C-C bond formation by sequential intramolecular hydrogen atom transfer/intermolecular radical allylation reaction in carbohydrate systems

Article abstract of DOI:10.1002/ejoc.201200300

A tandem 1,5-, 1,6- or 1,8-intramolecular hydrogen atom transfer (HAT)/intermolecular radical allylation using mono- or (1→4)-O-disaccharide models is described. It is a simple, sequential, stereocontrolled methodology for C-C bond formation by remote free radical functionalization, giving access to interesting carbohydrate structures carrying differently functionalized tethers. A tandem intramolecular hydrogen atom transfer (HAT)/intermolecular radical allylation is described. This process occurs by a completely regio- and stereoselective route that provides a simple methodology for C-C bond formation on remote positions without modifying the remainder of the carbohydrate. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Full text of DOI:10.1002/ejoc.201200300

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FULL PAPER
DOI: 10.1002/ejoc.201200300
C–C Bond Formation by Sequential Intramolecular Hydrogen Atom Transfer/
Intermolecular Radical Allylation Reaction in Carbohydrate Systems
Elisa I. León,[a] Ángeles Martín,*[a] Inés Pérez-Martín,*[a] Luís M. Quintanal,[a] and
Ernesto Suárez[a]
Keywords: Carbohydrates / Radical reactions / Hydrogen transfer / Radical allylation / C–C coupling
A tandem 1,5-, 1,6- or 1,8-intramolecular hydrogen atom
transfer (HAT)/intermolecular radical allylation using mono-
or (1Ǟ4)-O-disaccharide models is described. It is a simple,
sequential, stereocontrolled methodology for C–C bond for-
mation by remote free radical functionalization, giving ac-
cess to interesting carbohydrate structures carrying dif-
ferently functionalized tethers.
anomeric centre, and the resulting C-radical intermediate
could be added intermolecularly to allylstannane to give the
corresponding C-ketoside as depicted in Scheme 1. The ste-
reochemistry of the quaternary carbon atom, carrying two
differently functionalized carbon tethers, is stereoelectron-
ically controlled and independent of that of the starting iso-
mer.
Introduction
The use of radical methods in carbohydrate chemistry
has been recently and thoroughly reviewed.[1] Furthermore,
a number of reviews have arisen where the main topic fo-
cuses on inter- and intramolecular carbon–carbon bond-
forming radical reactions, with emphasis placed on the
preparation of C-glycosides, C-ketosides, C-disaccharides,
branched-chain sugars, and carbocycles.[2–7] However, the
regioselective generation of C-radicals in specific nonacti-
vated positions of the sugar skeleton is not an easy task
unless it is conducted intramolecularly. In this sense, remote
free radical functionalization, especially carbon–carbon
bond formation, on unactivated carbon atoms by intramo-
lecular hydrogen atom transfer (HAT) reactions might be a
valuable methodology.[8] The transposition of a radical cen-
tre from an oxygen atom to a remote nonactivated carbon
atom offers possibilities for the introduction of different
functional groups,[1,9] or to form new C–C bonds otherwise
difficult to achieve, particularly in carbohydrate struc-
tures.[10,11] However, despite its potential usefulness, this ap-
proach has not been widely employed, probably because of
the difficulties encountered in the preparation of alkoxyl
radicals under nonoxidative conditions.[12] Related to this,
we have recently envisaged a straightforward methodology
for the preparation of C-ketosides using an intramolecular
HAT reaction under reductive conditions as the key step
in elaborating monosaccharide systems.[10a] A conveniently
disposed alkoxyl radical generated from a phthalimide sup-
ported on a three-carbon chain of a C-glycoside, would
trigger the intramolecular HAT reaction at the pseudo-
Scheme 1. Synthesis of C-ketosides by sequential HAT/radical
allylation. ATBT = allyltri-n-butyltin. AIBN = azobis(isobutyro-
nitrile).
Results and Discussion
We reasoned that our previous work would be incom-
plete if we did not perform a similar study starting from O-
glycosides, analogous to the C-glycosides employed be-
fore.[10a] We did similar work a few years ago with the radi-
cal study of the conformational differences between C- and
O-glycosides when treated with tri-n-butyltin hydride
(TBTH)/AIBN.[13] In order to acquire additional insight
into the HAT reaction mechanism, we decided to investi-
gate the reaction course of the sequential intramolecular
HAT/intermolecular allylation in O-glycosides. For this
[a] Instituto de Productos Naturales y Agrobioogía del C.S.I.C
Carretera de la Esperanza 3, 38206 La Laguna, Tenerife, Spain
Fax: +34-922-260-135
E-mail: angelesmartin@ipna.csic.es
ines@ipna.csic.es
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200300.
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purpose, we have used the fragmentation of N-hydroxy- Table 1. Intramolecular HAT/intermolecular radical allylation of
O-phthalimido-O-glycosides.
phthalimide derivatives to generate the alkoxyl radicals and
allyltri-n-butyltin (ATBT) as a radical trap. The synthesis
of the O-phthalimido derivatives was readily achieved from
the corresponding alcohol and N-hydroxyphthalimide un-
der Mitsunobu conditions in accordance with a previously
described protocol.[14] In our earlier work with C-glycos-
ides, it was observed that when phthalimide 1 was treated
with ATBT/AIBN, product 2 was obtained resulting from
the regio- and stereoselective functionalization at C-1
(Scheme 2).[10a] However, the thermally initiated reaction of
phthalimide 3 with ATBT/AIBN gave 4 in 48% yield as a
mixture of diastereomers (inseparable by ordinary column
chromatography) and 10% of prematurely reduced alcohol
(Scheme 2; Table 1, Entry 1). Product 4 resulted from the
intramolecular 1,5-HAT at C-1, giving a C-radical suffi-
ciently stable to undergo a subsequent β-fragmentation to
generate a C-5 radical, which was finally trapped by ATBT.
[a] The phthalimide precursor (1 mmol) in dry benzene (10 mL)
containing ATBT (10 mmol) was refluxed, and AIBN (0.01 mmol)
was added every hour until the starting material was completely
consumed. [b] Previously reduced alcohol was also obtained in 10–
39% yield.
sition state (TS). The reaction with the C-counterpart 7
happened fairly well and gave
8
in 35% yield
Scheme 2. Sequential HAT/radical allylations of C- and O-glycos-
ides derived from d-mannopyranose with four-atom tethers. ATBT
= allyltri-n-butyltin. AIBN = azobis(isobutyronitrile).
(Scheme 3).[10a] Unfortunately, direct allylation of the O-
radical intermediate derived from 10 occurred, giving 11 in
20% yield together with the prematurely reduced alcohol in
Curiously, although the resulting products came from 39% yield (Table 1, Entry 3). A possible explanation could
HAT at C-1, no products derived from radical quenching be the destabilizing electronic interactions between the allyl-
at this carbon atom were obtained, as was observed for the stannyl radical intermediates and the nonbonding electron
C-glycoside counterpart 1 (Scheme 2). Probably, this dis- pairs of the oxygen atom in the glycosidic tether, which in
parity between C- and O-glycosides was due to the presence some way could disfavour the HAT at C-1, directing the
of the exo-anomeric effect in the O-glycoside precursors, reaction to the premature capture of the starting O-radical.
which renders the C-1 radical stable enough to promote the It is interesting to note that when the same starting phthal-
intramolecular β-fragmentation reaction of the C5–O bond imides 7 and 10 were treated with the sterically less hin-
before being trapped by the allylstannane. At the same time, dered tri-n-butyltin hydride (TBTH) different results were
possible electronic interactions between the nonbonding obtained. Radical abstraction in the intermediate derived
electron pairs of the O-glycoside fragment and the stann- from 7 was successfully and exclusively achieved at C-1 giv-
ylated radical intermediates could support the radical frag- ing 9 by a 1,6-HAT for the more flexible C-glycoside. On
mentation to the detriment of the allyl trapping at C-1.
the other hand, radical abstraction in the intermediate de-
We also synthesized tetraacetate 5. The presence of such rived from 10 occurred mainly at C-5 by a 1,8-HAT, afford-
electron-withdrawing groups (EWGs) should deactivate the ing products 13 in 27% yield, together with a 13% yield of
hydrogen atoms for abstraction by the electrophilic alkoxyl the C-1-inverted derivative 12 (Scheme 3).[13] In our opin-
radicals (Table 1, Entry 2).[15] In fact, only product 6, origi- ion, this disparity in selectivity was probably caused by the
nating from direct allylation of the O-radical intermediate, different steric natures of the corresponding stannylated
was obtained in low yield, and no product derived from radical intermediates resulting from TBTH and ATBT
HAT was observed, confirming such a deactivation. Sub- treatments.
sequently, the reaction was also extended to isomer 10,
Next, we studied the HAT of the α- and β-isomers of d-
where the additional carbon atom in the tether would re- glucose derivatives 14 and 17. We observed that in these
quire a less-favoured HAT through a seven-membered tran- cases, an inseparable mixture of epimers 16 was mainly ob-
2
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C–C Bond Formation in Carbohydrate Systems
Scheme 3. Sequential 1,6-HAT/radical allylation of C- and O-glycosides derived from d-mannopyranose with five-atom tethers. TBTH =
tri-n-butyltin hydride.
Table 2. Intramolecular HAT/intermolecular radical allylation of O-phthalimido-O-glycosides.
[a] The phthalimide precursor (1 mmol) in dry benzene (10 mL) containing ATBT (10 mmol) was refluxed, and AIBN (0.01 mmol) was
added every hour until the starting material was consumed. [b] Previously reduced alcohol was also obtained in 3–10% yield. [c] 5 equiv.
of ATBT and 10 mL/mmol PhH were employed. [d] 5 equiv. of ATBT and 30 mL/mmol PhH were employed.
tained, derived from the sequential 1,5-HAT at C-1, β-frag- and 3). It was observed that smaller amounts of ATBT,
mentation and radical allyl trapping at C-5 (Table 2, En- such as 5 equiv. instead of 10, gave much more β-frag-
tries 1–4), as was previously observed in Entry 1, Table 1. mented product 16 relative to 1-allyl product 15 or prema-
However, in these cases, product 15, resulting from 1,5- turely reduced alcohol (Table 2, Entry 2). Moreover, when
HAT at C-1 and subsequent radical allylation was also the benzene dilution was increased to 30 mL/mmol and
achieved as expected, together with a small amount of 5 equiv. of ATBT was added, only β-fragmented product 16
prematurely reduced alcohol. It is interesting to note that was obtained in 50% yield, which shows that stabilization
regardless of the stereochemistry at the anomeric centre of of the C-1 radical was enhanced, favouring the intramolecu-
the phthalimide precursors (α- or β-isomer), the C-radical lar rupture of the C5–O bond before being trapped by the
quenching occurred stereoselectively along the axial direc- allylstannane (Table 2, Entry 3). Reactions with dilutions
tion, consistent with previous studies.[16] Since electrophilic Ͼ30 mL/mmol did not enhance the yield of the fragmented
radicals abstract axial hydrogen atoms much faster than the product.
equatorial ones, it is not surprising that the reaction of the
β-isomer 17 gave somewhat better results (Table 2, En- methodology to functionalize specific (1Ǟ4)-O-disacchar-
try 4).[17]
ide systems that fulfill the stereochemical and conforma-
We next focused our attention on applying this sequential
Additionally, dilution experiments were made with pre- tional requirements [i.e., with the correct relative stereo-
cursor 14 in order to analyze the influence of concentration chemistry at the four chiral centers (C-4, C-5, C-1Ј and C-
over the course of the radical reaction (Table 2, Entries 2 5Ј)] to carry out long-distance HAT exclusively at C-5Ј
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E. I. León, Á. Martín, I. Pérez-Martín, L. M. Quintanal, E. Suárez
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through a nine-membered transition state.[9a,18] Accord- minor products resulted from the 1,8-HAT, which suggests
ingly, switching the (1Ǟ4)-O-disaccharide structure with that the electron-withdrawing acetyl group at C-4Ј could
the requisites mentioned before (Scheme 4).
somehow inhibit hydrogen abstraction at C-5Ј. O-Allyl de-
rivative 23 came from the early quenching of the O-radical
by allylstannane, while 24 probably resulted from the radi-
cal reduction with ATBT of a feasible aldehyde intermedi-
ate.[20] The stereochemistry at C-6 was tentatively estab-
lished as (S) according to the guidelines of the Felkin–Anh
rule for radicals.[21]
To better understand the scope and stereoselectivity of
this C-5Ј radical stannane quenching, we prepared α-d-
Talp-(1Ǟ4)-α-d-Glcp 25 (Table 3, Entry 3). In this case 26
was obtained in 53% yield as an inseparable (by ordinary
column chromatography) mixture of epimers at C-5Ј, to-
gether with the corresponding prematurely reduced alcohol
in 10% yield. Possibly, the presence of the three axial sub-
stituents of the α-d-talose ring could trigger a modest chair
inversion, yielding a small amount of (5ЈR) derivative,
which would result, as expected, from the axial quenching.
Next, acetylated α-d-Glcp-(1Ǟ4)-β-d-Glcp derivative (β-
maltose) 27 was submitted to the radical sequence. Unfor-
tunately, no products were obtained from the HAT, but
rather from β-fragmentation followed by allylation (Table 3,
Entry 4), in contrast to the good results observed with the
TBTH/AIBN treatment.[18b] Products 28 were generated in
Scheme 4. Sequential intramolecular 1,8-HAT/intermolecular radi-
cal allylation of O-phthalimide precursors in (1Ǟ4)-O-disacchar-
ides.
First, we prepared a pair of α-l-Rhap-(1Ǟ4)-α-d-Galp 68% yield as an inseparable mixture of diastereomers, to-
disaccharides, which gave good results with TBTH/AIBN gether with an 11% yield of the prematurely reduced
treatment.[18] Phthalimides 18 and 21 were successfully syn- alcohol. The stereochemistry at C-5 of the major product
thesized and submitted to the intramolecular HAT/inter- was tentatively established as (R) according to the NOE
molecular radical allylation reaction, with ATBT and correlation observed between 5-H and 1- and 3-H. Simi-
AIBN in dry benzene at reflux (Table 3, Entries 1 and 2). larly, methylated derivative 29 also gave 30 as a mixture
Precursor 18 gave a mixture of two compounds 19 and 20, of epimers in 35% yield, in which NOE interactions were
with a global yield of 87% as a result of the 1,8-HAT reac- observed for the major isomer (5R) between 5-H and 3-H.
tion. The major product 19 was derived from the intramo- The corresponding prematurely reduced alcohol was also
lecular 1,8-HAT to give a C-5Ј radical intermediate, which produced in 9% yield (Table 3, Entry 5). The main product
was intermolecularly trapped by allylstannane. This com- consisted of the homoallylic alcohol 31 which, as with prod-
pound was obtained as a single diastereoisomer within the uct 24 (Table 3, Entry 2), probably resulted from the radical
1
detection limits of H and 13C NMR spectroscopy, by the reduction with ATBT of a feasible aldehyde intermediate.
analysis of the crude reaction mixtures. The stereochemistry As previously, the stereochemistry at C-6 was tentatively
at the quaternary centre was tentatively assigned as (R) on assigned as (S) according to the Felkin–Anh rule for radi-
the basis of the NOE interaction observed between 4Ј-H cals.[21] This result is consistent with that obtained for d-
and 6Ј-Me, showing that the radical quenching took place mannose derivative 10 (Table 1, Entry 3), where the ex-
axially as expected.[19] On the other hand, the minor prod- pected 1,8-HAT was also not observed when treated with
uct 20, which involves a 4Ј-deoxygenated carbon atom and ATBT; probably due to the hindrance and instability of the
a 1,3,5-trioxocane ring as principal features, could be ob- supposed allylated stannyl intermediate resulting from the
tained by a plausible mechanism, which consists of a 5Ј- HAT.
radical reductive elimination to give a 4Ј-enol ether and
Next, the question arose as to whether the substituent at
subsequent alcohol addition. Interestingly, the oxygen atom C-5Ј in the hexopyranose disaccharide models could some-
at C-6 acted with an umpolung reactivity during the reac- how hinder the intramolecular abstraction and subsequent
tion, first as an electrophilic alkoxyl radical and later as a allylation and thereby favour other radical processes. The
nucleophile.
absence of such a substituent would reduce the steric hin-
Acetylated derivative 21 also gave the expected allyl drance at C-5Ј. At the same time, this would be detrimental
product 22 in 42% yield as a single diastereomer with a to the stability of the corresponding C-radical, because a
configuration at C-5Ј determined as (R) on the basis of the secondary C-5Ј-radical would be generated instead of a ter-
NOE interaction observed between 4Ј-H and 6Ј-Me tiary one. To test this, we prepared α-d-Lyxp-(1Ǟ4)-α-d-
(Table 3, Entry 2). Moreover, three other minor products, Glcp 32, a pentopyranose derivative with no substitution at
23, 24 and prematurely reduced alcohol, were also obtained C-5Ј, and submitted it to the HAT/radical allylation condi-
in 11%, 10% and 14% yields, respectively. None of the tions (Table 4, Entry 1). An inseparable mixture of allyl epi-
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C–C Bond Formation in Carbohydrate Systems
Table 3. Intramolecular 1,8-HAT/intermolecular radical allylation of O-phthalimido-(1Ǟ4)-O-disaccharides.
[a] Previously reduced alcohol was also obtained in 10–14% yield.
mers at C-5Ј, 33, was obtained in 29% yield together with view of this result, it appears that the presence of any group
the O-allyl derivative 34 in 17% yield (resulting from the at C-5Ј apparently does not have a crucial effect on HAT,
early quenching of the O-radical by allylstannane) and the because C-5Ј-allyl product 33 was produced, although in
prematurely reduced alcohol generated in 29% yield. In lower yield.
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Table 4. Intramolecular 1,8-HAT/intermolecular radical allylation of O-phthalimido-(1Ǟ4)-O-disaccharides.
[a] Previously reduced alcohol was also obtained in 12–29% yield.
Until now, only pento- and hexopyranose models have obtained for the methylated phthalimide 38, which also
been researched. Hence we thought that to complete the gave the C-4Ј-allyl products 39 and 40 in 51% global yield.
study, pento- and hexofuranose models should be also ex- The stereochemistry at C-4Ј was well defined by NOE inter-
amined where, unlike pyranosyl radicals, steric effects seem actions between 6Ј-H and 3Ј-H for 39 and 5Ј-H and 1Ј-H
to control the stereoselectivity.[10a,22,23] We prepared the for 40, confirming that this time the allylation took place
acetylated pentofuranose α-d-Araf-(1Ǟ4)-α-d-Glcp 35, slightly more favourably on the less hindered β-face. O-Allyl
which was submitted to the HAT/allylation standard condi- product 41 was also generated in 21% yield, together with
tions, giving rise to C-4Ј-allyl derivatives 36 and 37 in 52% the previously reduced alcohol in 22% yield (Table 4, En-
global yield, together with the corresponding prematurely try 3).
reduced alcohol in 12% (Table 4, Entry 2). The stereochem-
Finally, the hexofuranose α-d-Manf-(1Ǟ4)-α-d-Glcp 42
istry at the quaternary centre was established by the NOE was studied, giving as expected an inseparable mixture of
correlation observed between 6Ј-H and 2Ј-H in 36 and be- allyl epimers 43 in 52% yield together with O-allyl deriva-
tween 6Ј-H and 3Ј-H in 37. Almost the same result was tive 44 obtained in 22% yield (Table 4, Entry 4).
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C–C Bond Formation in Carbohydrate Systems
dry benzene (10 mL) was treated with allyltri-n-butyltin (10 mmol)
and AIBN (0.01 mmol) and heated at reflux for a specific period
of time (Tables 1, 2, and 3). When the starting material was totally
consumed, the reaction mixture was poured directly onto a silica
gel chromatography column [n-hexanes/EtOAc + KF (10% weight
of the employed SiO2)].
Conclusions
This procedure provides a simple stereocontrolled meth-
odology for C–C bond formation by a remote free radical
functionalization. The resulting interesting carbohydrate
structures may be useful as scaffolds and synthetic building
blocks. To the best of our knowledge, no precedents exist
for this tandem intramolecular HAT/intermolecular allyl-
ation reaction, with the exception of our preliminary report
on C-glycosides. In this present work, we have extended this
methodology to more complex O-glycosides and (1Ǟ4)-O-
disaccharide structures in order to study the influence of
the oxygen atom of the O-glycosidic bond over the course
of the sequential process.
In the case of four-atom O-glycosides, HAT at C-1 was
less efficient due to a more restricted conformation com-
pared to its C-glycoside analogues. Also, because of pos-
sible electronic interactions between the nonbonding elec-
tron pairs of the O-glycoside fragment and the stannylated
radical intermediates, a radical evolution by means of a β-
fragmentation reaction was observed, giving mainly the
more stable C-5 radical, which was trapped by ATBT to
yield a mixture of diastereomers. When a five-atom O-
glycoside was submitted to the ATBT/AIBN protocol, the
HAT reaction was expected to proceed preferentially at C-
5 as occurred with the TBTH/AIBN treatment, but because
of the steric hindrance of the possible allylstannylated inter-
mediate, in this case no abstraction took place, and the O-
radical was prematurely trapped.
2-Hydroxyethyl
5-Allyl-5-deoxy-2,3,4,6-tetra-O-methyl-D-lyxo-
hexonate (4): Compound 4 was obtained as a colourless oil in 48%
yield as a diastereomeric mixture (1.1:1). 1H NMR (500 MHz): δ
= 1.96–2.05 (m, 2 H), 2.16–2.22 (m, 3 H), 2.27 (m, 1 H), 2.35 (br.
s, 2 H), 2.29 (s, 3 H), 3.34 (s, 3 H), 3.34–3.38 (m, 2 H), 3.39 (s, 3
H), 3.41 (s, 3 H), 3.46 (s, 3 H), 3.48 (s, 6 H), 3.52 (s, 3 H), 3.57–
3.59 (m, 2 H), 3.63 (dd, J = 7.2, 3.4 Hz, 2 H), 3.67 (dd, J = 5.6,
4.4 Hz, 1 H), 3.77–3.85 (m, 4 H), 3.89 (d, J = 3.4 Hz, 1 H), 4.04
(d, J = 4.4 Hz, 1 H), 4.13 (ddd, J = 11.6, 5.6, 3.7 Hz, 1 H), 4.27
(dd, J = 6.3, 3.5 Hz, 1 H), 4.30 (dd, J = 6.0, 3.2 Hz, 1 H), 4.39–
4.45 (m, 2 H), 5.01–5.09 (m, 4 H), 5.72–5.83 (m, 2 H) ppm. 13C
NMR (125.7 MHz): δ = 30.4 (CH2), 33.3 (CH2), 40.2 (CH), 40.3
(CH), 58.2 (CH3), 58.4 (CH3), 58.6 (2ϫ CH3), 60.4 (CH2), 60.5
(CH2), 60.7 (CH3), 60.8 (CH3), 61.0 (CH3), 61.4 (CH3), 66.5 (CH2),
66.8 (CH2), 71.5 (CH2), 72.4 (CH2), 81.0 (CH), 81.4 (CH), 81.5
(CH), 81.7 (CH), 84.3 (CH), 84.9 (CH), 116.4 (CH2), 116.6 (CH2),
136.7 (2ϫ CH), 169.8 (C), 171.1 (C) ppm. IR (CCl ): ν = 3480,
˜
4
2929, 1760, 1450 cm–1. MS (ESI+): m/z (%) = 343 (100) [M + Na]+.
HRMS (ESI+): calcd. for C15H28NaO7 [M + Na]+ 343.1733; found
343.1730. C15H28O7 (320.38): calcd. C 56.23, H 8.81; found C
56.26, H 8.55.
2-(Allyloxy)ethyl 2,3,4,6-Tetra-O-acetyl-α-D-mannopyranoside (6):
Compound 6 was obtained as an amorphous solid in 33% yield
1
from 5. [α]D = +20.6 (c = 0.17, CHCl3). H NMR: δ = 1.99 (s, 3
H), 2.03 (s, 3 H), 2.10 (s, 3 H), 2.15 (s, 3 H), 3.61–3.63 (m, 2 H),
3.66 (m, 1 H), 3.82 (ddd, J = 9.6, 5.3, 4.5 Hz, 1 H), 4.02 (ddd, J =
5.6, 1.6, 1.6 Hz, 2 H), 4.05–4.12 (m, 2 H), 4.28 (dd, J = 12.2,
5.0 Hz, 1 H), 4.88 (d, J = 1.6 Hz, 1 H), 5.19 (dddd, J = 10.3, 1.3,
1.3, 1.3 Hz, 1 H), 5.25–5.29 (m, 2 H), 5.30 (dd, J = 3.4, 1.8 Hz, 1
H), 5.37 (dd, J = 9.8, 3.4 Hz, 1 H), 5.89 (dddd, J = 17.2, 10.3, 5.6,
5.6 Hz, 1 H) ppm. 13C NMR: δ = 20.7 (2ϫ CH3), 20.7 (CH3), 20.9
(CH3), 62.4 (CH2), 66.2 (CH), 67.4 (CH), 68.4 (CH2), 68.8 (CH),
69.1 (CH), 69.6 (CH2), 72.2 (CH2), 97.7 (CH), 117.1 (CH2), 134.5
In the case of (1Ǟ4)-O-disaccharides, the 6-O-yl radical
triggered a 1,8-HAT reaction by exclusive abstraction of 5Ј-
H on the pyranose and 4Ј-H on the furanose derivatives
giving a C-radical which was mostly axially trapped by
ATBT.
Experimental Section
(CH), 169.7 (C), 169.9 (C), 170.0 (C), 170.7 (C) ppm. IR (CCl ): ν
˜
4
General Methods: Melting points were determined with a hot-plate
apparatus. Optical rotations were measured with a Perkin–Elmer
Polarimeter PE-241 at the sodium line at ambient temperature in
CHCl3. IR spectra were recorded with a Perkin–Elmer 1600/FTIR
instrument in CCl4. NMR spectra were recorded with a Bruker
= 2960, 1759, 1644, 1230 cm–1. MS (ESI+): m/z (%) = 455 (100) [M
+ Na]+. HRMS (ESI+): calcd. for C19H28NaO11 [M + Na]+
455.1529; found 455.1526. C19H28O11 (432.42): calcd. C 52.77, H
6.53; found C 52.81, H 6.71.
AMX 400 spectrometer at 400 MHz for 1H and 100.6 MHz for 13
C
3-(Allyloxy)propyl
2,3,4,6-Tetra-O-methyl-α-D-mannopyranoside
(11): Compound 11 was obtained as a colourless oil in 20% yield.
[α]D = +46.8 (c = 0.22, CHCl3). 1H NMR: δ = 1.86 (dddd, J = 6.4,
6.4, 6.4, 6.4 Hz, 2 H), 3.37–3.59 (m, 9 H), 3.40 (s, 3 H), 3.47 (s, 3
H), 3.50 (s, 3 H), 3.52 (s, 3 H), 3.79 (ddd, J = 9.8, 6.4, 6.4 Hz, 1
H), 3.96 (ddd, J = 5.6, 1.3, 1.3 Hz, 2 H), 4.87 (d, J = 1.9 Hz, 1 H),
5.17 (d, J = 10.3 Hz, 1 H), 5.26 (d, J = 17.2 Hz, 1 H), 5.91 (dddd,
J = 17.2, 10.6, 10.6, 5.6 Hz, 1 H) ppm. 13C NMR: δ = 29.8 (CH2),
57.6 (CH3), 58.8 (CH3), 59.1 (CH3), 60.6 (CH3), 64.5 (CH2), 67.0
(CH2), 71.2 (CH), 71.7 (CH2), 71.8 (CH2), 76.5 (CH), 77.2 (CH),
in CDCl3, unless otherwise stated, with TMS as internal standard.
Mass spectra were recorded with a Waters LCT Premier XE spec-
trometer by using electrospray ionization (ESI+) or with a Micro-
mass AutoSpec by using electron impact (EI) at 70 eV or fast atom
bombardment (FAB), as stated in each case. Elemental analyses
were performed with a Leco TrueSpec Micro instrument. Merck
silica gel 60 PF (0.063–0.2 mm) was used for column chromatog-
raphy. Circular layers of 1 mm of Merck silica gel 60 PF254 were
used with a Chromatotron for centrifugally assisted chromatog-
raphy. Commercially available reagents and solvents were of analyt-
ical grade or were purified by standard procedures prior to use. All
reactions involving air- or moisture-sensitive materials were carried
out under nitrogen. TLC analysis was conducted with a spray of
0.5% vanillin in H2SO4/EtOH (4:1) and heating until the develop-
ment of a color.
81.2 (CH), 96.8 (CH), 116.7 (CH ), 134.8 (CH) ppm. IR (CCl ): ν
˜
2
4
= 2930, 1115 cm–1. MS (70 eV, EI): m/z (%) = 219 (2) [M –
C6H11O2]+, 159 (56) [M – C6H11O2 – C2H4O]+, 88 (100). HRMS
(EI): calcd. for C8H15O3 [M – C6H11O2 – C2H4O]+ 159.1021; found
159.1021. C16H30O7 (334.40): calcd. C 57.47, H 9.04; found C
57.47, H 9.09.
General Procedure for the Reductive HAT/Radical Allylation: A
2-Hydroxyethyl 1,2,3-Trideoxy-5,6,7,9-tetra-O-methyl-β-
D-gluco-
solution of the corresponding phthalimide derivative (1 mmol) in
non-1-en-4-ulopyranoside (15): Compound 15 was obtained as a
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O20300
/KAP1
Date: 30-05-12 16:35:30
Pages: 13
E. I. León, Á. Martín, I. Pérez-Martín, L. M. Quintanal, E. Suárez
FULL PAPER
colourless oil in 13% yield from 14 and in 20% from 17 under
the standard conditions. [α]D = +9.0 (c = 0.50, CHCl3). H NMR
(500 MHz): δ = 1.97 (br. s, 1 H), 2.48 (dd, J = 15.5, 7.2 Hz, 1 H),
2.61 (dd, J = 15.5, 5.3 Hz, 1 H), 3.24 (dd, J = 4.5, 1.3 Hz, 2 H),
1
36% yield from 18. [α]D = +103.3 (c = 0.12, CHCl3). H NMR: δ
1
= 1.38 (s, 3 H), 1.94 (dd, J = 12.5, 12.5 Hz, 1 H), 2.10 (dd, J =
12.7, 4.8 Hz, 1 H), 3.40 (s, 3 H), 3.42 (s, 3 H), 3.48–3.55 (m, 2 H),
3.49 (s, 3 H), 3.52 (s, 3 H), 3.54 (s, 3 H), 3.62 (dd, J = 10.0, 3.7 Hz,
3.37 (s, 3 H), 3.38 (m, 1 H), 3.44 (m, 1 H), 3.51 (s, 6 H), 3.53 (dd, 1 H), 3.75 (m, 1 H), 3.79 (dd, J = 13.5, 2.4 Hz, 1 H), 3.97 (ddd, J
J = 7.2, 3.8 Hz, 2 H), 3.58 (s, 3 H), 3.68 (ddd, J = 4.1, 4.1, 0 Hz, = 11.9, 4.8, 2.9 Hz, 1 H), 4.10 (dd, J = 13.5, 1.3 Hz, 1 H), 4.18 (dd,
2 H), 3.75 (ddd, J = 4.1, 4.1, 0 Hz, 2 H), 5.09 (d, J = 10.1 Hz, 1
H), 5.10 (d, J = 17.0 Hz, 1 H), 5.84 (dddd, J = 17.6, 10.7, 6.9,
6.9 Hz, 1 H) ppm; an NOE correlation was observed between 1Ј-
H2 with 3- and 5-H. 13C NMR (125.7 MHz): δ = 35.7 (CH2), 59.2
J = 3.2, 0 Hz, 1 H), 4.97 (d, J = 3.7 Hz, 1 H), 5.02 (d, J = 1.8 Hz,
1 H) ppm. 13C NMR: δ = 22.2 (CH3), 36.0 (CH2), 55.7 (CH3), 56.4
(CH3), 58.4 (CH3), 59.0 (CH3), 59.6 (CH3), 63.7 (CH2), 67.8 (CH),
72.5 (CH), 73.9 (CH), 74.8 (CH), 78.9 (CH), 82.4 (CH), 98.4 (CH),
(CH3), 59.3 (CH3), 59.9 (CH3), 60.1 (CH3), 63.1 (CH2), 63.7 (CH2), 99.1 (CH), 100.8 (C) ppm. IR (CCl ): ν = 2930, 1737, 1385 cm–1.
˜
4
71.4 (CH2), 72.5 (CH), 79.2 (CH), 81.6 (CH), 85.6 (CH), 101.6 (C), MS (70 eV, EI): m/z (%) = 378 (18) [M]+, 88 (100). HRMS (EI):
118.0 (CH ), 132.1 (CH) ppm. IR (CCl ): ν = 3502, 2932,
calcd. for C17H30O9 [M]+ 378.1890; found 378.1886. C17H30O9
˜
2
4
1709 cm–1. MS (70 eV, EI): m/z (%) = 279 (95) [M – C3H5]+, 88 (378.41): calcd. C 53.96, H 7.99; found C 54.07, H 7.97.
(100). HRMS (EI): calcd. for C12H23O7 [M – C3H5]+ 279.1444;
Methyl 2,3-Di-O-methyl-4-O-(6,7,8-trideoxy-5-methyl-2,3,4-tri-O-
acetyl-β-D-gulo-oct-7-enopyranosyl)-α-D-galactopyranoside (22):
Compound 22 was obtained as a colourless oil in 42% yield from
21 under the standard conditions. [α]D = +35.4 (c = 1.00, CHCl3).
1H NMR: δ = 1.26 (s, 3 H), 2.07 (s, 3 H), 2.10 (s, 3 H), 2.13 (s, 3
found 279.1440. C15H28O7 (320.18): calcd. C 56.23, H 8.81; found
C 56.27, H 8.54.
2-Hydroxyethyl
5-Allyl-5-deoxy-2,3,4,6-tetra-O-methyl-D-xylo-
hexonate (16): Compound 16 was obtained as a colourless oil in
1
40% yield from 14 and in 46% yield from 17. H NMR: δ = 1.32 H), 2.43 (dd, J = 14.6, 7.2 Hz, 1 H), 2.70 (dd, J = 14.3, 7.1 Hz, 1
(m, 1 H), 1.82 (m, 1 H), 1.94 (m, 1 H), 2.07–2.24 (m, 2 H), 2.32 H), 3.40 (s, 3 H), 3.48 (s, 3 H), 3.51 (s, 3 H), 3.52 (dd, J = 4.8,
(ddd, J = 14.8, 6.6, 0 Hz, 1 H), 2.50 (br. s, 2 H), 3.27–3.38 (m, 2
H), 3.51 (s, 3 H), 3.40–3.52 (m, 2 H), 3.41 (s, 3 H), 3.44 (s, 3 H),
3.45 (s, 3 H), 3.46 (s, 3 H), 3.47 (s, 3 H), 3.48 (s, 3 H), 3.51 (s, 3
H), 3.53–3.59 (m, 2 H), 3.61–3.69 (m, 2 H), 3.70–3.76 (m, 2 H),
3.4 Hz, 1 H), 3.54 (dd, J = 5.0, 2.6 Hz, 2 H), 3.68–3.79 (m, 3 H),
4.12 (dd, J = 5.0, 2.6 Hz, 1 H), 4.82 (d, J = 3.2 Hz, 1 H), 5.03 (d,
J = 5.6 Hz, 1 H), 5.08 (d, J = 6.4 Hz, 1 H), 5.16 (dd, J = 16.9,
1.8 Hz, 1 H), 5.21 (dd, J = 10.3, 1.8 Hz, 1 H), 5.28 (dd, J = 6.4,
3.78–3.85 (m, 2 H), 3.96 (d, J = 4.2 Hz, 1 H), 4.08 (d, J = 3.7 Hz, 3.6 Hz, 1 H), 5.38 (dd, J = 5.6, 3.7 Hz, 1 H), 5.84 (dddd, J = 17.2,
1 H), 4.14 (m, 1 H), 4.27 (m, 1 H), 4.39 (m, 1 H), 4.49 (m, 1 H), 10.0, 7.1, 7.1 Hz, 1 H) ppm; an NOE correlation was observed
5.00–5.12 (m, 4 H), 5.71–5.83 (m, 2 H) ppm. 13C NMR: δ = 33.4 between 4Ј-H and 6Ј-H3, and between 7Ј-H2 and 2Ј-H or 3Ј-H. 13
(CH2), 34.5 (CH2), 39.8 (CH), 40.3 (CH), 58.5 (CH3), 58.6 (CH3), NMR: δ = 14.6 (CH3), 21.1 (2ϫ CH3), 23.0 (CH3), 41.5 (CH2),
C
58.9 (2ϫ CH3), 59.8 (CH3), 59.9 (CH3), 60.2 (CH3), 60.6 (CH2),
60.7 (CH3), 60.8 (CH2), 66.4 (CH2), 66.6 (CH2), 71.9 (CH2), 72.4
55.7 (CH3), 59.0 (CH3), 59.6 (CH3), 61.2 (CH2), 68.8 (CH), 68.9
(CH), 69.8 (CH), 71.0 (CH), 74.9 (CH), 78.5 (C), 78.5 (CH), 79.8
(CH2), 80.2 (CH), 80.3 (CH), 81.0 (CH), 81.5 (CH), 82.6 (CH), (CH), 97.9 (CH), 98.4 (CH), 119.9 (CH2), 132.4 (CH), 169.5 (C),
83.8 (CH), 116.3 (CH2), 116.4 (CH2), 135.0 (CH), 136.9 (CH),
169.9 (2ϫ C) ppm. IR (CCl ): ν = 3511, 2933, 1755, 1223 cm–1.
˜
4
170.8 (C), 171.0 (C) ppm. IR (CCl ): ν = 3488, 2929, 1752, MS (70 eV, EI): m/z (%) = 475 (13) [M – OAc]+, 429 (100) [M –
˜
4
1448 cm–1. MS (ESI+): m/z (%) = 343 (100) [M + Na]+. HRMS C5H13O2]+. HRMS (EI): calcd. for C22H35O11 [M – OAc]+
(ESI+): calcd. for C15H28NaO7 [M + Na]+ 343.1733; found
343.1733. C15H28O7 (320.38): calcd. C 56.23, H 8.81; found C
56.24, H 8.72.
475.2179; found 475.2160. C24H38O13 (534.55): calcd. C 53.93, H
7.17; found C 53.80, H 7.12.
Methyl 6-O-Allyl-2,3-di-O-methyl-4-O-(2,3,4-tri-O-acetyl-6-deoxy-
Methyl 2,3-Di-O-methyl-4-O-(6,7,8-trideoxy-5-methyl-2,3,4-tri-O-
α-L-mannopyranosyl)-α-D-galactopyranoside (23): Compound 23
methyl-β-
D
-gulo-oct-7-enopyranosyl)-α-
D
-galactopyranoside
(19):
was obtained as a colourless oil in 11% yield from 21. [α]D = +18.2
(c = 0.50, CHCl3). H NMR: δ = 1.35 (d, J = 7.4 Hz, 3 H), 1.99
(s, 3 H), 2.05 (s, 3 H), 2.14 (s, 3 H), 3.42 (s, 3 H), 3.47 (s, 3 H),
3.53 (s, 3 H), 3.53 (m, 1 H), 3.56 (dd, J = 6.3, 2.4 Hz, 1 H), 3.59
(dd, J = 9.2, 6.9 Hz, 1 H), 3.66 (dd, J = 9.8, 3.4 Hz, 1 H), 3.91
1
Compound 19 was obtained as a colourless oil in 51% yield from
18. [α]D = +29.1 (c = 0.57, CHCl3). 1H NMR (500 MHz): δ = 1.27
(s, 3 H), 2.37 (dd, J = 11.6, 5.6 Hz, 1 H), 2.69 (dd, J = 11.6, 6.0 Hz,
1 H), 3.21 (d, J = 6.0 Hz, 1 H), 3.40 (s, 3 H), 3.47 (s, 3 H), 3.49 (s,
3 H), 3.50 (s, 3 H), 3.51 (s, 3 H), 3.54 (dd, J = 5.6, 3.6 Hz, 1 H), (ddd, J = 6.4, 6.4, 0 Hz, 1 H), 3.97 (m, 1 H), 4.03 (d, J = 5.6 Hz,
3.57 (s, 3 H), 3.57–3.59 (m, 2 H), 3.63 (dd, J = 9.3, 4.3 Hz, 1 H),
3.69 (dd, J = 5.8, 3.5 Hz, 1 H), 3.74–3.82 (m, 2 H), 4.20 (m, 1 H),
2 H), 4.16 (dd, J = 2.4, 0 Hz, 1 H), 4.87 (d, J = 3.4 Hz, 1 H), 5.07
(dd, J = 10.1, 10.1 Hz, 1 H), 5.15 (d, J = 1.9 Hz, 1 H), 5.19 (dd, J
4.83 (d, J = 2.4 Hz, 1 H), 5.09 (d, J = 5.5 Hz, 1 H), 5.12 (d, J = = 10.3, 1.1 Hz, 1 H), 5.28 (dd, J = 16.7, 1.1 Hz, 1 H), 5.32 (dd, J
13.6 Hz, 1 H), 5.15 (d, J = 19.2 Hz, 1 H), 5.85 (m, 1 H) ppm; the
signal for 1 H from an OH group is missing, an NOE correlation
was observed between 4Ј-H and 6Ј-H3. 13C NMR (125.7 MHz): δ
= 9.8, 2.9 Hz, 1 H), 5.47 (dd, J = 3.2, 3.2 Hz, 1 H), 5.91 (m, 1 H)
ppm. 13C NMR: δ = 17.9 (CH3), 21.1 (CH3), 21.2 (CH3), 21.3
(CH3), 55.7 (CH3), 58.9 (CH3), 59.6 (CH3), 67.3 (CH), 68.9 (CH),
= 22.3 (CH3), 41.6 (CH2), 55.6 (CH3), 58.8 (CH3), 59.1 (CH3), 59.5 69.2 (CH2), 69.5 (CH2), 70.3 (CH), 71.5 (CH), 72.8 (CH), 73.8
(CH3), 59.7 (CH3), 60.4 (CH3), 60.9 (CH2), 69.9 (CH), 73.1 (CH), (CH), 78.2 (CH), 80.7 (CH), 98.5 (CH), 99.2 (CH), 117.6 (CH2),
78.3 (CH), 78.7 (CH), 79.0 (CH), 79.4 (C), 80.2 (2ϫCH), 98.5 134.8 (CH), 170.3 (3 ϫ C) ppm. IR (CCl ): ν = 2932, 1752,
˜
4
(CH), 99.2 (CH), 118.6 (CH ), 133.4 (CH) ppm. IR (CCl ): ν =
1223 cm–1. MS (70 eV, EI): m/z (%) = 434 (8) [M – C3H5 – OAc]+,
˜
2
4
3489, 2931, 1741, 1434 cm–1. MS (70 eV, EI): m/z (%) = 409 (29) 88 (100). HRMS (EI): calcd. for C19H30O11 [M – C3H5 – OAc]+
[M – C3H5]+, 88 (100). HRMS (EI): calcd. for C18H33O10 [M –
434.1788; found 434.1804. C24H38O13 (534.55): calcd. C 53.93, H
C3H5]+ 409.2074; found 409.2072. C21H38O10 (450.25): calcd. C 7.17; found C 54.18, H 6.98.
55.99, H 8.50; found C 55.96, H 8.37.
Methyl (6S)-7,8,9-Trideoxy-2,3-di-O-methyl-4-O-(2,3,4-tri-O-
acetyl-6-deoxy-α- -mannopyranosyl)- -glycero-α- -galacto-non-8-
Methyl (5ЈR)-5Ј,6-Anhydro-4-O-(4,6-dideoxy-2Ј,3Ј-di-O-methyl-β-
erythro-hexose-5Ј-ulopyranosyl)-2,3-di-O-methyl-α- -galacto-
pyranoside (20): Compound 20 was obtained as a colourless oil in
D-
L
L
D
D
enopyranoside (24): Compound 24 was obtained as a colourless oil
1
in 10% yield from 21. [α]D = +69.0 (c = 0.51, CHCl3). H NMR:
8
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20300
/KAP1
Date: 30-05-12 16:35:30
Pages: 13
C–C Bond Formation in Carbohydrate Systems
δ = 1.33 (d, J = 6.4 Hz, 3 H), 2.00 (s, 3 H), 2.06 (s, 3 H), 2.15 (s,
3 H), 2.21 (m, 1 H), 2.56 (br. s, 1 H), 2.58 (m, 1 H), 3.41 (s, 3 H),
3.47 (s, 3 H), 3.48 (dd, J = 6.9, 1.6 Hz, 1 H), 3.52 (dd, J = 9.3,
C), 170.3 (2ϫ C), 170.5 (2ϫ C), 170.7 (2ϫ C) ppm. IR (CCl ): ν
˜
4
= 2960, 1758, 1368 cm–1. MS (70 eV, EI): m/z (%) = 618 (6) [M –
1]+, 575 (35) [M – C2H3O]+, 169 (100). HRMS (EI): calcd. for
2.9 Hz, 1 H), 3.53 (s, 3 H), 3.62 (dd, J = 10.1, 3.4 Hz, 1 H), 3.74 C27H38O16 [M – 1]+ 618.2160; found 618.2180. C27H38O16 (618.58):
(m, 1 H), 4.10 (dddd, J = 9.6, 6.4, 6.4, 6.4 Hz, 1 H), 4.30 (dd, J =
6.7, 1.1 Hz, 1 H), 4.84 (d, J = 3.7 Hz, 1 H), 5.02 (d, J = 2.1 Hz, 1
H), 5.08 (dd, J = 9.8, 9.8 Hz, 1 H), 5.15–5.21 (m, 2 H), 5.35 (dd,
J = 9.8, 3.5 Hz, 1 H), 5.49 (dd, J = 3.2, 2.1 Hz, 1 H), 5.91 (m, 1
H) ppm. 13C NMR: δ = 17.5 (CH3), 20.8 (2ϫCH3), 21.0 (CH3),
38.0 (CH2), 55.5 (CH3), 58.6 (CH3), 59.3 (CH3), 67.9 (CH), 68.7
(CH), 69.0 (CH), 69.9 (CH), 71.0 (CH), 71.9 (CH), 76.2 (CH), 77.9
(CH), 79.5 (CH), 98.2 (CH), 100.5 (CH), 118.2 (CH2), 134.5 (CH),
calcd. C 52.42, H 6.19; found C 52.33, H 6.18.
Methyl
methyl-α-
6,7,8-Trideoxy-2,3-di-O-methyl-4-O-(2,3,4,6-tetra-O-
-glucopyranosyl)-β- -xylo-oct-7-enopyranoside (30):
D
D
Compound 30 was obtained as a colourless oil in 35% yield from
29, (5R/5S, 2.3:1). 1H NMR: δ = 2.19 (m, 1 H), 2.27–2.40 (m, 3
H), 3.00 (dd, J = 8.3, 7.7 Hz, 1 H), 3.03 (dd, J = 9.1, 7.6 Hz, 1 H),
3.16 (dd, J = 9.9, 4.0 Hz, 2 H), 3.21 (dd, J = 9.3, 9.3 Hz, 2 H), 3.38
(s, 6 H), 3.42 (dd, J = 8.5, 8.5 Hz, 4 H), 3.42–3.45 (m, 2 H), 3.46–
3.48 (m, 2 H), 3.52 (s, 6 H), 3.53 (s, 6 H), 3.54 (s, 12 H), 3.56 (s, 6
H), 3.62 (s, 6 H), 3.72–3.76 (m, 2 H), 3.82–3.85 (m, 2 H), 3.90–3.93
(m, 2 H), 4.17 (d, J = 7.8 Hz, 1 H), 4.19 (d, J = 7.7 Hz, 1 H), 5.12–
5.18 (m, 4 H), 5.55 (d, J = 2.5 Hz, 1 H), 5.59 (d, J = 4.0 Hz, 1 H),
5.78–5.88 (m, 2 H) ppm; an NOE correlation was observed between
5-H and 3-H for the major (5R) isomer. 13C NMR: δ = 33.3 (2ϫ
CH2), 55.0 (CH3), 55.4 (CH3), 57.1 (CH3), 57.6 (CH3), 58.2 (2ϫ
CH3), 58.3 (2ϫ CH3), 58.5 (2ϫ CH3), 58.8 (2ϫ CH3), 59.1 (2ϫ
CH3), 68.2 (2ϫ CH), 69.2 (CH2), 69.4 (2ϫ CH), 70.1 (CH2), 73.0
(2ϫ CH), 77.7 (2ϫ CH), 79.9 (2ϫ CH), 81.5 (2ϫ CH), 82.6 (2ϫ
CH), 84.5 (2ϫ CH), 95.2 (CH), 95.7 (CH), 102.7 (CH), 102.8 (CH),
170.3 (3ϫ C) ppm. IR (CCl ): ν = 3527, 2933, 1753, 1223 cm–1.
˜
4
MS (FAB+): m/z (%) = 557 (2) [M + Na]+, 273 (100). HRMS
(FAB+): calcd. for C24H38O13 [M + Na]+ 557.2210; found 557.2218.
C24H38O13 (534.55): calcd. C 53.93, H 7.17; found C 54.29, H 7.18.
Methyl 2,3-Di-O-methyl-4-O-(6,7,8-trideoxy-5-methyl-2,3,4-tri-O-
methyl-β-
L-ribo-oct-7-enopyranosyl)-α-D-glucopyranoside
(26):
Compound 26 was obtained as a colourless oil from 25 in 53%
yield as a mixture of diastereomers (5ЈS/5ЈR 3:1). 1H NMR: δ =
1.25 (s, 3 H), 1.37 (s, 3 H), 1.65 (br. s, 2 H), 2.20–2.31 (m, 2 H),
2.86 (dd, J = 7.6, 2.3 Hz, 1 H), 2.95 (dd, J = 6.8, 3.5 Hz, 1 H),
3.12–3.26 (m, 6 H), 3.40–3.66 (m, 8 H), 3.38 (s, 3 H), 3.39 (s, 3 H),
3.40 (s, 3 H), 3.44 (s, 3 H), 3.51 (s, 3 H), 3.52 (s, 6 H), 3.54 (s, 3
H), 3.57 (s, 3 H), 3.58 (s, 3 H), 3.63 (s, 3 H), 3.64 (s, 3 H), 3.90–
3.95 (m, 2 H), 4.03 (dd, J = 2.8, 2.8 Hz, 2 H), 4.81 (d, J = 3.3 Hz,
2 H), 5.07–5.23 (m, 6 H), 5.82–5.92 (m, 2 H) ppm; an NOE corre-
lation was observed between 6Ј-H3 and 3Ј-OMe for the major (5ЈS)
isomer. 13C NMR: δ = 19.7 (CH3), 25.5 (CH3), 35.6 (CH2), 45.6
(CH2), 55.1 (2ϫ CH3), 56.9 (CH3), 57.8 (CH3), 59.0 (3ϫ CH3),
59.2 (CH3), 60.9 (CH3), 61.1 (3ϫ CH3), 62.0 (2ϫ CH2), 70.0 (CH),
70.2 (CH), 75.3 (CH), 75.5 (CH), 75.7 (2ϫ CH), 77.9 (C), 78.2 (C),
80.8 (CH), 81.3 (CH), 82.1 (2ϫ CH), 83.4 (CH), 83.6 (CH), 85.3
(2ϫ CH), 97.1 (2ϫ CH), 97.6 (CH), 97.8 (CH), 118.5 (CH2), 119.0
116.1 (2ϫ CH ), 133.2 (2ϫ CH) ppm. IR (CCl ): ν = 2933, 1445,
˜
2
4
1103 cm–1. MS (70 eV, EI): m/z (%) = 450 (5) [M]+, 449 (48) [M –
1]+, 88 (100). HRMS (EI): calcd. for C21H38O10 [M]+ 450.2465;
found 450.2454. C21H38O10 (450.52): calcd. C 55.99, H 8.50; found
C 55.71, H 8.42.
Methyl
methyl-α-
7,8,9-Trideoxy-2,3-di-O-methyl-4-O-(2,3,4,6-tetra-O-
-glucopyranosyl)- -glycero-β- -gluco-non-8-eno-
D
L
D
pyranoside (31): Compound 31 was obtained as a colourless oil in
44% yield from 29. [α]D = +59.5 (c = 0.19, CHCl3). 1H NMR: δ =
1.64 (br. s, 1 H), 2.37 (ddd, J = 14.8, 7.1, 7.1 Hz, 1 H), 2.45 (ddd,
J = 13.8, 7.4, 7.4 Hz, 1 H), 3.04 (m, 1 H), 3.07 (dd, J = 8.2, 8.2 Hz,
1 H), 3.18 (dd, J = 9.8, 4.2 Hz, 1 H), 3.23 (dd, J = 9.8, 1.6 Hz, 1
H), 3.39 (s, 3 H), 3.42 (dd, J = 9.0, 9.0 Hz, 2 H), 3.48 (dd, J =
10.3, 6.4 Hz, 1 H), 3.51 (s, 3 H), 3.53 (s, 3 H), 3.55 (s, 3 H), 3.57
(s, 3 H), 3.58 (s, 3 H), 3.62–3.68 (m, 2 H), 3.64 (s, 3 H), 3.87 (ddd,
J = 6.9, 6.9, 0 Hz, 1 H), 3.93 (dd, J = 9.2, 9.2 Hz, 1 H), 4.10 (d, J
= 7.7 Hz, 1 H), 5.06 (dd, J = 18.8, 1.9 Hz, 1 H), 5.58 (d, J = 4.2 Hz,
1 H), 5.79 (m, 1 H) ppm; the signal for 1 H from an OH group is
missing. 13C NMR: δ = 38.7 (CH2), 57.1 (CH3), 59.6 (CH3), 60.2
(CH3), 60.3 (CH3), 60.5 (CH3), 60.9 (CH3), 61.2 (CH3), 67.7 (CH),
71.6 (CH), 72.0 (CH2), 73.2 (CH), 75.0 (CH), 80.5 (CH), 82.2 (CH),
84.0 (CH), 84.6 (CH), 86.9 (CH), 97.4 (CH), 104.8 (CH), 117.5
(CH ), 133.3 (CH), 133.4 (CH) ppm. IR (CCl ): ν = 3504, 2931,
˜
2
4
1445, 1105 cm–1. MS (70 eV, EI): m/z (%) = 409 (19) [M – C3H5]+,
88 (100). HRMS (EI): calcd. for C18H33O10 [M – C3H5]+ 409.2074;
found 409.2075. C21H38O10 (450.52): calcd. C 55.99, H 8.50; found
C 55.96, H 8.39.
Methyl 2,3-Di-O-acetyl-6,7,8-trideoxy-4-O-(2,3,4,6-tetra-O-acetyl-
α-D-glucopyranosyl)-β-D-xylo-oct-7-enopyranoside (28): Compound
28 was obtained as an amorphous solid in 68% yield from 27 as a
mixture of diastereomers (5R/5S, 2.5:1). 1H NMR: δ = 2.00 (s, 6
H), 2.01 (s, 12 H), 2.04 (s, 12 H), 2.10 (s, 6 H), 2.43 (ddd, J = 14.4,
7.3, 7.3 Hz, 2 H), 2.55 (ddd, J = 13.9, 7.1, 7.1 Hz, 2 H), 3.37 (ddd,
J = 8.4, 0, 0 Hz, 1 H), 3.48 (s, 3 H), 3.49 (s, 3 H), 3.54 (m, 1 H),
3.70 (dd, J = 11.6, 1.8 Hz, 1 H), 3.81 (dd, J = 11.6, 3.5 Hz, 1 H),
3.90 (dd, J = 15.4, 7.3 Hz, 2 H), 4.01–4.12 (m, 2 H), 4.21 (dd, J =
9.4, 9.4 Hz, 1 H), 4.30 (dd, J = 12.4, 4.0 Hz, 1 H), 4.38 (d, J =
7.8 Hz, 1 H), 4.39 (d, J = 7.8 Hz, 1 H), 4.77 (dd, J = 9.4, 7.8 Hz,
2 H), 4.83 (dd, J = 10.6, 4.0 Hz, 2 H), 5.02 (dd, J = 9.8, 9.8 Hz, 1
H), 5.04 (dd, J = 9.6, 9.6 Hz, 1 H), 5.15 (d, J = 11.1 Hz, 2 H), 5.16
(d, J = 16.4 Hz, 2 H), 5.26 (dd, J = 9.4, 9.4 Hz, 2 H), 5.36 (dd, J
= 10.1, 10.1 Hz, 2 H), 5.42 (d, J = 4.0 Hz, 1 H), 5.47 (d, J = 4.1 Hz,
1 H), 5.79–5.94 (m, 2 H) ppm; an NOE correlation was observed
between 5-H and 1-H and 3-H for the major (5R) isomer. 13C
NMR: δ = 20.5 (6ϫ CH3), 20.6 (2ϫ CH3), 20.7 (2ϫ CH3), 20.9
(2ϫ CH3), 38.3 (2ϫ CH2), 56.7 (CH3), 57.1 (CH3), 61.6 (CH2),
(CH ), 135.4 (CH) ppm. IR (CCl ): ν = 3486, 2932, 1445 cm–1. MS
˜
2
4
(FAB+): m/z (%) = 503 (82) [M + Na]+. HRMS (FAB+): calcd. for
C22H40NaO11 503.2468; found 503.2469. C22H40O11 (480.55):
calcd. C 54.99, H 8.39; found C 55.03, H 8.34.
Methyl 2,3-Di-O-methyl-4-O-(2,3,4-tri-O-acetyl-6,7,8-trideoxy-α-
D-
lyxo-oct-7-enopyranosyl)-α- -glucopyranoside (33): A mixture of
D
isomers 33 (5ЈS/5ЈR 6.3:1) was obtained as a colourless oil in 29%
1
yield from 32. H NMR: δ = 1.82 (br. s, 2 H), 1.98 (s, 6 H), 2.03
(s, 6 H), 2.13 (s, 6 H), 2.29–2.36 (m, 4 H), 3.17–3.21 (m, 2 H), 3.42
(s, 6 H), 3.49 (s, 3 H), 3.50 (s, 3 H), 3.56–3.66 (m, 6 H), 3.59 (s, 6
H), 3.73–3.89 (m, 6 H), 4.81 (d, J = 3.4 Hz, 1 H), 4.84 (d, J =
3.4 Hz, 1 H), 5.09–5.17 (m, 6 H), 5.20 (d, J = 1.8 Hz, 2 H), 5.25
61.9 (CH2), 67.8 (CH), 68.0 (CH), 68.2 (CH), 68.3 (CH), 69.5 (CH), (dd, J = 9.8, 3.2 Hz, 2 H), 5.30 (dd, J = 3.3, 2.0 Hz, 2 H), 5.81–
69.6 (CH), 70.2 (CH), 70.3 (CH), 71.1 (CH), 71.4 (CH), 72.1 (CH),
72.4 (CH), 74.4 (CH), 74.7 (CH), 75.5 (CH), 75.6 (CH), 94.9 (CH),
95.1 (CH), 101.3 (CH), 101.6 (CH), 117.4 (CH2), 118.2 (CH2),
133.9 (CH), 134.3 (CH), 169.4 (2ϫ C), 169.6 (2ϫ C), 170.0 (2ϫ
5.92 (m, 2 H) ppm. 13C NMR: δ = 20.7 (2ϫ CH3), 20.8 (4ϫ CH3),
36.1 (2ϫ CH2), 55.2 (2ϫ CH3), 58.9 (2ϫ CH3), 61.2 (2ϫ CH3),
61.8 (2ϫ CH2), 69.1 (2ϫ CH), 69.4 (2ϫ CH), 69.8 (2ϫ CH), 70.1
(2ϫ CH), 70.7 (2ϫ CH), 76.4 (2ϫ CH), 82.4 (2ϫ CH), 83.1 (2ϫ
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9

Job/Unit: O20300
/KAP1
Date: 30-05-12 16:35:30
Pages: 13
E. I. León, Á. Martín, I. Pérez-Martín, L. M. Quintanal, E. Suárez
Na]+ 543.2054; found 543.2061. C23H36O13 (520.52): calcd. C
FULL PAPER
CH), 97.4 (2ϫ CH), 99.2 (2ϫ CH), 117.9 (2ϫ CH2), 133.4 (2ϫ
CH), 169.8 (2ϫ C), 169.9 (2ϫ C), 170.0 (2ϫ C) ppm. IR (CCl4): 53.07, H 6.97; found C 53.17, H 6.99.
ν = 3606, 2930, 1754 cm–1. MS (ESI+): m/z (%) = 543 (100) [M +
˜
Methyl 2,3-Di-O-methyl-4-O-(4-C-allyl-2,3,5-tri-O-methyl-β-L-xylo-
furanosyl)-α-D-glucopyranoside (39): Compound 39 was obtained as
Na]+. HRMS (ESI+): calcd. for C23H36NaO13 [M + Na]+ 543.2054;
found 543.2054. C23H36O13 (520.52): calcd. C 53.07, H 6.97; found
C 53.27, H 7.19.
a colourless oil in 36% yield from 38. [α]D = +61.3 (c = 0.43,
CHCl3). 1H NMR: (500 MHz) δ = 2.31 (dd, J = 14.2, 7.9 Hz, 1
H), 2.41 (dd, J = 14.2, 6.6 Hz, 1 H), 3.24 (dd, J = 9.5, 3.8 Hz, 1
H), 3.35 (d, J = 10.1 Hz, 1 H), 3.36 (s, 3 H), 3.40 (s, 3 H), 3.42 (s,
3 H), 3.45 (d, J = 10.1 Hz, 1 H), 3.48 (s, 3 H), 3.49 (s, 3 H), 3.52–
3.56 (m, 2 H), 3.59 (s, 3 H), 3.63 (d, J = 6.3 Hz, 1 H), 3.67 (dd, J
= 12.3, 2.2 Hz, 2 H), 3.84 (dd, J = 6.5, 4.3 Hz, 1 H), 3.98 (dd, J =
12.6, 2.5 Hz, 1 H), 4.82 (d, J = 3.5 Hz, 1 H), 5.07–5.15 (m, 2 H),
5.30 (d, J = 4.1 Hz, 1 H), 5.77 (m, 1 H) ppm; the signal for 1 H
from an OH group is missing; NOE correlations were observed
between 6Ј-H and 3Ј-H, and between 5Ј-H and 2Ј-H. 13C NMR
(125.7 MHz): δ = 40.2 (CH2), 55.0 (CH3), 58.1 (CH3), 58.6 (CH3),
58.9 (CH3), 59.1 (CH3), 60.8 (CH3), 61.2 (CH2), 70.6 (CH), 74.2
(CH2), 75.2 (CH), 82.6 (CH), 83.2 (CH), 85.1 (C), 86.5 (CH), 89.0
(CH), 97.4 (CH), 106.9 (CH), 118.9 (CH2), 132.9 (CH) ppm. IR
Methyl
6-O-Allyl-2,3-di-O-methyl-4-O-(2,3,4-tri-O-acetyl-α-
D-
lyxopyranosyl)-α-
D-glucopyranoside (34): Compound 34 was ob-
tained as a colourless oil in 17% yield from 32. [α]D = +155.0 (c =
1
0.34, CHCl3). H NMR: δ = 2.03 (s, 3 H), 2.06 (s, 3 H), 2.11 (s, 3
H), 3.23 (dd, J = 9.4, 3.6 Hz, 1 H), 3.43 (s, 3 H), 3.49 (s, 3 H),
3.53–3.71 (m, 6 H), 3.60 (s, 3 H), 3.88 (dd, J = 11.3, 5.2 Hz, 1 H),
4.02–4.04 (m, 2 H), 4.83 (d, J = 3.4 Hz, 1 H), 5.14–5.18 (m, 3 H),
5.23–5.34 (m, 3 H), 5.92 (dddd, J = 10.3, 10.3, 10.3, 5.6 Hz, 1 H)
ppm. 13C NMR: δ = 20.7 (CH3), 20.8 (2ϫ CH3), 55.3 (CH3), 58.8
(CH3), 60.9 (CH2), 61.1 (CH3), 67.1 (CH), 68.5 (CH), 68.6 (CH2),
69.4 (CH), 69.7 (CH), 72.5 (CH2), 76.5 (CH), 82.4 (CH), 83.2 (CH),
97.4 (CH), 99.2 (CH), 117.1 (CH2), 134.7 (CH), 169.8 (2ϫ C),
170.0 (C) ppm. IR (CCl ): ν = 2931, 1753, 1223 cm–1. MS (ESI+):
˜
4
(CCl ): ν = 3517, 2929, 1053 cm–1. MS (ESI+): m/z (%) = 459 (100)
˜
m/z (%) = 543 (100) [M + Na]+. HRMS (ESI+): calcd. for
C23H36NaO13 543.2054; found 543.2047. C23H36O13 (520.52):
calcd. C 53.07, H 6.97; found C 53.13, H 7.06.
4
[M + Na]+. HRMS (ESI+): calcd. for C20H36NaO10 [M + Na]+
459.2206; found 459.2209. C20H36O10 (436.49): calcd. C 55.03, H
8.31; found C 55.07, H 8.05.
Methyl 2,3-Di-O-methyl-4-O-(2,3,5-tri-O-acetyl-4-C-allyl-α-
D-arab-
Methyl
arabinofuranosyl)-α-
2,3-Di-O-methyl-4-O-(4-C-allyl-2,3,5-tri-O-methyl-α-
D-
inofuranosyl)-α- -glucopyranoside (36): Compound 36 was ob-
D
D-glucopyranoside (40): Compound 40 was ob-
tained as a colourless oil in 27% yield from 35. [α]D = +112.0 (c =
0.20, CHCl3). 1H NMR: (500 MHz) δ = 2.06 (s, 3 H), 2.11 (s, 3
H), 2.14 (s, 3 H), 2.34 (dd, J = 7.5, 0 Hz, 2 H), 3.20–3.23 (m, 1 H),
3.42 (s, 3 H), 3.46–3.51 (m, 2 H), 3.51 (s, 3 H), 3.56 (s, 3 H), 3.70
(m, 1 H), 4.06 (d, J = 6.3 Hz, 1 H), 4.16 (d, J = 12.0 Hz, 1 H), 4.28
(d, J = 12.0 Hz, 1 H), 4.29 (dd, J = 12.0, 0 Hz, 1 H), 4.35 (dd, J =
12.0, 5.0 Hz, 1 H), 4.82 (d, J = 3.5 Hz, 1 H), 5.11 (dd, J = 6.3,
4.1 Hz, 2 H), 5.11 (dd, J = 10.4, 0 Hz, 1 H), 5.16 (dd, J = 17.0,
0 Hz, 1 H), 5.35 (d, J = 3.8 Hz, 1 H), 5.77 (dddd, J = 17.4, 10.4,
7.5, 7.5 Hz, 1 H) ppm; an NOE correlation was observed between
6Ј-H and 2Ј-H. 13C NMR (125.7 MHz): δ = 20.8 (2ϫ CH3), 21.1
(CH3), 39.9 (CH2), 55.3 (CH3), 58.9 (CH3), 61.1 (CH3), 63.2 (CH2),
65.5 (CH2), 68.2 (CH), 77.4 (CH), 78.2 (CH), 81.9 (CH), 83.0 (CH),
85.7 (CH), 85.9 (C) 97.3 (CH), 106.3 (CH), 119.5 (CH2), 132.1
tained as a colourless oil in 15% yield from 38. [α]D = +42.1 (c =
0.33, CHCl3). 1H NMR (500 MHz): δ = 2.42 (dd, J = 14.5, 7.9 Hz,
1 H), 2.48 (dd, J = 14.1, 6.3 Hz, 1 H), 3.21 (dd, J = 9.1, 3.5 Hz, 1
H), 3.26 (d, J = 9.8 Hz, 1 H), 3.30 (d, J = 9.8 Hz, 1 H), 3.34 (s, 3
H), 3.40 (s, 3 H), 3.42 (s, 3 H), 3.48 (s, 3 H), 3.49 (s, 3 H), 3.52–
3.60 (m, 3 H), 3.59 (s, 3 H), 3.68–3.73 (m, 3 H), 3.94 (dd, J = 12.6,
2.8 Hz, 1 H), 4.81 (d, J = 3.8 Hz, 1 H), 5.10–5.15 (m, 2 H), 5.31
(d, J = 3.1 Hz, 1 H), 5.85 (m, 1 H) ppm; the signal for 1 H from
an OH group is missing; an NOE correlation was observed between
5Ј-H and 1Ј-H. 13C NMR: δ = 37.2 (CH2), 55.1 (CH3), 58.0 (CH3),
58.6 (CH3), 58.8 (CH3), 59.3 (CH3), 60.9 (CH3), 61.9 (CH2), 70.4
(CH), 74.9 (CH2), 76.3 (CH), 82.5 (CH), 83.1 (CH), 85.1 (C), 86.2
(CH), 88.7 (CH), 97.4 (CH), 106.9 (CH), 118.4 (CH2), 133.4 (CH)
ppm. IR (CCl ): ν = 3518, 2931, 1055 cm–1. MS (ESI+): m/z (%) =
˜
4
459 (100) [M + Na]+. HRMS (ESI+): calcd. for C20H36NaO10 [M
+ Na]+ 459.2206; found 459.2212. C20H36O10 (436.49): calcd. C
55.03, H 8.31; found C 55.18, H 8.03.
(CH), 170.6 (2ϫ C), 172.1 (C) ppm. IR (CCl ): ν = 3519, 3421,
˜
4
1747, 1242 cm–1. MS (ESI+): m/z (%) = 543 (100) [M + Na]+.
HRMS (ESI+): calcd. for C23H36NaO13 [M + Na]+ 543.2054; found
543.2056. C23H36O13 (520.52): calcd. C 53.07, H 6.97; found C
53.23, H 7.01.
Methyl
6-O-Allyl-2,3-di-O-methyl-4-O-(2,3,5-tri-O-methyl-α-
D-
arabinofuranosyl)-α-
D-glucopyranoside (41): Compound 41 was ob-
tained as an amorphous solid in 21% yield from 38. [α]D = +56.2
(c = 0.38, CHCl3). 1H NMR (500 MHz): δ = 3.24 (dd, J = 9.5,
3.5 Hz, 1 H), 3.29 (s, 3 H), 3.40 (s, 3 H), 3.41 (s, 3 H), 3.43 (s, 3
H), 3.49 (s, 3 H), 3.52 (dd, J = 5.0, 0 Hz, 2 H), 3.54–3.62 (m, 3 H),
3.58 (s, 3 H), 3.70–3.72 (m, 2 H), 3.75 (dd, J = 2.2, 0 Hz, 1 H),
4.01 (dd, J = 12.6, 5.7 Hz, 1 H), 4.07 (m, 2 H), 4.09 (dd, J = 10.7,
5.0 Hz, 1 H), 4.84 (d, J = 3.5 Hz, 1 H), 5.15 (dd, J = 10.4, 1.5 Hz,
1 H), 5.27 (dd, J = 17.0, 1.5 Hz, 1 H), 5.40 (d, J = 0 Hz, 1 H), 5.94
(dddd, J = 17.2, 10.3, 5.6, 5.6 Hz, 1 H) ppm. 13C NMR
(125.7 MHz): δ = 55.0 (CH3), 57.5 (CH3), 58.0 (CH3), 58.6 (CH3),
59.3 (CH3), 60.8 (CH3), 69.0 (CH), 69.6 (CH), 72.4 (CH2), 72.8
(CH2), 74.7 (CH), 81.4 (CH2), 82.2 (CH), 83.3 (CH), 86.3 (CH),
89.8 (CH), 97.1 (CH), 106.7 (CH), 116.8 (CH2), 135.0 (CH) ppm.
Methyl 2,3-Di-O-methyl-4-O-(2,3,5-tri-O-acetyl-4-C-allyl-β-
L-xylo-
furanosyl)-α- -glucopyranoside (37): Compound 37 was obtained as
D
a colourless oil in 25% yield from 35. [α]D = +132.8 (c = 0.29,
CHCl3). 1H NMR (500 MHz): δ = 2.05 (s, 3 H), 2.08 (s, 3 H), 2.14
(s, 3 H), 2.36–2.44 (m, 2 H), 3.20 (dd, J = 9.3, 3.6 Hz, 1 H), 3.40
(s, 3 H), 3.50 (s, 3 H), 3.52 (s, 3 H), 3.52 (dd, J = 9.4, 5.0 Hz, 1 H),
3.55–3.61 (m, 2 H), 3.73 (dd, J = 12.4, 2.0 Hz, 1 H), 3.90 (dd, J =
12.6, 3.1 Hz, 1 H), 4.12 (d, J = 12.0 Hz, 1 H), 4.23 (d, J = 12.0 Hz,
1 H), 4.81 (d, J = 3.5 Hz, 1 H), 5.13–5.21 (m, 2 H), 5.32 (d, J =
6.0 Hz, 1 H), 5.41 (d, J = 6.0 Hz, 1 H), 5.44 (d, J = 4.1 Hz, 1 H),
5.75 (dddd, J = 17.3, 10.1, 7.2, 7.2 Hz, 1 H) ppm; the signal for 1
H from an OH group is missing; an NOE correlation was observed
between 6Ј-H and 3Ј-H. 13C NMR (125.7 MHz): δ = 20.7 (CH3),
20.8 (CH3), 20.9 (CH3), 39.9 (CH2), 55.2 (CH3), 59.0 (CH3), 61.0
(CH3), 61.3 (CH2), 65.1 (CH2), 70.3 (CH), 76.6 (CH), 77.1 (CH),
80.0 (CH), 82.2 (CH), 83.0 (CH), 84.5 (C), 97.6 (CH), 106.2 (CH),
120.5 (CH2), 130.9 (CH), 169.6 (C), 169.8 (C), 170.4 (C) ppm. IR
IR (CCl ): ν = 2931, 2360, 1054 cm–1. MS (ESI+): m/z (%) = 459
˜
4
(100) [M
+
Na]+. HRMS (ESI+): calcd. for C20H36NaO10
[M + Na]+ 459.2206; found 459.2214. C20H36O10 (436.49): calcd.
C 55.03, H 8.31; found C 55.23, H 8.43.
(CCl ): ν = 3520, 3551, 2932, 1752 cm–1. MS (ESI+): m/z (%) = 543
Methyl 2,3-Di-O-methyl-4-O-(4-C-allyl-2,3,5,6-tetra-O-methyl-α-
D-
˜
4
(100) [M + Na]+. HRMS (ESI+): calcd. for C23H36NaO13 [M +
mannofuranosyl)-α- -glucopyranoside (43): A mixture of isomers 43
D
10
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20300
/KAP1
Date: 30-05-12 16:35:30
Pages: 13
C–C Bond Formation in Carbohydrate Systems
[4]
[5]
[6]
[7]
[8]
S. G. Hansen, T. Skrydstrup, Top. Curr. Chem. 2006, 264, 135–
was obtained as a colourless oil in 52% yield (4ЈR/4ЈS, 1:1) from
42. H NMR: δ = 2.33 (m, 1 H), 2.47 (dd, J = 13.5, 7.4 Hz, 1 H),
1
162.
D. E. Levy, P. Fügedi, The Organic Chemistry of Sugars, CRC
Taylor & Francis, Boca Raton, 2006.
O. Arjona, A. M. Gómez, J. C. López, J. Plumet, Chem. Rev.
2007, 107, 1919–2036.
B. Fraser-Reid, J. C. López, Curr. Org. Chem. 2009, 13, 532–
553.
2.54–2.62 (m, 2 H), 3.22 (dd, J = 9.1, 3.6 Hz, 1 H), 3.24 (dd, J =
9.0, 3.4 Hz, 1 H), 3.30 (dd, J = 5.4, 2.8 Hz, 1 H), 3.35–3.75 (m, 16
H), 3.35 (s, 6 H), 3.39 (s, 6 H), 3.44 (s, 3 H), 3.45 (s, 3 H), 3.48 (s,
3 H), 3.49 (s, 6 H), 3.50 (s, 6 H), 3.51 (s, 3 H), 3.59 (s, 3 H), 3.60
(s, 3 H), 3.97 (m, 1 H), 4.01 (d, J = 6.1 Hz, 2 H), 4.82 (d, J =
3.7 Hz, 2 H), 5.01–5.14 (m, 4 H), 5.32 (d, J = 5.3 Hz, 1 H), 5.40
(d, J = 2.9 Hz, 1 H), 5.79–5.95 (m, 2 H) ppm; the signals for 2 H
from OH groups are missing. 13C NMR: δ = 37.8 (CH2), 39.6
(CH2), 55.1 (2ϫ CH3), 58.4 (2ϫ CH3), 58.7 (CH3), 58.8 (CH3),
59.0 (CH3), 59.1 (CH3), 59.3 (CH3), 59.4 (CH3), 60.2 (CH3), 60.4
(CH3), 60.9 (CH3), 61.0 (CH2), 61.1 (CH2), 61.3 (CH3), 70.4 (CH),
70.6 (CH), 71.6 (CH2), 73.1 (CH2), 76.5 (CH), 77.9 (CH), 79.8
(CH), 79.9 (CH), 82.0 (CH), 82.2 (CH), 82.3 (2ϫ CH), 82.9 (CH),
83.0 (CH), 83.2 (CH), 84.4 (CH), 87.3 (2ϫ C), 97.5 (CH), 97.6
(CH), 106.0 (CH), 107.2 (CH), 117.6 (CH2), 118.3 (CH2), 133.7
For general recent reports on intramolecular HAT/C–C bond
formation, see: a) A. Baralle, A. Baroudi, M. Daniel, L. Fen-
sterbank, J.-P. Goddard, E. Lacote, M.-H. Larraufie, G. Maes-
tri, M. Malacria, C. Ollivier in Radical Cascade Reactions –
Encyclopedia of Radicals in Chemistry, Biology and Materials
(Eds.: C. Chatgilialoglu, A. Studer), John Wiley & Sons Ltd,
Chichester, 2012, vol. 2; b) G. J. Rowlands, Tetrahedron 2010,
66, 1593–1636; c) R. Jahjah, A. Gassama, V. Bulach, C. Suzuki,
M. Abe, N. Hoffmann, A. Martínez, J.-M. Nuzillard, Chem.
Eur. J. 2010, 16, 3341–3354; d) M. Albert, L. Fensterbank, E.
Lacôte, M. Malacria, Top. Curr. Chem. 2006, 264, 1–62; e) Z.
Cekovic, J. Serb. Chem. Soc. 2005, 70, 287–318; f) S. Z. Zard
in Radical Reactions in Organic Synthesis (Eds.: R. G. Comp-
ton, S. G. Davies, J. Evans), Oxford University Press Inc., New
York, 2003, pp. 75–79; g) L. Feray, N. Kuznetsov, P. Renaud
in Radicals in Organic Synthesis vol. 2 (Eds.: P. Renaud, M.
Sibi), Wiley-VCH, Weinheim, 2001, pp. 246–278; h) J. Robert-
son, J. Pillai, R. K. Lush, Chem. Soc. Rev. 2001, 30, 94–103; i)
G. Majetich, Tetrahedron 1995, 51, 7095–7129.
a) E. I. León, A. Martín, I. Pérez-Martín, L. M. Quintanal, E.
Suárez, Eur. J. Org. Chem. 2010, 5248–5262; b) C. G. Francisco,
R. Freire, A. J. Herrera, I. Pérez-Martín, E. Suárez, Tetrahe-
dron 2007, 63, 8910–8920; c) C. G. Francisco, A. J. Herrera, E.
Suárez, J. Org. Chem. 2002, 67, 7439–7445; d) C. Chatgilialo-
glu, T. Gimisis, G. P. Spada, Chem. Eur. J. 1999, 5, 2866–2876;
e) R. L. Dorta, A. Martín, J. A. Salazar, E. Suárez, J. Org.
Chem. 1998, 63, 2251–2261; f) G. Descotes, J. Carbohydr.
Chem. 1988, 7, 1–20. For an interesting synthesis of natural
products containing spiroketals by radical HAT on non-carbo-
hydrate systems, see: g) J. Sperry, Y.-C. (W.) Liu, M. A. Brim-
ble, Org. Biomol. Chem. 2010, 8, 29–38.
For tandem intramolecular alkoxyl radical promoted HAT/C–
C bond formation reactions in carbohydrate models, see: a) A.
Martín, I. Pérez-Martín, L. M. Quintanal, E. Suárez, Tetrahe-
dron Lett. 2008, 49, 5179–5181; b) A. J. Herrera, M. Rondón,
E. Suárez, J. Org. Chem. 2008, 73, 3384–3391; c) M. Stark, J.
Thiem, Carbohydr. Res. 2006, 341, 1543–1556; d) J. C. López,
B. Fraser-Reid, Chem. Commun. 1997, 2251–2257; e) J. C.
López, R. Alonso, B. Fraser-Reid, J. Am. Chem. Soc. 1989,
111, 6471–6473.
For O-centered radical-promoted HAT/C–C bond-forming re-
actions on non-carbohydrate substrates, see: a) H. Zhu, J. G.
Wickenden, N. E. Campbell, J. C. T. Leung, K. M. Johnson,
G. M. Sammis, Org. Lett. 2009, 11, 2019–2022; b) G. Petrovic,
Z. Cekovic, Synthesis 2004, 1671–1679; c) G. Petrovic, Z. Ce-
kovic, Org. Lett. 2000, 2, 3769–3772; d) G. Petrovic, Z. Ce-
kovic, Tetrahedron 1999, 55, 1377–1390; e) G. Petrovic, Z. Ce-
kovic, Tetrahedron Lett. 1997, 38, 627–630; f) Z. Cekovic, D.
Ilijev, Tetrahedron Lett. 1988, 29, 1441–1444.
(CH), 134.4 (CH) ppm. IR (CCl ): ν = 3507, 2931, 1101 cm–1. MS
˜
4
(ESI+): m/z (%) = 503 (100) [M + Na]+. HRMS (ESI+): calcd. for
C22H40NaO11 [M + Na]+ 503.2468; found 503.2459. C22H40O11
(480.56): calcd. C 54.99, H 8.39; found C 55.12, H 8.53.
Methyl 6-O-Allyl-2,3-di-O-methyl-4-O-(2,3,5,6-tetra-O-methyl-α-
D-
mannofuranosyl)-α- -glucopyranoside (44): Compound 44 was ob-
D
tained as a colourless oil in 22% yield from 42. [α]D = +67.5 (c =
1
0.28, CHCl3). H NMR: δ = 3.21 (dd, J = 9.4, 3.6 Hz, 1 H), 3.37–
[9]
3.62 (m, 6 H), 3.38 (s, 3 H), 3.42 (s, 3 H), 3.45 (s, 3 H), 3.48 (s, 3
H), 3.49 (s, 3 H), 3.53 (s, 3 H), 3.57 (s, 3 H), 3.67–3.74 (m, 3 H),
3.92 (dd, J = 3.7, 3.7 Hz, 1 H), 4.01–4.07 (m, 3 H), 4.82 (d, J =
3.4 Hz, 1 H), 5.15 (dddd, J = 10.3, 1.3, 1.3, 1.3 Hz, 1 H), 5.27
(dddd, J = 17.2, 1.6, 1.6, 1.6 Hz, 1 H), 5.38 (d, J = 3.7 Hz, 1 H),
5.92 (dddd, J = 17.2, 10.3, 5.6, 5.6 Hz, 1 H) ppm. 13C NMR: δ =
55.1 (CH3), 57.6 (CH3), 58.6 (CH3), 58.7 (CH3), 59.3 (CH3), 60.1
(CH3), 61.0 (CH3), 69.7 (CH), 69.7 (CH2), 71.3 (CH2), 72.2 (CH2),
75.4 (CH), 77.2 (CH), 77.8 (CH), 80.0 (CH), 82.2 (CH), 83.4 (CH),
87.3 (CH), 97.1 (CH), 106.4 (CH), 116.6 (CH2), 135.0 (CH) ppm.
IR (CCl ): ν = 2929, 1708, 1064 cm–1. MS (ESI+): m/z (%) = 503
˜
+
4
[10]
[11]
[12]
(100) [M
Na]+. HRMS (ESI+): calcd. for C22H40O11Na
[M + Na]+ 503.2468; found 503.2460. C22H40O11 (480.55): calcd.
C 54.99, H 8.39; found C 55.03, H 8.66.
Supporting Information (see footnote on the first page of this arti-
cle): Complete description of the experimental details of precursors
and analytical data for all new compounds.
Acknowledgments
This work was supported by the Research Programs of the Gobi-
erno de Canarias (SolSubC200801000192 and CTQ2010-18244) of
the Ministerio de Ciencia e Innovación, cofinanced by the Fondo
Europeo de Desarrollo Regional (FEDER). I. P.-M. thanks the
Spanish Ministerio de Ciencia e Innovación for the Research Pro-
gram PIE 200930I138. L. M. Q. thanks the Consejo Superior de
Investigaciones Científicas (CSIC) (Program I3P) for fellowships.
For some recent reviews on oxygen-centered radicals, see: a) A.
Baralle, A. Baroudi, M. Daniel, L. Fensterbank, J.-P. Goddard,
E. Lacôte, M.-H. Larraufie, G. Maestri, M. Malacria, C. Olliv-
ier in Main-Group Elements in Radical Chemistry – Encyclope-
dia of Radicals in Chemistry, Biology and Materials (Eds.: C.
Chatgilialoglu, A. Studer), John Wiley & Sons Ltd, Chichester,
2012, vol. 2; b) J. Hartung, T. Gottwald, K. Spehar, Synthesis
2002, 1469–1498.
A. Martín, L. M. Quintanal, E. Suárez, Tetrahedron Lett. 2007,
48, 5507–5511.
a) O. Mitsunobu, Synthesis 1981, 1–28; b) E. Grochowski, J.
Jurczak, Synthesis 1976, 682–684.
[1] a) I. Pérez-Martín, E. Suárez in Radicals and Carbohydrates –
Encyclopedia of Radicals in Chemistry, Biology and Materials
(Eds.: C. Chatgilialoglu, A. Studer), John Wiley & Sons Ltd,
Chichester, 2012, vol. 2, pp. 1131–1174; b) A. J. Pearce, J.-M.
Mallet, P. Sinaÿ in Radicals in Organic Synthesis vol. 2 (Eds.:
P. Renaud, M. Sibi), Wiley-VCH, Weinheim, 2001, pp. 538–
577.
[2] R. J. Ferrier, J. O. Hoberg, Adv. Carbohydr. Chem. Biochem.
2003, 58, 55–119.
[3] C. Taillefumier, Y. Chapleur, Chem. Rev. 2004, 104, 263–292.
[13]
[14]
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Pages: 13
E. I. León, Á. Martín, I. Pérez-Martín, L. M. Quintanal, E. Suárez
FULL PAPER
[15] For studies of the influence of polar factors on the intermo-
lecular HAT reactions, see: a) A. L. J. Beckwith, A. A. Zavitsas,
J. Am. Chem. Soc. 1995, 117, 607–614; b) A. A. Zavitsas, C.
Chatgilialoglu, J. Am. Chem. Soc. 1995, 117, 10645–10654; for
examples of intramolecular HAT reactions, see: c) C. G. Fran-
cisco, R. Freire, A. J. Herrera, I. Pérez-Martín, E. Suárez, Org.
Lett. 2002, 4, 1959–1961.
[16] a) J.-P. Praly, Adv. Carbohydr. Chem. Biochem. 2001, 56, 65–
151; b) D. Crich, S. Sun, J. Brunckova, J. Org. Chem. 1996,
61, 605–615; c) N. Yamazaki, E. Eichenberger, D. P. Curran,
Tetrahedron Lett. 1994, 35, 6623–6626; d) J. Brunckova, D.
Crich, Q. Yao, Tetrahedron Lett. 1994, 35, 6619–6622; e) B.
Giese, Radicals in Organic Synthesis: Formation of Carbon–
Carbon Bonds, Pergamon Press, Oxford, 1986; f) B. Giese, J.
Dupuis, Tetrahedron Lett. 1984, 25, 1349–1352; g) J.-P. Praly,
Tetrahedron Lett. 1983, 24, 3075–3078.
Eur. J. 2008, 14, 10369–10381; b) A. Martín, I. Pérez-Martín,
L. M. Quintanal, E. Suárez, J. Org. Chem. 2008, 73, 7710–
7720; c) A. Martín, I. Pérez-Martín, L. M. Quintanal, E. Suá-
rez, Org. Lett. 2007, 9, 1785–1788; d) C. G. Francisco, A. J.
Herrera, A. R. Kennedy, D. Melián, E. Suárez, Angew. Chem.
2002, 114, 884; Angew. Chem. Int. Ed. 2002, 41, 856–858.
D. P. Curran, N. A. Porter, B. Giese, Stereochemistry of Radical
Reactions, Wiley-VCH Verlag GmbH, Weinheim, 1996, pp.
131–135.
K. Miura, H. Saito, D. Itoh, T. Matsuda, N. Fujisawa, D.
Wang, A. Hosomi, J. Org. Chem. 2001, 66, 3348–3355.
D. P. Curran, N. A. Porter, B. Giese, Stereochemistry of Radical
Reactions, Wiley-VCH Verlag GmbH, Weinheim, 1996, pp.
164–168.
[19]
[20]
[21]
[22] D. P. Curran, N. A. Porter, B. Giese, Stereochemistry of Radical
Reactions, Wiley-VCH Verlag GmbH, Weinheim, 1996, pp.
119–128.
[17] a) A. L. J. Beckwith, S. Brumby, J. Chem. Soc. Perkin Trans. 2
1987, 1801–1807; b) A. L. J. Beckwith, C. J. Easton, J. Am.
Chem. Soc. 1981, 103, 615–619; c) K. Hayday, R. D. McKelvey,
J. Org. Chem. 1976, 41, 2222–2226.
[18] a) C. G. Francisco, A. J. Herrera, A. R. Kennedy, A. Martín,
D. Melián, I. Pérez-Martín, L. M. Quintanal, E. Suárez, Chem.
[23] B. Giese, Angew. Chem. 1989, 101, 993; Angew. Chem. Int. Ed.
Engl. 1989, 28, 969–980.
Received: March 12, 2012
Published Online: ᭿
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Date: 30-05-12 16:35:30
Pages: 13
C–C Bond Formation in Carbohydrate Systems
C–C Bond Formation
A tandem intramolecular hydrogen atom
transfer (HAT)/intermolecular radical all-
ylation is described. This process occurs by
E. I. León, Á. Martín,* I. Pérez-Martín,*
L. M. Quintanal, E. Suárez ............ 1–13
a
completely regio- and stereoselective
C–C Bond Formation by Sequential Intra-
molecular Hydrogen Atom Transfer/Inter-
molecular Radical Allylation Reaction in
Carbohydrate Systems
route that provides a simple methodology
for C–C bond formation on remote pos-
itions without modifying the remainder of
the carbohydrate.
Keywords: Carbohydrates / Radical reac-
tions / Hydrogen transfer / Radical all-
ylation / C–C coupling
Eur. J. Org. Chem. 0000, 0–0
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