with NBS and methanol/primary
alcohols to give predominantly bromo(alkoxy) products of type
6, which can usually be isolated in a near-stereopure state by
fractional crystallisation.
Removal of the auxiliary from bromo(alkoxy) derivatives of
type 6 was readily achieved under transacetalisation conditions.
Thus, when treated with trifluoroacetic acid (TFA) and ethane-
1,2-diol, the bromo(propoxy) derivative 11c was transformed
into mainly a 50:50 mixture of the acetal 40a and the tetra-
acetate 13; a simple work-up [in which the mixture was left in
acidic methanol (to convert 13 into -glucose)] gave the acetal
40a, as a near-pure oil (by 1H NMR spectroscopy) in 63% yield.
A chromatographed sample possessed an ee of 98%.
Evaporations were conducted under reduced pressure (using
a water-pump or an oil-pump) at ≤40 ЊC with a Büchi rotary
evaporator (fitted with a water or Me2CO–solid CO2 con-
denser). Mps were determined with a Büchi 512 melting point
apparatus. Specific optical rotations, given in 10Ϫ1 deg cm2 gϪ1
,
were measured at ≈20 ЊC using a Thorn Automation Type 243
or an Optical Activity 1000 polarimeter with a cell of path
length 0.1 dm.
Carbon, hydrogen and nitrogen contents were determined
with a Carlo Erba Model 1108 analyser; bromine content was
measured by oxygen combustion followed by automatic argen-
tometric titration on a Mettler DL25 titrator. A Perkin-Elmer
Lambda 15 spectrometer was used to determine UV spectra;
extinction coefficients (ε) are presented in cm2 mmolϪ1. IR spec-
tra were recorded using a Perkin-Elmer 783 spectrometer.
NMR spectra were measured using a Bruker AM 300 or a
Bruker AM 400 [with distortionless enhancement by polaris-
ation transfer (DEPT) editing for 13C spectra]; J-values and
separations are given in Hz. FAB mass spectra (m-NO2C6H4-
CH2OH as matrix) and CI mass spectra (NH3 as carrier gas)
were measured using a Kratos MS 50 spectrometer; high-
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resolution mass spectra were recorded on a Kratos Concept IS
spectrometer. A Rigaku AFC6S diffractometer was used for the
single-crystal X-ray analysis.
appropriate alcohol. After the time specified, the mixture was
concentrated and a solution of the residue in ethyl acetate or
dichloromethane was washed successively with 1% aq. sodium
metabisulfite and water. Evaporation of the dried (MgSO4)
organic phase gave a residue, which was analysed by NMR
spectroscopy and then purified in the manner described.
(E)-4-Methoxymethoxy-3-methylbut-3-en-2-one 17b
Chloromethyl methyl ether (2.00 g, 24.8 mmol) was added to a
stirred mixture of the sodium salt 17a6 (2.44 g, 20.0 mmol) and
acetonitrile (20 cm3). After 15 h, the mixture was concentrated
and the product partitioned between dichloromethane and
water. Evaporation of the dried (MgSO4) organic phase left a
syrup that was predominantly compound 17b. Subjection of the
material to column chromatography [hexanes–EtOAc (4:1)
as eluent] gave the title compound 17b (1.01 g, 35%); λmax (EtOH)/
Reaction involving the butenone 10 and methanol. The reac-
tion of the butenone 104 (0.225 g, 0.52 mmol) in methanol
(5 cm3) for 1 h gave rise to a product comprising mainly a 75:25
mixture of the bromo(methoxy) adducts 11a and 12a [the ratio
was estimated from the integrals of the singlets at δ 2.32 and
2.38 (attributed to the 1-H3 signals of 11a and 12a) and of the
singlets at δ 3.46 and 3.59 (ascribed to the methoxy signals of
11a and 12a)]; ≈5% of succinimide (δ 2.72) was also present.
Crystallisation of the material from dichloromethane–diethyl
ether–light petroleum gave a 96:4 mixture of the bromo-
(methoxy) adducts 11a and 12a (0.153 g, 54%). A further
crystallisation from methanol provided (3R,4R)-3-bromo-4-
methoxy-3-methyl-4-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β--glucopyran-
osyloxy)butan-2-one 11a (0.133 g, 47%); mp 150–152 ЊC; [α]D
Ϫ20 (c 2.0, CH2Cl2) (Found: C, 44.5; H, 5.4; Br, 15.3.
C20H29BrO12 requires C, 44.4; H, 5.4; Br, 14.8%); λmax (EtOH)/
nm 249 (ε 10000); νmax (film)/cmϪ1 1720 (vinylogous ester C᎐O)
᎐
and 1650 (C᎐C); δ (300 MHz; CDCl ) 1.73 (3 H, d, J 1, 3-Me),
᎐
H
3
2.22 (3 H, s, 1-H3), 3.44 (3 H, s, MeO), 5.00 (2 H, s, OCH2O)
and 7.41 (1 H, apparent d, separation 1, 4-H); δC (100 MHz;
CDCl3) 8.3 (CH3C), 25.3 (1-CH3), 56.3 (CH3O), 97.4 (OCH2O),
119.5 (3-C), 156.1 (4-CH) and 197.7 (2-CO); m/z (CI) 145
(MHϩ, 100%) (Found: MHϩ, 145.0867. C7H13O3 requires m/z
145.0865).
(E)-2-Methyl-1-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-ꢁ-D-gluocopyranosyl-
nm 294 (ε 85); νmax (KBr)/cmϪ1 1750 (ester C᎐O) and 1725
᎐
oxy)pent-1-en-3-one 24
(ketone C᎐O); δH (300 MHz; CDCl3) 1.78 (3 H, s, 3-Me), 2.02,
᎐
2.05, 2.06 and 2.08 (each 3 H, s, 4 × MeCO2), 2.32 (3 H, s,
1-H3), 3.46 (3 H, s, MeO), 3.79 (1 H, ddd, J 2.5, 5 and 10, 5Ј-H),
4.18 and 4.25 [each 1 H, dd (J 5 and 12) and dd (J 2.5 and 12),
6Ј-H2], 4.83 (1 H, d, J 8, 1Ј-H), 4.95 (1 H, s, 4-H), 5.08 (1 H, t,
J 9.5, 4Ј-H), 5.13 (1 H, dd, J 8 and 9.5, 2Ј-H) and 5.28 (1 H,
t, J 9.5, 3Ј-H); δC (100 MHz; CDCl3) 19.3 (CH3C), 20.7, 20.8,
21.0 and 21.2 (4 × CH3CO2), 24.9 (1-CH3), 57.4 (CH3O), 62.1
(6Ј-CH2), 66.4 (3-C), 68.6, 71.1, 72.1 and 72.6 (2Ј-, 3Ј-, 4Ј- and
5Ј-CH), 100.8 (1Ј-CH), 106.4 (4-CH), 169.4, 169.5, 170.3 and
170.5 (4 × MeCO) and 200.2 (2-CO); m/z (FAB) 331
(C14H19O9ϩ, 80%), 195 and 193 (C6H10BrO2ϩ, each 15), and 169
(100).
A solution of the salt 268 (6.80 g, 50 mmol) in water (20 cm3)
and the acetobromoglucose 279 (10.3 g, 25 mmol) in acetone
(40 cm3) was stirred for 3 days. After partial concentration (to
remove Me2CO), the mixture was extracted twice with dichloro-
methane. Evaporation of the dried (MgSO4) organic phase and
crystallisation of the residue from dichloromethane–diethyl
ether gave compound 24 (4.91 g, 44%) in a pure state; mp 107–
108 ЊC (lit.,6 97–99 ЊC); δH (300 MHz; CDCl3) 1.10 (3 H, t, J 7,
5-H3), 1.72 (3 H, d, J 1, 2-Me), 2.03, 2.05, 2.06 and 2.09 (each
3 H, s, 4 × MeCO2), 2.56 (2 H, q, J 7, 4-H2), 3.83 (1 H, ddd,
J 2.5, 5 and 10, 5Ј-H), 4.16 and 4.30 [each 1 H, dd (J 2.5 and
12.5) and dd (J 5 and 12.5), 6Ј-H2], 4.90 (1 H, d, J 8, 1Ј-H),
5.13–5.30 (3 H, m, 2Ј-, 3Ј and 4Ј-H) and 7.36 (1 H, apparent d,
separation 1, 1-H).
The filtrate from the first crystallisation was concentrated
and the residue was triturated with light petroleum to give
mainly
(3S,4S)-3-bromo-4-methoxy-3-methyl-4-(2Ј,3Ј,4Ј,6Ј-
tetra-O-acetyl-β--glucopyranosyloxy)butan-2-one 12a (0.028
g, ≈10%); δH(300 MHz; CDCl3) inter alia 1.77 (3 H, s, 3-Me),
2.01, 2.03, 2.05 and 2.08 (each 3 H, s, 4 × MeCO2), 2.38 (3 H, s,
1-H3), 3.59 (3 H, s, MeO), 3.73 (1 H, ddd, J 2.5, 5 and 10, 5Ј-H),
4.15 and 4.24 [each 1 H, dd (J 2.5 and 12.5) and dd (J 5 and
12.5), 6Ј-H2], 4.83 (1 H, dd, J 8, 1Ј-H), 5.03 (1 H, s, 4-H), 5.08
(1 H, d, J 8 and 9.5, 2Ј-H), 5.09 (1 H, t, J 9.5, 4Ј-H) and 5.24
(1 H, t, J 9.5, 3Ј-H).
Reaction involving the butenone 10 and ethanol. (a) The
reaction of the butenone 10 (0.225 g, 0.52 mmol) in ethanol
(5 cm3) for 1 h gave rise to a product comprising mainly an
80:20 mixture of the bromo(ethoxy) adducts 11b and 12b [the
ratio was estimated from the heights of the singlets at δ 2.32 and
2.39 (ascribed to the 1-H3 signals of 11b and 12b)]; ≈8% of
succinimide was also present.
Methyl (E)-3-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-ꢁ-D-glucopyranosyl-
oxy)prop-2-enoate 32b
A solution of the formyl ester 356 (4.00 g, 10.6 mmol) and the
phosphorane 36 [obtained by washing a solution of Bu3PϩCH2-
CO2Me BrϪ (5.10 g, 14.4 mmol) in CH2Cl2 with 10% aq.
NaOH and removing the solvent by evaporation] in toluene
(100 cm3) was heated under reflux for 30 min. The solid,
obtained after concentration, was washed with light petroleum
and the product crystallised from dichloromethane–light
petroleum to give the title compound 32b (3.34 g, 73%); mp 142–
143 ЊC; [α]D Ϫ21 (c 0.27, CH2Cl2) (Found: C, 49.7; H, 5.6.
C18H24O12 requires C, 50.0; H, 5.6%); λmax (EtOH)/nm
223 (ε 16000); νmax (KBr)/cmϪ1 1750 (ester C᎐O), 1720 and 1710
᎐
(vinylogous carbonate C᎐O), and 1630 (C᎐C); δ (300 MHz;
᎐
᎐
H
CDCl3) 2.04, 2.06, 2.07 and 2.12 (each 3 H, s, 4 × MeCO2), 3.73
(3 H, s, MeO2C), 3.83 (1 H, ddd, J 2.5, 5 and 10, 5Ј-H), 4.17 and
4.29 [each 1 H, dd (J 2.5 and 12.5) and dd (J 5 and 12.5), 6Ј-H2],
4.92 (1 H, d, J 8, 1Ј-H), 5.14 (1 H, t, J 9.5, 4Ј-H), 5.16 (1 H, dd,
J 8 and 9, 2Ј-H), 5.27 (1 H, t, J 9, 3Ј-H), 5.51 (1 H, d, J 12.5,
2-H) and 7.52 (1 H, d, J 12.5, 3-H); δC (100 MHz; CDCl3) 20.9
and 21.0 (4 × CH3CO2), 51.7 (CH3O), 61.9 (6Ј-CH2), 68.1, 71.0,
72.7 and 73.0 (2Ј-, 3Ј-, 4Ј- and 5Ј-CH), 100.3 (1Ј-CH), 102.1
(2-CH), 158.9 (3-CH), 167.6 (CO2Me) and 169.4, 169.6, 170.4
and 170.9 (4 × MeCO); m/z (FAB) 433 (MHϩ, 10%), 331
(C14H19O9ϩ, 45), 169 (70), 109 (55) and 43 (100) [(after addition
of KI) 471 (MKϩ, 40%)].
Two crystallisations of the mixture from chloroform–diethyl
ether–light petroleum gave (3R,4R)-3-bromo-4-ethoxy-3-
methyl-4-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β--glucopyranosyloxy)-
butan-2-one 11b (0.110 g, 38%); mp 152–153 ЊC; [α]D Ϫ29 (c
0.53, CH2Cl2) (Found: C, 45.1; H, 5.5; Br, 14.5. C21H31BrO12
requires C, 45.4; H, 5.6; Br, 14.4%); λmax (EtOH)/nm 293 (ε 90);
νmax (KBr)/cmϪ1 1760 (ester C᎐O) and 1730 (ketone C᎐O);
δH (300 MHz; CDCl3) 1.11 (3 H, t, J 7, MeCH2), 1.78 (3 H, s,
3-Me), 2.02, 2.04, 2.06 and 2.08 (each 3 H, s, 4 × MeCO2), 2.32
(3 H, s, 1-H3), 3.49 and 3.94 (each 1 H, dq, J 9.5 and 7,
MeCH2O), 3.77 (1 H, ddd, J 2.5, 5.5 and 10, 5Ј-H), 4.16 and
4.24 [each 1 H, dd (J 5.5 and 12) and dd (J 2.5 and 12), 6Ј-H2],
4.84 (1 H, d, J 8, 1Ј-H), 5.05 (1 H, s, 4-H), 5.06 (1 H, t, J 9.5,
4Ј-H), 5.12 (1 H, dd, J 8 and 9.5, 2Ј-H) and 5.27 (1 H, t, J 9.5,
3Ј-H); δC (100 MHz; CDCl3) 14.8 (CH3CH2), 19.5 (CH3C), 20.7,
20.8 and 21.1 (4 × CH3CO2), 25.0 (1-CH3), 62.2 (6Ј-CH2), 65.5
᎐
᎐
Bromo(alkoxylation) studies
General procedure. NBS (0.214 g, 1.2 mmol) was added to a
stirred mixture of the vinylogous ester/carbonate (1 mmol) in the
J. Chem. Soc., Perkin Trans. 1, 2000, 2195–2204
2199

View Article Online
(MeCH2), 66.8 (3-C), 68.6, 71.2, 72.1 and 72.6 (2Ј-, 3Ј-, 4Ј- and
5Ј-CH), 100.8 (1Ј-CH), 104.9 (4-CH), 169.4, 169.6, 170.3 and
170.5 (4 × MeCO) and 200.2 (2-CO); m/z (FAB) 331
(C14H19O9ϩ, 80%), 209 and 207 (C7H12BrO2ϩ, each 50), and 169
(100).
and 170.5 (4 × MeCO) and 200.1 (2-CO); m/z (FAB) 331
(C14H19O9ϩ, 50%), 237 and 235 (C9H16BrO2ϩ, each 20), 181
and 179 (C5H8BrO2ϩ, each 15) and 169 (100); m/z (CI) 602
and 600 (MNH4ϩ, 15 and 10%), 331 (C14H19O9ϩ, 20) and 157
(100).
(b) The reaction of the butenone 10 (4.30 g, 10.0 mmol) in
ethanol (50 cm3) for 15 h deposited a solid. The mixture was
cooled (Ϫ30 ЊC) and the solid collected by filtration. After hav-
ing been washed with a small volume of cold ethanol and dried,
the solid (3.57 g, 64%) was identified as the bromo(ethoxy)
adduct 11b.
Reaction involving the butenone 10 and propan-1-ol. (a) The
reaction of the butenone 10 (2.00 g, 4.7 mmol) in propan-1-ol
(40 cm3) for 1 h gave rise to a product comprising mainly an
86:14 mixture of the bromo(propoxy) adducts 11c and 12c [the
ratio was estimated from the integrals of the singlets at δ 2.31
and 2.37 (ascribed to the 1-H3 signals of 11c and 12c)]; ≈10% of
succinimide was also present.
Reaction involving the butenone 10 and propan-2-ol. The
reaction of the butenone 10 (0.215 g, 0.50 mmol) in propan-2-ol
(60 cm3) for 2 h gave rise to a product comprising mainly the
tetraacetylglucose 13 as a 1:1 mixture of α- and β-anomer [on
the basis of the triplets (J 10) at δ 5.22 and 5.52 (attributable to
the 3-H signals of the β- and α-anomer]; there was also evidence
for the presence of ≈25% of the dibromide 14 as an 80:20 mix-
ture of diastereomers [on the basis of the singlets at δ 6.35 and
6.50 (attributed to the 4-H signals of the minor and major
dibromides)].
Reaction involving the butenone 10 and 2-methylpropan-2-
ol. The reaction of the butenone 10 (0.215 g, 0.50 mmol) in
2-methylpropan-2-ol (30 cm3) at ≈30 ЊC for 2 h gave rise to a
product containing largely the tetraacetylglucose 13 as a 2:1
mixture of α- and β-anomer; there was also evidence for the
presence of ≈10% of the dibromide 14 as an 80:20 mixture of
diastereomers.
Reaction involving the butenone 10 and benzyl alcohol. The
reaction of the butenone 10 (0.225 g, 0.52 mmol) in benzyl
alcohol (2 cm3) for 1 h gave rise (after removal of PhCH2OH by
azeotropic distillation with water) to a product comprising
mainly an 89:11 mixture of the bromo(benzyloxy) adducts 11e
and 12e [the ratio was estimated from the integrals of the sing-
lets at δ 2.20 and 2.38 (attributed to the 1-H3 signals of 11e and
12e)]; ≈2% of succinimide was also present.
Two crystallisations of the mixture from chloroform–diethyl
ether–light petroleum gave (3R,4R)-3-bromo-3-methyl-4-
propoxy-4-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β--glucopyranosyloxy)-
butan-2-one 11c (1.51 g, 57%); mp 134–136 ЊC; [α]D Ϫ28 (c 1.2,
CH2Cl2) (Found: C, 46.3; H, 6.0; Br, 14.1. C22H33BrO12 requires
C, 46.4; H, 5.8; Br, 14.0%); λmax (EtOH)/nm 294 (ε 90); νmax
(KBr)/cmϪ1 1760 (ester C᎐O) and 1730 (ketone C᎐O); δ (300
᎐
᎐
H
MHz; CDCl3) 0.82 (3 H, t, J 7.5, MeCH2), 1.44–1.56 (2 H, m,
MeCH2), 1.77 (3 H, s, 3-Me), 2.01, 2.04, 2.06 and 2.07 (each
3 H, s, 4 × MeCO2), 2.31 (3 H, s, 1-H3), 3.33 and 3.87 (each 1 H,
dt, J 9.5 and 6.5, EtCH2O), 3.76 (1 H, ddd, J 2.5, 5 and 10,
5Ј-H), 4.15 and 4.23 [each 1 H, dd (J 5 and 12) and dd (J 2.5 and
12), 6Ј-H2], 4.84 (1 H, d, J 8, 1Ј-H), 5.03 (1 H, s, 4-H), 5.06 (1 H,
t, J 10, 4Ј-H), 5.11 (1 H, dd, J 8 and 9.5, 2Ј-H) and 5.26 (1 H, t,
J 9.5, 3Ј-H); δC (100 MHz; CDCl3) 10.2 (CH3CH2), 19.2
(CH3C), 20.4, 20.5 and 20.7 (4 × CH3CO2), 22.3 (MeCH2), 24.7
(1-CH3), 61.8 (6Ј-CH2), 66.4 (3-C), 68.3, 70.9, 71.7 and 72.3
(2Ј-, 3Ј-, 4Ј- and 5Ј-CH), 71.3 (EtCH2), 100.5 (1Ј-CH), 104.7
(4-CH), 169.1, 169.2, 170.0 and 170.2 (4 × MeCO) and 199.8
(2-CO); m/z (FAB) 331 (C14H19O9ϩ, 70%), 223 and 221
(C8H14BrO2ϩ, each 40), 181 and 179 (C5H8BrO2ϩ, each 20), and
169 (100).
(b) The reaction of the butenone 10 (0.430 g, 1.00 mmol) in
propan-1-ol (50 cm3) was left for 1 h at 38 ЊC and 60 h at ≈20 ЊC.
After concentration to ≈50% of its volume, the mixture was
allowed to crystallise (first at ≈20 ЊC and then at Ϫ30 ЊC);
filtration gave the bromo(propoxy) adduct 11c (0.298 g, 52%).
Reaction involving the butenone 10 and butan-1-ol.—The reac-
tion of the butenone 10 (0.225 mmol, 0.52 mmol) in butan-1-ol
(18 cm3) for 1 h gave rise to a product comprising mainly an
86:14 mixture of the bromo(butoxy) adducts 11d and 12d [the
ratio was estimated from the integrals of the singlets at δ 2.32
and 2.39 (ascribed to the 1-H3 signals of 11d and 12d)].
Crystallisation of the mixture from diethyl ether–hexanes
gave
(3R,4R)-4-benzyloxy-3-bromo-3-methyl-4-(2Ј,3Ј,4Ј,6Ј-
tetra-O-acetyl-β--glucopyranosyloxy)butan-2-one 11e (0.139 g,
43%); mp 118–120 ЊC; [α]D Ϫ41 (c 0.57, CH2Cl2) (Found: C,
50.8; H, 5.3; Br, 12.9. C26H33BrO12 requires C, 50.6; H, 5.4; Br,
13.0%); λmax (EtOH)/nm 206 (ε 9700), 251 (210), 257 (230), 263
(180), 267 (120) and 294 (65); νmax (KBr)/cmϪ1 1755 (ester
C᎐O) and 1725 (ketone C᎐O); δ (300 MHz; CDCl ) 1.81 (3 H,
᎐
᎐
H
3
s, 3-Me), 2.00, 2.03, 2.06 and 2.10 (each 3 H, s, 4 × MeCO2),
2.20 (3 H, s, 1-H3), 3.83 (1 H, ddd, J 2.5, 5 and 10, 5Ј-H), 4.20
and 4.28 [each 1 H, dd (J 5 and 12.5) and dd (J 2.5 and 12.5),
6Ј-H2], 4.53 and 4.91 (each 1 H, d, J 11.5, PhCH2), 4.93 (1 H, d,
J 8, 1Ј-H), 5.11 (1 H, t, J 10, 4Ј-H), 5.17 (1 H, dd, J 8 and 9.5,
2Ј-H), 5.19 (1 H, s, 4-H), 5.30 (1 H, t, J 9.5, 3Ј-H) and 7.22–7.35
(m, C6H5 and CHCl3); δC (100 MHz; CDCl3) 19.5 (CH3C), 20.6,
20.7 and 20.9 (4 × CH3CO2), 24.9 (1-CH3), 62.0 (6Ј-CH2), 66.8
(3-C), 68.4, 71.1, 72.1 and 72.6 (2Ј-, 3Ј-, 4Ј- and 5Ј-CH), 71.1
(PhCH2), 100.7 (1Ј-CH), 104.2 (4-CH), 127.9, 128.0 and 128.4
(5 × phenyl CH), 136.9 (phenyl C), 169.3, 169.4, 170.2 and
170.4 (4 × MeCO) and 200.0 (2-CO); m/z (FAB) 331
(C14H19O9ϩ, 60%), 169 (70), 109 (70) and 91 (C7H7ϩ, 100).
Reaction involving the butenone 10 and 2-methylpropan-1-
ol. The reaction of the butenone 10 (0.225 g, 0.52 mmol) in
2-methylpropan-1-ol (10 cm3) for 3 h gave rise to a product
comprising mainly an 88:12 mixture of the bromo(methyl-
propoxy) adducts 11f and 12f [the ratio was estimated from the
integrals of the singlets at δ 2.32 and 2.38 (attributed to the 1-H3
signals of 11f and 12f)]; ≈11% of succinimide was also present.
Crystallisation of the mixture from chloroform–diethyl
ether–light petroleum gave (3R,4R)-3-bromo-3-methyl-4-(2-
methylpropoxy)-4-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β--glucopyrano-
syloxy)butan-2-one 11f (0.167 g, 55%); mp 124–126 ЊC; [α]D
Ϫ24 (c 0.5, CH2Cl2) (Found: C, 47.1; H, 5.9; Br, 14.0.
C23H35BrO12 requires C, 47.3; H, 6.0; Br, 13.7%); λmax (EtOH)/
Crystallisation of the mixture from chloroform–diethyl
ether–light petroleum gave (3R,4R)-3-bromo-4-butoxy-3-
methyl-4-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β--glucopyranosyloxy)-
butan-2-one 11d (0.125 g, 41%); mp 75–77 ЊC; [α]D Ϫ12 (c 0.08,
CH2Cl2) (Found: C, 47.4; H, 6.1; Br, 13.8. C23H35BrO12 requires
C, 47.3; H, 6.0; Br, 13.7%); λmax (EtOH)/nm 294 (ε 110); νmax
(KBr)/cmϪ1 1760 (ester C᎐O) and 1730 (ketone C᎐O); δ (300
᎐
᎐
H
MHz; CDCl3) 0.86 (3 H, t, J 7.5, MeCH2), 1.19–1.33 and 1.35–
1.52 (each 2 H, m, MeCH2CH2), 1.78 (3 H, s, 3-Me), 2.02, 2.04,
2.06 and 2.08 (each 3 H, s, 4 × MeCO2), 2.32 (3 H, s, 1-H3), 3.37
and 3.92 (each 1 H, dt, J 9.5 and 6.5, PrCH2O), 3.76 (1 H, ddd,
J 3, 5 and 10, 5Ј-H), 4.16 and 4.23 [each 1 H, dd (J 5 and 12)
and dd (J 3 and 12), 6Ј-H2], 4.84 (1 H, d, J 8, 1Ј-H), 5.03 (1 H, s,
4-H), 5.07 (1 H, t, J 9.5, 4Ј-H), 5.12 (1 H, dd, J 8 and 9.5, 2Ј-H)
and 5.27 (1 H, t, J 9.5, 3Ј-H); δC (100 MHz; CDCl3) 13.8
(CH3CH2), 19.2 (MeCH2), 19.4 (CH3C), 20.7 and 21.0
(4 × CH3CO2), 25.0 (1-CH3), 31.4 (EtCH2), 62.1 (6Ј-CH2), 66.7
(3-C), 68.5, 71.1, 72.0 and 72.6 (2Ј-, 3Ј-, 4Ј- and 5Ј-CH), 69.7
(PrCH2), 100.7 (1Ј-CH), 105.0 (4-CH), 169.4, 169.5, 170.3
nm 294 (ε 100); νmax (KBr)/cmϪ1 1760 and 1740 (ester C᎐O) and
᎐
1730 (ketone C᎐O); δH (300 MHz; CDCl3) 0.80 and 0.81 (each
᎐
3 H, d, J 7, Me2CH), 1.72–1.82 (1 H, m, Me2CH), 1.78 (3 H, s,
3-Me), 2.02, 2.04, 2.07 and 2.08 (each 3 H, s, 4 × MeCO2), 2.32
(3 H, s, 1-H3), 3.08 and 3.72 (each 1 H, dd, J 7 and 9, Me2-
CHCH2O), 3.73–3.79 (1 H, m, 5Ј-H), 4.16 and 4.24 [each 1 H,
2200
J. Chem. Soc., Perkin Trans. 1, 2000, 2195–2204

View Article Online
dd (J 5 and 12.5) and dd (J 2.5 and 12.5), 6Ј-H2], 4.84 (1 H, d,
J 8, 1Ј-H), 5.02 (1 H, s, 4-H), 5.08 (1 H, t, J 10, 4Ј-H), 5.11 (1 H,
dd, J 8 and 10, 2Ј-H) and 5.26 (1 H, t, J 9.5, 3Ј-H); δC (100
MHz; CDCl3) 19.1, 19.2 and 19.3 [(CH3)2CH and CH3C], 20.6,
20.7 and 20.9 (4 × CH3CO2), 24.9 (1-CH3), 28.2 (Me2CH), 62.0
(6Ј-CH2), 66.6 (3-C), 68.4, 71.1, 71.9 and 72.6 (2Ј-, 3Ј-, 4Ј- and
5Ј-CH), 76.4 (CH2O), 100.6 (1Ј-CH), 104.9 (4-CH), 169.3,
169.4, 170.2 and 170.4 (4 × MeCO) and 200.0 (2-CO); m/z
(FAB) 331 (C14H19O9ϩ, 90), 235 and 233 (C9H16BrO2ϩ, each 30),
and 169 (100).
Reaction involving the butenone 10 and 2,2-dimethylpropan-1-
ol. The reaction of the butenone 10 (0.157 g, 0.37 mmol) in
2,2-dimethylpropan-1-ol (3.0 cm3) at ≈55 ЊC for 1 h gave rise
to a product comprising mainly a 76:10:14 mixture of
compounds 11g, 12g and 14 [the proportions were estim-
ated from the integrals of the singlets at δ 2.32, 2.38 and 2.41
(attributed to the 1-H3 signals of 11g, 12g and 14)].
Crystallisation of the material from dichloromethane–diethyl
ether–light petroleum gave a 91:9 mixture of (3R,4R)-3-
bromo-4-(2,2-dimethylpropoxy)-3-methyl-4-(2Ј,3Ј,4Ј,6Ј-tetra-
O-acetyl-β--glucopyranosyloxy)butan-2-one 11g and 3,4-di-
bromo-3-methyl-4-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β--glucopyrano-
syloxy)butan-2-one 14 (as a single diastereomer) (0.043 g);
δH (300 MHz; CDCl3) (for 11g) 0.82 (9 H, s, Me3C), 1.78 (3 H, s,
3-Me), 2.02, 2.05, 2.07 and 2.08 (each 3 H, s, 4 × MeCO2), 2.32
(3 H, s, 1-H3), 2.95 and 3.63 (each 1 H, d, J 9, CH2O), 3.76 (1 H,
ddd, J 2.5, 5 and 10, 5Ј-H), 4.16 and 4.25 [each 1 H, dd (J 5 and
12.5) and dd (J 2.5 and 12.5), 6Ј-H2], 4.83 (1 H, d, J 8, 1Ј-H),
5.01 (1 H, s, 4-H), 5.06–5.14 (2 H, m, 2Ј- and 4Ј-H) and 5.27
(1 H, t, J 9.5, 3Ј-H).
5Ј-H), 4.15 and 4.22 [each 1 H, dd, (J 5.5 and 12) and dd (J 3
and 12), 6Ј-H2], 4.29 (1 H, d, J 7.5, 3-H), 4.81 (1 H, d, J 8, 1Ј-H),
4.95 (1 H, d, J 7.5, 4-H), 5.06 (1 H, t, J 10, 4Ј-H), 5.07 (1 H, dd,
J 8 and 9.5, 2Ј-H) and 5.24 (1 H, t, J 9.5, 3Ј-H); m/z (FAB) 565
and 563 (MNaϩ, each 1%), 543 and 541 (MHϩ, each 1), 331
(C14H19O9ϩ, 100), 195 and 193 (C6H10BrO2ϩ, each 60) and 169
(90).
Reaction involving the butenone 21 and propan-1-ol. The reac-
tion of the butenone 21 (0.279 g, 0.67 mmol) in propan-1-ol (3
cm3) gave rise to a product comprising mainly a 72:28 mixture
of the bromo(propoxy) adducts 22b and 23b [the ratio was
estimated from the integrals of the singlets at δ 2.31 and 2.35
(attributed to the 1-H3 signals of 22b and 23b)]; ≈25% of the
tetraacetylglucose 13 was also present.
Subjection of the mixture to column chromatography
(CHCl3 as eluent) gave an orange oil (0.238 g) comprising
mainly a 75:25 mixture of the bromo(propoxy) adducts 22b
and 23b. Crystallisation of the material from ethyl acetate–light
petroleum gave a 50:50 mixture of the bromo(propoxy)
adducts 22b and 23b (0.044 g, 12%) as an off-white solid; evap-
oration of the mother liquor gave a residue (0.140 g, 38%) com-
prising a 80:20 mixture of the bromo(propoxy) adducts 22b
and 23b. A further crystallisation of the 80:20 mixture failed
to provide pure material; on storage, however, the filtrate
deposited another crop of crystals (0.016 g, 4%) comprising
a 94:6 mixture of (3R,4R)-3-bromo-4-propoxy-4-(2Ј,3Ј,4Ј,6Ј-
tetra-O-acetyl-β--glucopyranosyloxy)butan-2-one 22b and its
(3S,4S)-diastereomer 23b; mp 62–73 ЊC; [α]D Ϫ6 (c 0.33,
CH2Cl2) (Found: C, 45.7; H, 5.9; Br, 14.1. C21H31BrO12 requires
C, 45.5; H, 5.6; Br, 14.4%); λmax (EtOH)/nm 291 (ε 150); νmax
(KBr)/cmϪ1 1755 (ester C᎐O) and 1740sh (ketone C᎐O);
Reaction involving the butenone 17b and propan-1-ol. The
reaction of butenone 17b (0.225 g, 1.56 mmol) in propan-1-ol
(18 cm3) for 1 h gave rise to a product that was mainly the
bromo(propoxy) adduct 18. Column chromatography
[hexanes–EtOAc (9.1) as eluent] provided (3R*,4R*)-3-bromo-
4-methoxymethoxy-3-methyl-4-propoxybutan-2-one 18 (0.250 g,
57%) as a clear oil (Found: C, 42.1; H, 7.0; Br, 28.5. C10H19BrO4
requires C, 42.4; H, 6.8; Br, 28.2%); λmax (EtOH)/nm 291 (ε 95);
᎐
᎐
δH (300 MHz; CDCl3) (for 22b) 0.86 (3 H, t, J 7.5, MeCH2),
1.47–1.57 (2 H, m, MeCH2), 2.01, 2.04, 2.06 and 2.08 (each
3 H, s, 4 × MeCO2), 2.31 (3 H, s, 1-H3), 3.40 (1 H, dt, J 9.5
and 7, EtCHHO), 3.71–3.82 (2 H, m, 5Ј-H and EtCHHO),
4.16 and 4.21 [each 1 H, dd (J 5.5 and 12.5) and dd (J 3 and
12.5), 6Ј-H2], 4.29 (1 H, d, J 7.5, 3-H), 4.81 (1 H, d, J 8,
1Ј-H), 4.94 (1 H, d, J 7.5, 4-H), 5.06 (1 H, t, J 10, 4Ј-H), 5.07
(1 H, dd, J 8 and 9.5, 2Ј-H) and 5.23 (1 H, t, J 9.5, 3Ј-H); m/z
(FAB) 579 and 577 (MNaϩ, each 2%), 331 (C14H19O9ϩ, 60),
209 and 207 (C7H12BrO2ϩ, each 50) and 169 (100).
νmax (film)/cmϪ1 1725 (ketone C᎐O); δH (300 MHz; CDCl3) 0.86
᎐
(3 H, t, J 7.5, MeCH2), 1.54 (2 H, sextet, separation 7, MeCH2),
1.81 (3 H, s, 3-Me), 2.35 (3 H, s, 1-H3), 3.43 (3 H, s, MeO), 3.46
and 3.74 (each 1 H, dt, J 9 and 6.5, EtCH2O), 4.81 (2 H, AB q,
J 7, separation of inner lines 3, OCH2O) and 4.98 (1 H, s, 4-H);
δC (100 MHz; CDCl3) 10.6 (CH3CH2), 20.6 (CH3C), 23.0
(MeCH2), 25.6 (1-CH3), 56.3 (CH3O), 67.6 (3-C), 72.2
(EtCH2O), 96.1 (OCH2O), 103.7 (4-CH) and 200.9 (2-CO);
m/z (CI) 302 and 300 (MNH4ϩ, each 100%), 240 and 238
(C7H11BrO4ϩ, each 25), 180 and 178 (C5H7BrO2ϩ, each 35), 160
(45) and 143 (95).
Reaction involving the butenone 21 and ethanol. The reac-
tion of the butenone 217 (0.217 g, 0.52 mmol) in ethanol
(3 cm3) for 0.5 h gave rise to a product comprising mainly a
71:29 mixture of the bromo(ethoxy) adducts 22a and 23a [the
ratio was estimated from the integrals of the singlets at δ 2.32
and 2.35 (attributed to the 1-H3 signals of 22a and 23a)]; ≈20%
of the tetraacetylglucose 13 was also present.
Reaction involving the butenone 21 and benzyl alcohol. The
reaction of the butenone 21 (0.635 g, 1.53 mmol) in benzyl
alcohol (16 cm3) for 40 min gave (after removal of PhCH2OH
by azeotropic distillation with water) a product comprising
mainly an 80:20 mixture of the bromo(benzyloxy) adducts 22c
and 23c [the ratio was estimated from the integrals of the
singlets at δ 2.25 and 2.31 (attributed to the 1-H3 signals of 22c
and 23c)]; ≈10% of the tetraacetylglucose 13 was also present.
Subjection of the mixture to column chromatography
(CHCl3 as eluent) and crystallisation of the product from
methanol gave an 84:16 mixture of (3R,4R)-4-benzyloxy-3-
bromo-4-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β--glucopyranosyloxy)-
butan-2-one 22c and its (3S,4S)-diastereomer 23c (0.411 g,
45%); mp 84–86 ЊC; [α]D Ϫ5 (c 0.35, CH2Cl2) (Found: C, 49.8;
H, 5.2; Br, 13.3. C25H31BrO12 requires C, 49.8; H, 5.1; Br,
13.1%); λmax (EtOH)/nm 205 (ε 9100), 252 (250), 257 (280), 263
Subjection of the mixture to column chromatography
(CHCl3 as eluent) gave an orange oil (0.211 g) comprising
mainly a 75:25 mixture of the bromo(ethoxy) adducts 22a and
23a. Three crystallisations of the material from ethyl acetate–
light petroleum gave a 97:3 mixture of (3R,4R)-3-bromo-4-
ethoxy-4-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β--glucopyranosyloxy)-
butan-2-one 22a and its (3S,4S)-diastereomer 23a (0.020 g, 7%);
mp 90–93 ЊC; [α]D Ϫ9 (c 0.27, CH2Cl2) (Found: C, 44.2; H, 5.4;
Br, 15.2. C20H29BrO12 requires C, 44.4; H, 5.4; Br, 14.8%); λmax
(230), 267 (170) and 294 (90); νmax (KBr)/cmϪ1 1760 (ester C᎐O)
᎐
and 1740 (ester and ketone C᎐O); δ (300 MHz; CDCl3) (for
᎐
H
22c) 2.01, 2.02, 2.04 and 2.08 (each 3 H, s, 4 × MeCO2), 2.25
(3 H, s, 1-H3), 3.75 (1 H, dt, J 10 and 4, 5Ј-H), 4.19 (2 H, d,
separation 4, 6Ј-H2), 4.33 (1 H, d, J 7.5, 3-H), 4.55 and 4.85
(each 1 H, d, J 11.5, PhCH2O), 4.86 (1 H, d, J 8, 1Ј-H), 5.07–
5.15 (3 H, m, 4-, 2Ј- and 4Ј-H), 5.25 (1 H, t, J 9.5, 3Ј-H) and
ϩ
7.24–7.39 (m, C6H5 and CHCl3); m/z (FAB) 331 (C14H19O9
,
(EtOH)/nm 294 (ε 90); νmax(KBr)/cmϪ1 1755 (ester C᎐O) and
60%), 169 (75) and 91 (C7H7ϩ, 100).
᎐
1745 (ester and ketone C᎐O); δ (300 MHz; CDCl3) (for 22a)
Reaction involving the pentenone 24 and propan-1-ol. (a) The
reaction of the pentenone 246 (0.225 g, 0.51 mmol) in propan-
1-ol (15 cm3) for 5 h gave rise to a product comprising
mainly an 87:13 mixture of the bromo(propoxy) adducts 28
᎐
H
1.14 (3 H, t, J 7, MeCH2), 2.01, 2.04, 2.06 and 2.07 (each 3 H,
s, 4 × MeCO2), 2.32 (3 H, s, 1-H3), 3.54 and 3.87 (each 1 H,
dq, J 9.5 and 7, MeCH2O), 3.74 (1 H, ddd, J 3, 5.5 and 10,
J. Chem. Soc., Perkin Trans. 1, 2000, 2195–2204
2201

View Article Online
and 29 [the ratio was estimated from the heights of the singlets
at δ 203.3 and 204.9 (attributed to the 3-CO groups of 28
and 29)].
110 ЊC; [α]D ϩ70 (c 0.44, CH2Cl2) (Found: C, 48.3; H, 5.9; Br,
13.2. C24H35BrO12 requires C, 48.4; H, 5.9; Br, 13.4%); νmax
(KBr)/cmϪ1 1760 and 1745sh (ester C᎐O) and 1720 (ketone
᎐
Crystallisation of the mixture from methanol afforded
(1R,2R)-2-bromo-2-methyl-1-propoxy-1-(2Ј,3Ј,4Ј,6Ј-tetra-O-
acetyl-β--glucopyranosyloxy)pentan-3-one 28 (0.150 g, 51%);
mp 174–175 ЊC; [α]D Ϫ24 (c 0.9, CH2Cl2) (Found: C, 47.4; H,
6.0; Br, 14.0. C23H35BrO12 requires C, 47.4; H, 6.1; Br, 13.7%);
C᎐O); δ (400 MHz; CDCl ) 0.84 (3 H, t, J 7.5, MeCH ), 1.45–
᎐
H 3 2
1.61 (2 H, m, MeCH2), 1.80–2.40 (≈7 H, m, 3-, 4- and 5-H2 and
6-Heq), 2.03, 2.06, 2.07 and 2.08 (each 3 H, s, 4 × MeCO2), 2.96
(1 H, ddd, J 6.5, 14 and 16, 6-Hax), 3.50 and 3.93 (each 1 H, dt,
J 9 and 6.5, EtCH2O), 3.78 (1 H, ddd, J 2.5, 5.5 and 10, 5Ј-H),
4.18 and 4.24 [each 1 H, dd (J 5.5 and 12) and dd (J 2.5 and 12),
6Ј-H2], 4.82 (1 H, d, J 8, 1Ј-H), 5.06 (1 H, t, J 9.5, 4Ј-H), 5.13
(1 H, dd, J 8 and 9.5, 2Ј-H), 5.15 (1 H, s, OCHO) and 5.28 (1 H,
t, J 9.5, 3Ј-H); δC (100 MHz; CDCl3) 10.5 (CH3CH2), 20.3 (4- or
5-CH2), 20.7 and 21.1 (4 × CH3CO2), 22.7 (MeCH2), 24.8 (5- or
4-CH2), 31.7 (3-CH2), 36.8 (6-CH2), 62.3 (6Ј-CH2), 68.6, 71.2,
72.0 and 72.6 (2Ј-, 3Ј-, 4Ј- and 5Ј-CH), 68.7 (2-C), 71.9 (EtCH2),
101.0 (1Ј-CH), 105.2 (OCHO), 169.3, 169.5, 170.2 and 170.5
λmax (EtOH)/nm 295 (ε 80); νmax(KBr)/cmϪ1 1760 (ester C᎐O)
᎐
and 1730 (ketone C᎐O); δ (300 MHz; CDCl3) 0.80 (3 H, t,
᎐
H
J 7.5, MeCH2), 1.09 (3 H, t, J 7, 5-H3), 1.48 (2 H, sextet, separ-
ation 7, MeCH2), 1.79 (3 H, s, 2-Me), 2.01, 2.03, 2.05 and 2.06
(each 3 H, s, 4 × MeCO2), 2.52–2.81 (2 H, m, 4-H2), 3.31 and
3.85 (each 1 H, dt, J 9.5 and 7, EtCH2O), 3.76 (1 H, ddd, J 2.5, 5
and 10, 5Ј-H), 4.15 and 4.23 [each 1 H, dd (J 5 and 12.5) and dd
(J 2.5 and 12.5), 6Ј-H2], 4.83 (1 H, d, J 8, 1Ј-H), 5.02–5.14 (2 H,
m, 2Ј- and 4Ј-H), 5.06 (1 H, s, 1-H) and 5.26 (1 H, t, J 9.5, 3Ј-H);
δC (100 MHz; CDCl3) 8.1 (5-CH3), 10.4 (CH3CH2), 19.3
(CH3C), 20.6, 20.7 and 21.0 (4 × CH3CO2), 22.5 (MeCH2), 30.3
(4-CH2), 62.1 (6Ј-CH2), 66.5 (2-C), 68.5, 71.1, 71.9 and 72.6
(2Ј-, 3Ј-, 4Ј- and 5Ј-CH), 71.5 (EtCH2), 100.7 (1Ј-CH), 105.0
(1-CH), 169.3, 169.5, 170.2 and 170.4 (4 × MeCO) and 203.3
(3-CO); m/z (FAB) 331 (C14H19O9ϩ, 100%), 237 and 235
(C9H16BrO2ϩ, each 25), and 169 (70).
(b) The reaction of the pentenone 24 (1.54 g, 3.5 mmol) in
propan-1-ol (170 cm3) was left for 6 h at 30 ЊC and overnight at
Ϫ30 ЊC. Filtration and recrystallisation of the product from hot
propan-1-ol gave the bromo(propoxy) adduct 28a (1.11 g, 55%).
Reaction involving the methylenecyclopentanone 25a and
propan-ol. The reaction of the cyclopentanone 25a4 (0.442 g,
1.00 mmol) in propan-1-ol (50 cm3) for 2 h gave rise to a prod-
uct comprising mainly an 87:13 mixture of the bromo-
(propoxy) adducts 30a and 31a [the ratio was estimated from
the heights of the singlets at δ 22.4 and 22.8 (attributed to the
MeCH2 signals of 30a and 31a)].
(4 × MeCO) and 202.4 (1-CO); m/z (FAB) 331 (C14H19O9ϩ, 65),
ϩ
249 and 247 (C10H16BrO2ϩ, each 35), 207 and 205 (C7H10BrO2
,
each 45), 179 and 177 (C6H10BrOϩ, each 30) and 169 (100)
[(after addition of KI) 635 and 633 (MKϩ, each 90%)].
(b) The aforecited reaction of the cyclohexanone 25b (2.53 g,
5.5 mmol) was repeated but, additionally, the solution was
washed with 5% aq. sodium hydroxide. Evaporation left a
brown residue (containing no tetraacetate 13 by 1H NMR spec-
troscopy), which was dissolved in boiling ethanol, treated with
charcoal and filtered. On cooling, the filtrate deposited com-
pound 30b (0.670 g, 20%). The filtrate was evaporated and the
residue crystallised from ethyl acetate–light petroleum to give a
further quantity (0.640 g, 19%) of compound 30b.
Reaction involving the propenoate 32a and propan-1-ol. The
reaction of the propenoate 32a4 (0.500 g, 1.12 mmol) in
propan-1-ol (20 cm3) for 1 h gave rise to a residue comprising
mainly an 85:15 mixture of the bromo(propoxy) adducts 33a
and 34a [the ratio was estimated from the heights of the sing-
lets at δ 22.4 and 23.0 (attributed to the MeCH2 signals of 33a
and 34a)].
Crystallisation of the material from ethyl acetate–hexanes
gave (2R)-2-bromo-2-[(R)-propoxy-(2,3,4,6-tetra-O-acetyl-β-
-glucopyranosyloxy)methyl]cyclopentanone 30a (0.304 g, 52%);
mp 112 ЊC; [α]D Ϫ12 (c 0.63, CH2Cl2) (Found: C, 47.2; H, 5.5;
Br, 13.4. C23H33BrO12 requires C, 47.5; H, 5.7; Br, 13.7%);
Crystallisation of the material from diethyl ether gave methyl
(2R,3R)-2-bromo-2-methyl-3-propoxy-3-(2Ј,3Ј,4Ј,6Ј-tetra-O-
acetyl-β--glucopyranosyloxy)propanoate 33a (0.343 g, 52%);
mp 155–157 ЊC; [α]D Ϫ16 (c 0.1, CH2Cl2) (Found: C, 45.4; H,
5.8; Br, 14.2. C22H33BrO13 requires C, 45.1; H, 5.7; Br, 13.7%);
νmax(KBr)/cmϪ1 1760 and 1730 (ester C᎐O); δ (300 MHz;
νmax(KBr)/cmϪ1 1760 (easter C᎐O) and 1750 (ester and ketone
᎐
C᎐O); δH (300 MHz; CDCl3) 0.82 (3 H, t, J 7.5, MeCH2), 1.50
᎐
᎐
H
(2 H, sextet, separation 7, MeCH2), 2.04, 2.06, 2.08 and 2.09
(each 3 H, s, 4 × MeCO2), 2.41–2.53 and 2.58–2.71 (each 1 H,
m, 5-H2), 3.38 and 3.87 (each 1 H, dt, J 9 and 6.5, EtCH2O),
3.77 (1 H, ddd, J 2.5, 5.5 and 10, 5Ј-H), 4.17 and 4.23 [each 1 H,
dd (J 5.5 and 12.5) and dd (J 2.5 and 12.5), 6Ј-H2], 4.86 (1 H, d,
J 8, 1Ј-H), 4.98 (OCHO), 5.07 (1 H, t, J 9.5, 4Ј-H), 5.12 (1 H,
dd, J 8 and 10, 2Ј-H) and 5.29 (1 H, t, J 10, 3Ј-H) (the 3- and
4-H2 signals appeared in the δ 1.97–2.21 region and were partly
obscured by the MeCO2 signals); δC (100 MHz; CDCl3) 10.3
(CH3CH2), 18.7 (4-CH2), 20.5 and 20.9 (4 × CH3CO2), 22.4
(MeCH2), 32.6 (3-CH2), 36.5 (5-CH2), 62.1 (6Ј-CH2), 66.0
(2-C), 68.4, 71.0, 71.8 and 72.4 (2Ј-, 3Ј-, 4Ј- and 5Ј-CH), 71.9
(EtCH2), 100.7 (1Ј-CH), 105.1 (OCHO), 169.1, 169.4, 170.0 and
170.3 (4 × MeCO) and 209.7 (1-CO); m/z (FAB) 331
(C14H19O9ϩ, 100%), 235 and 233 (C9H14BrO2ϩ, each 25), 193
and 191 (C6H8BrO2ϩ, each 65) and 169 (95) [(after addition of
KI) 621 and 619 (MKϩ, each 100%)].
Reaction involving the methylenecyclohexanone 25b and
propan-1-ol. (a) The reaction of the cyclohexanone 25b4
(0.456 g, 1.00 mmol) in propan-1-ol (50 cm3) for 2 h gave rise to
a product comprising mainly an 87:13 mixture of the bromo-
(propoxy) adducts 30b and 31b [the ratio was estimated from
the integrals of the singlets at δ 202.4 and 202.8 (attributed to
the 1-CO signals of 30b and 31b)]; ≈20% of the tetraacetyl-
glucose 13 was also present.
CDCl3) 0.82 (3 H, t, J 7, MeCH2), 1.40–1.60 (2 H, m, MeCH2),
1.80 (3 H, s, 2-Me), 2.02, 2.04, 2.06 and 2.08 (each 3 H, s,
4 × MeCO2), 3.35 and 3.87 [each 1 H, dt (J 9.5 and 7) and dt
(J 9.5 and 6), EtCH2O], 3.73–3.81 (1 H, m, 5Ј-H), 3.79 (3 H, s,
MeO), 4.16 and 4.24 [each 1 H, dd (J 5 and 12.5) and dd (J 5
and 12.5), 6Ј-H2], 4.85 (1 H, d, J 8, 1Ј-H), 5.06 (1 H, t, J 10,
4Ј-H), 5.08 (1 H, s, 3-H), 5.13 (1 H, dd, J 8 and 10, 2Ј-H) and
5.28 (1 H, t, J 9.5, 3Ј-H); δC (100 MHz; CDCl3) 10.3 (CH3CH2),
19.4 (CH3C), 20.5, 20.6 and 20.9 (4 × CH3CO2), 22.4 (MeCH2),
52.9 (CH3O), 60.0 (2-C), 62.0 (6Ј-CH2), 68.5, 71.0, 71.8 and 72.4
(2Ј-, 3Ј-, 4Ј- and 5Ј-CH), 71.6 (EtCH2), 100.8 (1Ј-CH), 105.0
(3-CH) and 169.2, 169.3, 169.4, 170.0 and 170.2 (1-CO and
4 × MeCO); m/z (FAB) 331 (C14H19O9ϩ, 80), 239 and 237
(C8H14BrO3ϩ, each 90), 197 and 195 (C5H8BrO3ϩ, each 90) and
169 (100).
Reaction involving the propenoate 32b and propan-1-ol.
(With P. M. Cowley.) The reaction of the propenoate 32b
(0.500 g, 1.16 mmol) in propan-1-ol (70 cm3) for 3 h gave rise to
a residue comprising mainly a 78:22 mixture of the bromo-
(propoxy) adducts 33b and 34b [the ratio was estimated from
the heights of the singlets at δ 22.8 and 23.1 (attributed to the
MeCH2 signals of 33b and 34b)].
Subjection of the product to column chromatography [Et2O–
light petroleum (2:1) as eluent] and crystallisation of the chro-
matographed material (from Et2O–light petroleum) gave
Crystallisation of the material from ethanol gave (2R)-
2-bromo-2-[(R)-propoxy-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β--gluco-
pyranosyloxy)methyl]cyclohexanone 30b (0.120 g, 20%); mp
methyl
(2R,3R)-2-bromo-3-propoxy-3-(2Ј,3Ј,4Ј,6Ј-tetra-O-
acetyl-β--glucopyranosyloxy)propanoate 33b (0.118 g, 18%);
mp 67–68 ЊC; [α]D Ϫ27 (c 0.2, CH2Cl2) (Found: C, 44.1; H, 5.4;
2202
J. Chem. Soc., Perkin Trans. 1, 2000, 2195–2204

View Article Online
Br, 14.4. C21H31BrO13 requires C, 44.1; H, 5.5; Br, 14.0); νmax
169.2, 169.5, 170.2 and 170.5 (4 × MeCO) and 172.4 (γ-lactone
ϩ
(KBr)/cmϪ1 1750 (ester C᎐O); δH (300 MHz; CDCl3) 0.86 (3 H,
CO); m/z (FAB) 331 (C14H19O9 , 90%), 237 and 235
᎐
t, J 7.5, MeCH2), 1.40–1.60 (2 H, m, MeCH2), 2.01, 2.04, 2.06
and 2.09 (each 3 H, s, 4 × MeCO2), 3.43 (1 H, dt, J 9.5 and 7,
EtCHHO), 3.72–3.83 (2 H, m, 5Ј-H and EtCHHO), 3.78 (3 H,
s, MeO), 4.15 and 4.21 [each 1 H, dd (J 6 and 12.5) and dd (J 3
and 12.5), 6Ј-H2], 4.27 (1 H, d, J 8, 2-H), 4.86 (1 H, d, J 8, 1Ј-H),
4.97–5.12 (3 H, m, 2Ј-, 3- and 4Ј-H) and 5.24 (1 H, t, J 9.5,
3Ј-H); δC (100 MHz; CDCl3) 10.7 (CH3CH2), 20.9 and 21.1
(4 × CH3CO2), 22.8 (MeCH2), 45.6 (2-CH), 53.3 (CH3O), 62.5
(6Ј-CH2), 68.9, 71.4, 72.4 and 73.1 (2Ј-, 3Ј-, 4Ј- and 5Ј-CH),
71.8 (EtCH2), 98.6 (1Ј-CH), 103.1 (3-CH) and 168.3, 169.5,
169.8, 170.6 and 170.8 (1-CO and 4 × MeCO); m/z (FAB) 331
(C14H19O9ϩ, 80%), 225 and 223 (C7H12BrO3ϩ, each 50), 183
and 181 (C4H6BrO3ϩ, each 100) and 169 (100).
Reaction involving the propenoate 32c and propan-1-ol. The
reaction of the propenoate 32c4 (2.30 g, 5.0 mmol) in propan-1-
ol (25 cm3) for 18 h gave rise to a residue comprising mainly an
85:15 mixture of the bromo(propoxy) adducts 33c and 34c
[the ratio was estimated from the heights of the singlets at
δ 22.6 and 23.2 (attributed to the MeCH2CH2 signals of 33c
and 34c)].
(C8H12BrO3ϩ, each 20), 195 and 193 (C5H6BrO3ϩ, each 50) and
169 (100).
Reaction involving the methylenevalerolactone 37b and propan-
1-ol. The reaction of valerolactone 37b4 (0.450 g, 0.98 mmol)
in propan-1-ol (20 cm3) for 2 h gave rise to a product compris-
ing mainly a 90:10 mixture of the bromo(propoxy) adducts 38b
and 39b [the ratio was estimated from the heights of the singlets
at δ 22.6 and 23.1 (attributed to the MeCH2 signals of 38b and
39b)].
Crystallisation of the mixture from dichloromethane–diethyl
ether–hexanes gave (αR)-α-bromo-α-[(R)-propoxy-(2Ј,3Ј,4Ј,6Ј-
tetra-O-acetyl-β--glucopyranosyloxy)methyl]-δ-valerolactone
38b (0.390 g, 66%); mp 155 ЊC; [α]D Ϫ35 (c 0.8, CH2Cl2)
(Found: C, 46.3; H, 5.5; Br, 13.1. C23H33BrO13 requires C, 46.2;
H, 5.6; Br, 13.4%); νmax (KBr)/cmϪ1 1750br (ester and δ-lactone
C᎐O); δ (400 MHz; CDCl ) 0.86 (3 H, t, J 7, MeCH ), 1.54 (2 H,
᎐
H
3
2
sextet, separation 7, MeCH2), 1.83–1.93, 2.14–2.35 and 2.55–
2.68 (1, 2 and 1 H, each m, β- and γ-H2), 2.04, 2.07 and 2.08
(3, 3 and 6 H, each s, 4 × MeCO2), 3.47 and 3.93 [each 1 H, dt
(J 9 and 7) and dt (J 9 and 6), EtCH2O], 3.79 (1 H, ddd, J 2.5,
5.5 and 10, 5Ј-H), 4.18 and 4.23 [each 1 H, dd (J 5.5 and 12)
and dd (J 2.5 and 12), 6Ј-H2], 4.33 and 4.50–4.60 [each 1 H, dt
(J 3.5 and 11.5) and m, δ-H2], 4.88 (1 H, d, J 8, 1Ј-H), 5.07 (1 H,
t, J 9.5, 4Ј-H), 5.13 (1 H, dd, J 8 and 9.5, 2Ј-H), 5.27 (1 H, s,
OCHO) and 5.29 (1 H, t, J 9.5, 3Ј-H); δC (100 MHz; CDCl3)
10.4 (CH3CH2), 19.7 (γ-CH2), 20.6, 20.7 and 21.1 (4 ×
CH3CO2), 22.6 (MeCH2), 29.2 (β-CH2), 60.6 (α-C), 62.2
(6Ј-CH2), 68.5, 71.2, 72.2 and 72.6 (2Ј-, 3Ј-, 4Ј- and 5Ј-CH),
70.8 (δ-CH2), 72.4 (EtCH2), 101.1 (1Ј-CH), 105.9 (OCHO),
166.9 (δ-lactone CO) and 169.3, 169.5, 170.1 and 170.4
(4 × MeCO); m/z (FAB) 331 (C14H19O9ϩ, 25%), 251 and 249
(C9H14BrO3ϩ, each 10), 209 and 207 (C6H8BrO3ϩ, each 20), 169
(40) and 43 (C3H7ϩ, 100) [(after addition of KI) 637 and 635
(each MKϩ, 15%)].
Crystallisation of the material from propan-2-ol gave ethyl
(2R,3R)-2-bromo-2-methyl-3-propoxy-3-(2Ј,3Ј,4Ј,6Ј-tetra-O-
acetyl-β--glucopyranosyloxy)propanoate 33c (2.18 g, 73%); mp
127 ЊC; [α]D Ϫ15 (c 0.9, CH2Cl2) (Found: C, 46.0; H, 6.2; Br,
13.4. C23H35BrO13 requires C, 46.1; H, 5.9; Br, 13.3%); νmax
(KBr)/cmϪ1 1760, 1740 and 1730 (ester C᎐O); δ (300 MHz;
᎐
H
CDCl3) 0.82 (3 H, t, J 7.5, MeCH2CH2), 1.30 (3 H, t, J 7,
MeCH2O), 1.43–1.58 (2 H, m, MeCH2CH2), 1.79 (3 H, s,
2-Me), 2.02, 2.04, 2.06 and 2.08 (each 3 H, s, 4 × MeCO2), 3.34
and 3.88 (each 1 H, dt, J 9 and 6.5, EtCH2O), 3.77 (1 H, ddd,
J 2.5, 5 and 10, 5Ј-H), 4.13–4.27 (4 H, m, 6Ј-H2 and MeCH2O),
4.85 (1 H, d, J 7.5, 1Ј-H), 5.03–5.15 (2 H, m, 2Ј- and 4Ј-H), 5.07
(1H, s, 3-H) and 5.27 (1 H, t, J 9.5, 3Ј-H); δC (100 MHz; CDCl3)
10.5 (CH3CH2CH2), 14.0 (CH3CH2O), 19.5 (CH3C), 20.7
and 21.1 (4 × CH3CO2), 22.6 (MeCH2CH2), 60.5 (2-C), 62.2
(6Ј-CH2), 68.6, 71.2, 72.0 and 72.6 (2Ј-, 3Ј-, 4Ј- and 5Ј-CH), 71.7
(2 × CH2O), 100.9 (1Ј-CH), 105.2 (3-CH) and 169.1, 169.4,
169.5, 170.3 and 170.5 (1-CO and 4 × MeCO); m/z (FAB) 623
and 621 (MNaϩ, each 30%), 331 (C14H19O9ϩ, 100), 253 and 251
(C9H16BrO3ϩ, each 70), 211 and 209 (C6H10BrO3ϩ, each 95) and
169 (55).
Reaction involving the methylenebutyrolactone 37a and
propan-1-ol. The reaction of the butyrolactone 37a4 (0.500 g,
1.13 mmol) in propan-1-ol (20 cm3) for 2 h gave rise to a
product comprising mainly an 85:15 mixture of the bromo-
(propoxy) adducts 38a and 39a [the ratio was estimated from
the heights of the singlets at δ 22.6 and 23.1 (attributed to the
MeCH2 signals of 38a and 39a)]; ≈11% of succinimide was also
present.
Auxiliary-detachment studies
General procedure.
A mixture of the bromo(alkoxy)
compound (1 mmol), ethane-1,2-diol (0.62 g, 10 mmol) and
TFA (5 cm3) was stirred for 2 h and then partitioned between
dichloromethane and water.The organic phase was washed suc-
cessively with aq. sodium hydrogen carbonate and water, dried
(MgSO4) and concentrated to leave mainly a 50:50 mixture of
1
the ethylene glycol acetal and the tetraacetate 13 by H NMR
spectroscopy. A solution of the product in methanol (20 cm3)
containing toluene-p-sulfonic acid monohydrate (0.200 g) was
left overnight and concentrated. The residue was then par-
titioned between dichloromethane and water. Evaporation
of the dried (MgSO4) organic phase gave the ethylene glycol
acetal.
Crystallisation of the mixture from cold methanol gave (αR)-
α-bromo-α-[(R)-propoxy-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β--gluco-
pyranosyloxy)methyl]-γ-butyrolactone 38a (0.357 g, 54%); mp
145–148 ЊC; [α]D Ϫ17 (c 0.5, CH2Cl2) (Found: C, 45.0; H, 5.3;
Br, 13.8. C22H31BrO13 requires C, 45.3; H, 5.4; Br, 13.7%);
(3R)-3-Bromo-3-(1Ј,3Ј-dioxolan-2Ј-yl)butan-2-one 40a. (a)
The reaction involving the bromo(propoxy) compound 11c
(0.500 g, 0.88 mmol) gave rise to the title compound 40a (0.123
g, 63%) as a near-pure oil. A chromatographed sample showed
[α]D Ϫ33 (c 0.85, CH2Cl2) (Found: C, 37.7; H, 5.0; Br, 36.0.
C7H11BrO3 requires C, 37.7; H, 5.0; Br, 35.8%); λmax (EtOH)/nm
296 (ε 90); νmax (film)/cmϪ1 1720 (ketone C᎐O); δ (300 MHz;
νmax(KBr)/cmϪ1 1775 (γ-lactone C᎐O) and 1755 and 1745 (ester
᎐
C᎐O); δH (300 MHz; CDCl3) 0.84 (3 H, t, J 7.5, MeCH2), 1.53
᎐
(2 H, sextet, separation 7, MeCH2), 2.02, 2.05 and 2.06 (3, 3 and
6 H, each s, 4 × MeCO2), 2.31 and 3.07 [each 1 H, ddd (J 2.5,
5.5 and 15) and dt (J 15 and 9), β-H2], 3.47 and 3.89 [each 1 H,
dt (J 9 and 7) and dt (J 9 and 6.5), EtCH2O], 3.77 (1 H, ddd,
J 2.5, 5.5 and 10, 5Ј-H), 4.15 and 4.22 [each 1 H, dd (J 5.5 and
12.5) and dd (J 2.5 and 12.5), 6Ј-H2], 4.32–4.47 (2 H, m, γ-H2),
4.85 (1 H, d, J 8, 1Ј-H), 5.03 (1 H, s, OCHO), 5.05 (1 H, t, J 9.5,
4Ј-H), 5.10 (1 H, dd, J 8 and 9.5, 2Ј-H) and 5.27 (1 H, t, J 9.5,
3Ј-H); δC (100 MHz; CDCl3) 10.4 (CH3CH2), 20.7 and 21.1
(4 × CH3CO2), 22.6 (MeCH2), 32.7 (β-CH2), 58.0 (α-C), 62.2
(6Ј-CH2), 66.2 (γ-CH2), 68.5, 71.3, 72.2 and 72.5 (2Ј-, 3Ј-,
4Ј- and 5Ј-CH), 72.5 (EtCH2), 100.9 (1Ј-CH), 104.4 (OCHO),
᎐
H
CDCl3) 1.77 (3 H, s, 4-H3), 2.44 (3 H, s, 1-H3), 3.96–4.13 (4 H,
m, 4Ј- and 5Ј-H2) and 5.30 (1 H, s, 2Ј-H); δC (100 MHz; CDCl3)
20.9 (4-CH3), 26.3 (1-CH3), 66.1 and 66.4 (4Ј- and 5Ј-CH2), 67.2
(3-C), 105.0 (2Ј-CH) and 201.6 (2-CO); m/z (CI) 242 and 240
(MNH4ϩ, each 100%).
By HPLC analysis, the sample possessed an ee of 98%
[hexanes–Me2CHOH (99:1) as eluent with a flow rate of 0.75
cm3 minϪ1; retention times: 9.0 min for 40a and 10.0 min for
ent-40a].
(b) The aforecited reaction was repeated but the mixture was
partitioned between dichloromethane and 5% aq. sodium
J. Chem. Soc., Perkin Trans. 1, 2000, 2195–2204
2203

View Article Online
hydroxide. After having been washed with water (2 ×), the
organic phase was dried (MgSO4) and concentrated to leave
compound 40a (0.102 g, 52%) with an ee of 95%.
MHz; CDCl3) 14.0 (CH3CH2), 21.0 (3-CH3), 60.0 (2-C), 62.5
(MeCH2), 66.4 and 66.8 (4Ј- and 5Ј-CH2), 105.2 (2Ј-CH) and
169.4 (1-CO); m/z (CI) 272 and 270 (MNH4ϩ, each 100%), 255
and 253 (MHϩ, each 20), 192 (80) and 175 (50).
By HPLC analysis, the sample possessed an ee of 98%
[hexanes–Me2CHOH (99:1) as eluent with a flow rate of 0.75
cm3 minϪ1; retention times: 8.7 min for 40c and 10.0 min for
ent-40c].
(2R)-2-Bromo-2-(1Ј,3Ј-dioxolan-2Ј-yl)pentan-3-one 40b. The
reaction involving the bromo(propoxy) compound 28 (1.24 g,
2.1 mmol) gave rise to the title compound 40b (0.290 g, 58%) as
a near-pure oil. A chromatographed sample showed [α]D Ϫ18
(c 0.5, CH2Cl2) (Found: C, 40.8; H, 5.6; Br, 33.4. C8H13BrO3
requires C, 40.5; H, 5.5; Br, 33.7%); λmax (EtOH)/nm 295 (ε 100);
νmax (film)/cmϪ1 1720 (ketone C᎐O); δH (300 MHz; CDCl3) 1.10
Crystal structure determination of compound 11c
᎐
(3 H, t, J 7, 5-H3), 1.79 (3 H, s, 1-H3), 2.70–2.98 (2 H, m, 4-H2),
3.95–4.13 (4 H, m, 4Ј- and 5Ј-H2) and 5.31 (1 H, s, 2Ј-H); δC (100
MHz; CDCl3) 8.4 (5-CH3), 21.2 (1-CH3), 31.8 (4-CH2), 66.2 and
66.5 (4Ј- and 5Ј-CH2), 67.6 (3-C), 105.1 (2Ј-CH) and 204.9
(3-CO); m/z (FAB) 239 and 237 (MHϩ, each 100%) and 157
(C8H13O3ϩ, 90).
By HPLC analysis, the sample possessed an ee of 94%
[hexanes–Me2CHOH (99:1) as eluent with a flow rate of 0.75
cm3 minϪ1; retention times: 7.9 min for 40b and 8.7 min for
ent-40b].
Crystal data. C22H33BrO12, M = 569.39, orthorhombic,
a = 11.952(2), b = 13.551(2), c = 17.076(3) Å, V = 2765.8(8) Å3,
T = 293(2) K, space group P212121, Z = 4, µ(Mo-Kα) = 1.542
mmϪ1, 1879 reflections measured, 1824 unique (Rint = 0.043)
which were used in all calculations. The final wR(F2) was
0.144 (all data). CCDC reference number 207/435. See http://
www.rsc.org/suppdata/p1/b0/b002749i/ for crystallographic
files in .cif format.
(2R)-2-Bromo-2-(1Ј,3Ј-dioxolan-2Ј-yl)cyclohexan-1-one
41. TFA (2.75 cm3) was added to the bromo(propoxy) com-
pound 30b (0.549 g, 0.92 mmol) followed, after 20 min, by
ethane-1,2-diol (0.544 g, 8.8 mmol). After 15 min, the mixture
was diluted with dichloromethane and washed successively with
water (3 ×) and aq. sodium hydrogen carbonate. Evaporation of
the dried (MgSO4) organic phase and subjection of the product
to column chromatography [light petroleum–EtOAc (1:1) as
eluent] gave the title compound 41 (0.128 g, 56%) as an oil
that solidified; mp 33 ЊC; [α]D ϩ225 (c 0.75, CH2Cl2) (Found:
C, 43.3; H, 5.3; Br, 31.9. C9H13BrO3 requires C, 43.4; H, 5.3;
Br, 32.1%); νmax (film)/cmϪ1 1720 (ketone C᎐O); δ (300 MHz;
CDCl3) 1.59–1.77, 1.82–1.92, 1.98–2.14 and 2.27–2.45 (1, 1, 3
and 2 H, each m, 3-, 4- and 5-H2 and 6-Heq), 3.14 (1 H, dt,
J 6.5 and 14.5, 6-Hax), 3.96–4.15 (4 H, m, 4Ј- and 5Ј-H2)
and 5.45 (1 H, s, 2Ј-H); δC (100 MHz; CDCl3) 21.3, 26.3,
33.6 and 37.6 (3-, 4-, 5- and 6-CH2), 66.3 and 66.9 (4Ј-
and 5Ј-CH2), 68.2 (2-C), 104.2 (2Ј-CH) and 203.7 (1-CO); m/z
(FAB) 251, 249 and 247 (MHϩ and M Ϫ Hϩ, 6, 12 and 6%)
and 73 (100) [(after addition of KI) 289 and 287 (MKϩ, 100
and 70%)].
Acknowledgements
We thank the SERC for a research grant (GR/E/70238) and a
research studentship (to P. D. T.), the EPSRC for research grants
(GR/L/52246 to assist in the purchase of a 400 MHz NMR
spectrometer and GR/L/34391 to assist in the purchase of
HPLC equipment), and the Universiti Teknologi, Malaysia, for
providing sabbatical leave (to M. S. I.). We are also grateful to
Dr R. Perry for the elemental analyses, Mr K. Walkling for
recording the UV and IR spectra, Mr C. Evans for measuring
the NMR spectra, Mr R. Perkins for the mass spectral
determinations and Dr C. M. Raynor and Mr G. Hughes for
the chiral HPLC analyses.
᎐
H
References
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By HPLC analysis, the sample possessed an ee of 96%
[hexanes–Me2CHOH (98:2) as eluent with a flow rate of 1
cm3 minϪ1; retention times: 11.2 min for 41 and 10.8 min for
ent-41].
Ethyl
(2R)-2-bromo-2-(1Ј,3Ј-dioxolan-2Ј-yl)propanoate
40c. The reaction involving the bromo(propoxy) compound
33c (0.599 g, 1.00 mmol) gave rise to the title compound 40c
(0.169 g, 67%) as a near-pure oil. A chromatographed sample
showed [α]D ϩ9 (c 1.67, CH2Cl2) (Found: C, 38.1; H, 5.0; Br,
32.0. C8H13BrO4 requires C, 38.0; H, 5.2; Br, 31.6%); νmax (film)/
cmϪ1 1740 (ester C᎐O); δH (300 MHz; CDCl3) 1.31 (3 H, t, J 7,
᎐
MeCH2), 1.82 (3 H, s, 3-H3), 3.97–4.14 (4 H, m, 4Ј- and 5Ј-H2),
4.27 (2 H, q, J 7, MeCH2O) and 5.45 (1 H, s, 2Ј-H); δC (100
2204
J. Chem. Soc., Perkin Trans. 1, 2000, 2195–2204