Aldol reactions on 1-deoxy-3,4:5,6-di-O-isopropylidene-L-fructose as a route to higher-carbon carbohydrates.

Article abstract of DOI:10.1016/S0008-6215(00)00014-8

With a view to preparing higher-carbon carbohydrates, crossed-aldol reactions of the methyl ketone 1-deoxy-3,4:5,6-di-O-isopropylidene-L-fructose with a representative series of aldehydes have been investigated, and the feasibility has been demonstrated o

Full text of DOI:10.1016/S0008-6215(00)00014-8

www.elsevier.nl/locate/carres
Carbohydrate Research 325 (2000) 323–339
Aldol reactions on
1-deoxy-3,4:5,6-di-O-isopropylidene- -fructose as a route
L
to higher-carbon carbohydratesꢀ
Alan H. Haines *, Andrew J. Lamb
School of Chemical Sciences, Uni6ersity of East Anglia, Norwich NR4 7TJ, UK
Received 28 May 1999; accepted 24 July 1999
Abstract
With a view to preparing higher-carbon carbohydrates, crossed-aldol reactions of the methyl ketone 1-deoxy-
3,4:5,6-di-O-isopropylidene- -fructose with a representative series of aldehydes have been investigated, and the
L
feasibility has been demonstrated of constructing a C-11 unit containing some of the key functionality found in the
carbohydrate component of the herbicidins. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: Aldol reaction; Higher-carbon sugars; Herbicidins
tivity that were isolated from Streptomyces
1. Introduction
saganonensis and which contain an 11-carbon
sugar portion. Because of their potential as
selective herbicides, compounds of this class
are interesting synthetic targets and several
approaches towards their synthesis have been
reported [4]. Studies into the synthesis of the
carbohydrate moiety have largely centred on
the C-6 plus C-5 approach, and Newcombe
and co-workers [4a] have successfully con-
structed the 11-carbon skeleton 2 with correct
stereochemistry in an elegant approach based
on a C-6 carbohydrate-derived enolate as the
donor, and a C-5 aldehyde as the acceptor.
However, construction of the enolate precur-
sor, a bicyclic ketone, required considerable
manipulation and we were led to consider an
alternative C-6 plus C-5 strategy based on the
retrosynthesis shown in Scheme 1, involving a
straight-chain C-6 carbohydrate-derived ke-
tone 3 containing the functionality MeCOꢀR
and the same aldehyde 4 as used by New-
combe and co-workers, with formation of the
The synthesis of monosaccharides possess-
ing more than six carbon atoms, usually re-
ferred to as higher-carbon sugars, continues to
be of considerable interest. In addition to
widely distributed members of this class such
as the octulosonic acid KDO and the
aminononulosonic acids (sialic acids), there
are others which are constituents of natural
products possessing interesting biological
properties, such as the mildiomycins [1] and
tunicamycins [2], nucleoside antibiotics con-
taining carbohydrate moieties of 10 and 11
carbon atoms, respectively. Also of particular
interest are the herbicidins [3], of which herbi-
cidin C (1) is a particular example, a group of
nucleoside antibiotics exhibiting herbicidal ac-
ꢀ PII of original article S0008-6215(99)00191-3.
* Corresponding author. Tel.: +44-1603-593-133; fax:
+44-1603-592-015.
E-mail address: a.haines@uea.ac.uk (A.H. Haines)
0008-6215/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(00)00014-8

324
A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
Scheme 1. A retrosynthetic analysis for the herbicidin skeleton.
based on NMR spectroscopy, of the undec-5-
ulose as an oil in 30% yield with a 32%
recovery of starting ketone 5. The yield is not
surprising in view of the known low concen-
tration of dimeric product formed in aldol
reactions performed with two molecules of the
same ketone.
C-ring occurring at a late stage in the synthe-
sis through an alkoxide-based ring closure.
The ketone 3 of our retrosynthesis is a pro-
tected acyclic form of 1-deoxy- -fructose and
D
indeed subsequent to the start of our work,
Narkunan and Nagarajan [5] published their
results, which employed a related approach to
the synthesis of higher sugars including a Wit-
tig–Horner reaction between a protected 1-
To develop suitable conditions for forma-
tion of crossed-aldol products, reaction of 5
with benzaldehyde 8 was investigated under
three sets of conditions. Addition of freshly
distilled benzaldehyde to the lithium enolate
(from LDA) of 5 in THF solution led to
complete reaction from TLC evidence, but
product isolation by column chromatography
gave a significant amount (21%) of 5, pre-
sumably due to retro-aldol chemistry, a very
small amount of material tentatively identified
as the self-addition product (6 or 7), and an
oil that crystallised on standing and was re-
crystallised to give a sharp-melting mixture of
the diastereoisomeric crossed-aldol products
1-(R)- and 1-(S)-2-deoxy-4,5:6,7-di-O-iso-
phosphonate of 1-deoxy-
from 2,3:4,5-di-O-isopropylidene-
D
-fructose, prepared
-arabinose,
D
and aldehyde 4. Because of the ready
availability in three simple steps of the enan-
tiomeric 1-deoxy-
tected form 5 from commercially available
-rhamnose, we based our feasibility studies
on this -isomer and now report results of
L
-fructose in a suitable pro-
L
L
aldol reactions (Claisen–Schmidt condensa-
tions) between this ketone and a series of
aldehydes including 4 (Scheme 2).
2. Results and discussion
propylidene - 1 - C - phenyl - - arabino - hept - 3-
L
Because in crossed-aldol reactions of the
type envisaged there is the likelihood of self-
addition of components, a self-aldol addition
on 5 was first attempted, which was expected
to give a mixture of undec-5-uloses 6 and 7.
Aqueous sodium hydroxide, potassium t-bu-
toxide in tetrahydrofuran (THF) and 1,8-diaza-
bicyclo[5.4.0]undec-7-ene (DBU) in toluene
were unsuccessful in bringing about the de-
sired reaction, but reaction was achieved with
lithium diisopropylamide (LDA) in THF. Re-
action of 1 molar equivalent of LDA with 2
molar equivalents of 5 gave one stereoisomer,
ulose (9 and 10, respectively, 10%) in an ap-
proximately 1:1 ratio. This allocation of over-
1
all structure was supported by the H NMR
spectrum of the product, which showed sig-
nals for protons in isopropylidene methyl
groups and the phenyl groups in the ratio of
12:5 and signals for the isopropylidene methyl
1
13
groups in both H and C NMR spectra that
were attributable to the expected eight groups.
In addition, the AB portions of two ABX
systems could be identified centred on l 3.08
and l 3.09, arising in each case from the
diastereoisotopic methylene protons at C-2

A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
325
Scheme 2.
coupled to the proton at the adjacent chiral
centre at C-1. Analytical HPLC confirmed the
presence of two isomers, though lack of a
baseline separation prevented determination
of an accurate isomer ratio. Use of lithium
hexamethyldisilazide (LiHMDS) as the base in
THF resulted in an improved yield (67%) of
the combined stereoisomers 9 and 10, again in
an approximate 1:1 ratio, with only 5% recov-
ered starting ketone 5 and no self-reaction
product. In the third variation, the procedure
involving the use of boron enolates [6] for
aldol reactions was followed. Thus, ketone 5
in THF was added to dibutylboron triflate
and triethylamine in dichloromethane fol-
lowed by benzaldehyde. Chromatography af-
forded the combined diastereoisomers 9 and
10 in 43% yield, with an unassigned isomer
1
ratio, estimated by H NMR spectroscopy in
the presence of a europium shift reagent, of
7:3.
The crossed-aldol reaction between ketone 5
and
2,3-O-isopropylidene- -glyceraldehyde
D
(13) was performed using enolates prepared
from 5 with LiHMDS and with dibutylboron
triflate. From reaction of the lithium enolate
with a slight excess of aldehyde 13, following
chromatography, starting ketone 5 (12%), the

326
A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
mer. Reaction of the boron enolate of ketone
5 with aldehyde 4 gave after chromatography
a mixture of the two diastereoisomers in 19%
yield but also a recovery of starting ketone in
29% yield. The ratio of isomers in the conden-
self-addition product 6 or 7 (19%) and an oily
cross-reaction product as a mixture of the
diasteroisomeric non-5-uloses 14 and 15 (48%)
1
were isolated. The H NMR spectrum of the
mixture of diastereoisomers, with a consider-
ation of relative intensities because of some
signal overlap, showed 12 methyl signals and
the AB parts (H-4 and H-4%) of two ABX
systems (H-3, H-4 and H-4%) were discernible,
centred on l 2.90 and l 2.91. Comparative
integration of the isopropylidene methyl
groups indicated the ratio of the two unas-
signed diastereoisomers to be approximately
1
sation product was 1.5:1 from H NMR inte-
gration measurements, and results from a
subsequent reaction via the sodium enolate
suggested that the predominant stereoisomer
in the mixture of 23 and 24 was the 5-(R)-iso-
mer 24 (Scheme 3).
Reaction of aldehyde 4 with the sodium
enolate of ketone 5, prepared in THF solution
by reaction of the ketone with sodium hexam-
ethyldisilazide (NaHMDS), gave recovered
ketone 5 in 22% yield and, surprisingly, a
single diastereoisomer (based on NMR spec-
troscopic and HPLC evidence) in 53% yield,
which was tentatively identified on mechanis-
13
1.5:1. The C NMR spectrum of the mixture
contained peaks that could readily be assigned
to the 36 distinct carbon atoms expected for
the mixture of isomers. Reaction of the ketone
5 and aldehyde 13 using the boron enolate
procedure gave the same diastereoisomers in
an approximately 1:1 ratio in 35% yield with
10% starting ketone 5 and 9% of the self-addi-
tion products 6 and 7.
tic argument as the
L
-arabino-a- -gluco- iso-
D
mer. Thus, on the reasonable assumption that
a sodium ion might favour a metal ion-coordi-
nated transition state involving the oxygen of
the 3-O-benzyl group, the oxygen atom of the
aldehydic group at C-5 in 4, and the enolate
oxygen atom, two possible intermediates A
and B may be envisaged (Fig. 1), which differ
in disposition of the di-O-isopropylidene-con-
taining residue involving C-3 to C-6 in the
parent ketone 5. In structure A, this residue
occupies a position lying over the furanose
ring of the reactant aldehyde 4, whereas in
structure B, this residue is directed away from
this region in space and thus may be favoured.
If this is so, then the preferred stereoisomer
will have the R-configuration at the new chiral
centre and the predominant isomer will be
3-O-benzyl-6-deoxy-1,2:8,9:10,11-tri-O-iso-
Reaction between ketone 5 and 2,3:4,5-di-
O-isopropylidene- -arabinose (18) via the
D
lithium enolate of 5 gave, after chromatogra-
phy, 12% of 5, 13% of a mixture of 6 and 7
and the desired crossed-aldol product in 49%
yield as a mixture of the diastereoisomeric
undec-5-uloses 19 and 20. Analytical HPLC
indicated an unassigned isomer ratio of 1.2:1.
However, separation of the two stereoisomers
1
on an analytical HPLC column enabled an H
NMR spectrum to be obtained on each one
and allowed analysis of the individual ABX
systems. Performing the crossed-aldol reaction
on 5 and 18 via the boron enolate procedure
gave 19 and 20 in a combined yield of 80%
but with a reversed isomer ratio of 1:1.6,
indicating a selectivity for the isomer that had
been the minor constituent in the alternative
preparation.
propylidene-
L
-arabino-a- -gluco-undecofura-
D
nos-7-ulose (24). This procedure via the
sodium enolate was used in all subsequent
reactions between 4 and 5.
Reaction between ketone 5 and the C-5
aldehyde 3-O-benzyl-1,2-O-isopropylidene-a-
The route we envisaged for the transforma-
tion of 23 or 24 to the tricyclic skeleton of the
herbicidins involved first, elimination of the
hydroxy group at the newly formed chiral
centre to give an alkene 30 or 31 with subse-
quent O-10 to C-6 ring closure leading to
formation of ring C of the herbicidins. Such a
closure might be achieved through alkene
epoxidation followed by selective removal of
D-xylo-pentodialdo-1,4-furanose (4) via the
lithium enolate of 5 gave the self-addition
products 6 and 7 (15%) and a 25% yield of the
crossed-aldol products, the undecofuranos-7-
uloses 23 and 24, in a 1:1 ratio as indicated by
integration of signals for the anomeric hydro-
gens. Careful column chromatography of the
mixture afforded a sample of one diastereoiso-

A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
327
Scheme 3.
the acetal group at O-10 and O-11 and then
an alkoxide-mediated attack on the epoxide
involving O-10. Alternatively, in a more ambi-
tious approach, electrophilic attack at the
alkene might lead directly to formation of the
six-membered ring by nucleophilic attack of
O-10 at C-6 in which electrophilic character
had been generated, as for example in an
iodonium intermediate resulting from reaction
of the alkene with N-iodosuccinimide. In this
approach, prior cleavage of the 10,11-acetal is
not required; examples are known [7] where
just such functionality is involved in ring clo-
sure. Reliable methods exist for the removal
of the group introduced at C-5 during ring
closure, for example, hydroxy or iodo, and
control of the stereochemistry at C-6 may be
possible in view of the carbonyl group in the
a-position (C-7). Deprotection at O-3 should
then lead to spontaneous formation of ring B
and completion of the tricylic skeleton found
in herbicidins. In view of the central position
of alkene 30 or 31 in the proposed synthetic
sequence, elimination reactions were investi-
gated on the mixed-aldol products 9 and 10,
14 and 15, 19 and 20, 23 and 24, and the
single stereoisomer thought to be 24, in order
to develop the most favourable reaction
conditions.
Fig. 1. Possible intermediates in the aldol reaction between
sodium enolate of ketone 5 and aldehyde 4.

328
A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
latter case the chromatographically recovered
alkene was found to contain approximately
5% of the Z-isomer 31 (J5,6 11.9 Hz).
Treatment of the isomer mixture 9 and 10
with acetic anhydride–pyridine led to produc-
tion of the (E)-hept-1-en-3-ulose 27 (50%) in
addition to the expected acetates 11 and 12
(identified spectroscopically), the proportion
of 27 increasing with time. The structure of
the alkene was supported by elemental analy-
sis and its NMR parameters, with the E-
configuration indicated by the 16.2 Hz
coupling constant between the alkene protons.
Acetylation of the mixed stereoisomers 14
and 15 under the same conditions gave the
mixed 3-acetates 16 and 17 (6%) and an elimi-
nation product, the (E)-non-3-en-5-ulose (28)
in 39% yield, the E-configuration being confi-
rmed by the large coupling constant for the
alkenic protons of 15.5 Hz.
Our synthetic strategy involving elaboration
of 30 or 31 to form the C-ring of the herbi-
cidins via alkene epoxidation was thwarted by
an alternative sequence of reactions under-
gone by the epoxide. Thus, treatment of the
enone 30 with alkaline hydrogen peroxide
reagents in methanol gave a mixture of five
products, as indicated by methoxy resonances
1
in the H NMR spectrum, and these products
were only partially separable by chromatogra-
phy. NMR spectroscopic data suggested that
the products arose from the required epoxide
(or epoxides), four being stereoisomers (see 32
and 33) resulting from methoxide cleavage of
epoxides (MeO resonances at l 3.22, 3.24,
3.27, and 3.28) and one being a methyl ester
(see 34 and 35) (MeO resonance at l 3.71)
resulting from a Favorskii rearrangement of
the epoxide. Examples of the latter type of
rearrangement in such systems have been doc-
umented previously [8]. Use of a milder base
(K2CO3), afforded the methoxy derivatives
and no rearranged product. Reaction in THF
with H2O2–NaHCO3, a reportedly mild pro-
cedure for the epoxidation of enones [9], gave
Acetylation of the mixed stereoisomers 19
and 20 followed a similar path affording a
mixture of the expected 7-acetates 21 and 22
(19%), as identified by their spectroscopic
properties, and an elimination product, the
(E)-undec-6-en-5-ulose 29 (13%) (J6,7 15.5
Hz), as well as a considerable amount of
recovered starting materials. An elimination
reaction on the mixture of 19 and 20 using
p-tolylsulphonyl chloride in pyridine gave the
enone 29 in an improved yield of 27% and
recovered starting materials in 29% yield.
Dehydration of the mixed aldol adducts 23
and 24 was investigated under a variety of
conditions in view of the likely importance of
the elimination product for further transfor-
mations. Reaction of the mixed alcohols with
acetic anhydride–pyridine at room tempera-
ture gave after 6 days and chromatographic
separation the starting alcohols (16%), the
diastereoisomeric acetates 25 and 26 (10%) as
identified by NMR spectroscopy, and the (E)-
undec-5-enofuranos-7-ulose (30) (J5,6 15.8 Hz)
in 46% yield. TLC analysis of the progress of
the reaction indicated that the alkene 30 was
formed via the acetates, verification being ob-
tained when a sample of the mixed acetates
was converted to the alkene 30 when subject
to the original acetylation conditions. The
yield of 30 was raised to 61% by conducting
the acetylation at 45 °C for 8 h, and to 72%
when 4-dimethylaminopyridine (DMAP) was
present in the acetylation medium with reac-
tion at room temperature for 70 h, but in the
1
a product that was tentatively identified by H
NMR and IR spectroscopy was tentatively as
a carboxylic acid (rather than a methyl ester),
resulting presumably from a Favorskii rear-
rangement of an epoxide.
An attempt to bring about ring closure on
30 by an iodonium-ion-mediated cyclisation
was not successful; only starting material was
recovered on prolonged treatment of the
alkene with N-iodosuccinimide in dichlorome-
thane or with molecular iodine in THF.
In view of the difficulties encountered in
forming ring C at an early stage, prior forma-
tion of ring B was investigated. Elaboration of
a fused furano–pyrano ring system from 23 or
24 to mimic the A/B fused ring system found
in the herbicidins requires removal of the ben-
zyl protecting group, which should lead to
spontaneous hemiacetal formation and thus
the pyrano ring B. Hydrogenolysis of the ben-
zyl group in 24 was readily achieved using
palladium black as catalyst in acidic methanol

A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
329
tus using a PU 4015 pump connected to a PU
4025 UV detector operating at 300 nm unless
otherwise stated. HPLC grade solvents were
used on a Spherisorb S5W normal phase
column. Thin-layer chromatography (TLC)
was performed on pre-coated plates of silica
gel with fluorescent indicator (Machery–
Nagel SIL G UV254. Detection was either by
viewing under UV light (254 nm), or by spray-
ing with a 10% H2SO4, 1.5% molybdic acid,
1% ceric sulfate spray followed by heating to
150 °C. Column chromatography was per-
formed on Matrex Silica 60 (70–200 mm mesh,
Fisons) or Kieselgel 60 (70–230 mm mesh, E.
Merck). Solvents for reactions and column
chromatography were SLR grade or better
and were dried appropriately when required
anhydrous. Thus, THF was dried by storage
over and distillation from sodium wire;
CH2Cl2, pyridine and Et3N were obtained an-
hydrous by distilling from CaH2 and storage
to give 36 as a crystalline solid in high yield.
No carbonyl absorption was apparent in the
IR spectrum of this product, in contrast to the
absorption at 1720 cm−1 found in the starting
material. A signal in the 13C NMR spectrum
at 96.2 ppm was assigned to the carbon at the
newly created hemiacetal centre (C-7), the re-
action evidently affording a single isomer at
this centre. Thus, the number of peaks in the
13
1H and C NMR spectra was consistent with
only one isomer. The axial orientation of the
hydroxy group at C-7 and therefore also the
equatorial orientation of the C-8 to C-11 side
chain might reasonably be expected to be
more favoured rather than the reverse ar-
rangement.
Although the eventual aim of this project
has still to be achieved, current results indicate
that our approach leads to facile formation of
an undecose in a usefully functionalised form
and that closure to give ring B is not problem-
atical. The crucial step of ring C formation is
being pursued by reaction of enone 30 with
alternative more powerful electrophiles and by
a strategy involving cyclisation of the 10,11-
diol formed by the partial deprotection of 30.
,
over 4 A molecular sieves; MeOH was dried
by distillation from magnesium methoxide
(formed by reaction with activated magne-
,
sium) and stored over powdered 3 A molecu-
lar sieves. Light petroleum refers to the
fraction with a boiling range of 40–60 °C,
unless stated otherwise. When mixed solvents
were used, the ratios given are v/v except if
otherwise stated. Solvent A is 6:1 light
petroleum–EtOAc, and solvent B is 4:1 light
petroleum–EtOAc. Organic solutions were
3. Experimental
General methods.—1H NMR spectra were
recorded on a Jeol EX90 FT spectrometer, a
Jeol EX270 FT spectrometer or a Varian
Gemini 2000 FT spectrometer in CDCl3 with
Me4Si as internal standard. Where appropri-
ate, signal assignments were deduced by
DEPT, COSY and HETCOR NMR experi-
dried over anhydrous Na2SO4.
L
-Rhamnitol
was prepared from -rhamnose by adapting
L
the procedure described by Wolfrom and
Thompson for the preparation of galactitol
from
into 1,2:3,4-di-O-isopropylidene-
as described by Bukhari and co-workers [11].
2,3-O-Isopropylidene- -glyceraldehyde (13)
was prepared from 1,2:5,6-di-O-isopropyli-
dene- -mannitol [12,13] by periodate cleavage
according to the procedure of Jackson [14].
D
-galactose [10] and was then converted
1
ments. In H NMR spectra of products con-
L
-rhamnitol
taining two diastereoisomers, protons at
related centres in the isomers that give rise to
resolved and assignable signals are distin-
guished by subscripts ‘a’ and ‘b’, otherwise no
distinction is made. Optical rotations were
measured at 20 °C with a Perkin–Elmer 141
polarimeter. High-resolution mass spectra
were recorded by the EPSRC Mass Spec-
trometry Service at the University College of
Swansea. Low-resolution EI mass spectra and
elemental analyses were performed by A.W.R.
Saunders at the University of East Anglia.
HPLC was performed on Pye Unicam appara-
D
D
2,3:4,5-Di-O-isopropylidene- -arabinose (18)
D
was synthesised by the method of Inch and
co-workers [15] from 1,2:3,4-di-O-isopropyli-
dene-
propylidene-a-
(4) was prepared either by oxidative cleavage
of the 5,6-diol in 3-O-benzyl-1,2-O-isopropyli-
D
-mannitol [16]. 3-O-Benzyl-1,2-O-iso-
D
-xylo-pentodialdo-1,4-furanose
dene-a- -glucofuranose [17], as described by
D

330
A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
the solution was extracted repeatedly with
Et2O. The combined extracts were dried, con-
centrated, and the resulting oil was purified by
column chromatography (light petroleum–
EtOAc mixture).
Anderson and Fraser-Reid [18], or by the
method of Lemieux and Howard [19], directly
from 3-O-benzyl-1,2:5,6-di-O-isopropylidene-
a-
D-glucofuranose [20].
1-Deoxy-3,4:5,6-di-O-isopropylidene-
L-fruc-
(b) Method 2: using dibutylboron triflate/
Et3N. The procedure for the crossed-aldol re-
action via the boron enolate was essentially
that described by Paterson and co-workers [6]
but using dibutylboron triflate in place of
dicyclohexylboron chloride. A soln of 5 (1
molar equiv) in anhyd THF was added, drop-
wise, to a stirred soln of dibutylboron triflate
(1.0 M soln in CH2Cl2; 1.5 molar equiv) and
freshly distilled Et3N (8–10 molar equiv) in
anhyd THF (3 mL/mmol of boron reagent) at
−78 °C under N2. The soln was allowed to
warm to 0 °C, stirred at this temperature for
45 min and then re-cooled to −78 °C. Freshly
distilled aldehyde (1.2–3 molar equiv) was
added either neat or as a concd soln in anhy-
drous THF. After a further 30 min at
−78 °C, the mixture was stored at −30 °C
for 14 h then brought to rt and partitioned
between equal volumes (10 mL/mmol of 5) of
pH 7 buffer solution and Et2O. The aq layer
was extracted further with Et2O and the com-
bined organic layers were concd to give a
crude product which was dissolved in equal
volumes (6 mL/mmol of 5) of MeOH and pH
7 buffer soln. To this soln was cautiously
added 30% aq H2O2 (3 mL/mmol of 5). The
resulting mixture was stirred until TLC (light
petroleum–EtOAc mixture) indicated the ab-
sence of the boron-coordinated products,
which remained on or near the baseline on
TLC in such solvent systems employed; typi-
cally between 1 and 3 h were required. Extrac-
tion of the solution with CH2Cl2 (3×8 mL
for 1 mmol of 5) and concentration of the
dried organic soln gave crude material that
was purified by column chromatography (light
petroleum–EtOAc mixture).
tose (5).—To a stirred soln of oxalyl chloride
(2 mL, 20.8 mmol) in anhyd CH2Cl2 (40 mL)
at −50 °C under N2, was added an anhyd
soln of Me2SO (3.5 mL, 48.9 mmol) in CH2Cl2
(10 mL) and the solution was then cooled to
−78 °C. A soln of 1,2:3,4-di-O-isopropyli-
dene- -rhamnitol (4.88 g, 20.0 mmol) in an-
L
hyd CH2Cl2 (20 mL) was then added dropwise
over 10 min. After 15 min, Et3N (14.0 mL,
0.10 mol) was added and after a further 5 min,
the stirred reaction mixture was allowed to
warm to room temperature (rt) when water
(100 mL) was added. The organic and
aqueous layers were separated, the aqueous
layer was extracted with CH2Cl2 (2×100 mL)
and the combined organic layers were washed
consecutively with satd aq NaCl (200 mL), 0.1
M HCl (200 mL), aq Na2CO3 (5% w/v; 200
mL) and water (50 mL). The dried organic
solution was concentrated to give a pale yel-
low oil (5.0 g). Column chromatography (sol-
vent A) gave ketone 5 as a mobile liquid (4.17
g, 85%); [h]D −0.10° (c 1.2, CHCl3), lit. ꢀ0°
(c 4.2, CHCl3) [15] and lit. 0.0° (c 1.5, CHCl3)
[21]; IR (film): w 1730 (CꢁO), 1370 and 1385
(C(CH3)2) , no absorption near 3300 cm−1
1
(OH); H NMR (90 MHz): l 1.34, 1.36, 1.40,
1.45 (4×s, 4×3 H, 2×C(CH3)2), 2.29 (s, 3
H, H3C-1), 3.92–4.38 (complex, 5 H, H-3, 4,
13
5, 6, 6%); C NMR (67.9 MHz): l 24.9 (C-1),
26.0, 26.3, 26.5, 26.9 (2×C(CH3)2), 66.4 (C-
6), 76.3, 77.9 (C-4, 5), 83.1 (C-3), 109.7, 111.1
(2×C(CH3)2), 207.2 (CꢁO). Anal. Calcd for
C12H20O5: C, 59.0; H, 8.25. Found: C, 59.2; H,
8.4.
General procedures for aldol reactions on
5.—(a) Method 1: using LiHMDS. A solution
of 5 (1 molar equivalent) in anhyd THF was
added to LiHMDS (1.0 M solution in THF;
1.3 molar equiv) at −78 °C under N2, and the
reaction mixture was stirred at −78 °C for 20
min. Freshly distilled aldehyde (1.1–1.3 molar
equiv) was added either neat, in one portion,
or as a concd soln in anhyd THF. After 20
min at −78 °C, the mixture was allowed to
warm to rt, satd aq NaHCO3 was added, and
Where alternative procedures to (a) or (b)
have been used, the methods are described in
full.
Self-addition of ketone 5 to gi6e 6-deoxy-
1,2:3,4:8,9:10,11-tetra-O-isopropylidene-7-C-
methyl-
and 6-deoxy-1,2:3,4:8,9:10,11-tetra-O-iso-
propylidene-7-C-methyl- -arabino- -gulo-un-
L
-arabino- -manno-undec-5-ulose (6)
L
L
D

A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
331
dec-5-ulose (7).—To a stirred soln of diiso-
propylamine (0.17 mL, 0.12 g, 1.2 mmol) in
anhyd THF (5 mL) at 0 °C under nitrogen
was added dropwise n-butyllithium (2.5 M
soln in hexane; 0.5 mL, 1.25 mmol). After 10
min at 0 °C, the soln was cooled to −78 °C
and a soln of 5 (0.50 g, 2.05 mmol) in anhyd
THF (5 mL) was added dropwise in two ap-
proximately equal portions, at such a rate that
the temperature remained below −65 °C. Af-
ter a further 30 min stirring at −78 °C, satd
aq NaHCO3 (10 mL) was added and the
mixture was allowed to warm to rt. Extraction
of the aq soln with Et2O (3×15 mL) and
concentration of the combined, dried organic
solutions gave a pale yellow oil, which was
shown by TLC (solvent B) to contain starting
material (Rf 0.46) and another component (Rf
0.3). Column chromatography (solvent B)
yielded 5 (0.16 g, 32%) and the less mobile
component which, on spectroscopic evidence,
was a single diastereoisomer, the aldol
product 6 or 7 as an oil (0.15 g, 30%); IR
(film): w 3480 (OH), 1720 (CꢁO), 1380 and
1370 cm−1 (C(CH3)2); 1H NMR (270 MHz): l
1.32, 1.33, 1.35 (×2), 1.37, 1.39, 1.43 (×2),
1.45 (9×s, 9×3 H, 4×C(CH3)2 and H3C-7),
1.92 (br s, 1 H, OH), 2.97 (s, 2 H, H-6, 6%),
3.60–4.42 (complex, 10 H, H-1, 1%, 2, 3, 4, 8,
9, 10, 11, 11%); 13C NMR (67.9 MHz): l 23.2
(H3C-7), 25.2, 25.3, 26.3, 26.4, 26.6, 27.1, 27.2
(×2) (4×C(CH3)2), 47.0 (C-6), 66.7, 67.5
(C-1, 11), 71.4 (C-7), 76.6, 76.8, 77.6, 77.9
(C-2, 3, 9, 10), 83.7, 84.2 (C-4, 8), 109.3, 109.9,
110.0, 111.4 (4×C(CH3)2), 208.9 (CꢁO);
EIMS: m/z 473 (0.7, M−15). Anal. Calcd for
C24H40O10: C, 59.0; H, 8.25. Found: C, 58.7;
H, 8.2.
was added neat in one portion. The mixture
was stirred at −78 °C for 30 min and then
allowed to warm to rt when TLC (solvent A)
confirmed the disappearance of 5 (Rf 0.34)
and formation of two components (Rf 0.20
and 0.11). The reaction was quenched with
water (25 mL), extracted with CH2Cl2 (3×25
mL) and the combined organic extracts were
dried and concentrated to give an oil (1.37 g),
which on column chromatography (solvent A)
gave three components. The first, ketone 5
(0.21 g, 21%) presumably arose by a retro-al-
dol reaction on the silica column. The second
material (Rf 0.20; 4 mg) was tentatively iden-
tified as a mixture of 6 and 7. The least mobile
component (Rf 0.11; 0.28 g), isolated as an oil,
crystallised on storage under high vacuum and
was recrystallised from light petroleum–
EtOAc to give a product shown to be an
approximately equimolar mixture of the two
diastereoisomeric crossed-aldol products, 9
and 10 (0.14 g, 10%), mp 62–63 °C; IR (Nu-
jol): w 3480 (OH), 1720 (CꢁO), 1380 and 1370
cm−1 (C(CH3)2); 1H NMR (270 MHz): l 1.33,
1.34 (×2), 1.37, 1.40, 1.42, 1.44 (×2) (8×s,
8×3 H, 4×C(CH3)2), 3.00 (dd, 1 H, J1a,2a
3.3, J2a,2%a 17.8 Hz, H-2a), 3.03 (dd, 1 H, J1b,2b
4.0, J2b,2%b 18.5 Hz, H-2b), 3.12 (dd, 1 H, J1b,2%b
8.6 Hz, H-2%b), 3.13 (br s, 2×1 H, 2×OH),
3.17 (dd, 1 H, J1a,2%a 9.2, H-2%a), 3.96 (complex,
2×1 H, H-7), 4.08–4.22 (complex, 2×3 H,
H-5, 6, 7%), 4.37 and 4.39 (2×d, 2×1 H, J4a,5a
2.6, J4b,5b 3.0 Hz, H-4a and H-4b), 5.20 (com-
plex, 2×1 H, H-1), 7.26–7.37 (complex, 2×5
H, 2×C6H5); 13C NMR (67.9 MHz): l 25.1
(×2), 26.1, 26.2, 26.5 (×2) and 27.0 (×2)
(4×C(CH3)2), 48.1 (2×C-2), 66.7, 66.8 (2×
C-7), 69.6, 69.8, (2×C-6), 76.4, 76.5 (2×C-
1), 78.1, 78.2, 83, 83.2 (2×C-4, 5), 110.0
(×2), 111.5 and 111.6 (4×C(CH3)2), 125.6,
125.7, 127.7, 127.8, 128.6, 142.8 (C-aromatic),
209.2 and 209.5 (2×CꢁO). Anal. Calcd for
C19H26O6: C, 65.1; H, 7.5. Found: C, 65.1; H,
7.4.
Reaction of ketone 5 with benzaldehyde.
Preparation of 1-(R)- and 1-(S)-2-deoxy-
4,5:6,7-di-O-isopropylidene-1-C-phenyl- -ara-
L
bino-hept-3-ulose (9) and (10), respec-
ti6ely.—(a) Using LDA: to a stirred soln of
diisopropylamine (0.6 mL, 0.43 g, 4.3 mmol)
in anhyd THF (10 mL) at −78 °C under N2,
was added n-butyllithium (2.5 M soln in hex-
ane; 1.8 mL, 4.5 mmol). The mixture was
stirred for 15 min and then a soln of 5 (1.00 g,
4.09 mmol) in anhyd THF (5 mL) was added
dropwise, over 10 min. After 15 min, freshly
distilled benzaldehyde (0.42 mL, 4.09 mmol)
Analytical HPLC (detection at 254 nm) in-
dicated the presence of two isomers, but a
baseline separation was not obtained in a
1
variety of solvent systems. However, H and
13C NMR spectroscopy showed that the ratio
of the isomers was approximately 1:1.

332
A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
3.6 Hz, 2×OH), 3.05 (dd, 1 H, J3a,4%a 2.6 Hz,
(b) Using LiHMDS: reaction of ketone 5
H-4%a), 3.82–4.23 (complex, 2×8 H, H-1, 1%,
2, 3, 7, 8, 9, 9%), 4.34–4.42 (complex, 2×1 H,
H-6); 13C NMR (67.9 MHz): l 25.1 (×4),
26.2, 26.3, 26.4, 26.5 (×2), 26.6 and 27.0
(×2) (6×C(CH3)2), 42.5, 42.9 (2×C-4),
65.5, 66.7 (×3), 67.6, 68.7 (2×C-1, 3, 9),
76.4, 76.5, 77.6, 77.7, 78.0, 78.3 (2×C-2, 7, 8),
83.1, 83.3 (2×C-6), 109.5, 109.6, 110.0 (×2),
111.5 and 111.6 (6×C(CH3)2), 208.5, 209.8
(2×CꢁO); EIMS: m/z 374 (0.8, M+), 359
(7.6, M−15). Anal. Calcd for C18H30O8: C,
57.7; H, 8.1. Found: C, 57.5; H, 8.1.
(0.75 g, 3.07 mmol) with benzaldehyde (0.35
mL, 3.43 mmol) under Method 1 conditions
gave, after column chromatography (solvent
B), starting ketone 5 (0.04 g, 5%) followed by
the mixed crossed-aldol products 9 and 10
(0.72 g, 67%). Recrystallisation of the mix-
ture of two diastereoisomers from light
petroleum–EtOAc gave material with mp 60–
1
64 °C. The product was identical by IR, H
and 13C NMR spectroscopy to the sample of
the crossed-aldol product, prepared as in (a).
1H NMR spectroscopy indicated the isomer
ratio as approximately 1:1.
By comparison of the integration values of
1
certain peaks in the H NMR spectrum in the
(c) Using dibutylboron triflate–Et3N: reac-
tion of ketone 5 (0.15 g, 0.61 mmol) with
benzaldehyde (0.20 mL, 1.79 mmol) under
Method 2 conditions gave, after column chro-
matography (solvent B), the crossed-aldol
product as a pale yellow oil (0.12 g), which
solidified on storage. Recrystallisation from
light petroleum–EtOAc, gave a mixture of 9
and 10 (92 mg, 43%), mp 57–61 °C. The
isomeric ratio (unassigned) in this preparation
presence of Eu(fod)3, the ratio of isomers
(unassigned) was estimated as approximately
1.5:1.
(b) Using dibutylboron triflate–Et3N: reac-
tion of ketone 5 (0.61 g, 2.50 mmol) with
aldehyde 13 (0.36 g, 2.77 mmol) under
Method 2 conditions gave, after column chro-
matography (solvent B), 5 (62 mg, 10% recov-
ery), a small amount of the self-aldol product
6 and/or 7 (54 mg, 9%) and, as an oil, a
mixture of the crossed-aldol reaction products
14 and 15 (0.33 g, 35%). Spectroscopic data
1
as determined by H NMR spectroscopy in
the presence of Eu(fod)3 was 7:3. No self-con-
densation aldol products 6 or 7, or ketone 5
were obtained, although unreacted benzalde-
hyde was isolated (0.11 g, 58% recovery).
Reaction of ketone 5 with 2,3-O-isopropyli-
1
(IR, and H and 13C NMR) on this material
agreed with that for the mixture of 14 and 15
prepared in (a), but differing peak intensities
reflected a different ratio of diastereoisomers.
Analytical HPLC in hexane-2-propanol (24:1)
gave two peaks at Rt 11.62 min and Rt 13.19
min in a ratio of 13:12.
dene-
deoxy-1,2:6,7:8,9-tri-O-isopropylidene-
ro- -galacto-non-5-ulose (14) and 4-deoxy-
1,2:6,7:8,9-tri-O-isopropylidene- -glycero- -
D
-glyceraldehyde (13). Preparation of 4-
L
-glyce-
L
L
L
gulo-non-5-ulose (15).—(a) Using LiHMDS:
reaction of ketone 5 (2.0 g, 8.19 mmol) and
aldehyde 13 (1.17 g, 9.0 mmol) under Method
1 conditions gave, after column chromatogra-
phy (solvent B), starting ketone 5 (0.24 g,
12%), a product shown by comparison with a
known sample (TLC, and IR and NMR spec-
troscopy) to be 6 and/or 7 (0.38 g, 19%) and
finally, as an oil, a mixture of the title com-
pounds 14 and 15 (1.48 g, 48%); IR (film): w
3470 (OH), 1720 (CꢁO), 1380 and 1370 cm−1
(C(CH3)2); 1H NMR (270 MHz): l 1.33 (×2),
1.35 (×4), 1.38, 1.39, 1.41, 1.42, 1.43 and 1.46
(12×s, 12×3 H, 6×C(CH3)2), 2.74 (dd, 1 H,
J3a,4a 2.3, J4a,4%a 16.2 Hz, H-4a), 2.82 (dd, 1 H,
J3b,4b 8.3, J4b,4%b 18.2 Hz, H-4b), 2.99 (dd, 1 H,
J3b,4%b 9.2 Hz, H-4%b), 3.00 (br d, 21 H, J3,OH
Reaction between ketone 5 and 2,3:4,5-di-O-
isopropylidene- -arabinose (18). Preparation of
D
6-deoxy-1,2:3,4:8,9:10,11-tetra-O-isopropyli-
dene-
D
-arabino-
6-deoxy-1,2:3,4:8,9:10,11-tetra-O-iso-
-arabino- -gulo-undec-5-ulose
L
-manno-undec-5-ulose (19)
and
propylidene-
D
D
(20).—(a) Using LiHMDS: reaction of ketone
5 (0.40 g, 1.64 mmol) with aldehyde 18 (0.41
g, 1.78 mmol) under Method 1 conditions
gave, after column chromatography (solvent
B), ketone 5 (48 mg, 12% recovery), the self-
aldol product 6 and/or 7 (52 mg, 13%) and, as
a colourless oil, a mixture of the title com-
pounds 19 and 20 (0.38 g, 49%); IR (film): w
3470 (OH), 1720 (CꢁO), 1385 and 1375 cm−1
1
(C(CH3)2); H NMR (270 MHz): l 1.34–1.48
(complex, 48 H, 8×C(CH3)2), 2.88 (dd, 1 H,

A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
333
J6a,6%a 17.5, J6a,7a 8.9 Hz, H-6a), 2.92 (br s,
2×1 H, 2×OH), 2.97 (2×d, 2 H, J6b,7b 6.3,
J6%b,7b 4.6 Hz, H-6b and H-6%b), 3.06 (dd, 1 H,
J6%a,7a 3.6 Hz, H-6%a), 3.60–4.41 (complex, 2×
deoxy - 1,2:8,9:10,11 - tri - O - isopropylidene -
arabino-i- -ido-undecofuranos-7-ulose (23)
and 3-O-benzyl-6-deoxy-1,2:8,9:10,11 - tri - O -
isopropylidene - - arabino - h - -gluco-undeco-
L
-
L
L
D
13
furanos-7-ulose (24).—(a) Using LiHMDS:
reaction of ketone 5 (0.42 g, 1.72 mmol) with
aldehyde 4 (0.50 g, 1.80 mmol) under Method
1 conditions gave, after column chromatogra-
phy (solvent B), first the self-aldol reaction
product 6 and/or 7 (60 mg, 15%) and sec-
ondly, as an oil, a mixture of the title com-
pounds 23 and 24 (0.20 g, 25%). By
re-chromatography of the mixture of crossed-
aldol isomers 23 and 24, (solvent A), the faster
running isomer1 could be obtained pure (61
mg, 7%); IR (film): w 3470 (OH), 1720 (CꢁO),
1610 (weak, C6H5), 1380 and 1370 cm−1
11 H, H-1, 1%, 2, 3, 4, 7, 8, 9, 10, 11, 11%); C
NMR (67.9 MHz):
l
25.1–27.1 (8×
C(CH3)2), 42.9, 43.6 (2×C-6), 66.4, 66.6,
67.7, 67.8 (2×C-1, 11), 68.9 (2×C-7), 76.4–
83.4 (2×C-2, 3, 4, 8, 9, 10), 109.5, 109.6,
109.7, 109.8, 109.9, 110.2, 111.4, 111.5 (8×
C(CH3)2), 208.5, 208.6 (2×CꢁO); EIMS: m/z
474 (0.3, M+), 459 (2.7, M−15). Anal. Calcd
for C23H38O10: C, 58.2; H, 8.1. Found: C, 57.9;
H, 8.1.
Analytical HPLC (49:1 hexane–2-propanol)
showed two isomers (Rt 12.5 min and Rt 13.6
min) in a ratio of 1.2:1, respectively. Prepara-
tive HPLC was used to isolate pure samples of
1
(C(CH3)2); H NMR (270 MHz): l 1.31, 1.33,
1
1.34, 1.42, 1.44 and 1.48 (6×s, 6×3 H, 3×
C(CH3)2), 2.89 (br s, 1 H, OH), 2.93 (dd, 1 H,
J5,6 8.9, J6,6% 18.1 Hz, H-6), 3.12 (dd, 1 H, J5,6%
2.6 Hz, H-6%), 3.94–4.73 (complex, 9 H, H-2,
3, 4, 5, 8, 9, 10, 11, 11%), 4.59 (d, 1 H, JAB
11.6 Hz, C6H5CHAHB), 4.71 (d, 1 H,
C6H5CHAHB), 5.89 (d, 1 H, J1,2 4.0 Hz, H-1),
7.16–7.36 (complex, 5 H, C6H5); 13C NMR
(67.9 MHz): l 25.2, 26.2, 26.3, 26.5, 26.8 and
27.0 (3×C(CH3)2), 43.5 (C-6), 64.9 (C-11),
72.4 (C6H5CH2), 66.7, 76.5, 78.0, 81.3, 81.9,
82.5, 83.3 (C-2, 3, 4, 5, 8, 9, 10), 105.1 (C-1),
109.9, 111.5, 111.8 (3×C(CH3)2), 127.9,
128.1, 128.6, 137.4 (C-aromatic), 210.2 (CꢁO);
EIMS: m/z 273 (0.8, M−249), 249 (1.3, M−
273). Anal. Calcd for C27H38O10: C, 62.1; H,
7.3. Found: C, 61.7; H, 7.15.
both stereoisomers in order to obtain an H
NMR spectrum of each one.
1
Data for isomer with Rt 12.5 min; H NMR
(270 MHz): l 1.35, 1.36, 1.38, 1.39, 1.41, 1.43
(×2) and 1.46 (8×s, 8×3 H, 4×C(CH3)2),
2.82 (br d, 1 H, J7,OH 6.3 Hz, OH), 2.88 (dd, 1
H, J6,6% 17.5, J6,7 8.9 Hz, H-6), 3.06 (dd, 1 H,
J6%,7 3.6 Hz, H-6%), 3.89–4.58 (complex, 10 H,
H-1, 1%, 2, 3, 7, 8, 9, 10, 11, 11%), 4.41 (d, 1 H,
J3,4 3.3 Hz, H-4).
1
Data for isomer with Rt 13.6 min; H NMR
(270 MHz): l 1.36 (×4), 1.37, 1.44 (×2),
1.46 (8×s, 8×3 H, 4×C(CH3)2), 2.97 (2×d,
2 H, J6,7 6.3, J6%,7 4.6 Hz, H-6, 6%), 3.55 (br d,
1 H, J7,OH 1.6 Hz, OH), 3.73–4.30 (complex,
10 H, H-1, 1%, 2, 3, 7, 8, 9, 10, 11, 11%), 4.41 (d,
1 H, J3,4 5.6 Hz, H-4).
Integration of the signals for H-1 in the
NMR spectrum of the original isomeric mix-
ture of 23 and 24, gave an approximate
diastereoisomeric ratio of 1:1.
(b) Using dibutylboron triflate–Et3N: reac-
tion of ketone 5 (1.00 g, 4.09 mmol) with
aldehyde 4 (1.23 g, 4.42 mmol) under Method
2 conditions gave, on column chromatography
(solvent B) as the first eluted material, ketone
5 (0.29 g, 29%). Further elution gave, as a
mixture of isomers, the crossed-aldol products
23 and 24 (0.41 g, 19%). The spectroscopic
(b) Using dibutylboron triflate–Et3N: reac-
tion of ketone 5 (1.00 g, 4.09 mmol) with
aldehyde 18 (1.04 g, 4.52 mmol) under
Method 2 conditions gave, after column chro-
matography (solvent B), only the crossed-al-
dol reaction products 19 and 20 (1.57 g, 80%).
The spectroscopic data for a mixed-isomer
sample agreed with those for the previous
sample, differing only because of its different
diastereoisomeric ratio.
Analytical HPLC (49:1 hexane-2-propanol)
showed two isomers (Rt 12.7 min and Rt 13.7
min) in a ratio of 1:1.6, respectively.
Reaction of ketone 5 with 3-O-benzyl-1,2-O-
1 By comparison with the single-isomer sample obtained via
the sodium enolate of 5, which is tentatively assigned as 24,
this material obtained from chromatography is also 24.
isopropylidene-h- -xylo-pentodialdo-1,4-fura-
D
nose (4). Preparation of 3-O-benzyl-6-

334
A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
rt (18 °C) for 45 h and water (0.3 mL) and
satd aq NaHCO3 (2.5 mL) were then added
sequentially. After being stirred for 30 min,
the soln was extracted with CH2Cl2 (2×10
mL) and the combined organic solutions were
washed with 0.1 M HCl (5 mL), water (5 mL),
satd aq NaHCO3 (5 mL) and water (5 mL).
The dried organic soln was co-evaporated
with toluene (2×15 mL) to remove residual
pyridine and then concentrated to give a crude
syrup (87 mg) containing three components.
Column chromatography (solvent A) yielded,
initially, as an oil, alkene 27 (62 mg, 50%);
[h]D −17.0° (c 5.3, CHCl3); IR (film): w 1700
(CꢁO), 1630 (CꢁC), 1595 (C6H5), 1380 and
1370 cm−1 (C(CH3)2); 1H NMR (270 MHz): l
1.37, 1.38, 1.43 and 1.51 (4×s, 4×3 H, 2×
C(CH3)2), 4.01 (dd, 1 H, J6,7 5.0, J7,7% 8.6 Hz,
H-7), 4.14 (dd, 1 H, J6,7% 6.3 Hz, H-7%), 4.25
(ddd, 1 H, J5,6 7.0 Hz, H-6), 4.35 (dd, 1 H, J4,5
5.3 Hz, H-5), 4.62 (d, 1 H, H-4), 7.20 (d, 1 H,
J1,2 16.2 Hz, H-2), 7.39–7.42 and 7.58–7.62
data for this mixture of isomers were identical,
except for differences resulting from a differ-
ent diastereoisomeric ratio, to those described
above in (a) for the aldol product obtained
from the reaction using LiHMDS.
Integration of the signals for H-1 in the
NMR spectrum of the original isomeric mix-
ture of 23 and 24 gave an approximate
diastereoisomeric ratio of 1.5:1. The major
isomer was identical to the single isomer sam-
ple prepared as described in (c) below, which
is tentatively assigned as 24.
(c) Using NaHMDS: to a stirred soln of
NaHMDS (1.0 M in THF; 25 mL, 25 mmol)
under argon at −78 °C was added dropwise a
soln of ketone 5 (5.00 g, 20.5 mmol) in anhyd
THF (50 mL) such that the temperature of the
reaction mixture remained below −65 °C.
The soln was stirred at −78 °C for 30 min
and then a concd soln of aldehyde 4 (6.56 g,
23.6 mmol) in anhyd THF (10 mL) was added
in three rapidly consecutive portions. After 20
min at −78 °C, the reaction mixture was
allowed to warm to −20 °C and after a fur-
ther 10 min, it was quenched by the addition
of satd aq NaHCO3 (100 mL). Separation of
the two phases, extraction of the aq phase
with Et2O (3×100 mL) and concentration of
the combined, dried organic solutions gave a
syrup (10.86 g). This material mainly con-
tained the desired aldol products 23 and 24
plus some of the starting materials 4 and 5, as
indicated by TLC (solvent B); for further
transformations it could be used in this crude
form or purified by column chromatography
in solvent B. Such purification on a portion of
the crude syrup (1.0 g) yielded as the first-
eluted material ketone 5 (0.10 g; 22%), then a
single isomer (as indicated by NMR spec-
troscopy and analytical HPLC) of the crossed-
aldol product, tentatively assigned (see Section
2) as 24 (0.52 g, 53%); [h]D −18.7° (c 6.3,
CHCl3). Other spectroscopic data were identi-
cal to those for the related component in the
previously separated sample of mixed isomers.
(E) - 1,2 - Dideoxy - 4,5:6,7 - di - O - isopropyli-
13
(complex, 5 H, C6H5), 7.76 (d, 1 H, H-1); C
NMR (67.9 MHz): l 25.2, 26.3, 26.6 and 27.2
(2×C(CH3)2), 66.7 (C-7), 76.6 (C-6), 78.5 (C-
5), 82.6 (C-4), 109.9 and 111.4 (2×C(CH3)2),
121.6 (C-2), 128.6, 128.9, 130.8, 134.5 (C-aro-
matic), 144.4 (C-1), 197.6 (CꢁO); EIMS: m/z
332 (1.9, M+), 317 (7.3, M−15). Anal. Calcd
for C19H24O5: C, 68.7; H, 7.3. Found: C, 68.4;
H, 7.3.
Further elution gave a mixture of the 1-(R)-
and 1-(S)-acetates, 11 and 12, respectively,
combined with alkene 27, from which, by
re-chromatography, could be obtained as an
oily material identified by NMR spectroscopy
as one of the acetates 11 or 12 (6.5 mg, 5%);
1H NMR (270 MHz): l 1.41, 1.55 and 1.56
and 1.57 (4×s, 4×3 H, 2×C(CH3)2), 1.99–
2.17 (complex, 2 H, and H-2, 2%), 2.03 (s, 3 H,
CH3CO), 3.67–4.14 (complex, 6 H, H-1, 4, 5,
13
6, 7, 7%), 7.26–7.47 (complex, 5 H, C6H5); C
NMR (75.4 MHz): l 21.0 (COCH3), 25.1,
25.9, 26.5 and 26.7 (2×C(CH3)2), 60.0 (C-2),
67.8 (C-7), 73.1, 76.5 (C-5, 6), 77.1 (C-4), 80.8
(C-1), 110.3 and 111.0 (2×C(CH3)2), 128.1,
129.8, 129.0, 135.7 (C-aromatic), 169.5
(CH3CꢁO), 209.4 (CꢁO).
dene-1-C-phenyl- -arabino-hept-1-en-3-ulose
L
(27).—A solution of aldol adducts 9 and 10
(130 mg, 0.37 mmol) and Ac2O (0.15 mL, 0.11
g, 1.08 mmol) in pyridine (2 mL) was stored at
Finally, a mixture of starting materials 9
and 10 (2.7 mg, 2%) was recovered.

A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
335
(3×C(CH3)2), 48.2 (C-4), 65.6, 67.0 (C-1, 9),
69.0, 74.1, 75.9, 78.0 (C-2, 3, 7, 8), 84.2 (C-6),
109.8, 109.9, 112.4 (3×C(CH3)2), 170.0
(CH3CꢁO), 205.1 (CꢁO); EIMS: m/z 417 (1.8,
M++1), 401 (2.7, M+−15). Anal. Calcd for
C20H32O9: C, 57.7; H, 7.7. Found: C, 58.0; H,
8.0. From the 13C NMR spectrum the two
isomers were in a ratio of 2:1.
3-O-Acetyl-4-deoxy-1,2:6,7:8,9-tri-O-iso-
propylidene- -glycero- -galacto-non-5-ulose
(16), 3-O-acetyl-4-deoxy-1,2:6,7:8,9-tri-O-iso-
propylidene- -glycero- -gulo-non-5-ulose (17),
and (E)-3,4-dideoxy-1,2:6,7:8,9-tri-O-isopro-
pylidene- -gluco-non-3-en-5-ulose (28).—To a
L
L
L
L
L
soln of a mixture of 14 and 15 (0.30 g, 0.80
mmol) in pyridine (3 mL) was added Ac2O
(0.15 mL, 0.11 g, 1.09 mmol) and the reaction
mixture was stored at rt (18 °C) for 2 h.
Product isolation, as described for the prepa-
ration of 27, gave a syrup (0.20 g) containing
[TLC (solvent B)] three components, Rf 0.34
(major), Rf 0.23 (minor), and Rf 0.11 (14 and
15). On column chromatography (solvent B),
first eluted as an oil was alkene 28 (0.11 g,
39%); [h]D+13.6° (c 0.93, CHCl3); IR (film): w
1700 (CꢁO), 1630 (CꢁC), 1380 and 1370 cm−1
(C(CH3)2); 1H NMR (270 MHz): l 1.35 (×2),
1.42 (×2) 1.46 and 1.47 (6×s, 6×3 H, 3×
C(CH3)2), 3.68 (dd, 1 H, J1,1% 7.6, J1,2 7.6 Hz,
H-1), 3.96 (dd, 1 H, J8,9 4.6, J9,9% 8.6 Hz, H-9),
4.09–4.30 (complex, 4 H, H-1%, 7, 8, 9%), 4.53
(d, 1 H, J6,7 5.3 Hz, H-6), 4.71 (m, 1 H, H-2),
6.81 (dd, 1 H, J2,3 5.6, J3,4 15.5 Hz, H-3), 6.97
Eluted last as an inseparable mixture were
starting materials 14 and 15 (30 mg, 10%).
(E) - 6,7 - Dideoxy - 1,2:3,4:8,9:10,11 - tetra-
O-isopropylidene-
D
-erythro- -manno-undec-6-
L
en-5-ulose (29).—(a) A solution of 19 and 20,
(0.15 g, 0.32 mmol) and Ac2O (0.10 mL, 0.72
mmol) in pyridine (2 mL) was stored at rt for
48 h, and the reaction mixture then worked-up
as in the preparation of 27 to yield a crude oil
(0.12 g), which was subjected to column chro-
matography (solvent B). First eluted, as a
colourless oil (Rf 0.60), was the alkene 29 (19
mg, 13%); [h]D−15.1° (c 1.65, CHCl3); IR
(film): w 1695 (CꢁO), 1630 (CꢁC), 1380 and
1370 cm−1 (C(CH3)2); 1H NMR (270 MHz): l
1.33, 1.34, 1.35, 1.39, 1.41, 1.43 (×2), 1.47
(8×s, 8×3 H, 4×C(CH3)2), 3.65–4.30
(complex, 8 H, H-1, 1%, 2, 3, 9, 10, 11, 11%),
4.53 (d, 1 H, J3,4 5.0 Hz, H-4), 4.58 (ddd, 1 H,
4J6,8 1.7, J7,8 4.3, J8,9 7.9 Hz, H-8), 6.89 (dd, 1
4
(dd, 1 H, J2,4 5.0 Hz, H-4); 13C NMR (67.9
MHz): l 25.1, 25.6, 26.2, 26.4, 26.5 and 27.1
(3×C(CH3)2), 66.6 (C-9), 68.6 (C-1), 75.1,
76.4 (C-7, 8), 78.2 (C-2), 82.2 (C-6), 109.8,
110.2 and 111.4 (3×C(CH3)2), 125.5 (C-4),
144.6 (C-3), 197.1 (CꢁO); EIMS: m/z 356 (1.9,
M+), 341 (18.1, M−15), 255 (1.2, M−101),
155 (4.7, M−201); HRMS: calcd for
C18H28O7: 356.1835; found: m/z 356.1835.
Anal. Calcd for C18H28O7: C, 60.7; H, 7.9.
Found: C, 60.25; H, 7.8.
13
H, J6,7 15.5 Hz, H-6), 7.09 (dd, 1 H, H-7); C
NMR (67.9 MHz): l 25.2 (×2), 26.3, 26.5,
26.7, 26.8, 27.0 and 27.2 (4×C(CH3)2), 66.7,
67.5 (C-1, 11), 76.5, 77.0, 78.3, 79.4 (C-2, 3, 9,
10), 81.2, 82.4 (C-4, 8), 109.9, 110.0, 110.3 and
111.5 (4×C(CH3)2), 124.7 (C-6), 145.2 (C-7),
197.5 (CꢁO); EIMS: m/z 456 (3.5, M+), 441
(23.4, M−15). Anal. Calcd for C23H36O9: C,
60.5; H, 7.95. Found: C, 60.5; H, 8.1.
Further elution gave an unseparated mix-
ture of two slower-running components (Rf
0.25 and 0.28) as an oil, shown by spec-
troscopy to be an approximately equimolar
mixture of the two isomers 21 and 22 (32 mg,
19%); IR (film): w 1710 (br, CꢁO), 1380 and
1375 (C(CH31)2), no absorption near 3400
cm−1 (OH); H NMR (270 MHz): l 1.32–
1.47 (complex, 16×3 H, 8×C(CH3)2), 2.04,
2.06 (2×s, 2×3 H, 2×COCH3), 2.88 (dd, 1
H, J6a,6%a 17.1, J6a,7a 3.4 Hz, H-6a), 2.97 (d, 2
H, J6b,7b 6.2, J6%b,7b 6.2 Hz, H-6b, 6%b), 3.07
(dd, 1 H, J6a,6%a 8.8, J6%a,7a 8.8 Hz, H-6%a),
Further elution gave, as an oil, the mixture
of stereoisomers, 16 and 17, (21 mg, 6%); IR
(film): w 1760–1700 (br, CꢁO), 1380 and 1370
1
cm−1 (C(CH3)2); H NMR (270 MHz): l
1.24–1.44 (complex, 18 H, 3×C(CH3)2), 1.98,
2.00 (2×s, 3 H in total, COCH3), 3.67–4.74
(complex, 10 H, H-1, 1%, 2, 4, 4%, 6, 7, 8, 9, 9%),
5.31–5.47 (complex, 1 H, H-3); 13C NMR
(67.9 MHz): l major isomer: 20.8 (COCH3),
25.1 (×2), 26.1, 26.2, 26.3 and 26.4 (3×
C(CH3)2), 48.8 (C-4), 65.8, 66.4 (C-1, 9), 69.3,
71.7, 74.5, 77.9 (C-2, 3, 7, 8), 82.6 (C-6), 109.7,
109.8 and 110.0 (3×C(CH3)2), 169.7
(COCH3), 207.5 (CꢁO); minor isomer: 20.9
(COCH3), 25.1, 25.2, 25.3, 26.0, 27.0 and 27.1

336
A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
H-11%), 4.19 (ddd, 1 H, J9,10 6.9 Hz, H-10),
4.29 (dd, 1 H, J8,9 5.4 Hz, H-9), 4.47 (d, 1 H,
JAB 12.0 Hz, C6H5HAHB), 4.54 (d, 1 H, H-8),
4.60 (d, 1 H, C6H5HAHB), 4.65 (d, 1 H, J1,2 3.8
Hz, H-2), 4.84 (ddd, 1 H, J4,5 4.8, J4,6 1.6 Hz,
H-4), 6.01 (d, 1 H, H-1), 6.88 (dd, 1 H, J5,6
3.66–4.87 (complex, 2×11 H, H-1, 1%, 2, 3, 4,
13
7, 8, 9, 10, 11, 11%); C NMR (22.4 MHz)): l
25.2 and 25.4 (2×COCH3), 26.4–27.5 (8×
C(CH3)2), 52.0, 54.7 (2×C-6), 65.8–84.8 (2×
C-1, 2, 3, 4, 7, 8, 9, 10, 11), 109.4–112.0
(8×C(CH3)2), 175.3 and 175.4 (2×
CH3CꢁO), 204.9 and 209.7 (2×CꢁO).
Further elution with 2:1 light petroleum–
EtOAc gave a mixture of starting materials 19
and 20 (33 mg, 22%).
(b) Treatment of 19 and 20 (0.207 g, 0.44
mmol) in pyridine (2 mL) with p-tolylsulfonyl
chloride (0.102 g, 0.54 mmol) at rt for 5 days
and conventional work-up gave a crude oil
(0.13 g) which, when subjected to column
chromatography (solvent B), gave as an oil
alkene 29 (54 mg, 27%).
4
15.8 Hz, H-5), 7.06 (dd, 1 H, H-6), 7.24–7.36
13
(complex, 5 H, C6H5); C NMR (75.4 MHz):
l 25.2, 26.2, 26.3, 26.6, 26.9 and 27.2 (3×
C(CH3)2), 66.9 (C6H5CH2), 72.3 (C-11), 76.8,
78.4, 80.0, 82.5, 83.0, 83.2 (C-2, 3, 4, 8, 9, 10),
105.2 (C-1), 110.1, 111.8 and 112.1 (3×
C(CH3)2), 126.9 (C-6), 128.0, 128.8, 128.3,
137.3 (C-aromatic), 141.9 (C-5), 197.3 (CꢁO);
HRMS: calcd for C27H36O9: m/z 504.2359;
found: 504.2360.
Further elution gave, according to NMR
spectroscopy, a mixture of the isomeric ac-
etates 25 and 26 containing a small amount of
the elimination product 30. Re-chromatogra-
phy of the mixture gave a sample mostly
comprising one of the acetates (presumably
isomer 26, as shown by comparison with the
single isomeric O-acetate isolated in a similar
reaction conducted in the presence of DMAP
on the compound tentatively identified as 24,
see later) containing approximately 10 mol%
of the second isomer 25 (15 mg, 10%); IR
(film): w 1745 (CH3CꢁO), 1720 (CꢁO), 1375
Further elution (2:1 light petroleum–
EtOAc) gave a mixture of 19 and 20 (61 mg,
29% recovery). No products of O-p-tolylsul-
fonylation could be identified.
(E)-3-O-Benzyl-5,6-dideoxy-1,2:8,9:10,11-
tri-O-isopropylidene-
L
-erythro-h- -gluco-un-
D
dec-5-enofuranos-7-ulose (30).—Acetylation/
elimination reactions on the mixed isomer
sample of the aldol adducts 23 and 24 to give
the a,b-unsaturated ketone and an isomeric
mixture of the corresponding acetates 25 and
26 were carried out under four different reac-
tion conditions to optimise the yield and to
increase the rate of the reaction. That per-
formed in the presence of a catalytic quantity
of DMAP was adopted for the bulk prepara-
tion of product and was also used to acetylate
and eliminate the single-isomer sample of the
aldol adduct (i.e., the isomer presumed to be
24) to give 26 and (E)-enone 30.
1
and 1365 cm−1 (C(CH3)2); H NMR (300
MHz) major isomer: l 1.24, 1.31, 1.34, 1.42
(×2) and 1.47 (6×s, 6×3 H, 3×C(CH3)2),
1.93 (s, 3 H, CH3CꢁO), 3.12 (dd, 1 H, J5,6 7.0,
J6,6% 18.0 Hz, H-6), 3.21 (dd, 1 H, J5,6% 4.2, J6,6%
Hz, H-6%), 3.92–4.37 (complex, 7 H, H-2, 3, 4,
9, 10, 11, H-11%), 4.47 (d, 1 H, JAB 11.5 Hz,
C6H5CHAHB), 4.58 (d, 1 H, J8,9 3.6 Hz, H-8),
4.60 (d, 1 H, C6H5CHAHB), 5.60 (ddd, 1 H,
J4,5 5.6 Hz, H-5), 5.91 (d, 1 H, J1,2 3.7 Hz,
H-1), 7.27–7.37 (complex, 5 H, C6H5); minor
isomer: 1.25 (×2), 1.34, 1.39 and 1.45 (×2)
(6×s, 6×3 H, 3×C(CH3)2), 1.95 (s, 3 H,
CH3CꢁO), 2.74 (dd, 1 H, J5,6 8.2, J6,6% 16.2 Hz,
H-6), 2.98 (dd, 1 H, J5,6% 3.3 Hz, H-6%), 3.90–
4.34 (complex, 7 H, H-2, 3, 4, 9, 10, 11, 11%),
4.48 (d, 1 H, JAB 11.8 Hz, C6H5CHAHB), 4.54
(d, 1 H, J8,9 5.3 Hz, H-8), 4.62 (d, 1 H,
C6H5CHAHB), 5.53 (ddd, 1 H, J4,5 6.3 Hz,
H-5), 6.01 (d, 1 H, J1,2 3.9 Hz, H-1), 7.27–7.37
(complex, 5 H, C6H5); 13C NMR (75.4 MHz)
Acetylation of a solution of 23 and 24 (137
mg, 0.26 mmol) with Ac2O (0.12 mL, 0.87
mmol) in pyridine (2 mL) for 6 days, and
product isolation, as described in the prepara-
tion of 27, gave a crude syrup (119 mg), which
on column chromatography (solvent A)
yielded initially, as an oil, the enone 30 (62
mg, 46%); [h]D −44.9° (c 4.5, CHCl3); IR
(film): w 1700 (CꢁO), 1640 (CꢁC), 1620 (C6H5),
1
1385 and 1370 cm−1 (C(CH3)2); H NMR
(300 MHz) l 1.32, 1.33, 1.35, 1.42, 1.45 and
1.49 (6×s, 6×3 H, 3×C(CH3)2), 3.97 (dd, 1
H, J10,11 4.8, J11,11% 8.5 Hz, H-11), 4.00 (d, 1 H,
J3,4 3.4 Hz, H-3), 4.12 (dd, 1 H, J10,11% 6.2 Hz,

A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
337
ulose (30).—(a) Using hydrogen peroxide and
NaOH in MeOH: to a stirred solution of 30
(101 mg, 0.20 mmol) and aq 30% H2O2 (0.1
mL) in MeOH (5 mL), at 0 °C was added aq
2.5 M NaOH (0.1 mL, 0.25 mmol). The mix-
ture was then allowed to warm to rt and TLC
(solvent B) indicated that after 2 h, all the
starting material had been consumed and five
new, closely-running materials were formed,
all with lower Rf values than 30. The reaction
mixture was then poured into cold water (5
mL), the aqueous solution was extracted with
Et2O (3×5 mL) and the combined organic
solutions were washed with water (10 mL),
dried and then concentrated to give a syrup
(81 mg). Column chromatography (solvent A)
allowed only mixtures of the components to
be isolated.
(for 26): l 21.0 (CH3CO), 25.2, 26.1, 26.3,
26.5, 26.9, 27.1 (3×C(CH3)2), 40.3 (C-6),
66.7, 67.6, 77.3, 78.0, 80.7, 81.7, 82.1 and 83.1
(C-2, 3, 4, 5, 8, 9, 10, 11), 72.3 (C6H5CH2),
105.2 (C-1), 110.1, 111.6, 112.1 (3×C(CH3)2),
128.3, 128.7, 128.8, 137.2 (C-aromatic), 170.3
(CH3CꢁO), 206.5 (CꢁO); EIMS: m/z 473 (2.2,
M−91).
Finally, the starting alcohols 23 and 24 were
recovered (22 mg, 16%).
The isomeric mixture of acetates 25 and 26
was subjected to the same acetylation condi-
tions used in their preparation. Monitoring of
the reaction by TLC (solvent A) revealed slow
conversion of acetates 26 and 26 to an elimi-
nation product. After 3 days, the concentra-
tion of the starting acetate was negligible, and
the major product was confirmed as (E)-enone
30, by TLC and NMR spectroscopic compari-
son with an authentic sample.
A fast-running fraction appeared to contain
three distinct but inseparable isomeric compo-
nents in a ratio of approximately 1:1:1. Evi-
dence as to the structure of these components
Repetition of the reaction on the mixture of
23 and 24 at 45 °C for 8 h gave (E)-enone 30
(0.17 g, 61%) and the mixed acetates 25 and
26 (55 mg, 18%). Acetylation at 60 °C gave a
negligible amount of 25 and 26, and (E)-enone
30 in 40% yield. Reaction of the single
stereoisomer, presumed to be 24, with Ac2O–
pyridine containing DMAP for 70 h at 18 °C
gave a 20:1 mixture of the (E)- and (Z)-
enones 30 and 31 in 72% yield. Thus, the 300
MHz 1H NMR spectrum of the product
showed alkenic couplings of 11.9 and 15.8 Hz.
Additional peaks that could be assigned to the
(Z)-enone 31 are: lH 5.56 (ddd, 1 H, J3,4 3.5,
J4,5 6.7, 4J4,6 1.6 Hz, H-4), 5.98 (d, 1 H, J1,2 3.8
Hz, H-1), 6.48 (dd, 1 H, J5,6 11.9 Hz, H-5),
6.77 (dd, 1 H, H-6). Negligible quantities of
both the acetate 26 and starting material 24
were obtained from the column separation.
However, if this reaction was quenched after
shorter reaction times then, in addition to the
enones 30 and 31, a single acetate 26 was
1
was based solely on the H NMR spectrum of
the mixture. Two of these isomers appeared to
result from opening of an epoxide by methox-
ide to yield two of the eight possible stereoiso-
mers depicted by 32 and 33. The third
component in the faster-running mixture, on
1
the basis of its H NMR spectrum, was a 6-
or 7-C-methoxycarbonyl derivative of a
stereoisomer of 3-O-benzyl-6-deoxy-1,2:7,8:-
9,10-tri-O-isopropylidene- -decafuranose, 34
L
and 35, originating from Favorskii rearrange-
ment of the intermediate epoxide [8] (11 mg,
11%); 1H NMR (300 MHz): l 1.31–1.52
(complex, 18 H, 3×C(CH3)2), 1.60 (br s, 1 H,
OH), 2.20–3.33 (complex), 3.27, 3.28 and 3.71
(3s, 3 H, 2×CH3O (32, 33) and CO2CH3 (34,
35), respectively), 3.85–4.75 (complex), 5.86,
5.88 and 5.91 (3×d, 1 H, J1,2 3.9, 3.7 and 3.7,
respectively, H-1), 7.27–7.37 (complex, 5 H,
C6H5).
1
1
obtained; [h]D −26.3° (c 4.75, CHCl3). The H
A slower-running fraction was shown by H
and 13C NMR spectra of this material were
identical to those of the major isomer ob-
tained by column chromatography of the
product of acetylation of the mixture of 23
and 24 with Ac2O–pyridine.
NMR spectroscopy to contain two further
components in a ratio of 2:1, tentatively iden-
1
tified from the H NMR spectrum to be two
other stereoisomers of 32, 33 (19 mg, 17%);
1
major isomer: H NMR (270 MHz): l 1.32,
Attempted epoxidation of (E)-3-O-benzyl-
5,6-dideoxy-1,2:8,9:10,11-tri-O-isopropylidene-
1.33, 1.35, 1.47 (×2) and 1.49 (6×s, 6×3 H,
3×C(CH3)2), 1.65 (br s, 1 H, OH), 2.69–3.19
(complex, 2 H), 3.24 (s, 3 H, CH3O), 3.99–
L
-erythro-h- -gluco-undec-5-enofuranos-7-
D

338
A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
4.18 (complex, 6 H), 4.34 (ddd, 1 H, J9,10 5.6,
J10,11 5.6, J10,11% 5.6 Hz, H-10), 4.49 (d, 1 H,
JAB 11.6 Hz, C6H5CHAHB), 4.65, (d, 1 H, J8,9
4.0 Hz, H-8), 4.73 (d, 1 H, C6H5CHAHB), 6.01
(d, 1 H, J1,2 3.6 Hz, H-1), 7.26–7.38 (complex,
l 1.22–1.54 (complex, 18 H, 3×C(CH3)2),
1.59 (br s, 1 H, OH), 1.70–2.02 (complex, 2
H, H-6, 6%), 3.78–4.79 (complex, 10 H), 5.52–
5.58 (complex, 1 H, H-1), 7.10–7.38 (complex,
5 H, C6H5), 8.55 (CO2H).
1
Attempted iodonium-induced cyclisation re-
action on (E)-3-O-benzyl-5,6-dideoxy-1,2:8,9:-
5 H, C6H5); minor isomer: H NMR (270
MHz): l 1.25, 1.33, 1.39, 1.47, 1.50 and 1.51
(6s, 6×3 H, 3×C(CH3)2), 1.65 (br s, 1 H,
OH), 2.69–3.19 (complex, 2 H), 3.22 (s, 3 H,
CH3O), 3.84–4.18 complex 6 H), 4.30 (ddd, 1
H, J9,10 5.6, J10,11 5.6, J10,11% 5.6 Hz, H-10), 4.52
(d, 1 H, JAB 11.9 Hz, C6H5CHAHB), 4.65 (d, 1
H, J8,9 4.0 Hz, H-8), 4.74 (d, 1 H,
C6H5CHAHB), 6.02 (d, 1 H, J1,2 2.5 Hz, 1-H),
7.26–7.38 (complex, 5 H, C6H5); EIMS: m/z
537 (0.3, M−15,), 534 (0.3, M−18).
10,11 - tri - O - isopropylidene -
L
- erythro - h - -
D
gluco-undec-5-enofuranos-7-ulose (30).—(a)
Using N-iodosuccinimide (NIS): a soln of 30
(78 mg, 0.15 mmol) in anhyd CH2Cl2 (5 mL)
containing NIS (129 mg, 0.57 mmol) was
stirred under N2 at rt. TLC (solvent B) indi-
cated that after 2 weeks, only starting material
was present; the mixture was filtered through
Kieselguhr and then concentrated to give 30
(59 mg, 76%).
(b) Using hydrogen peroxide and potassium
carbonate in MeOH: treatment of 30 (41 mg,
81 mmol) with aq 30% H2O2 (0.05 mL) in
MeOH (2 mL) and water (1 mL) at 0 °C
containing K2CO3 led to loss of starting mate-
rial, (TLC). Product isolation gave crude ma-
(b) Using iodine: a soln of 30 (54 mg, 0.11
mmol) in anhyd THF (2 mL) containing re-
sublimed iodine (0.14 g, 0.55 mmol) and
NaHCO3 (0.10 g, 1.19 mmol) was stirred at rt.
TLC (solvent B) indicated that only starting
material was apparent after 6 days. The mix-
ture was filtered through Kieselguhr and parti-
tioned between water (5 mL) and CH2Cl2 (5
mL). The dried organic solution was concen-
trated to yield 30 (21.6 mg, 40%).
1
terial which by H NMR spectroscopy was
consistent with it containing four possible iso-
1
mers of 32, 33: H NMR (300 MHz): l 1.26–
1.55 (complex, 18 H, 3×C(CH3)2), 1.60 (br s,
1 H, OH), 2.77–5.29 (complex 12 H,), 3.22,
3.24, 3.28 and 3.29 (4×s, 3 H total, CH3O),
5.86, 5.90, 6.01, and 6.22 (4×d, 1 H total, J1,2
4.1, 3.9, 3.9, and 3.7, respectively, H-1), 7.20–
7.45 (complex, 5 H, C6H5). No products due
to Favorskii rearrangement were observed in
the crude mixture.
6-Deoxy-1,2:8,9:10,11-tri-O-isopropylidene-
L
-arabino-h- -gluco-undecofuranos-7-ulo-7,3-
D
pyranose (36).—(a) Using H2 and palladium
black, catalysed by a trace amount of acid: to
a soln of 24 (307 mg, 0.59 mmol) in anhyd
MeOH (5 mL) containing palladium black (50
mg) was added a 0.014 M soln of HCl in
anhyd MeOH (1.5 mL). The reaction mixture
was stirred under H2 at rt and atmospheric
pressure for 4 h after which time TLC (1:1
light petroleum–EtOAc) indicated that all
starting material (Rf 0.72) had reacted to give
a single product (Rf 0.47). The suspension was
filtered through a pad of Kieselguhr and the
filtrate, which was slightly acidic to moist
indicator paper, was stirred with Amberlite
IRA-400 ion-exchange resin (HO− form; 5
mL) for 1 h. After removal of the resin by
filtration, the solution was concentrated to a
colourless oil. Dissolution of this oil in Et2O
and subsequent removal of the solvent under
vacuum resulted in crystallisation to give a
single anomer of the title product 36 (201 mg,
79%) mp 145.5–148°C; [h]D+11.9° (c 1.0,
(c) Using hydrogen peroxide and NaHCO3
in THF [9]: treatment of 30 (195 mg, 0.39
mmol) with aq 30% H2O2 (0.1 mL) in a THF
(5 mL)/satd aq NaHCO3 (0.1 mL) mixture at
0 °C gave [TLC (solvent B)] a product running
as a single component in an approximately
equal proportion to remaining starting mate-
rial. Column chromatography (14:1 toluene–
acetone) gave initially 30 (86 mg, 44%) and a
new component (11 mg, 5%), tentatively iden-
1
tified, on the basis of its IR and H NMR
spectra, as a mixture of 6- and/or 7-C-carboxy
derivatives of a stereoisomer of 3-O-benzyl-6-
deoxy - 1,2:7,8:9,10 - tri - O - isopropylidene - -
L
deca-1,4-furanose arising from the Favorskii
rearrangement of the intermediate epoxide [8];
IR (film): w 3400 (br, CO2H), 1750–1600
1
cm−1 (CꢁO and C6H5); H NMR (300 MHz):

A.H. Haines, A.J. Lamb / Carbohydrate Research 325 (2000) 323–339
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1
and 1375 cm−1 (C(CH3)2); H NMR (270
MHz): l 1.33, 1.35, 1.36, 1.38, 1.48 and 1.52
(6×s, 6×3 H, 3×C(CH3)2), 1.84 (dd, 1 H,
J5,6 4.6 and J6,6% 12.6 Hz, H-6), 2.02 (ddd, 1 H,
4
J5,6% 11.9, J6%,8 2.0 Hz, H-6%), 2.13 (d, 1 H,
J5,OH 10.6 Hz, 5-OH), 3.76 (d, 1 H, J8,9ꢀ0,
J9,10 7.6 Hz, H-9), 4.02–4.30 (complex, 5 H,
H-5, 10 11, 11%, 7-OH), 4.31 (d, 1 H, J2,3ꢀ0,
J3,4 2.0 Hz, H-3), 4.40 (dd, 1 H, J3,4 and J4,5
3.0 Hz, H-4), 4.56 (d, 1 H, J1,2 3.6 Hz, H-2),
4.81 (d, 1 H, H-8), 5.87 (d, 1 H, H-1); 13C
NMR (67.9 MHz): l 25.0, 26.3 (×2), 26.4,
26.8 and 27.0 (3×C(CH3)2), 35.2 (C-6), 63.8
(C-11), 67.9, 74.9, 75.7, 76.5, 77.4, 84.4, 84.8
(C-2, 3, 4, 5, 8, 9, 10), 96.2 (C-7), 105.1 (C-1),
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417 (2.6, M−15), 399 (0.7, M−33), 289 (1.2,
M−143), 143 (17.2, M−289); HRMS: calcd
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Acknowledgements
A.J.L. thanks the University of East Anglia
for financial support in the form of a stu-
dentship. The authors thank the EPSRC Mass
Spectrometry Service Centre, Swansea, for de-
termination of the high-resolution mass
spectra.
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