Sigmatropic rearrangement of uronic acid derived saccharide allyl ketene acetals. A study of stereochemistry and structural limitations

Article abstract of DOI:10.1055/s-1999-3686

Allyl ketene acetal Claisen rearrangement of uronic acid derivatives with furanoside structure was studied. Reproducibility of the observed stereodiscrimination was confirmed in the conversion of enantiomeric starting materials. From X-ray structural data

Full text of DOI:10.1055/s-1999-3686

PAPER
121
Sigmatropic Rearrangement of Uronic Acid Derived Saccharide Allyl Ketene
Acetals. A Study of Stereochemistry and Structural Limitations
Barbara Werschkun, Joachim Thiem*
Institut fŸr Organische Chemie, UniversitŠt Hamburg, Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany
Fax: +49(40)41234325; E-mail: thiem@chemie.uni-hamburg.de
Received 4 May 1998; revised 30 June 1998
Profitable use of this reaction in carbohydrate chemistry
Abstract: Allyl ketene acetal Claisen rearrangement of uronic acid
has been made employing glycal starting material as allyl-
derivatives with furanoside structure was studied. Reproducibility
ic component and generating a ketene acetal function
of the observed stereodiscrimination was confirmed in the conver-
sion of enantiomeric starting materials. From X-ray structural data
from an external, non-carbohydrate acyl residue.5 The re-
of the major reaction product obtained from a cis-pentenyl uronate,
the transition state was proven to preferentially adopt a chair-like
geometry. Alterations in the protecting group pattern led to a signif-
icant decrease in total yields. Use of b-deoxygenated starting mate-
rial allowed a greater extent of variation, but was accompanied by
the total loss of stereodiscrimination. For the first time, the reaction
was applied to pyranoid starting material structures. The conversion
of a gluco-configurated compound remaining unsuccessful, with
the corresponding galacto and 4-deoxy derivatives an interesting
stereoselectivity could be observed. This was lost by further struc-
tural simplification to a 1,4-dideoxypyranoid ring. This way, how-
ever, a substantial improvement in yield could be achieved.
verse combination of placing the ketene acetal structural
unit within the carbohydrate moiety, as can be achieved
by enolization of allyl uronates, has received much less at-
tention, so far. The first example of uronic acid derived
ketene acetals was introduced by Ireland et al. in the
course of polyether-type natural product synthesis in the
mid-eighties.6 Since then, repetition of the reaction has
been performed only once by Rizzacasa et al. employing
virtually the same furanoid starting material.7 Apart from
these two instances, however, the formation and sigmatro-
pic rearrangement of saccharide ketene acetals has not
been investigated. With regard to conceptional applica-
tions for future synthetic purposes, several basic reaction
features had to be elucidated. The investigations presented
in this study covered subjects such as the stereochemistry
of the newly generated quarternary carbon atom, the tran-
sition state geometry, the effect of the number and the na-
ture of ring substituents, and studies on the feasability to
extend the reaction to pyranoid starting material.
Key words: Claisen rearrangements, allyl ketene acetals, furano-
siduronates, pyranosiduronates
Modified carbohydrate derivatives frequently receive at-
tention as interesting synthetic targets from several as-
pects. The constantly increasing knowledge concerning
the outstanding relevance of carbohydrates in biological
processes1 has generated substantial demands for potent
artificial mimetics of naturally occurring glyco structures.
Additionally, carbohydrate derived building blocks have
been successfully employed for a long time as chiral start-
ing materials in many natural product syntheses.2 Particu-
larly for this latter purpose, often fundamental changes in
the molecular frame are required, above all the substitu-
tion of oxygen functionalities by carbonÐcarbon bonds.
Due to their complex structures, however, carbohydrate
derivatives have often proved to cause unexpected diffi-
culties even in well-established synthetic transformations.
For the initial experiments, allyl D-lyxofuranosiduronate
(1) was prepared from D-mannose according to literature
procedures.6Ð8 Successful transformation of the same
starting material in a ketene acetal Claisen rearrangement
has already been reported by Rizzacasa et al.,7 following
the results obtained earlier by Ireland et al. with the anal-
ogous crotyl ester.6 The fundamental problem that is en-
countered during enolate formation from esters
containing a suitable leaving group in the â-position is il-
lustrated in Scheme 1. Subsequent to deprotonation adja-
cent to the carbonyl carbon atom, two competing reaction
pathways can originate from the enolate anion which is
represented by the mesomeric structures 2 and 3. If the de-
sired ketene acetal formation by O-silylation to 4 cannot
be achieved in time, â-elimination will occur to generate
the conjugated intermediate 5, from which further frag-
mentation can emerge. To suppress the latter unwanted
process, Ireland et al. developed a strategy of in situ trap-
ping, which should secure that any amount of enolate
formed is instantly reacted to the silyl ketene acetal before
elimination can occur.6
With respect to CÐC bond formation, an especially valu-
able method for the manipulation of sensitive starting ma-
terial is provided by application of sigmatropic
rearrangements. Among these, easy preparative access to
compounds bearing an oxygen functionality has rendered
the Claisen rearrangement, in particular, a powerful syn-
thetic tool, which is frequently employed even in the most
delicate problems of natural product chemistry.3 Substan-
tial benefits in terms of availability of starting materials,
as well as influence on the stereochemically crucial matter
of double bond geometry, have been derived from the ex-
tensive work of Ireland et al., who established the synthet-
ic variant of silylketene acetal Claisen rearrangement.4
According to the published experimental protocol, a solu-
tion of lithium diisopropylamide in tetrahydrofuran and
hexamethylphosphoramide is premixed with chlorotrime-
thylsilane at Ð100¡C before the respective allyl ester is
Synthesis 1999, No. 1, 121Ð137 ISSN 0039-7881 © Thieme Stuttgart á New York

122
B. Werschkun, J. Thiem
PAPER
Scheme 1
added at the same temperature. The rearrangement prod- In the course of the Claisen rearrangement of ketene ace-
ucts from the crotyl uronate analogous to 1 were reported tal 4, the C-allyl branched diastereomers 6a and 6b were
to be obtained in 80% yield, this way. Our attempts, formed in a ratio of 4 to 1 in favour of the D-lyxo config-
though, to transform allyl ester 1 in the same manner, re- urated product, resulting from CÐC bond formation pre-
mained unsuccessful. Instead of the fragmentation reac- dominantly taking place trans to the isopropylidenedioxy
tions which could have been expected, however, in all moiety. This finding was largely in accordance with the
cases ester 1 was isolated almost quantitatively. This was results published by Rizzacasa et al. who could also deter-
considered to be unchanged starting material, since hy- mine the absolute configuration at C-4 by X-ray crystal-
drolysis of unreacted silyl ketene acetal 5 should addition- lography of a derivative of 6a.7 With regard to the above
ally produce the C-4 epimer, which was in no case mentioned difficulties to exactly reproduce the rearrange-
detected. Therefore, and in accordance with observations ment reaction, however, additional evidence for the ob-
reported earlier by others,9 our assumption was that in the served stereodiscrimination being displayed indepen-
premixed reagent solution, the alkylamide base might dently from the somewhat varying total reaction outcome
have been consumed in a reaction with the chlorosilane was thought to be desirable. For this purpose, comparison
before the ester starting material ever entered the reaction of two separately transformed enantiomeric ketene acetals
mixture. Since under such circumstances the order in was considered particularly instructive, since apart from
which the respective compounds are added seemed to be the respective absolute configurations, these should give
a crucial point, several variations were tested. Fairly good entirely identical results.
results of up to 70% of rearrangement products 6a and 6b
Thus, the diastereomeric allyl esters 7 and 10 were synthe-
could be obtained by simultanously adding chlorosilane
sized from the corresponding D-lyxo- and D-ribofurano-
and ester to the cooled base solution.
siduronic acids,10 respectively. Due to the chelating effect
Unfortunately, this method turned out to be extremely dif- of the ring oxygen atom, during enolate formation the (E)-
ficult to reproduce and was therefore considered too unre- isomer should be strongly favoured, as had been demon-
liable for further systematic investigations or preparative strated before.11 Assuming that silylation is taking place
purposes. The reverse procedure of adding the base to a under retention of configuration,12 it should lead to the
cooled solution of both silylating agent and ester starting enantiomeric (Z)-ketene acetals 8 and 11 (Scheme 2). Fol-
material, which had already been described by Rizzacasa lowing sigmatropic rearrangement, the mixtures of C-4
et al.,7 resulted in our hands in only moderate yields of diastereomers 9a,b and 12a,b, respectively, were isolated.
around 50%. Losses of yield in all cases originated from The absolute configurations of the generated quarternary
the competing N-silylation of diisopropylamide, as could stereocentres were assigned by comparison of NMR data
be concluded from the amount of unchanged 1 recovered. with compounds 6a and 6b. The difference in total yields
Variations using lithium or sodium hexamethyldisilazide may be attributed to different deprotonation rates of the
as the base and chloro-tert-butyldimethylsilane or chloro- diastereomeric esters 7 and 10. Apparently, this does not
tert-butyldiphenylsilane as the silylating agent did not re- influence the stereochemical behaviour of the ketene ace-
sult in any improvement. Nevertheless, in terms of repro- tals 8 and 11, once they are formed, since the diastereo-
ducibility, this method still proved to be the best. Taking meric ratios within the respective product mixtures turned
into account how difficult the same quarternary allyl out to be virtually the same. Thus, for further investiga-
branched product might be to prepare by other means tions, the stereochemical course could be considered inde-
from notoriously delicate carbohydrate starting material, pendent from possibly slightly varying reaction
the obtained result still renders ketene acetal Claisen rear- conditions and total yields.
rangement in this class of compounds worthwhile for fur-
Regarding stereochemistry, a feature of general interest in
ther systematic investigations and preparative purposes
sigmatropic reactions has always been the transition state
possibly originating therefrom.
geometry.5c,5e,13 This can be investigated, if in the course
of rearrangement a new chiral centre is generated from the
Synthesis 1999, No. 1, 121–137 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Sigmatropic Rearrangement of Allyl Ketene Acetals
123
Scheme 2
terminal position of a stereochemically unequivocally
substituted allyl double bond. For this purpose, the (Z)-
pent-2-enyl ester 13 was prepared from commercially
available (Z)-pent-2-en-1-ol and the above mentioned D-
lyxofuranosiduronic acid.10a IrelandÐClaisen rearrange-
ment resulted in the formation of all four possible stereo-
isomers. Apart from the predominating D-lyxo products
16a and 16b, which are shown in Scheme 2, the corre-
sponding L-ribo isomers were formed in 4% total yield,
but due to this small amount they will be neglected in the
following discussion. From the product fraction 16, the
side chain epimers a and b were separated by chromato-
graphy and obtained in a 5:1 ratio. Fortunately, the major
component 16a formed crystals suitable for X-ray struc-
tural analysis, the ORTEP projection of which is shown in
the Figure. The absolute configuration of the newly
formed chiral centre could thus be assigned as R, allowing
the conclusion, that in the reaction pathway the chair-like
structure 15a for the transition state is predominating.
Since the strong general preference of sigmatropic rear-
rangements to proceed via chair-like transition state struc-
tures has long been established, this result is scarcely
surprising for a comparatively unhindered structure such
as 14. The contribution of the alternative boat-like struc-
ture 15b, however, although minor, can still be counted as
substantial, indicating the difference in energy levels be-
ing rather small. It can be well imagined, that in the case
of a sterically more biased system the reaction might eas-
ily take a different course.
Figure ORTEP Diagram of 16a
Subsequent to these findings of a more basic nature, the
effect of starting material structure variations should be
investigated. Retaining the same D-lyxo molecular back-
bone which had been employed before, the diolic allyl es-
ter 19 was prepared by standard synthetic steps from the
isopropylidene precursor 1714 and transformed into the
protected derivatives 20 and 21 (Scheme 3). The benzoyl
Synthesis 1999, No. 1, 121–137 ISSN 0039-7881 © Thieme Stuttgart · New York

124
B. Werschkun, J. Thiem
PAPER
anomeric arabinofuranosiduronates has already been re-
ported.15 Final acetylation enabled chromatographic sepa-
ration of the product mixture into the pure anomers 24a
and 24b. According to a common procedure,16 deoxygen-
ation was accomplished in two steps by b-elimination fol-
lowed by catalytic hydrogenation of the obtained
unsaturated esters. In the course of the latter, an interest-
ing difference in the stereochemical behaviour of both
anomers was observed. Whereas the 1,2-trans substituted
25 gave a mixture of both C-4 epimers 26a and 26b, from
the 1,2-cis isomer 31, the D-threo compound 32 was ob-
tained as the single product. All three diastereomers were
transformed into suitable precursors for ketene acetal for-
mation by transesterification to allyl esters 27, 29 and 33
followed by silver(I)-catalyzed methylation of the free hy-
droxy groups to give 28, 30 and 34.
Scheme 3
ester 20 was chosen as an example for an ester protecting
group which cannot be enolized itself, and the benzyl
ether 21 as a representative for any ether-type substituent.
Following the IrelandÐClaisen reaction of dibenzoate 20,
no product could be isolated. Instead, a substantial amount
of fragmentation was observed, which can be rationalized
by a destabilising effect of the electron-withdrawing ester
functions on the initially formed carbanion. In such terms,
benzyl ether 21 could be expected to provide less difficul-
ties. However, although the rearrangement product 22
was indeed obtained, the minor yield and the loss of ma-
terial by decomposition indicated again that this structure
was unsuitable for ketene acetal Claisen rearrangement. In
view of these scarcely encouraging results, no further ex-
periments with fully oxygenated furanosides were per-
formed. Instead, improvement was sought to be achieved
by simplification of starting material structures, namely
deoxygenation in the crucial 3-position.
Since there is no potential leaving group in the crucial 3-
position, the procedure of in situ silylation from the first
sight did not seem to be necessary, and hence for the reac-
tion of compound 28, the generally more common proto-
col of separate enolization prior to addition of the
silylating agent was employed (Scheme 5). Unexpectedly,
however, a new source of complication arose from a car-
bonyl addition reaction of the initially formed carbanion
with a second ester molecule to give the dimeric structure
37 as the sole product to be isolated. This compound was
obtained as a single stereoisomer, but due to its pro-
nounced instability, the absolute configuration of the
quarternary carbon atom could not be assigned. Thus,
even in the case of b-deoxy uronates, the modified proce-
dure of in situ silylation had to be used. Application to 28
gave the diastereomeric rearrangement products 38 as an
inseparable 1:1 mixture, the total yield of 48% was as be-
fore within the range observed for fully oxygenated deriv-
atives. As expected, the same product mixture was
obtained from the C-4-epimeric starting material 30,
thereby demonstrating that the configuration at the site of
deprotonation does not significantly affect the reaction
outcome. Remembering the stereochemical course during
Easy access to a variety of differently configurated 3-
deoxy uronates is provided by the divergent synthetic
pathway illustrated in Scheme 4. The glycol cleavage of
glucuronolactone 23 and subsequent acid-catalyzed ester-
ification and Fischer glycosylation to a mixture of the
Scheme 4
Synthesis 1999, No. 1, 121–137 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Sigmatropic Rearrangement of Allyl Ketene Acetals
125
Scheme 5
the hydrogenation reaction of 31 to 32, a similar directing tion of the rearrangement product 48 in very small
influence of the 1,2-cis-substitution pattern could be ex- amounts, whereas with the analogous gluco derivative 47
pected for the ketene acetal rearrangement of the corre- no transformation could be achieved at all. Taking into ac-
sponding allyl ester 34. The diastereomeric rearrangement count that loss of material by 4,5-elimination should be
products 39, however, again were formed in equal strongly favored by the trans-diaxial arrangement given
amounts. Changing the substitution at 2-position to larger in the case of galacto configuration, it appears even more
residues such as in methoxymethyl and benzyl derivatives surprising that the gluco isomer did not prove to give bet-
35 and 36, respectively, did not alter the diastereomeric ter results. The configuration of the newly formed quarter-
ratio. However, the yields decreased significantly, and the nary stereocentre in 48, which was assigned by means of
benzyl ether 36 gave the poorest result in accordance with NOE-NMR spectral data, reveals that during the rear-
the observations made in the D-lyxo series. Although rangement process bond forming exclusively occurs trans
â-deoxygenation proved to allow a greater extent of pro- to the C-4 methoxy substituent.
tecting group variation, acceptable yields could only be
obtained with acetal and methyl ether derivatives. In addi-
tion, regarding the total loss of stereoselectivity, the use of
deoxygenated starting material in the furanoside series did
not lead to a substantial synthetic benefit.
Although the first instance of ketene acetal rearrangement
employing uronate-type starting material is now more
than twelve years ago, to our knowledge, no efforts to ap-
ply this reaction to any of the far more common pyranoid
carbohydrate structures have been published, so far. Suit-
able precursor molecules were easily prepared from the
methyl galacto- and glucopyranosiduronates 4217 and
43,18 respectively, by transesterification and O-methyla-
tion to give the protected allyl esters 46 and 47 (Scheme
6). Application of the IrelandÐClaisen reaction, however,
Scheme 7
only in the case of galacto compound 46 led to the isola-
For further elucidation of the influence of substitution ad-
jacent to the ketene acetal moiety on the course of the re-
arrangement reaction, a C-4 deoxygenated derivative was
employed. Its preparation could be easily achieved from
the unsaturated uronate 4919 in analogy to the synthetic se-
quence used before in the furanoside series (Scheme 7).
The methylated allyl ester 52 was obtained as a suitable
starting material via the sole product 50 from the catalytic
hydrogenation of 49. The IrelandÐClaisen reaction of 52
led to the isolation of 53 as the single rearrangement prod-
uct. Again, the configuration at C-5 could be assigned by
NOE-NMR spectroscopy and turned out to be the same as
in the galacto compound obtained before. Since in this
case, no directing substituent in the neighbouring C-4 po-
Scheme 6
sition is present, the observed stereoselectivity seems as-
Synthesis 1999, No. 1, 121–137 ISSN 0039-7881 © Thieme Stuttgart · New York

126
B. Werschkun, J. Thiem
PAPER
tonishing. As a possible reason the conformation of the ated quarternary stereocentres, however, could not be as-
pyranoside ring should be considered, in particular the signed. In both NOESY-NMR spectra, no distinct
folding of the C-1 to C-3 moiety, which might hinder interactions could be recognized, and due to their sirupy
bond formation from above the ring surface. From this as- nature neither of the isomers enabled X-ray structural re-
pect, the above observed failure of the gluco derivative to solvement. An attempt to repeat the reaction with the
undergo any rearrangement reaction would become some- dibenzoylated derivative 59 in order to possibly obtain
what comprehensive. In that case, in addition to the as- crystalline rearrangement products failed as before in the
sumed hindrance on the top side, also the bottom face is lyxofuranoside series.
shielded by the equatorial methoxy group in position 4,
The material presented in this study certainly shows the
and thus there is no possible reaction pathway remaining.
formation and reaction of saccharide ketene acetals to be
With respect to the yield, b-deoxygenation gave a small,
of a rather delicate nature. To obtain satisfying results,
several structural restrictions have to be taken into ac-
count. Nevertheless, upon appropriate adjustments, pre-
parative purposes may still be realized. Efforts in this
but scarcely significant improvement compared to the ga-
lacto compound, the values obtained so far in the hexopy-
ranoside series altogether turned out to be rather poor. As
a crucial factor, the chair-like ring conformation could be
direction are under current investigation in our laborato-
responsible, because compared to the furanoid derivatives
ries and will be reported in due course.
rehybridization subsequent to deprotonation should be
more difficult.
Solvents were purified and dried according to standard procedures.
Petroleum ether used refers to bp 50Ð70¡C. TLC was performed on
As conformational rigidity to a substantial part is support-
ed by stereoelectronic influence of the ring substituents,
simplification of the molecular backbone by further deoxy-
genation could be expected to be an effective way to facil-
itate the IrelandÐClaisen rearrangement with pyranoid
starting material. For this purpose, 2,6-anhydrohexonate
54,20 prepared by radical reduction of the corresponding
glucuronyl bromide as described in the literature,21 was
manipulated in the common b-elimination-hydrogenation
sequence, which resulted in the isolation of the epimeric
dideoxygenated pyranoid esters 56a and 56b. The major
component 56a was transformed into the O-methylated
allyl ester 58, which, upon ketene acetal formation, gave
a mixture of the diastereomeric rearrangement products
60a and 60b (Scheme 8). The total yield of 48% corre-
sponds to the results obtained in the furanoid series and
within the pyranoid class of compounds represents a sub-
stantial improvement. The aforementioned assumption
that a decreased extent of ring substitution will enhance
conformational flexibility is confirmed not only by this in-
crease in yield, but also by the observed loss of stereose-
lectivity. The diastereomeric products are formed to
almost equal parts and obviously adopt opposite chair-like
conformations. The absolute configurations of the gener-
silica gel 60-coated aluminum sheets (Merck or Macherey-Nagel),
with detection by UV at 254 nm and by heating with H2SO4 (5% in
EtOH). Flash chromatography was carried out on silica gel 60
(0.04Ð0.063 mm) (Merck, Macherey-Nagel or ICN). NMR spectra
were recorded on a Bruker AMX-400 NMR spectrometer (1H:
400 MHz; 13C: 100 MHz) with TMS as internal standard. Melting
points were determined on a Leitz apparatus and are uncorrected.
The optical rotations were measured on a Perkin-Elmer 243 or 341
polarimeter at 20¡C. Due to inherent impurities in the case of all
Claisen rearrangement products, correct elemental analysis results
could only be obtained for crystalline derivatives. 1H and 13C NMR
data of the products are listed in Tables 1Ð12.
Ketene Acetal Formation and Sigmatropic Rearrangement;
General Procedure A
To a solution of the allyl uronate in anhyd THF (4 mL/mmol) and
HMPA (1 mL/mmol) under argon was added chlorotrimethylsilane
(3.4 equiv) at Ð100¡C. Then, a freshly prepared 1 M solution of
LDA in anhyd THF (2 equiv) was added dropwise maintaining the
same temperature. When addition was complete, the reaction mix-
ture was allowed to warm up to r.t. over a period of 40 min and
stirred for additional 2 or 3 h. After that time, a 1 M solution of
TBAF in THF (4 equiv) was added and the mixture was further
stirred at r.t. for 1 h. The solution was diluted with Et2O (10 mL/
mmol) and extracted with 1 M NaOH (3 × 20 mL/mmol). The com-
bined aqueous extracts were acidified with 10 M HCl to pH 1 or be-
Scheme 8
Synthesis 1999, No. 1, 121–137 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Sigmatropic Rearrangement of Allyl Ketene Acetals
127
low and quickly extracted with CH2Cl2 (3 × 50 mL/mmol). The
organic extracts were dried (MgSO4) and concentrated in vacuo. A
solution of the residual brown oil in benzene (6 mL/mmol) and
MeOH (2 mL/mmol) was treated with a 2 M solution of
TMSCHN222 in hexane (1.2 equiv) for 1 h under vigorous stirring at
r.t. After removal of the solvents in vacuo, the resulting viscous sol-
id was purified by flash chromatography.
Elimination to α,â-Unsaturated Uronates with DBU; General
Procedure D
A solution of the b-acetoxyuronate in anhyd CH2Cl2 (10 mL/mmol)
was stirred with DBU (2 equiv) at r.t. until conversion was complete
(TLC monitoring: petroleum ether/EtOAc, 2:1), washed with 4 M
HCl (5 mL/mmol), and dried (MgSO4). After evaporation of the sol-
vent in vacuo, the crude unsaturated uronate was purified by flash
chromatography.
Esterification of Uronic Acids via the Acid Chlorides; General
Procedure B
Hydrogenation of Unsaturated Uronates; General Procedure E
A solution of the unsaturated uronate in MeOH (10 mL/mmol) con-
taining 10% Pd on activated charcoal (40 mg/mmol) was stirred un-
der H2 at r.t. until conversion was complete (TLC monitoring:
petroleum ether/EtOAc, 2:1). The catalyst was filtered off, the fil-
trate was evaporated in vacuo, and the crude hydrogenation product
was purified by flash chromatography.
To a solution of the uronic acid and a few drops of anhyd DMF in
benzene (2.5 mL/mmol) was added oxalyl chloride (2 equiv) at
0¡C. The mixture was stirred under warming to r.t. until no further
gas formation could be observed (approximately 1 to 3 h). After
concentration in vacuo, the residue was taken up in Et2O (5 mL/
mmol), the solution was filtered through Celite, and the filtrate was
evaporated in vacuo. To a solution of the resulting crude acid chlo-
ride in anhyd CH2Cl2 (5 mL/mmol) the respective alcohol
(1.5 equiv) and DMAP (1.5 equiv) were added at 0¡C, and the mix-
ture was stirred under warming to r.t. Upon completion of conver-
sion as monitored by TLC (petroleum ether/EtOAc, 3:1), the
solution was diluted with Et2O (10 mL/mmol), washed with sat. aq
NaHCO3 (10 mL/mmol), and dried (MgSO4). The solvents were re-
moved in vacuo, and the crude ester was purified by flash chroma-
tography.
Methylation of Hydroxyl Groups with MeI/Ag2O; General Pro-
cedure F
A solution of the free alcohol in MeI (5 mL/mmol) containing Ag2O
(3 equiv/OH group) was heated under reflux until conversion was
complete (TLC monitoring: petroleum ether/EtOAc, 2:1). The sil-
ver salts were filtered off and extracted with CH2Cl2 (3 × 10 mL/
mmol), the combined filtrates were evaporated in vacuo, and the
crude methyl ether was purified by flash chromatography.
Transesterification with AllONa; General Procedure C
To a solution of the methyl uronate in anhyd allyl alcohol (AllOH,
10 mL/mmol) was added a freshly prepared 1 M solution of AllONa
in AllOH (0.25 equiv) at 0¡C. The solution was allowed to slowly
warm up to r.t. and upon completion of conversion (TLC monitor-
ing: petroleum ether/EtOAc/MeOH, 10:10:1) was neutralized by
stirring with ion exchange resin Amberlite IR 120 H+. The solution
was filtered, the filtrate was evaporated in vacuo, and the crude allyl
uronate was purified by flash chromatography.
Methyl (Benzyl 2,3-O-isopropylidene-4-C-(prop-2-enyl)-α-D-
lyxofuranosid)uronate (6a) and Methyl (Benzyl 2,3-O-isopro-
pylidene-4-C-(prop-2-enyl)-â-L-ribofuranosid)uronate (6b)
Prepared according to General Procedure A, from allyl (benzyl 2,3-
O-isopropylidene-a-D-lyxofuranosid)uronate (1;7 167 mg, 0.5 mmol);
flash chromatography: petroleum ether/EtOAc (10:1).
Table 1 1H NMR Data of Pentofuranosiduronates 7, 10, 13, 18–21, and 24
Prod- 1H NMR (400 MHz, CDCl3/TMS)
uct
d, J (Hz)
H-1
H-2
H-3
H-4
H-1'
H-2'
H-3'
Others
J1,2 J2,3
J3,4
7
10
13
5.01
4.51/4.53 4.94
4.51/4.53
4.62, 4.71
5.83–5.94
5.19, 5.31 1.23, 1.36 (CH3), 3.29
(OCH3)
0
0
0
4.1a
5.6
5.9
5.6a
5.00
5.01
4.52
4.50
5.20
4.92
4.59–4.62
5.85–5.95
5.44–5.50
5.22–5.34 1.30, 1.45 (CH3), 3.35
(OCH3)
0
4.51
4.59
4.66, 4.77
–
5.56–5.62 0.93 (CH3CH2), 1.23,
1.36 (CH3), 2.07 (CH2),
3.29 (OCH3)
3.6
18
4.96
4.02
4.53
6.12
–
–
3.31, 3.73 (OCH3), 3.69, 1.4
3.80 (OH)
4.9
5.6
19b
20
5.05
5.38
4.65–4.77
4.06
5.05
4.65–4.77
4.48, 4.59
5.90–5.99
5.61–5.71
5.28–5.41 2.95 (OH), 3.39 (OCH3)
–
–
–
5.63
5.00, 5.12 3.50 (OCH3), 7.27–7.36, 1.3
7.52, 7.84, 7.95 (Ar)
5.4
6.4
21
5.23
4.99
5.09
3.93, 4.38
4.54–4.77
5.79–5.89
5.18, 5.29 3.43 (OCH3), 4.54–4.77 3.9
(OCH2), 7.26–7.35 (Ar)
4.4
1.5
6.4
4.9
5.1
4.9
24a
24b
4.96
4.94
5.23
5.75
4.49
4.33
–
–
–
–
–
2.03, 2.06 (OCOCH3),
3.37, 3.75 (OCH3)
0
–
2.04 (OCOCH3), 3.36, 4.4
3.72 (OCH3)
a May be interchanged.
b Coupling constants of 19 are insufficiently resolved.
Synthesis 1999, No. 1, 121–137 ISSN 0039-7881 © Thieme Stuttgart · New York

128
B. Werschkun, J. Thiem
PAPER
Table 2 13C NMR Data of Pentofuranosiduronates 7, 10, 13, 18–21, and 24
Prod-
uct
13C NMR (100 MHz, CDCl3/TMS)
d
C-1
C-2, C-3, C-4
C-5
C-1'
C-2'
C-3'
Others
7
10
13
107.44
109.32
107.53
79.44, 80.53, 83.99
82.11, 83.60, 84.30
79.58, 80.65, 84.08
167.09
169.80
167.41
65.73
66.01
61.04
131.69
131.51
122.38
118.63
119.04
137.32
25.05, 25.89 (CH3), 55.01 (OCH3), 113.32 (OCO)
24.98, 26.33 (CH3), 55.45 (OCH3), 112.69 (OCO)
14.04 (CH3CH2), 20.91 (CH2), 25.16, 26.00 (CH3),
55.09 (OCH3), 113.39 (OCO)
18
19
20
107.94
108.95
106.82
70.69, 74.23, 77.83
71.73, 75.27, 78.91
72.02, 75.21, 76.72
170.19
170.49
–
–
–
51.60, 54.60 (OCH3)
55.63 (OCH3)
66.36
66.22
131.35
119.31
119.45
a
b
–
–
55.93 (OCH3), 128.37–134.54 (C-2', Ar), 164.82,
165.19, 167.51 (CO2)
b
21
107.79
106.59
100.73
78.29, 78.85, 82.96
77.39, 78.87, 79.69
75.46, 76.01, 76.95
168.33
65.88
–
118.92
56.29 (OCH3), 72.69, 73.72 (OCH2), 127.69–
137.77 (C–2', AR)
a
24a
24b
–
–
–
–
–
–
–
19.68 (CH3), 51.72, 54.44 (OCH3), 168.28, 168.65,
168.80 (CO2)
a
–
19.59, 19.73 (CH3), 51.52, 54.64 (OCH3), 168.82,
168.99, 169.33 (CO2)
a Not distinguishable from other carboxyl signals.
b Not distinguishable from aromatic signals.
Table 3 1H NMR Data of C-Branched Pentofuranosiduronates 6, 9, 12, 16, and 22
Prod-
uct
1H NMR (400 MHz, CDCl3/TMS)
d, J (Hz)
H-1
H-2
H-3
H-1'
H-2'
H-3'
5.12
Others
J1,2
J2,3
6a
6b
5.38
4.71, 4.78
2.67, 2.82
5.80–5.87
1.30, 1.42 (CH3), 3.79 (OCH3), 4.53,
4.82 (OCH2), 7.27–7.36 (Ar)
0
6.1
5.03
4.90
4.60
5.23
2.56, 2.71
5.65–5.73
5.03
1.27, 1.41 (CH3), 3.48 (OCH3), 4.41,
4.67 (OCH2), 7.17–7.27 (Ar)
0
6.1
a
a
9a
9b
4.68 (2 H), 5.16
2.58, 2.79
2.61, 2.75
2.50, 2.72
2.54, 2.67
2.27
5.74–5.84
5.69–5.80
5.66–5.75
5.63–5.73
5.79–5.88
5.13
1.30, 1.42 (CH3), 3.42, 3.78 (OCH3)
1.33, 1.49 (CH3), 3.32, 3.71 (OCH3)
1.23, 1.35 (CH3), 3.35, 3.71 (OCH3)
1.27, 1.42 (CH3), 3.26, 3.64 (OCH3)
–
–
4.58
5.27
5.10
0
6.1
a
a
12a
12b
16a
4.61 (2 H), 5.09
5.06
–
–
4.83
5.08
4.50
5.19
5.06
0
0
5.9
5.9
4.57, 4.89
5.00, 5.14
0.78 (CH3CH2), 1.00, 1.76 (CH2), 1.22,
1.33 (CH3), 3.34, 3.71 (OCH3)
16b
22
5.10
5.19
4.42
3.94
4.66
2.53
5.55–5.64
5.74–5.84
5.10, 5.16
5.08, 5.11
0.76 (CH3CH2), 1.33 (CH2), 1.21, 1.34 1.5
(CH3), 3.37, 3.72 (OCH3)
6.1
4.9
4.04
2.45, 2.76
3.44, 3.67 (OCH3), 4.59–4.73 (OCH2), 3.1
7.26–7.33 (Ar)
a Not identified due to overlapping signals.
6a; yield: 75 mg (43%); colourless crystals; mp 91¡C (petroleum
ether); [a]D20 +5.3 (c = 1, CHCl3); {Lit.7 mp 91Ð92¡C; [a]D20 +4.2 (c
= 1, CHCl3)}.
Methyl (Methyl 2,3-O-isopropylidene-4-C-(prop-2-enyl)-α-D-
lyxofuranosid)uronate (9a) and Methyl (Methyl 2,3-O-isopro-
pylidene-4-C-(prop-2-enyl)-â-L-ribofuranosid)uronate (9b)
Prepared according to General Procedure A, from 7 (129 mg,
0.5 mmol); flash chromatography: petroleum ether/EtOAc (10:1).
6b; yield: 18 mg (10%); yellow syrup; [a]D20 +75.8 (c = 2, CHCl3);
{Lit.7 [a]D20 +63.8 (c = 1.5, CHCl3)}.
9a; yield: 60 mg (44%); colourless crystals; mp 66¡C (petroleum
ether); [a]D20 Ð11.6 (c = 0.5, CHCl3).
Allyl (Methyl 2,3-O-isopropylidene-α-D-lyxofuranosid)uronate (7)
Prepared according to General Procedure B, from methyl 2,3-O-iso-
propylidene-a-D-lyxofuranosiduronic acid10a (1.73 g, 8 mmol);
Anal. C13H20O6 (272.3): calc. C 57.34, H 7.40; found C 57.28; H
7.49.
9b; yield: 17 mg (13%); yellow syrup; [a]D20 +1.3 (c = 0.1, CHCl3).
flash chromatography: petroleum ether/EtOAc (5:1); yield: 1.84 g
20
(90%); colourless syrup; [a] +28.3 (c = 2, CHCl3).
578
Anal. C12H18O6 (258.3): calc. C 55.81, H 7.03; found C 55.56, H 7.16.
Synthesis 1999, No. 1, 121–137 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Sigmatropic Rearrangement of Allyl Ketene Acetals
129
Table 4 13C NMR Chemical Data of C-Branched Pentofuranosiduronates 6, 9, 12, 16, and 22
Prod-
uct
13C NMR (100 MHz, CDCl3/TMS)
δ
C-1
C-2, C-3
C-4
C-5
C-1'
C-2'
C-3'
Others
a
6a
6b
106.97
84.33, 84.67
91.79
168.81 40.87
171.44 37.04
169.41 41.47
172.57 37.86
169.40 41.50
171.55 36.83
168.51 52.99
170.09 51.63
170.99 42.32
–
117.81
23.96, 24.95 (CH3), 51.21 (OCH3) 69.09 (OCH2),
112.24 (OCO), 126.80–136.10 (C-2', Ar)
a
105.04
109.37
108.42
109.39
107.37
108.86
109.86
107.80
80.11, 84.07
84.76, 85.15
81.04, 84.96
84.77, 85.17
80.00, 83.91
82.56, 84.46
83.36, 84.68
82.13, 82.85
88.01
92.13
88.73
92.15
87.70
93.52
93.92
88.59
–
117.82
118.30
118.86
118.31
117.85
117.94
118.37
119.03
23.85, 25.07 (CH3), 51.03 (OCH3), 68.16 (OCH2),
111.49 (OCO), 126.64–136.18 (C-2', Ar)
9a
131.72
131.54
131.74
130.51
136.89
135.73
24.54, 25.51 (CH3), 51.75, 55.39 (OCH3), 112.76
(OCO)
9b
24.92, 26.12 (CH3), 51.96, 55.36 (OCH3), 112.52
(OCO)
12a
12b
16a
16b
22
24.56, 25.53 (CH3), 51.76, 55.42 (OCH3), 112.76
(OCO)
23.88, 25.09 (CH3), 50.95, 54.34 (OCH3), 111.49
(OCO)
11.02 (CH3CH2), 20.90 (CH2), 24.06, 25.12 (CH3),
50.87, 54.36 (OCH3), 111.90 (OCO)
11.01 (CH3CH2), 21.83 (CH2), 24.15, 25.29 (CH3),
51.19, 55.04 (OCH3), 112.36 (OCO)
a
–
52.15, 56.23 (OCH3), 72.59, 73.83 (OCH2), 127.64–
137.88 (C-2', Ar)
a Not distinguishable from aromatic signals.
Table 5 1H NMR Data of Deoxy Pentofuranosiduronates 25–36a
Prod-
uct
1H NMR (400 MHz, CDCl3/TMS)
δ, J (Hz)
H-1
H-2
5.47
5.03
4.96
4.21
H-3a
H-3b
5.96
H-4
–
Others
J1,2
1.5
0
J2,3a
J2,3b
J3a,3b
–
J3a,4
–
J3b,4
25
5.31
4.90
5.02
4.84
2.01 (OCOCH3), 3.49, 3.78 (OCH3)
2.01 (OCOCH3), 3.36, 3.70 (OCH3)
1.96 (OCOCH3), 3.32, 3.73 (OCH3)
3.1
–
26a
26b
27
2.24
2.12
2.19
2.41
2.62
2.30
4.69
4.60
4.76
0
5.1
5.9
4.6
14.0
14.0
13.7
7.9
9.7
8.4
7.9
4.1
8.4
0
1.3
0
3.35 (OCH3), 4.58 (H-1'), 5.19, 5.27
(H-3'), 5.81–5.91 (H-2')
0
a
28
29
30
4.93
4.97
5.02
3.74
4.08
4.56
2.17–2.30
4.69
4.56
3.69
3.29, 3.37 (OCH3), 4.59 (H-1'), 5.19,
5.27 (H-3'), 5.81–5.91 (H-2')
0
0
0
0
4.6
5.1
9.2
–
8.4
2.3
1.8
8.4
1.93
2.50
2.42
3.30 (OCH3), 4.62 (H-1'), 5.21, 5.28
(H-3'), 5.82–5.90 (H-2')
0
14.0
13.2
10.0
5.4
2.15
3.23, 3.32 (OCH3), 4.61 (H-1'), 5.18,
5.27 (H-3'), 5.81–5.91 (H-2')
4.6
31
32
33
5.54
5.09
4.86
5.76
4.90
4.24
5.94
–
2.13 (OCOCH3), 3.52, 3.80 (OCH3)
2.10 (OCOCH3), 3.47, 3.78 (OCH3)
6.1
4.1
2.5
8.4
–
–
8.4
8.4
2.31
2.04
2.67
2.62
4.56
4.53
10.0
8.4
–
8.4
8.7
2.37 (OH), 3.53 (OCH3), 4.66 (H-1'), 4.4
5.25–5.38 (H-3'), 5.88–5.98 (H-2')
8.4
12.5
34
35
4.95
4.91
3.87
4.06
2.19
2.26
2.63
2.62
4.56
4.54
3.42, 3.51 (OCH3), 4.65 (H-1'), 5.25, 4.1
5.34 (H-3'), 5.88–5.98 (H-2')
10.2
12.2
8.1
8.1
12.5
11.7
8.7
8.6
8.4
8.6
3.40, 3.51 (COH3), 4.63–4.72 (H-1', 4.1
OCH2O), 5.24–5.37 (H-3'), 5.88–5.98
(H-2')
36
4.81
3.95
2.24
2.53
4.49
3.48 (OCH3), 4.60–4.64 (H-1', OCH2), 4.1
5.25, 5.33 (H-3'), 5.87–5.96 (H-2'),
7.28–7.37 (Ar)
10.7
8.1
12.2
9.0
8.4
a Not identified due to overlapping signals.
Synthesis 1999, No. 1, 121–137 ISSN 0039-7881 © Thieme Stuttgart · New York

130
B. Werschkun, J. Thiem
PAPER
Table 6 13C NMR Chemical Data of Deoxy Pentofuranosiduronates 25–36
Prod- 13C NMR (100 MHz, CDCl3/TMS)
uct
d
C-1
C-3
C-2
C-4
C-5
Others
25
26a
26b
27
28
29
30
31
32
33
34
35
36
106.90 108.92 79.43
150.56 159.05
19.78 (CH3), 51.49, 55.91 (OCH3), 168.93 (CO2)
a
107.74 33.62
108.02 34.24
108.72 35.12
106.02 32.23
110.58 36.16
107.57 33.73
105.01 108.0
101.48 30.89
102.39 35.04
101.40 31.29
102.01 31.67
101.50 31.55
76.78, 77.12
76.01, 76.71
74.28, 75.27
75.68, 83.21
74.69, 75.82
–
–
21.33 (CH3), 52.61, 55.23 (OCH3), 170.51, 172.92 (CO2)
21.26 (CH3), 55.78, 55.47 (OCH3), 170.53, 172.36 (CO2)
53.79 (OCH3), 64.67 (C-1'), 117.71 (C-3'), 130.72 (C-2')
53.75, 55.98 (OCH3), 64.62 (C-1'), 117.65 (C-3'), 130.76 (C-2')
54.96 (OCH3), 66.36 (C-1'), 119.41 (C-3'), 131.26 (C-2')
55.07, 56.92 (OCH3), 65.73 (C-1'), 118.61 (C-3'), 131.84 (C-2')
20.52 (CH3), 52.54, 57.92 (OCH3)
21.14 (CH3), 52.66, 55.63 (OCH3), 170.91, 172.60 (CO2)
55.33 (OCH3), 65.73 (C-1'), 118.77 (C-3'), 131.72 (C-2')
55.16, 58.14 (OCH3), 65.73 (C-1'), 118.82 (C-3'), 131.72 (C-2')
a
171.26
171.30
173.94
171.58
75.84, 83.62
73.85
b
b
–
–
a
73.04, 73.88
72.07, 74.64
74.21, 80.38
73.87, 77.06
73.96, 77.88
–
171.84
171.69
171.71
171.71
55.09, 55.78 (OCH3), 65.72 (C-1'), 96.80 (OCH2O), 118.78 (C-3'), 131.78 (C-2')
55.10 (OCH3), 65.71, 72.54 (C-1', OCH2), 118.79 (C-3'), 126.99–137.51 (C-2', Ar)
a Not distinguishable from other carboxyl signals.
b Signals of quaternary carbon atoms of 31 not detected.
Table 7 1H NMR Data of C-Branched Deoxy Pentofuranosiduronates 38–41
Prod- 1H NMR (400 MHz, CDCl3/TMS)
ucta
d, J (Hz)
H-1 H-2 H-3a
4.94 3.66 1.92
4.95 3.73 2.00
4.88 3.73
H-3b
2.50
H-1'
H-2'
H-3'
5.04
5.06
Others
J1,2
J2,3a
J2,3b J3a,3b
38
2.43, 2.57
3.20, 3.29, 3.34 (6 H),
3.67, 3.68 (OCH3)
0
1.5,
4.6
0,
13.7
5.67–5.77
6.1
2.51–2.65 2.51–2.65
b
b
b
39
3.31, 3.33, 3.40, 3.41,
3.67, 3.68 (OCH3)
4.1
–
–
–
1.99, 2.24, 2.35 (2 H), 2.58 (4 H)
5.64–5.73 5.03–5.11
4.94 3.83
4.92 3.99 2.15
4.97 4.11 2.40–2.70 2.40–2.70
40
2.32
3.39 (6 H), 3.47, 3.48,
4.1, 8.6,
4.4 11.2
8.4, 12.7
9.7
2.40–2.70 5.70–5.83 5.11–5.18 3.75 (6 H, OCH3),
4.64–4.71 (OCH2O)
41
4.81 3.89 2.14
4.87 4.01 2.22
2.37
2.16
2.49, 2.61
2.61
3.43, 3.44, 3.72, 3.73
(OCH3), 4.53–4.60
(OCH2), 7.26–7.37 (Ar)
4.0, 8.4,
4.3 11.0
7.8, 12.6,
5.65–5.80 5.11
9.8
13.1
a Data given for a 1:1 mixture of C-4 diastereoisomers.
b Not resolved.
Allyl (Methyl 2,3-O-isopropylidene-â-D-ribofuranosid)uronate
(10)
cis-Pent-2-enyl (Methyl 2,3-O-isopropylidene-α-D-lyxofura-
nosid)uronate (13)
Prepared according to General Procedure B, from methyl 2,3-O-iso-
propylidene-b-D-ribofuranosiduronic acid10b (654 mg, 3 mmol);
flash chromatography: petroleum ether/EtOAc (5:1); yield: 679 mg
(88%); colourless syrup; [a]D20 Ð47.6 (c = 1, CHCl3).
Prepared according to General Procedure B, from methyl 2,3-O-
isopropylidene-a-D-lyxofuranosiduronic acid10a (397 mg,
1.82 mmol); flash chromatography: petroleum ether/EtOAc (10:1);
yield: 430 mg (83%); colourless oil; [a]D20 +16.5 (c = 1.5, CHCl3).
Anal. C12H18O6 (258.3): calc. C 55.81, H 7.03; found C 55.52, H
6.91.
Anal. C14H22O6 (286.3): calc. C 58.73, H 7.75; found C 58.90, H
7.66.
Methyl (Methyl 2,3-O-isopropylidene-4-C-(prop-2-enyl)-â-L-
lyxofuranosid)uronate (12a) and Methyl (Methyl 2,3-O-isopro-
pylidene-4-C-(prop-2-enyl)-â-D-ribofuranosid)uronate (12b)
Prepared according to General Procedure A, from 10 (129 mg,
0.5 mmol); flash chromatography: petroleum ether/EtOAc (10:1).
Methyl {Methyl 2,3-O-isopropylidene-4-C-[(1R)-1-ethylprop-2-
enyl]-α-D-lyxofuranosid}uronate (16a) and Methyl {Methyl 2,3-
O-isopropylidene-4-C-[(1S)-1-ethylprop-2-enyl]-α-D-lyxofura-
nosid}uronate (16b)
Prepared according to General Procedure A, from 13 (1.46 g,
5 mmol); flash chromatography: petroleum ether/EtOAc (10:1).
12a; yield: 48 mg (35%); colourless crystals; mp 67 ¡C (petroleum
ether); [a]D20 +12.1 (c = 0.5, CHCl3).
16a; yield: 298 mg (20%); colourless crystals; mp 65¡C (EtOH);
[a]D20 +4.6 (c = 1, CHCl3).
Anal. C13H20O6 (272.3): calc. C 57.35, H 7.40; found C 57.31, H
7.51.
12b; yield: 13 mg (10%); yellow syrup; [a]D20 Ð0.9 (c = 0.1, CHCl3).
Anal. C15H24O6 (300.4): calc. C 59.98, H 8.05; found C 60.07; H
8.07.
16b; yield: 57 mg (4%); yellow syrup; [a]D20 +7.5 (c = 1, CHCl3).
Synthesis 1999, No. 1, 121–137 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Sigmatropic Rearrangement of Allyl Ketene Acetals
131
Table 8 13C NMR Chemical Data of C-Branched Deoxy Pentofuranosiduronates 38–41
Prod-
ucta
13C NMR (100 MHz, CDCl3/TMS)
d
C-1
C-2
C-3
C-4
C-5
C-1'
C-2'
C-3'
Others
38
39
40
41
106.52 83.04
106.68 83.89
100.89 78.78
101.31 79.04
102.53 76.47
103.03 76.85
102.03 78.03
102.49 78.05
36.31
36.43
34.10
35.59
35.42
37.11
35.38
36.98
85.56 173.12
86.23 173.24
82.72 172.44
83.72 173.16
83.33 173.43
84.36 174.24
83.47 173.45
84.46 174.22
42.87 131.31 117.63 51.10, 51.37, 53.87, 53.93, 55.53, 56.00 (OCH3)
43.10 131.39 117.76
42.40 130.57 118.02 51.24, 51.51, 54.10, 54.21, 56.94, 57.06 (OCH3)
43.30 131.09 118.60
43.38 131.54 119.03 52.26, 52.55, 55.06, 55.18, 55.78 (OCH3), 96.77
44.37 132.16 119.68 96.82 (OCH2O)
b
43.42
44.42
–
118.98 52.24, 52.49, 55.06, 55.18 (OCH3), 72.49, 72.58
119.54 (OCH2), 126.98–137.54 (C-2', Ar)
a Data given for a 1:1 mixture of C-4 diastereoisomers.
b Not distinguishable from aromatic signals.
Methyl (Methyl 2,3-di-O-benzyl-4-C-(2-propenyl)-α-D-lyxo-
furanosid)uronate (22)
Prepared according to General Procedure A, from 21 (178 mg,
0.45 mmol); flash chromatography: petroleum ether/EtOAc (10:1);
yield: 11 mg (6%) 22; yellow syrup; [a]D20 +3.2 (c = 0.5, CHCl3).
Methyl (Methyl α-D-lyxofuranosid)uronate (18)
A solution of methyl (methyl 2,3-O-isopropylidene-a-D-lyxofura-
nosid)uronate (17;14 1.42 g, 6.1 mmol) in anhyd MeOH (130 mL)
containing ion exchange resin Amberlite IR 120 H+ was heated un-
der reflux overnight. The mixture was filtered, the filtrate was evap-
orated in vacuo, and the residue was purified by flash
chromatography (petroleum ether/EtOAc, 1:1) to yield 820 mg
(70%) 18 as a colourless amorphous solid; [a]D20 +50.1 (c = 0.7,
CHCl3).
Methyl (Methyl 2,3-di-O-acetyl-α-D-arabinofuranosid)uronate
(24a) and Methyl (Methyl 2,3-di-O-acetyl-â-D-arabinofura-
nosid)uronate (24b)
D-Glucuronolactone 23 (3.52 g, 20 mmol) was added to a solution
of Pb(OAc)4 (12.6 g, 28.4 mmol) in AcOH (350 mL) at r.t. and
stirred for 2 h. The resulting clear solution was treated with a solu-
tion of oxalic acid in HOAc (10% m/v, 30 mL) for 0.5 h, filtered,
and the filtrate was coevaporated with toluene in vacuo. The residue
was taken up in H2O (50 mL), stirred with ion exchange resin Am-
berlite IR 120 H+ for a few min, filtered, and the filtrate was again
codistilled with toluene in vacuo. A solution of the residual solid in
anhyd MeOH (50 mL) containing Amberlite IR 120 H+ was heated
under reflux overnight. After removal of the ion exchange resin by
filtration, the filtrate was concentrated in vacuo, the residue was dis-
solved in pyridine (100 mL) and Ac2O (50 mL), and stirred under
warming from 0¡C to r.t. overnight. Coevaporation with toluene in
vacuo and flash chromatography (petroleum ether/Et2O, 2:1) of the
remaining crude product yielded the separated anomeric glycosides
24a and 24 b.
Anal. C7H12O6 (192.2): calc. C 43.75, H 6.29; found C 43.62, H
6.58.
Allyl (Methyl α-D-lyxofuranosid)uronate (19)
Prepared according to General Procedure C, from 18 (820 mg,
4.3 mmol); flash chromatography: petroleum ether/EtOAc (1:1);
yield: 756 mg (81%); colourless syrup; [a]D20 +101.4 (c = 1, CHCl3).
Anal. C9H14O6 (218.2): calc. C 49.54, H 6.47; found C 49.03, H
6.66.
Allyl (Methyl 2,3-di-O-benzoyl-α-D-lyxofuranosid)uronate (20)
To a solution of 19 (179 mg, 0.8 mmol) in anhyd pyridine and
CH2Cl2 (8 mL each) was added benzoyl chloride (0.24 ml, 2 mmol)
at 0¡C. The mixture was allowed to warm up to r.t. and stirred until
conversion was complete (TLC monitoring: petroleum ether/
EtOAc, 5:1). The solvents were evaporated by codistillation with
toluene in vacuo and the residue was purified by flash chromatog-
raphy (petroleum ether/EtOAc 15:1) to yield 284 mg (81%) 20 as a
colourless syrup; [a]D20 +12.0 (c = 1, CHCl3).
24a; yield: 1.53 g (28%); viscous oil; [a]D20 +56.0 (c = 1, CHCl3).
Anal. C11H16O8 (276.2): calc. C 47.83, H 5.84; found C 47.87, H 5.92.
24b; yield: 752 mg (14%); amorphous solid; [a]D20 Ð73.7 (c = 1,
CHCl3).
Anal. C23H22O8 (426.4): calc. C 64.78, H 5.20; found C 64.53, H
5.22.
Anal. C11H16O8 (276.2): calc. C 47.83, H 5.84; found C 48.34, H
6.22.
Allyl (Methyl 2,3-di-O-benzyl-α-D-lyxofuranosid)uronate (21)
To a solution of 19 (153 mg, 0.7 mmol) in anhyd dioxane (14 mL)
was added benzyl trichloroacetimidate (1 mL, 5.4 mmol) and trim-
ethylsilyl trifluoromethanesulfonate (1 drop) at 10ûC. The mixture
was allowed to warm up to r.t. and upon completion of conversion
(TLC monitoring: petroleum ether/EtOAc, 5:1) was stirred with py-
ridine (3 mL) for a few min. The solution was diluted with EtOAc
(30 mL), washed with H2O (2 × 40 mL), dried (MgSO4), and evap-
orated in vacuo. The residue after purification by flash chromatog-
raphy (petroleum ether/EtOAc, 10:1) yielded 180 mg (64%) 21 as a
colourless amorphous solid; [a]D20 +17.5 (c = 1, CHCl3).
Methyl (Methyl 2-O-acetyl-3-deoxy-â-L-glycero-pent-3-eno-
furanosid)uronate (25)
Prepared according to General Procedure D, from 24a (3.33 g,
12.1 mmol); flash chromatography: petroleum ether/EtOAc (5:1);
yield: 1.94 g (74%); colourless syrup;[a]D20 +107.0 (c = 0.5, CHCl3).
Anal. C9H12O6 (216.2): calc. C 47.79, H 5.35; found C 47.31, H
5.28.
Methyl (Methyl 2-O-acetyl-3-deoxy-â-L-erythro-pentofura-
nosid)uronate (26a) and Methyl (Methyl 2-O-acetyl-3-deoxy-α-
D-threo-pentofuranosid)uronate (26b)
Prepared according to General Procedure E, from 25 (1.94 g,
9.0 mmol); flash chromatography: petroleum ether/EtOAc (10:1).
Anal. C23H26O6 (398.5): calc. C 69.33, H 6.58; found C 69.48, H
6.30.
Synthesis 1999, No. 1, 121–137 ISSN 0039-7881 © Thieme Stuttgart · New York

Table 9 1H NMR Data of Hexopyranosiduronates 44–48 and 50–53
Prod- 1H NMR (400 MHz, CDCl3/TMS)
uct
d, J (Hz)
H-1
H-2
H-3
H-4eq
H-4ax
–
H-5
H-1'
H-2'
H-3'
Others
J1,2
J2,3
J3,4eq
J3,4ax
J4eq,4ax
J4eq,5
J4ax,5
44a
45
46
47
48
50
4.91
4.14, 4.47 (2 H)
4.00
4.72, 4.84 5.89–5.99 5.30, 5.40
3.33 (3 OH), 3.36
(OCH3)
–
–
–
–
–
–
–
4.83
4.90
4.86
4.85
4.31
3.61
3.69
3.26
4.10
4.85
3.72/3.80
3.82
–
3.72/3.80
4.13
3.96
4.07
–
4.72
4.64–4.75 5.89–5.99 5.25, 5.36
4.71 5.90–6.00 5.27–5.40
2.60, 2.76 5.81
5.90–6.00 5.26–5.39
3.46 (OCH3), 3.93
(3 OH)
3.6
0.5
3.5
0
9.7
2.8
9.5
6.4
9.2
–
9.2
–
–
4.1
–
9.7
–
4.24
–
–
3.36, 3.40, 3.42,
3.52 (OCH3)
6.6
–
–
3.38/3.52
3.85
3.38/3.52
3.45, 3.50, 3.52,
3.62 (OCH3)
9.1
–
–
–
9.8
–
3.57
1.77
–
5.04–5.13
–
3.31 (6 H), 3.32,
3.39, 3.66 (OCH3)
1.5
0
–
–
4.96
2.39
4.08
–
–
1.96, 1.99
7.6
5.1
12.5
0
2.0
(OCOCH3), 3.46,
3.72 (OCH3)
51
52
4.60
4.12
3.24
2.92
3.67
3.24
1.66
1.55
2.24
2.34
4.60
3.95
4.02–4.10 5.80–5.90 5.18–5.30
4.61 5.81–5.89 5.20, 5.26
3.49 (OCH3)
7.6
7.4
8.6
8.7
0
2.0
11.7
13.9
0
4.6
3.38, 3.49, 3.51
(OCH3)
5.4
11.5
2.3
12.2
53
4.55
3.10
3.43
2.18
1.98
–
2.51–2.64 5.68–5.78 5.11–5.15
3.41, 3.48, 3.50,
3.74 (OCH3)
4.6
7.1
4.6
11.2
13.7
–
–
a Coupling constants of 44 were insufficiently resolved.

PAPER
Sigmatropic Rearrangement of Allyl Ketene Acetals
133
Table 10 13C NMR Chemical Data of Hexopyranosiduronates 44–48 and 50–53
Prod- 13C NMR (100 MHz, CDCl3/TMS)
uct
d
C-1
C-2
C-3
C-4
C-5
C-6
C-7
C-8
C-9
Others
44
45
46
47
48
109.68
99.93
106.72
98.52
105.73
78.05, 79.98, 87.00
70.22
171.70
169.86
169.54
169.80
170.41
66.79
66.30
65.77
66.47
35.21
131.12
131.40
131.71
131.84
131.57
118.96
119.12
118.74
119.34
117.54
55.03 (OCH3)
55.85 (OCH3)
70.75, 71.49, 71.58, 73.56
79.91, 81.39, 84.59, 89.48
70.52, 81.68, 83.37
54.89, 57.55, 58.12, 59.95 (OCH3)
56.04, 59.60, 60.94, 61.40 (OCH3)
83.52, 83.94, 87.87
81.10
51.07, 51.87, 53.77, 56.17, 56.86
(OCH3)
a
50
101.02
69.34, 70.91
31.93
69.34
–
–
–
–
19.78, 19.85 (CH3), 51.40, 56.03
(OCH3), 168.19, 168.61, 169.25 (CO2)
51
52
53
102.77
104.56
101.04
69.47, 69.86
79.74, 83.36
75.72, 82.96
34.00
32.88
31.06
74.58
70.54
76.32
168.06
169.34
172.20
64.91
65.89
39.96
130.44
131.53
130.67
117.97
118.96
118.02
56.39 (OCH3)
57.12, 57.54, 60.66 (OCH3)
51.20, 55.84, 56.13, 58.02 (OCH3)
a Not distinguishable from other carboxyl signals.
26a; yield: 961 mg (49%), colourless syrup; [a]D20 +77.8 (c = 1,
CHCl3).
Methyl (Methyl 2-O-acetyl-3-deoxy-α-L-glycero-pent-3-eno-
furanosid)uronate (31)
Prepared according to General Procedure D, from 24b (2.06 g,
7.5 mmol); flash chromatography: petroleum ether/EtOAc (5:1);
yield: 1.08 g (65%) 31; colourless syrup; [a]D20 Ð120.0 (c = 1,
CHCl3).
Anal. C9H18O6 (218.2): calc. C 49.54, H 6.47; found C 49.21, H
6.55.
26b; yield: 561 mg (29%); colourless syrup; [a]D20 +54.5 (c = 1,
CHCl3).
Anal. C9H12O6 (216.2): calc. C 47.79, H 5.35; found C 47.52, H
5.33.
Anal. C9H18O6 (218.2): calc. C 49.54, H 6.47; found C 49.40, H
6.46.
Methyl (Methyl 2-O-acetyl-3-deoxy-â-D-threo-pentofura-
nosid)uronate (32)
Prepared according to General Procedure E, from 31 (1.08 g,
5 mmol); flash chromatography: petroleum ether/EtOAc (5:1);
yield: 899 mg (83%); colourless syrup;[a]D20 Ð145.0 (c = 1, CHCl3).
Allyl (Methyl 3-deoxy-â-L-erythro-pentofuranosid)uronate (27)
Prepared according to General Procedure C, from 26a (1.05 g,
4.8 mmol); flash chromatography: petroleum ether/EtOAc (2:1);
yield: 715 mg (74%); colourless syrup; [a]578 +96.5 (c = 1, CHCl3).
Anal. C9H14O5 (202.2): calc. C 53.46, H 6.98; found C 53.21, H
6.98.
Anal. C9H14O6 (218.2): calc. C 49.54, H 6.47; found C 49.60, H
6.57.
Allyl (Methyl 3-deoxy-2-O-methyl-â-L-erythro-pentofura-
nosid)uronate (28)
Prepared according to General Procedure F, from 27 (182 mg,
Allyl (Methyl 3-deoxy-â-D-threo-pentofuranosid)uronate (33)
Prepared according to General Procedure C, from 32 (899 mg,
4.1 mmol); flash chromatography: petroleum ether/EtOAc/MeOH
(10:10:1); yield: 770 mg (92%); colourless syrup; [a]D20 Ð129.4 (c =
1, CHCl3).
0.9 mmol); flash chromatography: petroleum ether/EtOAc (3:1);
20
yield: 133 mg (69%); colourless oil; [a] +13.5 (c = 0.2, CHCl3).
578
Anal. C10H16O5 (216.2): calc. C 55.55, H 7.46; found C 55.22, H
7.41.
Anal. C9H14O5 (202.2): calc. C 53.46, H 6.98; found C 52.94, H
7.27.
Allyl (Methyl 3-deoxy-α-D-threo-pentofuranosid)uronate (29)
Prepared according to the General Procedure C, from 26b (200 mg,
0.9 mmol); flash chromatography: petroleum ether/EtOAc/MeOH
(10:10:1); yield: 127 mg (68%); colourless syrup; [a]D20 +94.9 (c =
1, CHCl3).
Allyl (Methyl 3-deoxy-2-O-methyl-â-D-threo-pentofura-
nosid)uronate (34)
Prepared according to General Procedure F, from 33 (162 mg,
0.8 mmol); flash chromatography: petroleum ether/EtOAc (3:1);
yield: 124 mg (72%); colourless syrup; [a]D20 Ð224.0 (c = 1, CHCl3).
Anal. C9H14O5 (202.2): calc. C 53.46, H 6.98; found C 53.23, H 6.93.
Anal. C10H16O5 (216.2): calc. C 55.55, H 7.46; found C 55.27, H
7.70.
Allyl (Methyl 3-deoxy-2-O-methyl-α-D-threo-pentofura-
nosid)uronate (30)
Prepared according to General Procedure F, from 29 (202 mg,
1.1 mmol); flash chromatography: petroleum ether/EtOAc (3:1);
yield: 121 mg (51%); colourless syrup; [a]D20 +53.0 (c = 1, CHCl3).
Allyl (Methyl 3-deoxy-2-O-methoxymethyl-â-D-threo-pento-
furanosid)uronate (35)
A solution of 33 (162 mg, 0.8 mmol) in dimethoxymethane (8 mL)
¥
containing P4O10 (170 mg, 1.2 mmol) and BF3 OEt2 (2 drops) was
Anal. C10H16O5 (216.2): calc. C 55.55, H 7.46; found C 55.43, H 7.40.
stirred at r.t. overnight. The mixture was diluted with EtOAc
Synthesis 1999, No. 1, 121–137 ISSN 0039-7881 © Thieme Stuttgart · New York

Table 11 1H NMR Data of 2,6-Anhydrohexonates 55–60
Prod- 1H NMR (400 MHz, CDCl3/TMS)
uct
δ, J (Hz)
H-2
–
H-3ex H-3aq H-4
H-5
H-6eq H-6ax H-1'
H-2'
–
H-3'
–
Others
J2,3ax
J2,3eq
J3ax,3eq
J3ax,4
J3eq,4
J4,5
J5,6ax
J5,6eq
J6ax,6eq
55
6.08
5.07 4.92
3.98
4.18
4.07
4.07
4.34
3.31
3.89
3.16
4.22
–
2.01, 2.02 (OCOCH3),
3.77 (OCH3)
–
–
–
5.1
2.0
3.1
1.5
12.2
56a
56b
57
4.07 1.81
4.31 2.07
3.99 1.64
4.04 1.67
4.32 2.16
2.43
4.95 4.85
5.07 4.69
3.61 3.52
–
–
–
–
–
1.98, 1.99 (OCOCH3), 10.2
3.71 (OCH3)
3.1
3.0
2.5
3.4
3.6
–
13.2
11.2
13.0
13.2
13.2
14.4
13.2
10.2
6.9
5.1
3.2
5.1
4.4
4.6
0
8.7
2.9
8.4
8.7
2.2
9.7
9.0
5.1
0
11.7
13.0
11.5
15.7
11.7
12.9
10.9
2.16
2.31
2.44
2.72
–
2.11, 2.13 (OCOCH3), 11.0
3.80 (OCH3)
4.61
4.67
5.81– 5.19–
5.90 5.30
–
11.7
10.5
9.7
–
11.0
10.2
9.7
4.6
a
a
58
3.20–3.3588
5.88– 5.27– 3.44, 3.48 (OCH3)
5.98 5.35
–
–
b
a
59
5.47 5.21– 3.65
5.36
4.50–4.66
5.81– 5.21– 7.43, 7.54, 7.98 (Ar)
5.91 5.36
–
–
2.1
0
60a
60b
–
–
1.83
2.28– 3.43 3.06
2.39
3.76
4.09
3.94
2.28– 5.72– 4.96– 3.24, 3.35, 3.65
2.39
2.7
0
1.6
3.7
5.77
5.02
(OCH3)
b
a
a
1.25– 2.57
1.33
3.11–3.17
2.38
5.63– 4.99– 3.38, 3.39, 3.69
5.70 5.05 (OCH3)
–
–
–
4.1
–
–
a Not identified due to overlapping signals.
b Not resolved

PAPER
Sigmatropic Rearrangement of Allyl Ketene Acetals
135
Table 12. 13C NMR Chemical Data of 2,6-Anhydrohexonates 55–60
Prod- 13C NMR (100 MHz, CDCl3/TMS)
uct
δ
C-1
161.24
C-3
C-2
C-4
C-5
C-6
C-1'
–
C-2'
–
C-3'
–
Others
55
103.91
145.71
62.39, 65.43
63.76
19.83, 19.88 (CH3), 51.61
(OCH3), 168.41, 168.71 (CO2)
a
56a
56b
–
32.11
29.76
68.71, 69.97, 73.51
67.00, 71.57, 76.72
66.11
66.15
–
–
–
–
–
–
20.83, 20.93 (CH3), 52.46 (OCH3),
169.93, 170.07, 170.11 (CO2)
a
–
21.06, 21.41 (CH3), 52.80 (OCH3),
169.69, 170.29, 171.33 (CO2)
57
58
59
170.10
170.24
35.53
31.86
32.01
71.24, 72.50, 74.82
74.03, 78.47, 79.44
69.19, 70.23, 73.28
69.41, 66.05
65.88, 66.59
65.99, 66.07
131.36 119.27
–
131.57 119.11
57.08, 58.50 (OCH3)
a
b
–
–
119.31
128.47–133.62 (C-2', Ar), 165.55,
165.59, 169.52 (CO2)
60a
60b
172.64
172.80
30.23
34.99
75.76
79.86
72.60, 74.09
77.87, 78.35
60.50
63.93
43.81
43.41
131.08
130.40
117.39
118.15
50.68, 55.55, 55.98 (OCH3)
51.23, 56.21, 57.56 (OCH3)
a Not distinguishable from other carboxyl signals.
b Not distinguishable from aromatic signals.
(20 mL), washed with satd aq NaHCO3 solution (50 mL), and dried
(MgSO4). After evaporation in vacuo, the crude product was puri-
fied by flash chromatography (petroleum ether/EtOAc, 4:1) to af-
ford 35 (89 mg, 45%); colourless syrup; [a]D20 Ð78.7 (c = 1, CHCl3);
and its a-anomer (35 mg, 17%), which was not fully characterized.
91.17 (C-4 quart.), 107.19, 108.97 (C-1), 119.13 (C-3'), 131.65 (C-
2'), 171.30, 205.53 (C-5).
Due to its apparent instability, the compound could not be obtained
spectroscopically pure, and no other physical data were collected.
Efforts of further purification resulted in decomposition.
Anal. C11H18O6 (246.3): calc. C 53.65, H 7.37; found C 53.46, H
7.45.
Methyl (Methyl 3-deoxy-2-O-methyl-4-C-(prop-2-enyl)-α-D-
threo- and -â-L-erythro-pentofuranosid)uronate (38)
Allyl (Methyl 2-O-benzyl-3-deoxy-â-D-threo-pentofura-
nosid)uronate (36)
Prepared from 33 in analogy to 21 (340 mg, 1.7 mmol); flash chro-
matography: petroleum ether/EtOAc (10:1); yield: 263 mg (54%)
36; colourless syrup; [a]D20 Ð58.2 (c = 1, CHCl3).
Prepared according to General Procedure A, from 28 and 30, re-
spectively (108 mg, 0.5 mmol each); flash chromatography: petro-
leum ether/EtOAc (5:1); yield: 52 mg (45%) 38 from 28; 45 mg
(39%) 38 from 30; yellow syrup; 1:1 mixture of C-4 diastereomers.
Methyl (Methyl 3-deoxy-2-O-methyl-4-C-(prop-2-enyl)-â-D-
threo- and -α-L-erythro-pentofuranosid)uronate (39)
Prepared according to General Procedure A, from 34 (106 mg,
0.5 mmol); flash chromatography: petroleum ether/EtOAc (5:1);
yield: 62 mg (54%); yellow syrup; 1:1 mixture of C-4 diastere-
omers.
Anal. C16H20O5 (292.3): calc. C 65.75, H 6.90; found C 65.60, H
6.79.
Allyl (Methyl 3-deoxy-2-O-methyl-4-C-(methyl 3-deoxy-2-O-
methyl-â-L-erythro-pentodialdofuranosid-5-yl)-â-L-erythro- or
-α-D-threo-pentofuranosid)uronate (37)
A solution of diisopropylamine (100 µL, 0.8 mmol) in anhyd THF
(2 mL) and HMPA (0.5 mL) under argon was mixed with a 1.6 M
solution of BuLi in hexane (0.5 mL) and stirred for 10 min at r.t. A
solution of 28 (108 mg, 0.5 mmol) in THF (1 mL) and HMPA
(0.25 mL) was added dropwise at Ð78¡C. After stirring for 10 min
at Ð78¡C, chlorotrimethylsilane (125 µL, 1 mmol) was added, and
the mixture was allowed to warm up to r.t. and stirred for another
2 h. Following the addition of a 1 M solution of TBAF in THF
(1.2 mL) and further stirring at r.t. for 1 h, the mixture was diluted
with Et2O (20 mL) and washed with 1 M NaOH (20 mL). The ethe-
real layer was dried (MgSO4) and evaporated in vacuo. Purification
of the remaining crude product by flash chromatography (petroleum
ether/EtOAc, 5:1) yielded 37 (34 mg, 36%) as a yellow syrup.
1H NMR (400 MHz, CDCl3): d = 2.13 (m, 1 H, H-3), 2.50 (m, 1 H,
H-3), 2.59 (m, 1 H, H-3), 2.72 (m, 1 H, H-3), 3.25, 3.38, 3.39, 3.46
(4 s, 4 × 3 H, 4 OMe), 3.76 (m, 2 H, 2 H-2), 4.59Ð4.70 (m, 2 H, H-
1'), 4.93, 5.05 (2 s, 2 × 1 H, 2 H-1), 5.22Ð5.35 (m, 2 H, H-3'), 5.30
(s, 1 H, H-4), 5.89Ð5.91 (m, 1 H, H-2').
Methyl (Methyl 3-deoxy-2-O-methoxymethyl-4-C-(prop-2-enyl)-
â-D-threo- and -α-L-erythro-pentofuranosid)uronate (40)
Prepared according to General Procedure A, from 35 (75 mg,
0.3 mmol); flash chromatography: petroleum ether/EtOAc (5:1);
yield: 30 mg (38%); yellow syrup; 1:1 mixture of C-4 diastere-
omers.
Methyl (Methyl 2-O-benzyl-3-deoxy-4-C-(prop-2-enyl)-â-D-
threo- and -α-L-erythro-pentofuranosid)uronate (41)
Prepared according to General Procedure A, from 36 (150 mg,
0.5 mmol); flash chromatography: petroleum ether/EtOAc (5:1);
yield: 40 mg (26%); yellow syrup; 1:1 mixture of C-4 diastere-
omers.
Allyl (Methyl α-D-galactopyranosid)uronate (44)
Prepared according to General Procedure C, from 4217 (2.14 g,
9.6 mmol); flash chromatography: petroleum ether/EtOAc/MeOH (10:
10:1); yield: 1.82 g (71%); colourless syrup; [a]D20 Ð102.1 (c = 1,
CHCl3).
13C NMR (100 MHz, CDCl3): d = 32.92, 37.95 (C-3), 55.19, 55.39,
56.99, 57.42 (OCH3), 66.80 (C-1'), 81.26 (C-4), 83.70, 84.66 (C-2),
Anal. C10H16O7 (248.2): calc. C 48.39, H 6.50; found C 48.80, H
6.68.
Synthesis 1999, No. 1, 121–137 ISSN 0039-7881 © Thieme Stuttgart · New York

136
B. Werschkun, J. Thiem
PAPER
Allyl (Methyl α-D-glucopyranosid)uronate (45)
Anal. C11H14O7 (258.2): calc. C 51.16, H 5.46; found C 50.65, H
5.58.
Prepared according to General Procedure C, from 4318 (1.35 g,
6 mmol); flash chromatography: petroleum ether/EtOAc (3:1);
yield: 1.37 g (92%) 45; colourless crystals; mp 60 ûC (EtOAc/petro-
leum ether); [a]D20 +25.5 (c = 0.3, CHCl3).
Methyl 4,5-Di-O-acetyl-2,6-anhydro-3-deoxy-L-xylo-hexonate
(56a) and Methyl 4,5-Di-O-acetyl-2,6-anhydro-3-deoxy-L-lyxo-
hexonate (56b)
Prepared according to General Procedure E, from 55 (2.69 g,
10.4 mmol); flash chromatography: petroleum ether/EtOAc (5:1).
Anal. C10H16O7 (248.2): calc. C 48.39, H 6.50; found C 48.06, H
6.49.
Allyl(Methyl2,3,4-tri-O-methyl-α-D-galactopyranosid)uronate
(46)
56a; yield: 1.87 g (69%); colourless syrup; [a]D20 +57.2 (c = 1,
CHCl3).
Prepared according to General Procedure F, from 44 (500 mg,
2 mmol); flash chromatography: petroleum ether/EtOAc (4:1);
yield: 414 mg (71%); slightly yellow syrup; [a]D20 Ð118.5 (c = 1,
CHCl3).
Anal. C11H16O7 (260.2): calc. C 50.77, H 6.20; found C 50.77, H
6.40.
56b; yield: 622 mg (23%); colourless crystals; mp 107Ð108¡C
(EtOH); [a]D20 +57.5 (c = 1, CHCl3).
Anal. C13H22O7 (290.3): calc. C 53.79, H 7.64; found C 53.41, H
7.63.
Anal. C11H16O7 (260.2): calc. C 50.77, H 6.20; found C 50.82, H
6.27.
Allyl (Methyl 2,3,4-tri-O-methyl-α-D-glucopyranosid)uronate
(47)
Prepared according to General Procedure F, from 45 (248 mg,
1 mmol); flash chromatography: petroleum ether/EtOAc (10:1 to
8:1); yield: 200 mg (69%); colourless syrup; [a]D20 +51.7 (c = 0.5,
CHCl3).
Allyl 2,6-Anhydro-3-deoxy-L-xylo-hexonate (57)
Prepared according to General Procedure C, from 56a (2.60 g,
10 mmol); flash chromatography: petroleum ether/EtOAc/MeOH
(10:10:1); yield: 1.72 g (85%); colourless syrup; [a]D20 Ð4.0 (c = 1,
CHCl3).
Anal. C9H14O5 (202.2): calc. C 53.46, H 7.88; found C 53.30, H
7.79.
Anal. C13H22O7 (290.3): calc. C 53.79, H 7.64; found C 53.35, H
7.61.
Allyl 2,6-Anhydro-3-deoxy-4,5-di-O-methyl-L-xylo-hexonate
(58)
Methyl (Methyl 2,3,4-tri-O-methyl-5-C-(prop-2-enyl)-α-D-
galactopyranosid)uronate (48)
Prepared according to General Procedure F, from 57 (263 mg,
1.3 mmol); flash chromatography: petroleum ether/EtOAc (5:1);
yield: 156 mg (52%); colourless syrup; [a]D20 +44.1 (c = 1, CHCl3).
Prepared according to General Procedure A, from 46 (169 mg,
0.5 mmol); flash chromatography: petroleum ether/EtOAc (10:1);
20
yield: 13 mg (7%) 48; yellow syrup; [a] Ð45.8 (c = 1, CHCl3).
578
Anal. C11H18O5 (230.3): calc. C 57.38, H 7.88; found C 57.38, H
7.81.
Methyl (Methyl 2,3-di-O-acetyl-4-deoxy-â-D-xylo-hexopyra-
nosid)uronate (50)
Prepared according to General Procedure E, from 4919 (1.09 g,
3.8 mmol); flash chromatography: petroleum ether/EtOAc (4:1 to
2:1); yield: 843 mg (77%); colourless syrup; [a]D20 Ð14.3 (c = 0.5,
CHCl3).
Allyl 2,6-Anhydro-4,5-di-O-benzoyl-3-deoxy-L-xylo-hexonate
(59)
Prepared in analogy to 20 from 57 (404 mg, 2 mmol); flash chroma-
tography: petroleum ether/EtOAc (5:1); yield: 501 mg (61%); co-
lourless syrup; [a]D20 +103.0 (c = 1, CHCl3).
Anal. C12H20O6 (260.3): calc. C 55.37, H 7.75; found C 55.03, H 7.69.
Anal. C23H22O7 (410.4): calc. C 67.31, H 5.40; found C 66.94, H
5.47.
Allyl (Methyl 4-deoxy-â-D-xylo-hexopyranosid)uronate (51)
Prepared according to General Procedure C, from 50 (1.19 g,
4.1 mmol); flash chromatography: petroleum ether/EtOAc/MeOH
(10:10:1); yield: 485 mg (51%); colourless syrup; [a]D20 Ð76.3 (c =
1, CHCl3).
Methyl 2,6-Anhydro-3-deoxy-4,5-di-O-methyl-2-C-(2-prope-
nyl)-L-xylo- and -lyxo-hexonate (60a and 60b):
Prepared according to General Procedure A, from 58 (115 mg,
0.5 mmol); flash chromatography: petroleum ether/EtOAc (15:1).
Anal. C10H16O6 (232.2): calc. C 51.72, H 6.94; found C 51.51, H 7.03.
60a; yield: 35 mg (28%); yellow syrup; [a]52708 +37.5 (c = 1, CHCl3).
60b; yield: 25 mg (20%); yellow syrup; [a]D20 +0.2 (c = 0.2, CHCl3).
Allyl (Methyl 4-deoxy-2,3-di-O-methyl-â-D-xylo-hexopyra-
nosid)uronate (52)
Prepared according to General Procedure F, from 51 (142 mg,
0.6 mmol); flash chromatography: petroleum ether/EtOAc (4:1);
yield: 106 mg (67%); colourless syrup; [a]D20 Ð36.1 (c = 1, CHCl3).
Crystallographic Data for Compound 16a
C15H24O6 (300.3): monoclinic; P21: a = 8.222(2), b = 10.229(2), c =
10.271(2) •; a = 90, b = 112.10(2), g = 90¡; V = 800.35(5) •3; Z =
2; dc = 1.246 g cmÐ3; F(000) = 324. Data were collected with an En-
raf Nonius CAD 4 diffractometer at 153(2) K using graphite mono-
chromated Cu-Ka radiation, l = 1.54178 •, µ = 0.797 mmÐ1; scan
range 4.65 < Θ < 76.62 ¡. 2021 Independent reflections were used
in the analysis. The structure was solved with SHELXS-97, refine-
ment was done with SHELXL-97 based on 198 parameters. Full
crystallographic details have been deposited at the Cambridge Crys-
tallographic Data Centre, Lensfield Road, Cambridge CB2 1EW,
UK. The deposition number is 101441.
Anal. C12H20O6 (260.3): calc. C 55.37, H 7.75; found C 55.29, H 7.81.
Methyl (Methyl 4-deoxy-2,3-di-O-methyl-5-C-(prop-2-enyl)-â-
D-xylo-hexopyranosid)uronate (53)
Prepared according to General Procedure A, from 52 (89 mg,
0.34 mmol); flash chromatography: petroleum ether/EtOAc (5:1);
20
yield: 10 mg (11%); yellow syrup; [a] Ð13.3 (c = 0.5, CHCl3).
578
Methyl 4,5-Di-O-acetyl-2,6-anhydro-3-deoxy-L-threo-hex-2-
enonate (55)
Prepared according to General Procedure D, from 5420 (4.05 g,
12.7 mmol); flash chromatography: petroleum ether/EtOAc (2:1);
yield: 3.08 g (94%); colourless syrup; [a]D20 +225.5 (c = 1, CHCl3).
Synthesis 1999, No. 1, 121–137 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Sigmatropic Rearrangement of Allyl Ketene Acetals
137
(9) Corey, E. J.; Gross, A. Tetrahedron Lett. 1984, 495.
(10) (a) Barton, D. H. R.; GŽro, S. D.; Quiclet-Sire, B.; Samadi, M.
References
(1) Varki, A. Glycobiology 1993, 3, 97.
Tetrahedron Asym. 1994, 5, 2123.
(2) (a) Fraser-Reid, B.; Tsang, R. In Strategies and Tactics in Or-
ganic Synthesis; Lindberg, T., Ed.; Academic: Orlando, FL,
1989; Vol. 2, pp 123Ð162.
(b) Kunz, H.; RŸck, K. Angew. Chem. 1993, 105, 355; Angew.
Chem., Int. Ed. Engl. 1993, 32, 336.
(3) (a) Rhoads, S. J.; Raulins, N. R. Org. React. 1975, 22, 1.
(b) Bennett, G. B. Synthesis 1977, 589.
(b) Walton, E.; Rodin, J. O.; Stammer, C. H.; Holly, F. W.;
Folkers. K. J. Am. Chem. Soc. 1958, 80, 5168.
(11) (a) Bartlett, P. A.; Tanzella, D. J.; Barstow, J. F. J. Org. Chem.
1982, 47, 3941.
(b) Kallmerten, J.; Gould, T. J. Tetrahedron Lett. 1983, 24,
5177.
(c) Burke, S. D.; Fobare, W. F.; Pacofsky, G. J. J. Org. Chem.
1983, 48, 5221.
(c) Ziegler, F. E. Acc. Chem. Res. 1977, 10, 227.
(d) Bartlett, P. A. Tetrahedron 1980, 36, 3.
(e) Hill, R. K. In Asymmetric Synthesis, Vol. 3; Morrison, J.
D., Ed.; Academic: Orlando, FL, 1984; p 503.
(f) Ziegler, F. E. Chem. Rev. 1988, 88, 1423.
(g) Wipf, P. In Comprehensive Organic Synthesis, Vol.5;
Trost, B. M.; Fleming, I., Eds.; Pergamon: Oxford, 1991;
p 827.
(12) Wilcox, C. S.; Babston, R. E.; Lynch, V. Tetrahedron Lett.
1989, 30, 447.
(13) (a) Vittorelli, P.; Winkler, T.; Hansen, H.-J.; Schmid, H. Helv.
Chim. Acta 1968, 51, 1457.
(b) BŸchi, G.; Powell, J. E. J. Am. Chem. Soc. 1970, 92, 3126.
(c) Hansen, H.-J., Schmid, H. Tetrahedron 1974, 30, 1959.
(d) Vittorelli, P.; Hansen, H.-J.; Schmid, H. Helv. Chim. Acta
1975, 58, 1293.
(4) (a) Ireland, R. E.; Mueller, R. H.; Willard, A.K. J. Am. Chem.
Soc. 1976, 98, 2868.
(b) Pereira, S.; Srebnik, M. Aldrichim. Acta 1993, 26, 17.
(5) (a) Ireland, R. E.; Wilcox, C. S.; Thaisrivongs, S.; Vanier, N.
R. Can. J. Chem. 1979, 57, 1743.
(e) Chapleo, C. B.; Hallett, P.; Lythgoe, B.; Waterhouse, I.;
Wright, P. W. J. Chem. Soc., Perkin Trans. 1 1977, 1211.
(f) Cave, R. J.; Lythgoe, B.; Metcalfe, D. A.; Waterhouse, I.
J. Chem. Soc., Perkin Trans. 1 1977, 1218.
(14) Schmidt, R. R.; Hermentin, P. Chem. Ber. 1979, 112, 3616.
(15) Gorin, P. A.; Perlin, A. S. Can. J. Chem. 1956, 34, 693.
(16) Kiss, J. Adv. Carbohydr. Chem. Biochem. 1974, 29, 229.
(17) (a) Ehrlich, F.; Guttmann, R. Ber. Dtsch. Chem. Ges. 1933,
66, 220.
(b) Jones, J. K. N.; Stacey, M. J. Chem. Soc. 1947, 1340.
(18) Owen, L. N.; Peat, S.; Jones, W. J. G. J. Chem. Soc. 1941, 339.
(19) Schmidt, H. W. H.; Neukom, H. Tetrahedron Lett. 1969,
2011.
(b) Ireland, R. E., Thaisrivongs, S.; Vanier, N.; Wilcox, C. S.
J. Org. Chem. 1980, 45, 48.
(c) Ireland, R. E.; Vevert, J.-P. J. Org. Chem. 1980, 45, 4259.
(d) Ireland, R. E.; Vevert, J.-P. Can. J. Chem. 1981, 59, 572.
(e) Ireland, R. E.; Daub, J. P. J. Org. Chem. 1981, 46, 479.
(f) Ireland, R. E.; Wuts, P. G.; Ernst, B. J. Am. Chem. Soc.
1981, 103, 3205.
(g) Curran, D. P.; Suh, Y.-G. Carbohydr. Res. 1987, 171, 161.
(6) (a) Ireland, R. E.; Norbeck, D. W. J. Am. Chem. Soc. 1985,
107, 3279.
(b) Ireland, R. E.; Norbeck, D. W.; Mandel, G. S.; Mandel, N.
S. J. Am. Chem. Soc. 1985, 107, 3285.
(7) Gable, R. W.; McVinish, L. M.; Rizzacasa, M. A. Aust.
J. Chem. 1994, 47, 1537.
(8) Brimacombe, J. S.; Hunedy, F.; Tucker, L. C. N. J. Chem. Soc.
(20) Ferrier, R. J.; Furneaux, R. H. J. Chem. Soc., Chem. Commun.
1977, 332.
(21) (a) AugŽ, J.; David, S. Carbohydr. Res. 1977, 59, 255.
(b) Kocienski, P.; Pant, C. Carbohydr. Res. 1982, 110, 330.
(22) Hashimoto, N.; Aoyama, T.; Shioiri, T. Chem. Pharm. Bull.
1981, 29, 1475.
(C) 1968, 1381.
Synthesis 1999, No. 1, 121–137 ISSN 0039-7881 © Thieme Stuttgart · New York