Regiospecific synthesis of 4-deoxy-D-threo-hex-3-enopyranosides by simultaneous activation-elimination of the talopyranoside axial 4-OH with the NaH/Im2SO2 system: Manifestation of the stereoelectronic effect

Article abstract of DOI:10.1002/ejoc.200600526

A new and high-yielding method for the regioselective preparation of 4-deoxy- and 2,4-dideoxy-2-acetamido-β-D-threo-hex-3-enopyranosides has been developed. The process involves a simultaneous activation-elimination of the OH-4 group of β-D-talopyranoside

Full text of DOI:10.1002/ejoc.200600526

FULL PAPER
DOI: 10.1002/ejoc.200600526
Regiospecific Synthesis of 4-Deoxy- -threo-hex-3-enopyranosides by
D
Simultaneous Activation–Elimination of the Talopyranoside Axial 4-OH with
the NaH/Im2SO2 System: Manifestation of the Stereoelectronic Effect
Emanuele Attolino,[a] Giorgio Catelani,*[a] and Felicia D’Andrea[a]
Keywords: Carbohydrates / Hex-3-enopyranosides / Talopyranosides / Imidazylates / Elimination / Stereoelectronic effect
A new and high-yielding method for the regioselective prep-
aration of 4-deoxy- and 2,4-dideoxy-2-acetamido-β- -threo-
hex-3-enopyranosides has been developed. The process in-
volves a simultaneous activation–elimination of the OH-4
group of β-D-talopyranosides and 2-acetamido-2-deoxy-β-D-
talopyranosides, mediated by the NaH/N,NЈ-sulfuryldiimid-
azole system at –30 °C. The same reaction applied on the
analogous β-D-galactopyranosides takes place without any
regioselectivity, affording mixtures of hex-3- and hex-4-
enopyranosides. In the case of the methyl 2,3,6-tri-O-benzyl-
at –30 °C. Upon warming these crude products to room tem-
perature, the α-talo-4-O-imidazylate gives the corresponding
hex-3-eno derivative in very high yield, but its α-galacto ana-
logue gives the hex-4-enopyranoside enol ether in poor
yield. The different regiochemical outcome between the talo
and the galacto series has been attributed to the stereoelec-
tronic effect exerted, exclusively in talo-configured com-
pounds, by the axially disposed C-2 electronegative substitu-
ent, which selectively accelerates the breaking of the anti-
periplanar C(3)–H bond.
D
α-
D
-talo- and α-
D
-galactopyranosides, the corresponding 4-
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
O-imidazylates can be isolated by quenching the reactions
limited to specific cases[9] in which a β-elimination could be
favoured by an easily achievable antiperiplanar orientation
between the leaving group and a single type of β-hydrogen.
The introduction of trifluoromethanesulfonates (triflates)
has notably expanded the synthetically useful applications
of nucleophilic substitution reactions, owing to the high nu-
cleofugacity of this leaving group.[10] Elimination reactions
of triflates[11] have been used for preparative purposes and
also extensively investigated, owing to the presence of an
alternative elimination pathway starting with an α-hydrogen
abstraction, promoted by the strong electron-withdrawing
effect of the triflyl group.[11a] However, in the case of sec-
ondary triflates where two different types of hydrogen
atoms flank the leaving group, mixtures of unsaturated de-
rivatives are usually obtained.[11b,11c]
Imidazole-1-sulfonates (imidazylates) have been pro-
posed as efficient leaving groups characterised by an excel-
lent nucleofugal ability and by the possibility of remote ac-
tivation involving the basic nitrogen atom.[12] Actually, sig-
nificant improvements have been reported with imidazylates
instead of tosylates and triflates, particularly in those reac-
tions where the presence of unfavourable torsional or polar
effects caused a lowering of yields (e.g. glucopyranoside 2-
sulfonates.)[13] Elimination reactions of imidazylates had
been almost completely unknown,[14] until we reported the
formation of enol ethers 3,[15] which occurred when the β-
-talopyranosides 1 were submitted to the protocol of the
imidazylate preparation[12] (Figure 1). This result was con-
sidered particularly surprising in view of the presence of
Introduction
Sulfonylation of sugar hydroxy groups is one of the most
potent tool for their activation.[1] The resulting sulfonates
have been extensively used to perform bimolecular nucleo-
philic substitutions with a huge number of nucleophiles al-
lowing: a) the introduction of different heteroatoms into the
glycosyl framework (halogens, nitrogen, and sulfur),[2] b)
the epimerization of the stereogenic centre previously carry-
ing the alcoholic function[3] and c) deoxygenation.[4] Other
synthetic applications of carbohydrate sulfonates include
the formation of cyclic anhydro derivatives, including epox-
ides,[5] by intramolecular displacement and the installation
of double bonds through classical base-promoted elimi-
nations.
p-Toluenesulfonates (tosylates) and methanesulfonates
(mesylates) were first introduced in carbohydrate chemistry
in 1922[6] and still represent the most widespread sulfonates
in preparatively relevant syntheses of unsaturated sugars. In
particular, 6-O-tosyl-pyranosides have been employed for
the synthesis of 6-deoxy-hex-5-enopyranosides by treatment
with several bases and, in particular, with the high-yielding
NaH-DMF[7] and NaH-HMPA systems.[8] Elimination re-
actions of secondary tosylates are of less general use and
[a] Dipartimento di Chimica Bioorganica e Biofarmacia, Uni-
versità di Pisa,
Via Bonanno, 33 56126, Pisa, Italy
Fax: +39-050-43321
E-mail: giocate@farm.unipi.it
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E. Attolino, G. Catelani, F. D’Andrea
FULL PAPER
two different hydrogen atoms, H-3 and H-5, having an anti Synthesis of Substrates
disposition with respect to the 4-O-imidazylate group on
the putative intermediates 2.
Compounds 6a–i, selectively deprotected at C-4, were
synthesised according to the general procedure illustrated
in Scheme 1 and starting from derivatives 4a–i, obtained in
a few steps from commercially available -galactopyranos-
ides, including lactose.
The galactopyranosides 4f–h and the 2-deoxy compound
4i have been prepared in accordance with methods pre-
viously reported in the literature,[18] while the synthesis of
the talopyranosides 4a,b and e was achieved starting from
mixed acetals 7–9[19] (Scheme 2) by a completely diastereo-
selective oxidation–reduction sequence.
As previously experienced for the oxidation of 7 to 10,[20]
the TPAP-NMO system[21] effectively oxidised compound 8
and 9, giving access to the ulosides 11 and 12 in almost
quantitative yield and without removal of the labile 6-O-
methoxyisopropyl protecting group. The reduction of the
two β-2-ulosides 10 and 11 (NaBH4/MeOH) stereoselec-
tively afforded the desired β--talopyranosides in excellent
yields (94% and 98%, respectively). It is noteworthy that in
these reductions, the -talo stereoisomer was detected as
the sole reaction product, evidently because of the coopera-
tive effect of anomeric stereocontrol[22] and of the steric hin-
drance of the β-face, exerted by the 3,4-O-isopropylidene
Figure 1. Transformation of 4-OH-containing β--talopyranosides
into 4-deoxy-β--threo-hex-3-enopyranosides.
The β--threo-hex-3-enopyranosides 3 have not been de- protecting group, which is known to be much more effective
scribed previously, whereas their erythro analogues have in directing the hydride attack on β--lyxo-hexopyranosid-
been occasionally reported as by-products during substitu- 2-uloses[23] than other substituents.[24] However, our stere-
tion[16] or elimination[11c] reactions of 4-O-sulfonyl--galac- ospecific epimerisation at C-2 of the mixed acetals 7 and 8
topyranosides. Moreover, this type of endocyclic sugar enol proved to be by far the most efficient synthetic methodol-
ether proved to be an interesting synthetic intermediate due ogy for the β--galacto to β--talo transformation, ac-
to its application in the stereoselective synthesis of challeng- cessing compounds 13 and 14 in 85% and 60% overall
ing β--mannopyranosides.[17]
We present here a full account of the synthesis of 4-de- tose, respectively.
yield, starting from methyl β--galactopyranoside and lac-
oxy--threo-hex-3-enopyranosides starting from 6a–e as
The reduction of the α-uloside 12 yielded a 9:1 mixture
well as the extension of the activation–elimination pro- of the α-talo (15) and α-galacto (9) diastereoisomers as a
cedure to other pyranosides 6f–i, characterised by an iden- result of the opposite action of the steric effect exerted by
tical stereochemical relationship between the activable OH- the dioxolane ring and the anomeric stereocontrol of the
4 group and the two contiguous stereogenic centres (C-3 methoxy group. Separation of 15 and 9 by flash chromatog-
and C-5), in order to clarify the structural parameters regu- raphy was attempted with several eluents, but unfortunately,
lating the regioselective outcome of the elimination.
a satisfactory separation could not be obtained.
Scheme 1. General Procedure for the Preparation of 4-OH-containing -galacto- and -talopyranosides; Reagents and conditions: i: 80%
AcOH aq, 50 °C; ii: a) Bu2SnO, toluene, reflux; b) Bu4NBr, BnBr, reflux.
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Regiospecific Synthesis of 4-Deoxy--threo-hex-3-enopyranosides
FULL PAPER
The previously unreported methyl 2-acetamido-2-deoxy-
3,4-O-isopropylidene-β--talopyranoside (4c) was obtained
(Scheme 3) from the known oximino derivative 19,[20] rou-
tinely obtained from the uloside 10. Reduction of 19 (Li-
AlH4/Et2O), followed by N-acetylation and purification of
the crude product, yielded the pure N-acetyl--talosamino
derivative 20 (62% yield) and the galacto diastereoisomer
21 (17% yield, not shown). Benzylation of 20 gave, finally,
4c in high yield (84%). The preparation of the N-acetyl ta-
losamino disaccharide derivative 4d, starting from lactose
has been recently published as part of a project towards the
synthesis of the β--ManNAcp-(1Ǟ4)--Glc disaccha-
ride.[17b]
Compounds 6a–i were finally obtained, as previously an-
ticipated (Scheme 1), through a high-yielding hydrolysis of
the 4a–i isopropylidene protecting groups and subsequent
regioselective 3-O-benzylations. In particular, in the cases
of the galactopyranoside diols 5f–h,[25] treatment of the in-
termediate stannylidene acetals with BnBr gave the known
methyl galactopyranosides 6f and 6h[26] in excellent yields
(Ͼ90%), as well as the previously unreported derivative 6g.
In full accordance with previous reports regarding the
opening of 3,4-O-stannylidene acetals of galactopyranos-
ides with several electrophiles[27] (alkyl, acyl and sulfonyl
halides), only the product arising from the electrophilic at-
tack on the equatorial O-3 was detected, irrespective of the
anomeric configuration. In the β-galacto series, the com-
plete regioselectivity was attributed to the formation of di-
meric stannylidene acetal species, which reacted with elec-
trophiles only on the less hindered equatorial O-3 atom.[27]
An identical regioselective outcome was observed in the
stannylidenation–benzylation of the 2-deoxy-diol 5i, ob-
tained after hydrolysis of 4i.[18d] It is noteworthy that the
deacetonation of derivative 4i required very mild conditions
in order to avoid both hydrolysis of the glycosidic linkage
(80% aq AcOH) and the concurrent anomerization to the
more stable α-anomer 22. After a prolonged reaction in
MeOH, in the presence of a catalytic amount of TsOH (r.t.,
30 h), the product 5i was revealed in a 35:65 ratio with 22.
An excellent result (85% yield of anomerically pure 5i) was
obtained by employing DDQ in 10% aq CH3CN, pro-
posed[28] as a reagent operating under neutral conditions.
The transformation of compounds 4a–c and 4e into the
talopyranosides 6a–c and 6e (Scheme 1) followed the same
reaction sequence described above for the -galacto com-
pounds. The monosaccharide derivatives 4a and 4c were
routinely de-isopropylidenated in almost quantitative yields.
The hydrolysis of the 9:1 4h/4e mixture gave a crude prod-
uct containing a 9:1 5e/5h mixture, which afforded pure 5e
(88% yield) after chromatographic purification. In the case
of the disaccharide 4b, the deacetonation step with 60% aq
AcOH proved to be sufficiently regioselective, affording, af-
ter 3 h at room temperature, the diol 5b in a satisfactory
62% yield, along with the tetraol 23 (31%, Figure 2). Selec-
tively deprotected talopyranosides 6a,b,c and 6e were finally
obtained by benzylation of the intermediate stannylidene
acetals of diols 5a,b,c and 5e. To the best of our knowledge,
the reaction of 3,4-O-stannylidene acetals in the -talopyr-
Scheme 2. Preparation of protected -talopyranosides; Reagents
and conditions: i: TPAP, NMO, CH2Cl2; ii: NaBH4, MeOH; iii:
MeOH/H2O, cat. AcOH; iv: KOH, 18-crown-6, BnBr.
The fully protected -talopyranosides 4a and 4b were
subsequently obtained (Scheme 2) in high yield starting
from 13 and 14 through selective and mild acidic hydrolysis
of the 6-O-methoxyisopropyl acetal, followed by ben-
zylation. Performing the same sequence of reactions on the
15 + 9 mixture afforded a 9:1 diastereoisomeric mixture of
4e and 4h, which proved to be inseparable in our hands.
Scheme 3. Preparation of compound 4c; Reagents and conditions:
i: a) LiAlH4, Et2O, b) Ac2O, MeOH; ii: KOH, 18-crown-6, BnBr.
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E. Attolino, G. Catelani, F. D’Andrea
FULL PAPER
anoside series with electrophiles has been previously re- elimination process took place, but unfortunately, this time
ported only by our group[17b] in the case of derivative 5d, with an almost complete lack of regioselectivity, affording
which reacted exclusively at the equatorial O-3, similarly to mixtures of hex-3- and hex-4-enopyranosides 25 and 26. An
the reported galacto analogues.[27] An identical result was identical result was also obtained in the case of the 2-deoxy
obtained in the case of β-derivatives 5a–c, accessing com- derivative 6i, suggesting a fundamental and specific role ex-
pounds 6a–c, while the α-anomer 5e gave an appreciable erted by the axially disposed electronegative substituent at
amount (9% yield) of the isomer 24, along with predomi- C-2 in the control of the regioselectivity.
nant benzylation at O-3 (6e, 82% yield).
Table 1. 4-Deoxy-hexenopyranoside formation by reaction of 6
with the NaH/Im2SO2 system.
Compound
X
Y
Z
W
Time [h][a]
Isolated yield [%]
25
26
6a
6b
6c
6d
6e
6f
6g
6h
6i
OMe
OMe
OGlc
OGlc
H
OMe
OGlc
H
H
H
H
H
OMe
H
H
OMe
H
NHAc
OBn
OBn
NHAc
OBn
H
H
H
H
H
H
H
H
H
OBn
OBn
OBn
H
2
2
2
2
3
2
2
6
2
95
90
93
91
90
55[b]
46
–
48[c]
–
–
–
–
–
25[b]
30
12
32[c]
Figure 2. Compounds 22–24 and 27e and 27h.
Results and Discussion
When the β--talo alcohols 6a–d, previously transformed
into their sodium salts with NaH in dry DMF, were treated
at –30 °C with an excess (1.5 equiv.) of sulfuryldiimidazole
(Im2SO2), fast and clean reactions took place, revealing the
formation of faster-moving products (by TLC), containing
exclusively the hex-3-enopyranosides 25a–d (Table 1), as as-
certained by NMR analysis. We were not able to observe
(by TLC or NMR) the formation of the putative intermedi-
ate 4-O-imidazylates at any stage of the reaction, because
OMe
[a] All reactions were performed at –30 °C for 1 h, warmed to room
temperature and allowed to react for the reported time. [b] Evalu-
ated through 13C NMR analysis on an inseparable mixture of 25f
and 26f. [c] Estimated from the composition of two differently en-
riched mixtures of the two enol ethers (Experimental Section).
In order to evaluate the possible influence of the anom-
of their fast elimination under the reaction conditions. eric configuration on the reaction outcome, we treated the
Pleasingly in any case, only abstraction of the trans-oriented two α derivatives 6e and 6h, belonging to the talo and the
H-3, promoted by the sodium imidazolate present in the galacto series, respectively, with the NaH/Im2SO2 system.
reaction medium, was observed. After preliminary stud- In both cases, we observed, in the first stage of the reaction
ies,[15,17] we finally standardised the experimental condi- (1 h at –30 °C), the complete disappearance of the starting
tions for this reaction (Table 1), which afforded pure enol material and the formation of a major slower-moving prod-
ethers 25a–d in excellent yields (90–95%). Encouraged by uct (by TLC). Stimulated by the different reactivity of these
the unexpected, completely regioselective abstraction of H- two compounds compared to all the β-configured ones, the
3 with respect to H-5, both of them presenting the same crude mixtures were quenched at this stage, and the corre-
trans relationship with the leaving group at C-4, we ex- sponding 4-O-imidazylates 27e and 27h (Figure 2) were iso-
tended the reaction to the β--galacto derivatives 6f and 6g. lated. In a repetition of these reactions, when the crude mix-
Under the same conditions as described above, the β-gal- tures containing 27e and 27h were warmed to room tem-
acto compounds 6f and 6g showed an identical reactivity perature, the 4-O-imidazylates slowly disappeared. In the
to that of their talo analogues. A simultaneous activation– case of the talo derivative 27e, the 4-deoxy--threo-hex-3-
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Regiospecific Synthesis of 4-Deoxy--threo-hex-3-enopyranosides
FULL PAPER
enopyranoside 25e was the only isolated product (90%
yield), while in the case of the galacto compound 27h, the
known 4-deoxy--erythro-hex-4-enopyranoside 26h,[11a] de-
rived by the elimination with opposite regiochemistry, was
obtained in a very poor yield (12%), because of concurrent
reaction pathways.[29]
From the results collected in Table 1, it can be summa-
rised that: (a) talo-configured 4-O-imidazylate intermedi-
ates of both the α and β series, afforded the 4-deoxy-hex-
3-enopyranosides (25) with complete regioselectivity, while
their galacto and 2-deoxy analogues gave mixtures of 4-de-
oxy-hex-3- (25) and hex-4-pyranosides (26) and (b) 4-O-im-
idazylates belonging to the β anomeric configuration of
both the talo and the galacto series, gave spontaneous elimi-
nations even at low temperature (–30 °C), under the
strongly basic reaction medium, while their α-analogues
(27e and 27h) proved to be quite stable under the same con-
ditions and could be isolated. Although the latter observa-
tion shows a huge difference between α and β anomers, this
is not particularly surprising since it can be tentatively ex-
plained by taking into account Richardson’s general obser-
vations.[30] Richardson noted: a) that the anomeric configu-
ration exerts a strong influence on the reactivity of sulfo-
nates and on the substitution/elimination ratio obtained in
their displacement reactions and b) a lower reaction rate for
the anomer having the minor dipolar moment that is, in
both the -galacto and -talo series, the α anomer.
Much more surprising is the complete regioselectivity
observed in the reaction of the talo 4-O-imidazylates, evi-
dently due to the presence of the axial electronegative sub-
stituent at C-2. It is reasonable to suppose that, in the pres-
ence of a strong base such as the imidazolate anion, at low
temperature and in DMF, the mechanism of the elimination
reactions is an E2-like process with a strong E1cb character.
In particular, we hypothesise a transition state with the in-
termediate 4-O-imidazylates in the most likely chair confor-
mation and a considerable degree of “carbanion character”
at C-3. In the case of talo-configured imidazylates, the in-
coming non-bonding lone pair (in the sp3 carbanion or-
bital) could be stabilised by the parallel axially disposed
substituent at C-2 (Z = OBn or NHAc in Figure 3). This
negative hyperconjugation could arise from the nǞσءC(2)–Z
delocalization of the non-bonding lone pair into the anti-
periplanar antibonding σءC(2)–Z orbital.[31] Because of this
stereoelectronic assistance, H-3 should be more acidic in
this case and more easily abstracted than H-5.
Figure 3. Stereoelectronic interactions affecting the regioselectivity
of 4-O-imidazylate eliminations.
1
compared (Table 2) the JC–H values of a strictly similar
couple of talo- and galactopyranosides (6a and 6f), in order
to determine if there is spectroscopic evidence of the stereo-
electronic effect exerted by the axial benzyloxy group at C-
1
1
2 of 6a. As expected, both the axial JC1–H1 and JC3–H3
values of the talo compound 6a were smaller than the anal-
ogous coupling constants in the galactopyranoside 6f
(Table 2). These data confirm that the σ* acceptor ability
of the C-2 axial benzyloxy group in the talo derivative 6a is
definitely higher than that of the axial H-2 in the corre-
sponding galacto isomer 6f. Moreover, they reveal the fun-
damental role played by the axial substituent stereoelec-
tronic effect in weakening an antiperiplanar C–H bond,
which, to the best of our knowledge, has never been ob-
served before. Of course, we are fully aware that the struc-
ture and interactions present in 6a and 6f are, by far, more
complex than models reported in the literature, and that
1
both the origin[33] and the magnitude of the JC–H values
can be affected by torsional effects of the substituents.[34]
However, the 1JC–H values completely agree with considera-
tions we used to explain the regiospecificity observed in the
elimination reactions of talo 4-O-imidazylates.
1
Table 2. Comparison between JC–H values of a talo- and galacto-
pyranoside couple.
In the case of galacto- and 2-deoxy- 4-O-imidazylates (W
= OBn or H in Figure 3), the stereoelectronic assistance to
the C(3)–H bond breaking cannot be offered neither by the
antibonding σءC(2)–W orbital for geometrical reasons nor by
the antiperiplanar σءC(2)–H antibonding orbital, since the
C–H bond is a good σ donor but a poor σء acceptor.[32]
A spectroscopic manifestation of these hyperconjugative
1JC–H
1JC–H
∆J = Jgal – Jtal
C-1
C-2
C-3
C-4
C-5
C-6
154.1
140.4
137.3
145.0
138.1
143.4
156.4
145.0
139.6
145.7
136.6
143.0
2.3
4.6
2.3
0.7
–1.5
–0.4
1
interactions can be found in the experimental JC–H values.
Recent results from Cuevas and co-workers indicate that
In conclusion, we have reported a full account of a new
any stereoelectronic interaction weakening an axial C–H regiospecific methodology for the high-yielding, one-pot
1
bond is manifested in a smaller JC–Hax value, relative to synthesis of previously unreported 4-deoxy-threo-hex-3-
1
[33]
that of JC–Heq
.
Starting from these considerations, we enopyranosides and their 2-acetamido analogues, starting
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E. Attolino, G. Catelani, F. D’Andrea
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dried, filtered and concentrated. The crude products were com-
posed of 13–15 exclusively, as determined by NMR.
from talopyranosides selectively deprotected at C-4. Prepa-
ration of this uncommon class of sugars has been reported
in detail, and their reactivity in the elimination reactions
has been compared to that exhibited by the analogous gal-
actopyranosides. A specific role of the C-2 axial substituent
in determining the regiospecificity of the elimination of the
axial 4-O-imidazylate intermediates has been demonstrated
and tentatively explained on the basis of stereoelectronic
effects, never invoked before to explain the regioselectivity
of sulfonate elimination reactions. Further studies on other
stereoisomeric series are ongoing in order to define the
scope and limitations of this highly regiocontrolled syn-
thetic methodology for the preparation of useful and chal-
lenging hexenopyranoside enol ethers.
General Procedure for the Demethoxyisopropylation of 13–15: A
solution of 6-O-(1-methoxy-1-methylethyl) derivative (1 mmol) in
MeOH/H2O (10:1, 5 mL) was treated with AcOH (28 µL) and
heated to 50 °C while stirring. After 1 h, TLC analysis revealed the
complete deprotection of the starting material. The solution was
then cooled to room temperature and coevaporated with toluene
(4×20 mL). Purification of the crude residue by flash chromatog-
raphy on silica gel gave products 16–18.
Methyl 3,4-O-Isopropylidene-β-D-talopyranoside (16): Oxidation of
alcohol 7[19] (6.49 g, 21.2 mmol), performed as described above,
gave crude methyl 3,4-O-isopropylidene-6-O-(1-methoxy-1-methyl-
ethyl)-β--lyxo-hexopyranosid-2-ulose (10, 6.40 g, quantitative
yield) as a clear syrup.[20] Reduction of crude 10 (5.56 g, 18.3 mmol)
with NaBH4 in MeOH, according to the reported general pro-
cedure, afforded a clear syrup constituted exclusively by 13 (5.27 g,
94% yield). Some data for methyl 3,4-O-isopropylidene-6-O-(1-
Experimental Section
methoxy-1-methylethyl)-β--talopyranoside (13): Rf
=
0.33
(EtOAc). H NMR (200 MHz, C6D6): δ = 4.30 (d, J1,2 = 2.7 Hz, 1
H, 1-H), 3.93 (m, 2 H, H-3, 4-H), 3.84 (dd, J6a,6b = 9.6 Hz, J5,6a
1
General: Melting points were determined with a Kofler hot-stage
apparatus and are uncorrected. Optical rotations were measured
with a Perkin–Elmer 241 polarimeter at 20 2 °C. 1H and 13C
NMR measurements were performed with a Bruker AC 200 instru-
ment operating at 200 MHz and 50 MHz, respectively, in an appro-
priate solvent (Me4Si as an internal standard). Coupled 13C NMR
measurements were performed with a Varian INOVA600 spectrom-
eter operating at 150 MHz. NMR signal assignments were made,
when possible, with the aid of DEPT experiments, for comparison
with values for known compounds and applying the known addi-
tivity rules,[35] and, in the case of mixtures, referring to the differ-
ences in the peak intensities. All reactions were followed by TLC
on Kieselgel 60 F254 with detection by UV light and/or with etha-
nolic 10% phosphomolybdic or sulfuric acid and heating. Kieselgel
60 (Merck, 70–230 mesh and 230–400 mesh, respectively) was used
for column and flash chromatography. Solvents were dried by dis-
tillation according to standard procedures[36] and storage over 4-Å
molecular sieves, activated for at least 24 h at 400 °C. MgSO4 was
used as a drying agent for solutions. After isolation, all 6-O-(1-
methoxy-1-methylethyl) derivatives 10–12 and 13–15 were stored
at –18 °C in the presence of a trace of Et3N. Elemental analyses
and optical rotations of these compounds were not performed, and
their purity was determined by NMR spectroscopy.
=
3.0 Hz, 1 H, 6a-H), 3.78 (dd, J5,6b = 5.7 Hz, 1 H, 6b-H), 3.55 (m,
1 H, 5-H), 3.47 (dd, J2,3 = 4.7 Hz, 1 H, 2-H), 3.24 (s, 3 H) and 3.16
(s, 3 H) (OCH3-1, OCH3–MIP), 1.30 (s, 6 H, 2×CH3–MIP), 1.59
[s, 3 H, C(CH3)2], 1.20 [s, 3 H, C(CH3)2] ppm. 13C NMR (50 MHz,
C6D6): δ = 109.9 [C(CH3)2], 100.3 (C-1), 100.1 [C(CH3)2-MIP],
73.5, 72.5, 70.9 (C-3, C-4, C-5), 66.7 (C-2), 61.1 (C-6), 55.7 (OCH3-
1), 48.3 (OCH3-MIP), 25.6 [C(CH3)2], 25.3 [C(CH3)2], 24.7 (CH3-
MIP), 24.6 (CH3-MIP) ppm.
Hydrolysis of crude 13 (3.05 g, 10.0 mmol) was performed accord-
ing to the described general procedure. The crude product was puri-
fied by flash chromatography, eluting with EtOAc, and gave pure
16 (96% yield from 7) as a white solid. Rf = 0.16 (EtOAc); m.p.
69–72 °C (EtOAc/hexane). [α]2D0 = –21.2 (c = 1.0, CHCl3). 1H NMR
(200 MHz, CDCl3): δ = 4.46 (d, J1,2 = 1.9 Hz, 1 H, 1-H), 4.32 (dd,
J2,3 = 4.7 Hz, J3,4 = 6.6 Hz, 1 H, 3-H), 4.22 (dd, J4,5 = 2.3 Hz, 1
H, 4-H), 4.00 (dd, J6a,6b = 12.5 Hz, J5,6b = 8.2 Hz, 1 H, 6b-H),
3.90–3.73 (m, 4 H, H-2, H-5, 6a-H, OH), 3.54 (s, 3 H, OCH3), 2.51
(br. s, 1 H, OH), 1.58 [s, 3 H, C(CH3)2], 1.36 [s, 3 H, C(CH3)2]
ppm. 13C NMR (50 MHz, CDCl3): δ = 110.1 [C(CH3)2], 100.4 (C-
1), 73.4, 72.4, 71.6 (C-3, C-4, C-5), 66.1 (C-2), 62.1 (C-6), 56.5
(OCH3), 25.2 [C(CH3)2], 25.1 [C(CH3)2] ppm. C10H18O6 (234.25):
calcd. C 51.27, H 7.75; found C 51.29, H 7.74.
General Procedure for the Oxidation of 7–9: A mixture of alcohol
(1 mmol) and pre-dried 4-methylmorpholine N-oxide (NMO,
1.8 equiv.) in anhydrous CH2Cl2 (20 mL) containing 4 Å powdered
molecular sieves (1 g) was stirred for 30 min at room temperature
under argon. Tetrapropylammonium perruthenate (TPAP,
0.05 equiv.) was added, and the resulting green mixture was stirred
for 1–3 h at room temperature until TLC revealed complete oxi-
dation of the starting material. The mixture was filtered through a
celite-silica gel-celite triple alternate pad, and the filter was washed
with CH2Cl2 and EtOAc. The organic phase was concentrated in
vacuo and afforded the 2-ulose derivatives 10–12 almost pure by
NMR spectroscopy.
4-O-(3,4-O-Isopropylidene-β-
D-talopyranosyl)-2,3:5,6-di-O-iso-
propylidene-aldehydo- -glucose Dimethyl Acetal (17): Oxidation of
D
alcohol 8[18b] (9.0 g, 15.5 mmol) gave 11 (8.46 g, 94% yield) as a
clear syrup, which was almost pure by NMR. Some data for 4-O-
[3,4-O-isopropylidene-6-O-(1-methoxy-1-methylethyl)-β--lyxo-
hexopyranosyl-2-ulose]-2,3:5,6-di-O-isopropylidene-aldehydo--glu-
cose dimethyl acetal (11): Rf = 0.53 (9:1 CH2Cl2/Me2CO). 1H
NMR (200 MHz, C6D6): δ = 5.20 (d, J1Ј,3Ј = 0.7 Hz, 1 H, 1Ј-H),
4.77 (dd, J1,2 = 6.0 Hz, J2,3 = 7.3 Hz, 1 H, 2-H), 4.50–3.50 (m, 11
H, 1-H, 3-H, 4-H, 5-H, 6a-H, 6b-H, 3Ј-H, 4Ј-H, 5Ј-H, 6Јa-H, 6Јb-
H), 3.24 (s, 3 H, OCH3-1), 3.22 (s, 3 H, OCH3-1), 3.17 (s, 3 H,
OCH3-MIP), 1.42 (s, 6 H, 2×CH3-MIP), 1.54 [s, 3 H, C(CH3)2],
1.40 [s, 3 H, C(CH3)2], 1.35 [s, 3 H, C(CH3)2], 1.32 [s, 3 H,
C(CH3)2], 1.31 [s, 3 H, C(CH3)2], 1.20 [s, 3 H, C(CH3)2] ppm. 13C
NMR (50 MHz, C6D6): δ = 197.3 (C-2Ј), 111.0 [C(CH3)2], 110.7
[C(CH3)2], 108.2 [C(CH3)2], 105.8 (C-1), 100.9 (C-1Ј), 100.2
[C(CH3)2-MIP], 78.4, 78.3, 78.2, 77.8 (C-3, C-5, C-3Ј, C-4Ј), 76.7,
76.0 (C-2, C-4), 72.2 (C-5Ј), 65.9 (C-6), 59.9 (C-6Ј), 55.8 (OCH3-1),
53.5 (OCH3-1), 48.4 (OCH3-MIP), 27.7 [C(CH3)2], 27.4 [C(CH3)2],
General Procedure for the Reduction of 10–12: A solution of the
crude 2-uloside (1 mmol) in MeOH (20 mL) was cooled to 0 °C
under argon and treated with an excess of NaBH4 (3 equiv.). The
solution was left to react until TLC analysis showed complete dis-
appearance of the starting material (30 min–1 h). H2O was added
(10 mL), and the resulting solution stirred for an additional 30 min.
MeOH was evaporated under reduced pressure, and the residue was
extracted with CH2Cl2 (4×20 mL). The organic extracts were
5284
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 5279–5292

Regiospecific Synthesis of 4-Deoxy--threo-hex-3-enopyranosides
26.7 [C(CH3)2], 26.6 [C(CH3)2], 26.2 [C(CH3)2], 26.1 [C(CH3)2], by the relative H NMR signal integrations. Data for methyl 3,4-
FULL PAPER
1
24.6 (CH3-MIP), 24.5 (CH3-MIP) ppm.
O-isopropylidene-6-O-(1-methoxy-1-methylethyl)-α--talopyrano-
side (15): H NMR (200 MHz, CDCl3): δ = 4.73 (d, J1,2 = 5.4 Hz,
1
Reduction of crude uloside 11 (3.32 g, 5.74 mmol) gave 14 (3.30 g,
98% yield) as clear syrup, which was pure by NMR spectroscopy.
Data for 4-O-[3,4-O-isopropylidene-6-O-(1-methoxy-1-methyl-
ethyl)-β--talopyranosyl]-2,3:5,6-di-O-isopropylidene-aldehydo--
glucose dimethyl acetal (14): Rf = 0.18 (9:1 CH2Cl2/Me2CO). 1H
NMR (200 MHz, CDCl3): δ = 4.90 (d, J1Ј,2Ј = 2.2 Hz, 1 H, 1Ј-H),
4.53 (dd, J1,2 = 6.3 Hz, J2,3 = 7.4 Hz, 1 H, 2-H), 4.37 (d, 1 H, 1-
H), 4.30–4.17 (m, 3 H, 4-H, 5-H, 6a-H), 4.10–4.00 (m, 2 H, H-6b,
3Ј-H), 3.95 (dd, J3,4 = 1.4 Hz, 1 H, 3-H), 3.80 (ddd, J5Ј,6Јa = 3.9 Hz,
J5Ј,6Јb = 6.0 Hz, 1 H, J4Ј,5Ј = 2.0 Hz, 5Ј-H), 3.77 (dd, J3Ј,4Ј = 6.2 Hz,
1 H, 4Ј-H), 3.65 (dd, J6Јa,6Јb = 9.3 Hz, 1 H, 6Јa-H), 3.58 (dd, 1 H,
1 H, 1-H), 4.55 (dd, J2,3 = 3.4 Hz, J3,4 = 7.4 Hz, 1 H, 3-H), 4.32
(dd, J4,5 = 1.9 Hz, 1 H, 4-H), 3.80 (ddd, J5,6a = 5.4 Hz, J5,6b
=
7.2 Hz, 1 H, 5-H), 3.75–3.60 (m, 3 H, H-2, 6a-H, 6b-H), 3.45 (s, 3
H, OCH3-1), 3.22 (s, 3 H, OCH3-MIP), 2.81 (br. s, 1 H, OH), 1.36
(s, 6 H, 2 × CH3-MIP), 1.51 [s, 3 H, C(CH3)2], 1.35 [s, 3 H,
C(CH3)2] ppm. 13C NMR (50 MHz, CDCl3): δ = 110.1 [C(CH3)2],
101.5 (C-1), 100.0 [C(CH3)2-MIP], 73.5, 73.3 (C-3, C-4), 68.9, 68.6
(C-2, C-5), 59.7 (C-6), 55.1 (OCH3–1), 48.4 (OCH3-MIP), 25.9
[C(CH3)2], 25.1 [C(CH3)2], 24.3 (2×CH3-MIP) ppm.
Hydrolysis of the 15 + 9 (1.52 g, 5.0 mmol) 9:1 mixture gave a white
6Јb-H), 3.45 (m, 1 H, 2Ј-H), 3.43 (s, 6 H, 2×OCH3-1), 3.21 (s, 3 solid (1.15 g, quantitative yield) showing a single spot by TLC (Rf
H, OCH3-MIP), 2.84 (d, J2,OH = 9.7 Hz, 1 H, OH), 1.58 [s, 3 H, = 0.16, EtOAc). The NMR spectra showed a mixture of 18 and its
C(CH3)2], 1.43 [s, 3 H, C(CH3)2], 1.42 [s, 3 H, C(CH3)2], 1.38 [s, 3
galacto epimer in a 9:1 ratio. Some data for 18: 1H NMR
H, C(CH3)2], 1.36 [s, 3 H, C(CH3)2], 1.35, [s, 3 H, C(CH3)2], 1.34 (200 MHz, CDCl3): δ = 4.75 (d, J1,2 = 5.4 Hz, 1 H, 1-H), 4.54 (dd,
(s, 6 H, 2×CH3-MIP) ppm. 13C NMR (50 MHz, CDCl3): δ = 110.0 J2,3 = 3.4 Hz, J3,4 = 7.5 Hz, 1 H, 3-H), 4.32 (dd, J4,5 = 1.8 Hz, 1
[C(CH3)2], 109.4 [C(CH3)2], 107.5 [C(CH3)2], 104.7 (C-1), 100.6 H, 4-H), 3.88 (dd, J6a,6b = 12.0 Hz, J5,6b = 7.5 Hz, 1 H, 6b-H),
[C(CH3)2-MIP], 99.6 (C-1Ј), 77.8, 77.7 (C-3, C-5), 75.6, 74.5 (C-2,
C-4), 73.6, 71.5, 71.4 (C-3Ј, C-4Ј, C-5Ј), 66.9 (C-2Ј), 64.8 (C-6),
59.7 (C-6Ј), 55.3 (OCH3-1), 52.7 (OCH3-1), 48.1 (OCH3-MIP), 27.0
3.81–3.66 (m, 3 H, H-2, H-5, 6a-H), 3.46 (s, 3 H, OCH3), 3.35 (br.
s, 2 H, OH), 2.10 (br. s, 2 H, OH), 1.52 [s, 3 H, C(CH3)2], 1.36 [s,
3 H, C(CH3)2] ppm. 13C NMR (50 MHz, CDCl3): δ = 110.4
[C(CH3)2], 26.1 [C(CH3)2], 25.9 [C(CH3)2], 25.3 [C(CH3)2], 25.0 [C(CH3)2], 101.5 (C-1), 74.1, 73.5 (C-3, C-4), 69.2, 68.5 (C-2, C-
[C(CH3)2], 24.8 [C(CH3)2], 24.0 (CH3-MIP), 23.9 (CH3-MIP) ppm.
5), 62.1 (C-6), 55.5 (OCH3), 25.9 [C(CH3)2], 25.0 [C(CH3)2] ppm.
C10H18O6 (234.25): calcd. C 51.27, H 7.75; found C 51.24, H 7.71.
Hydrolysis of crude 14 (3.20 g, 5.52 mmol) gave 17 (2.10 g, 75%
yield from 8) as a white solid after flash chromatography (2:8 hex-
ane/EtOAc). Rf = 0.22 (2:8 hexane/EtOAc); m.p. 95–98 °C (EtOAc/
hexane). [α]2D0 = +18.3 (c = 1.2, CHCl3). 1H NMR (200 MHz,
CD3CN/D2O): δ = 4.59 (d, J1Ј,2Ј = 1.2 Hz, 1 H, 1Ј-H), 4.44 (dd,
J1,2 = 6.8 Hz, J2,3 = 7.3 Hz, 1 H, 2-H), 4.36 (d, 1 H, 1-H), 4.26–
4.16 (m, 2 H, 3Ј-H, 5-H), 4.06 (dd, J3Ј,4Ј = 5.9 Hz, J4Ј,5Ј = 2.2 Hz,
Methyl 2-Acetamido-2-deoxy-3,4-O-isopropylidene-β-
side (20) and Methyl 2-Acetamido-2-deoxy-3,4-O-isopropylidene-β-
-galactopyranoside (21): A solution of pure oxime 19[20] (988 mg,
D-talopyrano-
D
4.0 mmol), in dry Et2O (50 mL) was added dropwise to a suspen-
sion of LiAlH4 (900 mg, 23.7 mmol) in dry Et2O (80 mL) at room
temperature under argon. The mixture was stirred for 10 min at
1 H, 4Ј-H), 3.98 (dd, J3,4 = 1.4 Hz, 1 H, 3-H), 3.97–3.94 (m, 2 H, room temperature and then heated to reflux. After 2 h, a TLC
6a-H, 6b-H), 3.89 (dd, J4,5 = 4.4 Hz, 1 H, 4-H), 3.79–3.58 (m, 4 H, analysis (3:7 hexane/EtOAc) revealed the complete disappearance
2Ј-H, 5Ј-H, 6Јa-H, 6Јb-H), 3.41 (s, 3 H, OCH3), 3.39 (s, 3 H, of the starting material. The reaction mixture was quenched by
OCH3), 1.46 [s, 3 H, C(CH3)2], 1.34 [s, 3 H, C(CH3)2], 1.33 [s, 3 H,
C(CH3)2], 1.30 [s, 3 H, C(CH3)2], 1.28 [s, 3 H, C(CH3)2], 1.27 [s, 3
H, C(CH3)2] ppm. 13C NMR (50 MHz, CD3CN/D2O): δ = 110.5
the addition of H2O (1.0 mL), aq 15% NaOH (3.0 mL) and H2O
(1.0 mL), followed by an additional 15 min of stirring. The white
precipitated solid was filtered and repeatedly washed with EtOAc.
[C(CH3)2], 110.4 [C(CH3)2], 108.8 [C(CH3)2], 107.6 (C-1), 101.8 (C- The organic phase was dried, filtered and the solvents were evapo-
1Ј), 78.7, 78.2 (C-3, C-5), 76.2, 76.1, 75.2, 75.1, 72.2 (C-3Ј, C-4Ј, rated. The crude product was dissolved in MeOH (40 mL), treated
C-5Ј, C-2, C-4), 67.4 (C-2Ј), 65.9 (C-6), 62.3 (C-6Ј), 57.4 (OCH3), with Ac2O (4.0 mL) and left to react at room temperature over-
54.6 (OCH3), 27.4 [C(CH3)2], 26.8 [C(CH3)2], 26.7 [C(CH3)2], 25.9 night. The reaction mixture was then repeatedly co-evaporated with
[C(CH3)2], 25.7 [C(CH3)2], 25.5 [C(CH3)2] ppm. C23H40O12 toluene (4 × 10 mL), and purification of the residue by flash
(508.56): calcd. C 54.32, H 7.93; found C 54.34, H 7.91.
chromatography (92:8 CH2Cl2/MeOH) allowed the isolation of two
pure acetamido derivatives.
Methyl 3,4-O-Isopropylidene-α-D-talopyranoside (18): Oxidation of
alcohol 9[19] (3.93 g, 12.8 mmol) afforded 12 (3.80 g, 97% yield) as
Data for 20: White solid (680 mg, 62 % yield). Rf = 0.36 (92:8
CH2Cl2/MeOH); m.p. 139–142 °C. [α]2D0 = +7.5 (c = 0.9, CHCl3).
a clear syrup, which was almost pure by NMR spectroscopy. Data
for methyl 3,4-O-isopropylidene-6-O-(1-methoxy-1-methylethyl)-α- 1H NMR (200 MHz, CDCl3): δ = 6.78 (d, J2,NH = 9.2 Hz, 1 H,
-lyxo-hexopyranosyl-2-ulose (12): Rf = 0.65 (95:5 CHCl3/MeOH).
NH), 4.72 (d, J1,2 = 3.7 Hz, 1 H, 1-H), 4.44–4.28 (m, 3 H, 2-H, 3-
H, 4-H), 3.90–3.75 (m, 3 H, H-5, 6a-H, 6b-H), 3.44 (s, 3 H, OCH3),
2.06 (s, 3 H, CH3CO), 1.50 [s, 3 H, C(CH3)2], 1.31 [s, 3 H,
C(CH3)2] ppm. 13C NMR (50 MHz, CDCl3): δ = 170.2 (C=O),
110.1 [C(CH3)2], 98.3 (C-1), 72.5, 71.7, 71.2 (C-3, C-4, C-5), 62.5
1H NMR (200 MHz, C6D6): δ = 4.77 (s, 1 H, 1-H), 4.51 (d, J3,4
5.5 Hz, 1 H, 3-H), 4.34 (ddd, J5,6a = 5.7 Hz, J5,6b = 6.7 Hz, J4,5
=
=
1.9 Hz, 1 H, 5-H), 4.18 (dd, 1 H, 4-H), 3.99 (dd, J6a,6b = 9.7 Hz, 1
H, 6b-H), 3.89 (dd, 1 H, 6a-H), 3.22 (s, 3 H, OCH3-1), 3.11 (s, 3
H, OCH3-MIP), 1.37 (s, 6 H, 2 × CH3-MIP), 1.55 [s, 3 H, (C-6), 56.0 (OCH3), 46.6 (C-2), 25.4 [C(CH3)2], 24.7 [C(CH3)2],
C(CH3)2], 1.28 [s, 3 H, C(CH3)2] ppm. 13C NMR (50 MHz, C6D6):
δ = 198.7 (C-2), 110.6 [C(CH3)2], 100.9 (C-1), 100.1 [C(CH3)2-
MIP], 78.0 (C-4), 76.0 (C-3), 67.5 (C-5), 60.4 (C-6), 54.8 (OCH3-
1), 48.3 (OCH3-MIP), 27.4 [C(CH3)2], 26.3 [C(CH3)2], 24.5
(2×CH3-MIP) ppm.
23.2 (CH3CO) ppm. C12H21NO6 (275.30): calcd. C 52.35, H 7.69,
N 5.09; found C 52.38, H 7.68, N 4.99.
Data for 21: White solid (190 mg, 17 % yield). Rf = 0.26 (92:8
CH2Cl2/MeOH); m.p. 91–92 °C. [α]2D0 = +29.4 (c = 1.0, CHCl3). 1H
NMR (200 MHz, CDCl3): δ = 6.44 (d, J2,NH = 7.7 Hz, 1 H, NH),
Reduction of crude 12 (2.04 g, 6.7 mmol) with NaBH4 in MeOH
at –78 °C gave a clear syrup showing a single spot by TLC (Rf =
4.83 (d, J1,2 = 8.5 Hz, 1 H, 1-H), 4.66 (dd, J2,3 = 8.4 Hz, J3,4
5.4 Hz, 1 H, 3-H), 4.18 (dd, J4,5 = 1.5 Hz, 1 H, 4-H), 4.04–3.83 (m,
=
0.40, EtOAc). The NMR analysis revealed a mixture (1.95 g, 95% 3 H, H-5, 6a-H, 6b-H), 3.51 (s, 3 H, OCH3), 3.18 (m, 1 H, 2-H),
yield) of 15 and its galacto epimer 9[19] in a 9:1 ratio, as estimated
2.01 (s, 3 H, CH3CO), 1.52 [s, 3 H, C(CH3)2], 1.34 [s, 3 H,
Eur. J. Org. Chem. 2006, 5279–5292
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5285

E. Attolino, G. Catelani, F. D’Andrea
FULL PAPER
C(CH3)2] ppm. 13C NMR (50 MHz, CDCl3): δ = 171.0 (C=O), +9.4 (c = 1.0, CHCl3). 1H NMR (200 MHz, CD3CN): δ = 7.38–
110.1 [C(CH3)2], 100.4 (C-1), 75.5, 73.7, 73.3 (C-3, C-4, C-5), 62.4 7.32 (m, 5 H, Ar-H), 6.71 (d, J2,NH = 9.3 Hz, 1 H, NH), 4.60, 4.53
(C-6), 57.6 (C-2), 56.8 (OCH3), 28.1 [C(CH3)2], 26.2 [C(CH3)2],
(AB system, JA,B = 12.0 Hz, 2 H, PhCH2), 4.49 (d, J1,2 = 2.5 Hz,
23.6 (CH3CO) ppm. C12H21NO6 (275.30): calcd. C 52.35, H 7.69, 1 H, 1-H), 4.33 (dd, J2,3 = 5.1 Hz, J3,4 = 6.9 Hz, 1 H, 3-H), 4.26
N 5.09; found C 52.37, H 7.68, N 5.01.
(m, 1 H, H-2), 4.23 (dd, J4,5 = 2.4 Hz, 1 H, 4-H), 4.05 (ddd, J5,6a
= 6.7 Hz, J5,6b = 9.1 Hz, 1 H, 5-H), 3.73 (dd, J6a,6b = 10.2 Hz, 1
H, 6a-H), 3.66 (dd, 1 H, 6b-H), 3.37 (s, 3 H, OCH3), 1.90 (s, 3 H,
CH3CO), 1.41 [s, 3 H, C(CH3)2], 1.26 [s, 3 H, C(CH3)2] ppm. 13C
NMR (50 MHz, CD3CN): δ = 170.4 (C=O), 139.6 (Ar-C), 129.2–
128.4 (Ar-CH), 110.0 [C(CH3)2], 100.2 (C-1), 73.6 (PhCH2), 73.0
(C-3), 72.7 (C-4), 71.9 (C-5), 70.4 (C-6), 56.5 (OCH3), 48.3 (C-2),
26.1 [C(CH3)2], 25.4 [C(CH3)2], 23.3 (CH3CO) ppm. C19H27NO6
(365.43): calcd. C 62.45, H 7.55, N 3.83; found C 62.48, H 7.43, N
3.80.
General Procedure for the Benzylation of 16–18 and 20: Starting
material (1 mmol) was dissolved in THF/H2O (99.5:0.5, 5 mL).
Powdered KOH (4 equiv. per hydroxy group) and 18-crown-6
(0.05 equiv.) were added, and the resulting mixture was vigorously
stirred at room temperature for 30 min. Benzyl bromide (2 equiv.
per hydroxy group) was added, and the reacting mixture was stirred
at room temperature until TLC analysis revealed the complete dis-
appearance of the starting material and the formation of a major
faster-moving product. MeOH (5 mL) was added, and the mixture
was stirred for an additional 10 min. Solvents were evaporated in
vacuo, and the residue was dissolved in CH2Cl2 (10 mL) and
washed with H2O (4 mL). The two phases were separated, and the
aqueous phase was further extracted with CH2Cl2 (2×10 mL). The
organic extracts were dried, concentrated under reduced pressure,
and the residue was purified by flash chromatography.
Methyl 2,6-Di-O-benzyl-3,4-O-isopropylidene-α-D-talopyranoside
(4e): Benzylation of 18 (impure because of its galacto epimer,
1.21 g, 5.16 mmol) gave a clear syrup showing a single spot by TLC
analysis (Rf = 0.24, 8:2 hexane/EtOAc). Flash chromatography of
the crude (8:2 hexane/EtOAc) gave an inseparable mixture of 4e
and its galacto epimer 4h[18c] (1.71 g, 80% yield) in a 9:1 ratio, as
estimated by NMR.
Data for 4e: 1H NMR (200 MHz, CDCl3): δ = 7.42–7.25 (m, 10 H,
Ar-H), 4.83 (d, J1,2 = 5.8 Hz, 1 H, 1-H), 4.81, 4.70 (AB system, JA,B
= 12.4 Hz, 2 H, PhCH2), 4.59, 4.52 (AB system, JA,B = 12.1 Hz, 2
Methyl 2,6-Di-O-benzyl-3,4-O-isopropylidene-β-D-talopyranoside
(4a): Benzylation of crude 16 (3.18 g, 13.6 mmol) gave 4a (5.29 g,
94% yield) as a white solid after flash chromatography (6:4 hexane/
EtOAc). Rf = 0.36 (6:4 hexane/EtOAc); m.p. 50–52 °C. [α]2D0
=
–19.5 (c = 1.4, CHCl3). 1H NMR (200 MHz, CDCl3): δ = 7.40–
7.26 (m, 10 H, Ar-H), 4.78 (s, 2 H, PhCH2), 4.56 (d, J1,2 = 2.4 Hz,
1 H, 1-H), 4.64, 4.54 (AB system, JA,B = 12.0 Hz, 2 H, PhCH2),
H, PhCH2), 4.47 (dd, 1 H, 3-H), 4.20 (dd, J3,4 = 7.6 Hz, J4,5
=
1.7 Hz, 1 H, 4-H), 3.71(ddd, J5,6a = 4.7 Hz, J5,6b = 7.0 Hz, 1 H, 5-
H), 3.68 (dd, J6a,6b = 10.0 Hz, 1 H, 6a-H), 3.59 (dd, 1 H, 6b-H),
3.45 (s, 3 H, OCH3), 3.43 (dd, J2,3 = 2.8 Hz, 1 H, 2-H), 1.50 [s, 3
H, C(CH3)2], 1.33 [s, 3 H, C(CH3)2] ppm. 13C NMR (50 MHz,
CDCl3): δ = 138.2 (Ar-C), 137.8 (Ar-C), 128.2–127.4 (Ar-CH),
110.4 [C(CH3)2], 101.4 (C-1), 75.0, 74.5, 74.4, 73.4 (C-2, C-3, C-4,
C-5), 73.2 (PhCH2), 72.3 (PhCH2), 68.9 (C-6), 54.9 (OCH3), 26.1
[C(CH3)2], 25.2 [C(CH3)2] ppm. C24H30O6 (414.50): calcd. C 69.55,
H 7.30; found C 69.53, H 7.28.
4.37 (dd, J2,3 = 4.5 Hz, J3,4 = 7.3 Hz, 1 H, 3-H), 4.20 (dd, J4,5
=
1.8 Hz, 1 H, 4-H), 3.80–3.76 (m, 3 H, 5-H, 6a-H, 6b-H), 3.49 (dd,
1 H, 2-H), 3.47 (s, 3 H, OCH3), 1.56 [s, 3 H, C(CH3)2], 1.33 [s, 3
H, C(CH3)2] ppm. 13C NMR (50 MHz, CDCl3): δ = 138.1 (Ar-C),
137.8 (Ar-C), 128.2–127.5 (Ar-CH), 110.2 [C(CH3)2], 99.6 (C-1),
73.4 (PhCH2), 72.6 (PhCH2), 72.1, 72.0, 71.6, 71.0 (C-2, C-3, C-4,
C-5), 69.8 (C-6), 56.1 (OCH3), 25.4 [C(CH3)2], 25.1 [C(CH3)2] ppm.
C24H30O6 (414.50): calcd. C 69.55, H 7.30; found C 69.57, H 7.31.
General Procedure for the De-O-isopropylidenation of 4a, 4c and 4e:
The appropriate protected sugar (1 mmol) was dissolved in 80% aq
AcOH (13 mL) and heated to 50 °C while stirring. After 3–5 h,
TLC analysis revealed the complete disappearance of the starting
material and formation of a more retained product. The solution
was then cooled to room temperature and coevaporated with tolu-
ene (4 × 10 mL). The crude product was purified by flash
chromatography.
4-O-(2,6-Di-O-benzyl-3,4-O-isopropylidene-β-
D-talopyranosyl)-
2,3:5,6-di-O-isopropylidene-aldehydo- -glucose Dimethyl Acetal
D
(4b): Benzylation of 17 (2.0 g, 3.93 mmol) gave 4b (2.42 g, 90%
yield) as a clear syrup after flash chromatography (6:4 hexane/
EtOAc). Rf = 0.34 (6:4 hexane/EtOAc). [α]2D0 = –6.3 (c = 1.4,
CHCl3). 1H NMR (200 MHz, CD3CN): δ = 7.44–7.27 (m, 10 H,
Ar-H), 4.73 (s, 2 H, PhCH2), 4.67 (d, J1Ј,2Ј = 1.3 Hz, 1 H, 1Ј-H),
4.54 (s, 2 H, PhCH2), 4.44 (dd, J1,2 = 6.0 Hz, J2,3 = 7.4 Hz, 1 H,
Methyl 2,6-Di-O-benzyl-β-D-talopyranoside (5a): Hydrolysis of 4a
2-H), 4.34 (d, 1 H, 1-H), 4.29 (m, 1 H, 5-H), 4.19 (dd, J2Ј,3Ј
=
(2.64 g, 6.36 mmol) gave 5a (2.37 g, 98% yield) as a clear syrup
after flash chromatography (6:4 hexane/EtOAc). Rf = 0.17 (6:4 hex-
4.4 Hz, J3Ј,4 Ј = 6.1 Hz, 1 H, 3Ј-H), 4.07 (dd, J4Ј,5Ј = 2.7 Hz, 1 H,
4Ј-H), 4.04 (dd, J3,4 = 1.6 Hz, 1 H, 3-H), 3.97–3.83 (m, 5 H, 5Ј-H,
6Јb-H, 4-H, 6a-H, 6b-H), 3.72–3.61 (m, 2 H, 2Ј-H, 6Јa-H), 3.32 (s,
3 H, OCH3), 3.31 (s, 3 H, OCH3), 1.39 [s, 3 H, C(CH3)2], 1.33 [s,
3 H, C(CH3)2], 1.31 [s, 3 H, C(CH3)2], 1.30 [s, 3 H, C(CH3)2], 1.28
[s, 3 H, C(CH3)2], 1.27 [s, 3 H, C(CH3)2] ppm. 13C NMR (50 MHz,
CD3CN): δ = 139.7 (Ar-C), 139.6 (Ar-C), 129.2 –128.2 (Ar-CH),
110.5 [C(CH3)2], 110.4 [C(CH3)2], 108.8, [C(CH3)2], 106.1 (C-1),
102.4 (C-1Ј), 78.4, 78.2, 77.3, 76.4 (C-2, C-3, C-4, C-5), 75.2
(PhCH2), 73.7 (PhCH2), 74.7, 74.4, 72.9, 72.1 (C-2Ј, C-3Ј, C-4Ј, C-
5Ј), 69.9 (C-6Ј), 66.1 (C-6), 56.0 (OCH3), 54.34 (OCH3), 27.4
[C(CH3)2], 27.2 [C(CH3)2], 26.9 [C(CH3)2], 26.1 [C(CH3)2], 26.0
[C(CH3)2], 25.3 [C(CH3)2] ppm. C37H52O12 (688.81): calcd. C
64.52, H 7.61; found C 64.48, H 7.59.
ane/EtOAc). [α]2D0 = –82.3 (c = 1.4, CHCl3). H NMR (200 MHz,
1
CD3CN): δ = 7.39–7.28 (m, 10 H, Ar-H), 4.86, 4.66 (AB system,
JA,B = 11.4 Hz, 2 H, PhCH2), 4.55 (s, 2 H, PhCH2), 4.36 (d, J1,2
=
0.7 Hz, 1 H, 1-H), 3.81 (m, 1 H, 2-H), 3.77–3.64 (m, 2 H, H-4, 6a-
H), 3.61–3.53 (m, 3 H, 3-H,5- H, 6b-H), 3.50 (s, 3 H, OCH3), 3.08
(br. s, 2 H, 2×OH) ppm. 13C NMR (50 MHz, CD3CN): δ = 139.7
(Ar-C), 139.5 (Ar-C), 129.2–128.4 (Ar-CH), 103.6 (C-1), 80.3 (C-
2), 75.8 (C-5), 76.1 (PhCH2), 73.7 (PhCH2), 70.4 (C-6), 70.7, 69.8
(C-3, C-4), 57.2 (OCH3) ppm. C21H26O6 (374.43): calcd. C 67.36,
H 7.00; found C 67.34, H 7.03.
4-O-(2,6-Di-O-benzyl-β-
idene-aldehydo- -glucose Dimethyl Acetal (5b) and 4-O-(2,6-Di-O-
benzyl-β- -talopyranosyl)-2,3-O-isopropylidene-aldehydo- -glucose
D-talopyranosyl)-2,3:5,6-di-O-isopropyl-
D
D
D
Methyl 2-Acetamido-6-O-benzyl-2-deoxy-3,4-O-isopropylidene-β-
D
-
Dimethyl Acetal (23): A solution of 4b (1.13 g, 1.63 mmol) in 60%
aq AcOH (22 mL) was stirred at room temperature. After 3 h, TLC
analysis (2:8 hexane/EtOAc) revealed the complete disappearance
of the starting material (Rf = 0.65) and formation of two products
talopyranoside (4c): Benzylation of pure 20 (980 mg, 3.56 mmol)
gave 4c (1.09 g, 84% yield) as a clear syrup after flash chromatog-
raphy (2:8 hexane/EtOAc). Rf = 0.10 (2:8 hexane/EtOAc). [α]2D0
=
5286
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 5279–5292

Regiospecific Synthesis of 4-Deoxy--threo-hex-3-enopyranosides
FULL PAPER
(Rf = 0.51 and Rf = 0.06). The reacting mixture was neutralised by
the addition of aq 15 % NaOH and extracted with EtOAc
(4×20 mL). The organic phase was dried, filtered and concentrated
in vacuo. Flash chromatography (EtOAcǞ95:5 EtOAc/MeOH) of
the residue gave pure 5b (652 mg, 62% yield), and 23 (314 mg, 31%
yield).
3.83–3.68 (m, 4 H, 2-H, 4-H, 6a-H, 6b-H), 3.37 (s, 3 H, OCH3),
3.12 (d, J3,OH = 10.9 Hz, 1 H, OH-3), 2.98 (d, J4,OH = 11.3 Hz, 1
H, OH-4) ppm. 13C NMR (50 MHz, CDCl3): δ = 138.1 (Ar-C),
136.9 (Ar-C), 128.5–127.5 (Ar-CH), 98.4 (C-1), 78.5 (C-2), 73.7
(PhCH2), 73.4 (PhCH2), 70.4, 70.1 (C-3, C-5), 69.8 (C-6), 66.0 (C-
4), 55.0 (OCH3) ppm. C21H26O6 (374.43): calcd. C 67.36, H 7.00;
found C 67.33, H 7.02.
Data for 5b: Clear syrup. Rf = 0.51 (2:8 hexane/EtOAc). [α]2D0
=
–40.3 (c = 0.9, CHCl3). 1H NMR (200 MHz, CDCl3): δ = 7.34–
7.26 (m, 10 H, Ar-H), 4.77 (s, 1 H, 1Ј-H), 5.07, 4.61 (AB system,
JA,B = 11.4 Hz, 2 H, PhCH2), 4.54 (m, 1 H, 2-H), 4.57, 4.50 (AB
system, JA,B = 12.0 Hz, 2 H, PhCH2), 4.36 (d, J1,2 = 6.1 Hz, 1 H,
1-H), 4.30 (dt, J4,5 = 2.3 Hz, J5,6a = J5,6b = 6.9 Hz, 1 H, 5-H), 4.20
(m, 1 H, 4-H), 4.19–3.95 (m, 4 H, 2Ј-H, 3-H, 6a-H, 6b-H), 3.79–
3.48 (m, 5 H, 3Ј-H, 4Ј-H, 5Ј-H, 6Јa-H, 6Јb-H), 3.32 (s, 6 H,
2×OCH3), 3.03 (d, J = 13.0 Hz, 1 H, OH), 2.97 (d, J = 12.1 Hz,
1 H, OH), 1.39 [s, 3 H, C(CH3)2], 1.35 [s, 3 H, C(CH3)2], 1.34 [s, 3
H, C(CH3)2], 1.33 [s, 3 H, C(CH3)2] ppm. 13C NMR (50 MHz,
CDCl3): δ = 138.0 (Ar-C), 137.7 (Ar-C), 128.5–127.6 (Ar-CH),
109.9 [C(CH3)2], 107.8 [C(CH3)2], 104.8 (C-1), 102.5 (C-1Ј), 78.9,
78.4, 77.5 (C-2Ј, C-3, C-5), 75.1, 74.9, 74.8 (C-5Ј, C-2, C-4), 75.7
(PhCH2), 73.4 (PhCH2), 69.3, 69.2 (C-3Ј, C-4Ј), 68.4 (C-6Ј), 64.8
(C-6), 55.4 (OCH3), 52.9 (OCH3), 26.9 [C(CH3)2], 26.8 [C(CH3)2],
26.5 [C(CH3)2], 24.9 [C(CH3)2] ppm. C34H48O12 (648.75): calcd. C
62.95, H 7.46; found C 62.97, H 7.48.
Methyl 3,6-Di-O-benzyl-2-deoxy-β-D-lyxo-hexopyranoside (5i):
Method A [with MeOH/TsOH]: Compound 4i[18d] (774 mg,
2.51 mmol) was dissolved in MeOH (7.5 mL), treated with TsOH
(15 mg), and the reacting mixture was stirred at room temperature
for 3 h.[18d] Et3N (0.5 mL) was added, and the resulting solution
was stirred for an additional 10 min. The mixture was concentrated
in vacuo to give a yellow syrup showing a single spot by TLC
analysis (Rf = 0.23, 1:9 hexane/EtOAc). Flash chromatography (1:9
hexane/EtOAc) gave a white solid mixture of diols 5i and 22
(541 mg, 80% yield) in a 85:15 ratio, as estimated by NMR spec-
troscopy. In a repetition of the experiment, the solution was stirred
at room temperature for 30 h and a 35:65 mixture of 5i and 22 was
1
obtained. Selected H NMR signals (200 MHz, CDCl3): δ = 4.85
(22, t, J1,2ax = J1,2eq = 2.3 Hz, 1 H, 1-H), 4.34 (5i, dd, J1,2ax
=
9.7 Hz, J1,2eq = 2.3 Hz, 1 H, 1-H) ppm. Selected 13C NMR signals
(50 MHz, CDCl3): δ = 101.2 (5i, C-1), 98.7 (22, C-1), 73.5 (5i, C-
5), 70.6 (22, C-6), 69.7 (5i, C-6), 68.5, 67.8 (5i, C-3, C-4), 69.0, 68.5,
65.5 (22, C-3, C-4, C-5), 56.5 (5i, OCH3), 54.7 (22, OCH3), 34.7
(5i, C-2), 32.7 (22, C-2) ppm. Method B [with 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (DDQ)]: Compound 4i[18d] (820 mg,
2.66 mmol) was dissolved in a CH3CN/H2O (9:1, 16 mL), treated
with DDQ (31 mg), and the resulting dark red reaction mixture
was stirred at room temperature. After 7 h, a TLC analysis (2:8
hexane/EtOAc) revealed the complete disappearance of the starting
material. The solution was then decolourised by the addition of
charcoal (400 mg), and the mixture was stirred at room tempera-
ture for an additional 30 min. The suspension was filtered, and
the solution was concentrated in vacuo. The residue (525 mg) was
purified by flash chromatography (1:9 hexane/EtOAc) and gave
pure 5i (606 mg, 85% yield) as a white solid. Rf = 0.23 (1:9 hexane/
EtOAc); m.p. 81–82 °C, [α]2D0 = –42.4 (c = 1.1, CHCl3); ref.[18d]
Data for 23: White solid. Rf = 0.12 (95:5 EtOAc/MeOH); m.p. 51–
53 °C (EtOAc/hexane). [α]2D0 = –36.3 (c = 1.0, CHCl3). 1H NMR
(200 MHz, CDCl3): δ = 7.35–7.26 (m, 10 H, Ar-H), 4.71 (s, 1 H,
1Ј-H), 5.05, 4.62 (AB system, JA,B = 11.3 Hz, 2 H, PhCH2), 4.54
(s, 2 H, PhCH2), 4.52 (dd, J1,2 = 5.7 Hz, J2,3 = 7.7 Hz 1 H, 2-H),
4.39 (d, 1 H, 1-H), 4.22 (dd, J3,4 = 1.3 Hz, 1 H, 3-H), 4.03 (dd, J4,5
= 5.3 Hz, 1 H, 4-H), 3.98–3.42 (m, 9 H, 2Ј-H, 3Ј-H, 4Ј-H, 5Ј-H,
6Јa-H, 6Јb-H, 5-H, 6a-H, 6b-H), 3.35 (br. s, 1 H, OH), 3.34 (s, 6
H, 2×OCH3), 3.20 (br. s, 3 H, 3× OH), 1.40 [s, 3 H, C(CH3)2],
1.39 [s, 3 H, C(CH3)2] ppm. 13C NMR (50 MHz, CDCl3): δ = 137.9
(Ar-C), 137.6 (Ar-C), 128.5–127.7 (Ar-CH), 110.0 [C(CH3)2], 104.7
(C-1), 101.2 (C-1Ј), 79.0, 77.1 (C-2Ј, C-3), 75.7 (PhCH2), 73.5
(PhCH2), 76.1, 75.3, 75.0, 72.8 (C-5Ј, C-2, C-4, C-5), 69.3, 69.2 (C-
3Ј, C-4Ј), 68.8 (C-6Ј), 63.4 (C-6), 55.5 (OCH3), 53.6 (OCH3), 26.9
[C(CH3)2], 26.8 [C(CH3)2] ppm. C31H44O12 (608.68): calcd. C
61.17, H 7.29; found C 61.13, H 7.27.
[α]2D0 = –33 (c = 3.6, CHCl3), m.p. 81–82 °C. H NMR (200 MHz,
1
CDCl3): δ = 7.36–7.29 (m, 5 H, Ar-H), 4.58 (s, 2 H, PhCH2), 4.32
(dd, J1,2eq = 2.2 Hz, J1,2ax = 9.7 Hz, 1 H, 1-H), 3.81 (m, 1 H, 4-H),
3.68 (m, 1 H, 3-H), 3.75–3.50 (m, 3 H, 5-H, 6a-H, 6b-H), 3.50 (s,
Methyl 2-Acetamido-6-O-benzyl-2-deoxy-β-D-talopyranoside (5c):
Hydrolysis of 4c (538 mg, 1.47 mmol) gave 5c (2.37 g, quantitative
3 H, OCH3), 3.05 (d, J4,OH = 5.9 Hz, 1 H, OH-4), 2.90 (d, J3,OH
=
yield) as a solid foam. Rf = 0.26 (92:8 CH2Cl2/MeOH). [α]2D0
=
8.6 Hz 1 H, OH-3), 2.00 (ddd, J2ax,2eq = 12.2 Hz, J2eq,3 = 5.0 Hz,
1 H, 2eq-H), 1.70 (ddd, J2ax,3 = 12.6 Hz, 1 H, 2ax-H) ppm. 13C
NMR (50 MHz, CDCl3): δ = 137.8 (Ar-C), 128.1–127.4 (Ar-CH),
101.0 (C-1), 73.5 (C-5), 73.2 (PhCH2), 69.6 (C-6), 68.3, 67.5 (C-3,
C-4), 56.2 (OCH3), 34.3 (C-2) ppm. C14H20O5 (268.31): calcd. C
62.67, H 5.71; found C 62.65, H 5.72.
1
–50.6 (c = 1.6, CHCl3). H NMR (200 MHz, CD3CN): δ = 7.37–
7.32 (m, 5 H, Ar-H), 6.69 (d, J2,NH = 9.6 Hz, 1 H, NH), 4.55 (s, 2
H, PhCH2), 4.34 (d, J1,2 = 1.7 Hz 1 H, 1-H), 4.27 (m, 1 H, 2-H),
3.74 (m, 1 H, 4-H), 3.62 (dd, J2,3 = 4.3 Hz, J3,4 = 2.5 Hz, 1 H, 3-
H), 3.71–3.60 (m, 3 H, 5-H, 6a-H, 6b-H), 3.40 (s, 3 H, OCH3), 1.88
(s, 3 H, CH3CO) ppm. 13C NMR (50 MHz, CD3CN): δ = 173.7
(C=O), 139.1 (Ar-C), 129.3–128.6 (Ar-CH), 102.0 (C-1), 75.1 (C-
5), 73.7 (PhCH2), 70.5 (C-6), 69.1 (C-4), 68.5 (C-3), 57.1 (OCH3),
52.8 (C-2), 23.5 (CH3CO) ppm. C16H23NO6 (325.36): calcd. C
59.07, H 7.13, N 4.30; found C 59.10, H 7.11, N 4.27.
General Procedure for the Stannylidenation–Benzylation of 5a–i: A
mixture of the appropriate diol (1 mmol) and dibutyltin oxide
(1.28 equiv.) in toluene (15 mL) was heated to reflux with a Dean–
Stark apparatus overnight. Tetrabutylammonium bromide
(0.5 equiv.) and benzyl bromide (1.36 equiv.) were added, and the
reaction mixture was stirred at reflux until TLC analysis revealed
the complete disappearance of the starting material (5–6 h). The
solution was cooled to room temperature, concentrated to dryness,
and the resulting residue was purified by flash chromatography,
eluting first with hexane (100 mL) and then with the appropriate
eluent.
Methyl 2,6-Di-O-benzyl-α-D-talopyranoside (5e): Hydrolysis of the
9:1 4e/4h mixture (1.32 g, 3.18 mmol) yielded a crude residue con-
stituted by a 9:1 mixture of 5e/5h.[25c] Flash chromatography (1:1
hexane/EtOAc) gave pure 5e (1.05 g, 88% yield) as a white solid.
Rf = 0.37 (1:1 hexane/EtOAc); m.p. 73–75 °C. [α]2D0 = +11.2 (c =
1.1, CHCl3). 1H NMR (200 MHz, CDCl3): δ = 7.35–7.24 (m, 10
H, Ar-H), 4.85 (d, J1,2 = 1.4 Hz, 1 H, 1-H), 4.69, 4.57 (AB system,
JA,B = 11.4 Hz, 2 H, PhCH2), 4.63, 4.53 (AB system, JA,B
=
Methyl 2,3,6-Tri-O-benzyl-β-D-talopyranoside (6a): Selective ben-
11.9 Hz, 2 H, PhCH2), 3.91 (bt, 1 H, 5-H), 3.82 (bt, 1 H, 3-H), zylation of 5a (1.19 g, 3.18 mmol) gave 6a (1.44 g, 97% yield) as a
Eur. J. Org. Chem. 2006, 5279–5292
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5287

E. Attolino, G. Catelani, F. D’Andrea
FULL PAPER
clear syrup after flash chromatography (7:3 hexane/EtOAc). Rf =
0.23 (7:3 hexane/EtOAc). [α]2D0 = –47.1 (c = 1.5, CHCl3). 1H NMR
(200 MHz, CDCl3): δ = 7.41–7.25 (m, 15 H, Ar-H), 4.95, 4.80 (AB
system, JA,B = 11.9 Hz, 2 H, PhCH2), 4.59 (s, 2 H, PhCH2), 4.67,
Data for 6e: Clear syrup; Rf = 0.31 (7:3 hexane/EtOAc). [α]2D0
=
1
+36.2 (c = 1.1, CHCl3). H NMR (200 MHz, CD3CN): δ = 7.42–
7.28 (m, 15 H, Ar-H), 4.85 (d, J1,2 = 1.7 Hz, 1 H, 1-H), 4.76, 4.69
(AB system, JA,B = 11.5 Hz, 2 H, PhCH2), 4.67, 4.54 (AB system,
JA,B = 11.8 Hz, 2 H, PhCH2), 4.54 (s, 2 H, PhCH2), 3.95 (m, 1 H,
4-H), 3.82 (m, 1 H, 5-H), 3.79 (dd, J2,3 = 4.8 Hz, 1 H, 2-H), 3.69
(dd, J6a,6b = 9.9 Hz, J5,6a = 5.1 Hz, 1 H, 6a-H), 3.68 (s, 3 H, OCH3),
3.67 (dd, J3,4 = 5.0 Hz, 1 H, 3-H), 3.64 (dd, J5,6b = 7.1 Hz, 1 H, 6b-
4.48 (AB system, JA,B = 12.1 Hz, 2 H, PhCH2), 4.25 (d, J1,2
=
0.7 Hz, 1 H, 1-H), 4.05–3.91 (m, 3 H, 2-H, 4-H, 6a-H), 3.84 (dd,
J6a,6b = 13.2 Hz, 1 H, 6b-H), 3.73 (d, J4,OH = 10.3 Hz, 1 H, OH),
3.56 (s, 3 H, OCH3), 3.47 (dt, J4,5 = 1.0 Hz, J5,6a = J5,6b = 6.0 Hz,
1 H, 5-H), 3.33 (t, J2,3 = J3,4 = 3.0 Hz, 1 H, 3-H) ppm. 13C NMR H), 3.49 (d, J4,OH = 10.0 Hz, 1 H, OH) ppm. 13C NMR (50 MHz,
(50 MHz, CDCl3): δ = 138.1 (Ar-C), 137.8 (Ar-C), 137.7 (Ar-C),
128.3–126.8 (Ar-CH), 102.5 (C-1), 76.4 (C-2), 75.7, 75.6 (C-3, C-
5), 75.1 (PhCH2), 73.6 (PhCH2), 69.4, 69.3 (C-6, PhCH2), 66.8 (C-
CD3CN): δ = 139.7 (Ar-C), 139.6 (Ar-C), 139.0 (Ar-C), 129.4–
128.4 (Ar-CH), 100.1 (C-1), 77.5 (C-2), 74.2 (C-3), 74.3 (PhCH2),
73.7 (PhCH2), 71.4 (C-5), 70.9, 70.2 (C-6, PhCH2), 68.5 (C-4), 55.2
4), 57.0 (OCH3) ppm. C28H32O6 (464.56): calcd. C 72.39, H 6.94; (OCH3) ppm. C28H32O6 (464.56): calcd. C 72.39, H 6.94; found C
found C 72.37, H 6.93.
72.36, H 6.95.
4-O-(2,3,6-Tri-O-benzyl-β-
D
-talopyranosyl)-2,3:5,6-di-O-isopropyl- Data for 24: Clear syrup; Rf = 0.21 (7:3 hexane/EtOAc). [α]2D0
=
1
idene-aldehydo-
D
-glucose Dimethyl Acetal (6b): Selective ben- +15.3 (c = 0.9, CHCl3). H NMR (200 MHz, CD3CN): δ = 7.39–
zylation of 5b (640 mg, 0.98 mmol) gave 6b (716 mg, 98% yield) as
a white solid after flash chromatography (7:3 hexane/EtOAc). Rf =
0.19 (7:3 hexane/EtOAc); m.p. 90–94 °C. [α]2D0 = –31.2 (c = 1.0,
CHCl3). 1H NMR (200 MHz, CDCl3): δ = 7.44–7.25 (m, 15 H, Ar-
H), 4.93, 4.81 (AB system, JA,B = 11.6 Hz, 2 H, PhCH2), 4.66 (s,
7.24 (m, 15 H, Ar-H), 4.83 (d, J1,2 = 1.6 Hz, 1 H, 1-H), 4.67, 4.54
(AB system, JA,B = 11.6 Hz, 2 H, PhCH2), 4.69, 4.52 (AB system,
JA,B = 11.3 Hz, 2 H, PhCH2), 4.57, 4.50 (AB system, JA,B
=
11.8 Hz, 2 H, PhCH2), 3.94 (dt, J5,6a = J5,6b = 6.2 Hz, 1 H, 5-H),
3.82 (t, J2,3 = J3,4 = 4.0 Hz, 1 H, 3-H), 3.68 (dd, J4,5 = 1.8 Hz, 1
H, 4-H), 3.62 (m, 2 H, 6a-H, 6b-H), 3.48 (dd, 1 H, 2-H), 3.31 (s, 3
H, OCH3), 2.42 (br. s, 1 H, OH) ppm. 13C NMR (50 MHz,
CD3CN): δ = 140.1 (Ar-C), 139.5 (Ar-C), 139.4 (Ar-C), 129.3–
128.3 (Ar-CH), 99.6 (C-1), 78.1, 77.5 (C-2, C-4), 75.8 (PhCH2),
73.8 (PhCH2), 73.7 (PhCH2), 70.3 (C-6), 70.1 (C-5), 67.4 (C-3), 55.2
(OCH3) ppm. C28H32O6 (464.56): calcd. C 72.39, H 6.94; found C
72.38, H 6.93.
1 H, 1Ј-H), 4.52 (m, 1 H, 2-H), 4.58, 4.49 (AB system, JA,B
11.9 Hz, 2 H, PhCH2), 4.64, 4.48 (AB system, JA,B = 12.3 Hz, 2 H,
PhCH2), 4.34 (d, J1,2 = 6.0 Hz, 1 H, 1-H), 4.25 (dt, J5,6a = J5,6b
6.9 Hz, 1 H, 5-H), 4.13 (dd, J3,4 = 1.4 Hz, J4,5 = 2.4 Hz, 1 H, 4-
H), 4.07–3.97 (m, 4 H, 2Ј-H, 5Ј-H, 6a-H, 6b-H), 3.93 (dd, J2,3
7.6 Hz, 1 H, 3-H), 3.81 (dd, J6Јa,6Јb = 9.3 Hz, J5Ј,6Јb = 7.1 Hz, 1 H,
6Јb-H), 3.77 (d, J4Ј,OH = 10.7 Hz, 1 H, OH), 3.59 (dd, J5Ј,6Јa
=
=
=
=
5.2 Hz, 1 H, 6Јa-H), 3.46 (m, 1 H, 4Ј-H), 3.29 (s, 6 H, 2×OCH3),
3.27 (t, J2Ј,3Ј = J3Ј,4Ј = 2.9 Hz, 1 H, 3Ј-H), 1.36 [s, 3 H, C(CH3)2],
1.35 [s, 3 H, C(CH3)2], 1.33 [s, 3 H, C(CH3)2], 1.28 [s, 3 H,
C(CH3)2] ppm. 13C NMR (50 MHz, CDCl3): δ = 138.2 (Ar-C),
138.0 (Ar-C), 137.8 (Ar-C), 128.4–127.6 (Ar-CH), 110.0 [C(CH3)2],
107.8 [C(CH3)2], 104.7 (C-1), 102.1 (C-1Ј), 78.4, 77.6, 76.6 (C-2Ј,
C-3, C-5), 75.7, 75.3, 74.9, 74.7 (C-3Ј, C-5Ј, C-2, C-4), 75.2
(PhCH2), 73.5 (PhCH2), 69.4, 68.6 (C-6Ј, PhCH2), 66.6 (C-4Ј), 64.9
(C-6), 55.4 (OCH3), 52.8 (OCH3), 27.0 [C(CH3)2], 26.7 [C(CH3)2],
26.5 [C(CH3)2], 24.9 [C(CH3)2] ppm. C41H54O12 (738.87): calcd. C
66.65, H 7.37; found C 66.61, H 7.36.
Methyl 2,3,6-Tri-O-benzyl-β-D-galactopyranoside (6f): Selective
benzylation of 5f[25a] (3.91 g, 10.46 mmol) gave 6f (4.47 g, 92%
yield) as a clear syrup after flash chromatography (7:3 hexane/
EtOAc). Rf = 0.37 (7:3 hexane/EtOAc). [α]2D0 = +3.3 (c = 1.0,
CHCl3); ref.[26] [α]2D0 = +3.4 (c = 3.6, CHCl3). 1H NMR (200 MHz,
CDCl3): δ = 7.36–7.22 (m, 15 H, Ar-H), 4.89, 4.71 (AB system,
JA,B = 11.0 Hz, 2 H, PhCH2), 4.70 (s, 2 H, PhCH2), 4.58 (s, 2 H,
PhCH2), 4.27 (d, J1.2 = 7.6 Hz, 1 H, 1-H), 4.00 (dd, 1 H, 4-H), 3.80
(dd, J6a,6b = 9.9 Hz, J5,6a = 5.5 Hz, 1 H, 6a-H), 3.72 (dd, J5,6b
6.0 Hz, 1 H, 6b-H), 3.64 (dd, J2,3 = 9.4 Hz, 1 H, 2-H), 3.56 (s, 3
H, OCH3), 3.54 (ddd, J4,5 = 1.1 Hz, 1 H, 5-H), 3.48 (dd, J3,4
=
=
Methyl 2-Acetamido-3,6-di-O-benzyl-2-deoxy-β-
(6c): Selective benzylation of 5c (471 mg, 1.45 mmol) gave 6c
D
-talopyranoside
3.3 Hz, 1 H, 3-H), 2.60 (br. s, 1 H, OH) ppm. 13C NMR (50 MHz,
CDCl3): δ = 138.5 (Ar-C), 137.9 (Ar-C), 137.8 (Ar-C), 128.4–127.5
(Ar-CH), 104.6 (C-1), 80.4 (C-2), 78.9 (C-3), 73.0 (C-5), 75.0
(PhCH2), 73.6 (PhCH2), 72.3 (PhCH2), 69.1 (C-6), 66.7 (C-4), 56.9
(481 mg, 80% yield) as a clear syrup after flash chromatography
(2:8 hexane/EtOAc). Rf = 0.13 (2:8 hexane/EtOAc). [α]2D0 = –81.5
1
(c = 1.0, CHCl3). H NMR (200 MHz, CDCl3): δ = 7.35–7.27 (m, (OCH3) ppm.
10 H, Ar-H), 6.73 (d, J2,NH = 9.9 Hz, 1 H, NH), 4.79 (ddd, J1,2
1.6 Hz, J2,3 = 4.2 Hz, 1 H, 2-H), 4.72, 4.37 (AB system, JA,B
=
=
4-O-[2,3,6-Tri-O-benzyl-β-
propylidene-aldehydo-
D-galactopyranosyl)-2,3:5,6-di-O-iso-
D
-glucose Dimethyl Acetal (6g): Selective ben-
11.8 Hz, 2 H, PhCH2), 4.57 (s, 2 H, PhCH2), 4.25 (d, 1 H, 1-H),
3.89 (m, 1 H, 4-H), 3.81 (dd, J6a,6b = 9.8 Hz, J5,6b = 5.7 Hz, 1 H,
6b-H), 3.74 (dd, J5,6a = 5.4 Hz, 1 H, 6a-H), 3.50 (s, 3 H, OCH3),
3.49 (m, 2 H, H-5, OH), 3.38 (dd, J3,4 = 3.2 Hz, 1 H, 3-H), 2.00 (s,
3 H, CH3CO) ppm. 13C NMR (50 MHz, CD3CN): δ = 170.7
(C=O), 137.6 (Ar-C), 137.0 (Ar-C), 128.4–127.6 (Ar-CH), 101.3 (C-
1), 73.9 (C-5), 73.8 (C-3), 69.7 (C-6), 73.5 (PhCH2), 69.2 (PhCH2),
67.6 (C-4), 56.8 (OCH3), 47.7 (C-2), 23.5 (CH3CO) ppm.
C23H29NO6 (415.48): calcd. C 66.49, H 7.04, N 3.37; found C
66.52, H 7.02, N 3.34.
zylation of 5g[25b] (2.0 g, 3.08 mmol) gave 6g (2.1 g, 92% yield) as
a clear syrup after flash chromatography (6:4 hexane/EtOAc). Rf =
1
0.47 (4:6 hexane/EtOAc). [α]2D0 = +1.3 (c = 1.0, CHCl3). H NMR
(200 MHz, CDCl3): δ = 7.39–7.25 (m, 15 H, Ar-H), 4.68 (d, J1Ј,2Ј
= 7.3 Hz, 1 H, 1Ј-H), 4.72, 4.65 (AB system, JA,B = 11.7 Hz, 2 H,
PhCH2), 4.91, 4.63 (AB system, JA,B = 11.2 Hz, 2 H, PhCH2), 4.54
(dd, J1,2 = 6.4 Hz, J2,3 = 7.1 Hz, 1 H, 2-H), 4.59, 4.50 (AB system,
JA,B = 11.9 Hz, 2 H, PhCH2), 4.34 (d, 1 H, 1-H), 4.29 (m, 1 H, 5-
H), 4.20–3.92 (m, 5 H, 4Ј-H, 3-H, 4-H, 6a-H, 6b-H), 3.75 (dd, J2Ј,3Ј
= 9.4 Hz, 1 H, 2Ј-H), 3.68–3.54 (m, 3 H, 5Ј-H, 6Јa-H, 6Јb-H), 3.48
(dd, J3Ј,4Ј = 3.4 Hz, 1 H, 3Ј-H), 3.31 (s, 3 H, OCH3), 3.30 (s, 3 H,
OCH3), 2.52 (d, J4Ј,OH = 2.1 Hz, 1 H, OH), 1.43 [s, 3 H,
C(CH3)2], 1.41 [s, 3 H, C(CH3)2], 1.40 [s, 3 H, C(CH3)2], 1.32 [s, 3
H, C(CH3)2] ppm. 13C NMR (50 MHz, CDCl3): δ = 138.6 (Ar-C),
138.5 (Ar-C), 137.8 (Ar-C), 128.2–127.5 (Ar-CH), 110.2 [C(CH3)2],
108.4 [C(CH3)2], 105.1 (C-1), 103.1 (C-1Ј), 80.8, 79.3, 77.8, 77.5 (C-
Methyl 2,3,6-Tri-O-benzyl-α-
D-talopyranoside (6e) and Methyl
2,4,6-Tri-O-benzyl-α- -talopyranoside (24): Stannylidenation–ben-
D
zylation of 5e (520 mg, 1.39 mmol) gave a crude residue showing
two spots by TLC (Rf = 0.31 and 0.21, 7:3 hexane/EtOAc). After
chromatography (7:3 hexane/EtOAc), 6e (527 mg, 82% yield) and
24 (57 mg, 9% yield) were isolated.
5288
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 5279–5292

Regiospecific Synthesis of 4-Deoxy--threo-hex-3-enopyranosides
2Ј, C-3Ј, C-2, C-3), 74.7, 74.2 (C4, C-5), 72.7 (C-5Ј), 75.3 (PhCH2),
FULL PAPER
(AB system, JA,B = 12.5 Hz, 2 H, PhCH2), 4.76, 4.68 (AB system,
73.6 (PhCH2), 72.3 (PhCH2), 68.4 (C-6Ј), 66.4 (C-4Ј), 65.5 (C-6), JA,B = 11.5 Hz, 2 H, PhCH2), 4.65, 4.56 (AB system, JA,B
=
55.4 (OCH3), 52.6 (OCH3), 27.5 [C(CH3)2], 26.7 [C(CH3)2], 26.6
[C(CH3)2], 25.3 [C(CH3)2] ppm. C41H54O12 (738.87): calcd. C
66.65, H 7.37; found C 66.62, H 7.35.
11.9 Hz, 2 H, PhCH2), 4.51 (d, 1 H, 1-H), 4.42 (m, 1 H, 5-H), 3.97
(t, J1,2 = J2,5 = 1.9 Hz, 1 H, 2-H), 3.72 (dd, J6a,6b = 9.7 Hz, J5,6a
=
5.6 Hz, 1 H, 6a-H), 3.59 (s, 3 H, OCH3), 3.55 (dd, J5,6b = 6.2 Hz,
1 H, 6b-H) ppm. 13C NMR (50 MHz, CDCl3): δ = 152.1 (C-3),
138.8 (Ar-C), 138.0 (Ar-C), 136.3 (Ar-C), 128.2–127.6 (Ar-CH),
101.6 (C-1), 98.6 (C-4), 73.4 (PhCH2), 73.1 (PhCH2), 72.6 (PhCH2),
72.5, 72.1 (C-2, C-5), 69.1 (C-6), 56.7 (OCH3) ppm. C28H30O5
(446.54): calcd. C 75.31, H 6.77; found C 75.32, H 6.76.
Methyl 2,3,6-Tri-O-benzyl-α-D-galactopyranoside (6h): Selective
benzylation of 5h[25c] (1.86 g, 4.97 mmol) gave 6h (2.11 g, 91 %
yield) as a clear syrup after flash chromatography (7:3 hexane/
EtOAc). Rf = 0.23 (7:3 hexane/EtOAc). [α]2D0 = +32.7 (c = 1.1,
CHCl3); ref.[26] [α]2D0 = +34 (c = 3.0, CHCl3). H NMR (200 MHz,
1
CDCl3): δ = 7.38–7.25 (m, 15 H, Ar-H), 4.80, 4.69 (AB system,
JA,B = 11.6 Hz, 2 H, PhCH2), 4.68 (dd, J1.2 = 4.1 Hz, 1 H, 1-H),
4-O-[2,3,6-Tri-O-benzyl-4-deoxy-β-
2,3:5,6-di-O-isopropylidene-aldehydo-
D
-threo-hex-3-enopyranosyl)-
-glucose Dimethyl Acetal
D
4.82, 4.66 (AB system, JA,B = 12.1 Hz, 2 H, PhCH2), 4.60, 4.53 (25b): Activation–elimination of 6b (600 mg, 0.81 mmol) gave 25b
(AB system, JA,B = 11.0 Hz, 2 H, PhCH2), 4.05 (m, 1 H, 4-H), (525 mg, 90% yield) as a clear syrup after chromatography (6:4
3.86–3.92 (m, 3 H, 2-H, 3-H, 5-H), 3.73 (dd, J6a,6b = 9.9 Hz, J5,6b
= 6.3 Hz, 1 H, 6b-H), 3.66 (dd, J5,6a = 5.2 Hz, 1 H, 6a-H), 3.38 (s,
3 H, OCH3), 2.62 (br. s, 1 H, OH) ppm. 13C NMR (50 MHz,
CDCl3): δ = 138.2 (Ar-C), 138.0 (Ar-C), 137.8 (Ar-C), 128.3–127.5
(Ar-CH), 98.4 (C-1), 77.5, 75.6 (C-2, C-3), 73.5 (PhCH2), 73.4
hexane/EtOAc + 0.1% Et3N). Rf = 0.42 (6:4 hexane/EtOAc). [α]2D0
= +4.3 (c = 1.2, CHCl3). H NMR (200 MHz, CDCl3): δ = 7.39–
7.20 (m, 15 H, Ar-H), 4.99 (d, J4Ј,5Ј = 1.5 Hz, 1 H, H-4Ј), 4.90 (d,
J1Ј,2Ј = 1.9 Hz, 1 H, 1Ј-H), 4.91, 4.79 (AB system, JA,B = 12.3 Hz,
2 H, PhCH2), 4.77, 4.69 (AB system, JA,B = 13.2 Hz, 2 H, PhCH2),
1
(PhCH2), 72.6 (PhCH2), 69.5 (C-6), 68.2, 67.9 (C-4, C-5), 55.2 4.66 (dd, J1,2 = 6.0 Hz, J2,3 = 7.5 Hz, 1 H, 2-H), 4.60, 4.52 (AB
(OCH3) ppm.
system, JA,B = 12.2 Hz, 2 H, PhCH2), 4.37 (d, 1 H, 1-H), 4.33 (m,
1 H, 5Ј-H-), 4.30 (dt, J4,5 = 2.7 Hz, J5,6a = J5,6b = 6.9 Hz, 1 H, 5-
H), 4.18–3.95 (m, 5 H, 2Ј-H, 3-H, 4-H, 6a-H, 6b-H), 3.68 (dd,
Methyl 3,6-Di-O-benzyl-2-deoxy-β-D-lyxo-hexopyranoside (6i): Se-
lective benzylation of 5i (600 mg, 2.24 mmol) gave 6i (787 mg, 98%
yield) as a clear syrup after flash chromatography (6:4 hexane/
EtOAc). Rf = 0.36 (6:4 hexane/EtOAc). [α]2D0 = –11.9 (c = 1.1,
CHCl3), ref.[18d] [α]2D0 = –13. 1H NMR (200 MHz, CDCl3): δ =
7.30–7.26 (m, 10 H, Ar-H), 4.60 (s, 2 H, PhCH2), 4.64, 4.57 (AB
system, JA,B = 12.1 Hz, 2 H, PhCH2), 4.33 (dd, J1,2eq = 2.3 Hz,
J6Јa,6Јb = 9.5 Hz, J5Ј,6Јa = 5.3 Hz, 1 H, 6Јa-H), 3.47 (dd, J5Ј,6Јb
=
6.6 Hz, 1 H, 6Јb-H), 3.34 (s, 3 H, OCH3), 3.32 (s, 3 H, OCH3), 1.42
[s, 3 H, C(CH3)2], 1.38 [s, 3 H, C(CH3)2], 1.35 [s, 3 H, C(CH3)2],
1.34 [s, 3 H, C(CH3)2] ppm. 13C NMR (50 MHz, CDCl3): δ = 152.4
(C-3Ј), 138.7 (Ar-C), 138.1 (Ar-C), 136.5 (Ar-C), 128.3–127.2 (Ar-
CH), 110.2 [C(CH3)2], 107.8 [C(CH3)2], 104.8 (C-1), 101.6 (C-1Ј),
99.3 (C-4Ј), 78.3, 77.7 (C-2, C-3), 74.9, 74.8 (C-4, C-5), 73.3
(PhCH2), 73.1 (PhCH2), 72.7 (PhCH2), 72.9, 72.7 (C-2Ј, C-5Ј), 69.2
(C-6Ј), 65.0 (C-6), 55.3 (OCH3), 52.9 (OCH3), 27.2 [C(CH3)2], 26.6
[C(CH3)2], 26.5 [C(CH3)2], 25.1 [C(CH3)2] ppm. C41H52O11
(720.86): calcd. C 68.31, H 7.27; found C 68.33, H 7.25.
J1,2ax = 9.5 Hz, 1 H, 1-H), 4.00 (m, 1 H, 5-H), 3.84 (dd, J6a,6b
=
9.9 Hz, J5,6b = 5.9 Hz, 1 H, 6b-H), 3.83 (dd, J5,6a = 5.9 Hz, 1 H,
6a-H), 3.53 (ddd, J3,4 = 3.0 Hz, J2eq,3 = 5.0 Hz, J2ax,3 = 11.9 Hz, 1
H, 3-H), 3.50 (s, 3 H, OCH3), 3.49 (dd, J4,5 = 5.3 Hz, 1 H, 4-H),
2.03 (ddd, 1 H, J2ax,2eq = 12.3 Hz, 2eq-H), 1.83 (ddd, 1 H, 2ax-H),
1.64 (br. s, 1 H, OH) ppm. 13C NMR (50 MHz, CDCl3): δ = 138.0
(Ar-C), 137.6 (Ar-C), 128.5–126.7 (Ar-CH), 101.0 (C-1), 75.0, 73.7 Methyl 2-Acetamido-3,6-di-O-benzyl-2,4-dideoxy-β-
D-threo-hex-3-
(C-3, C-5), 73.7 (PhCH2), 69.9, 69.5 (C-6, PhCH2), 64.9 (C-4), 56.4 enopyranoside (25c): Activation–elimination reaction of 6c (360 mg,
(OCH3), 32.0 (C-2) ppm. C21H26O5 (358.43): calcd. C 70.37, H
7.31; found C 70.34, H 7.32.
0.86 mmol) gave 25c (317 mg, 93% yield) as a clear syrup after
flash chromatography (2:8 hexane/EtOAc + 0.1% Et3N). Rf = 0.21
(2:8 hexane/EtOAc). [α]2D0 = +2.2 (c = 1.1, CHCl3). 1H NMR
(200 MHz, CD3CN): δ = 7.38–7.29 (m, 10 H, Ar-H), 6.32 (d, J2,NH
= 9.0 Hz, 1 H, NH), 4.86 (d, J4,5 = 1.8 Hz, 1 H, 4-H), 4.80, 4.70
(AB system, JA,B = 12.0 Hz, 2 H, PhCH2), 4.58 (d, J1,2 = 1.9 Hz,
1 H, 1-H), 4.58–4.50 (m, 3 H, H-2, PhCH2), 4.42 (m, 1 H, 5-H),
3.57 (dd, J6a,6b = 9.9 Hz, J5,6 b = 6.1 Hz, 1 H, 6b-H), 3.50 (dd, J5,6a
= 4.9 Hz, 1 H, 6a-H), 3.41 (s, 3 H, OCH3), 1.82 (s, 3 H, CH3CO)
ppm. 13C NMR (50 MHz, CD3CN): δ = 152.6 (C-3), 138.7 (Ar-C),
137.2 (Ar-C), 128.7–127.2 (Ar-CH), 100.1 (C-1), 97.3 (C-4), 73.4
(PhCH2), 73.3 (PhCH2), 72.2 (C-5), 69.2 (C-6), 55.9 (OCH3), 48.6
(C-2), 22.8 (CH3CO) ppm. C23H27NO5 (397.47): calcd. C 69.50, H
6.85, N 3.52; found C 69.48, H 6.87, N 3.49.
General Procedure for the Activation–Elimination Reaction of 6a–i:
Sodium hydride (200 mg of a 60 % dispersion in mineral oil,
5.0 mmol), was washed with dry hexane (4×1 mL) and suspended
in dry DMF (5 mL). The mixture was treated with a solution of
the appropriate alcohol (1.0 mmol) in dry DMF (20 mL) at room
temperature under argon. The resulting mixture was stirred at room
temperature for 30 min and then cooled to –30 °C. Solid Im2SO2
(290 mg, 1.46 mmol) was added, and the reacting mixture was
stirred at –30 °C for an additional 1 h. The mixture was warmed
to room temperature and further stirred until TLC analysis re-
vealed the complete formation of a faster-moving product (see
Table 1). The reaction was quenched by the addition of MeOH
(1 mL), and the resulting solution was poured onto a mixture of
ice and diethyl ether (20 mL). The two phases were separated, and
the aqueous solution was further extracted with diethyl ether
4-O-(2-Acetamido-3,6-di-O-benzyl-2,4-dideoxy-β-
enopyranosyl)-2,3:5,6-di-O-isopropylidene-aldehydo-
methyl Acetal (25d): Activation–elimination reaction of 5d[17b]
D
-threo-hex-3-
D
-glucose Di-
(1×20 mL). The organic extracts were dried, filtered and concen- (525 mg, 0.76 mmol) gave 25d (465 mg, 91% yield) as a clear syrup
trated in vacuo. The crude residue was purified by flash chromatog-
raphy.
after chromatography. The spectroscopic and analytical data of 25d
completely agreed with those reported in the literature.[17b]
Methyl 2,3,6-Tri-O-benzyl-4-deoxy-β-
D
-threo-hex-3-enopyranoside
Methyl 2,3,6-Tri-O-benzyl-4-deoxy-α-D-threo-hex-3-enopyranoside
(25a): Activation–elimination of 6a (464 mg, 1.0 mmol) gave 25a (25e) and Methyl 2,3,6-Tri-O-benzyl-4-O-(1-imidazolylsulfonyl)-α-
(423 mg, 95% yield) as a clear syrup after chromatography (7:3
D-talopyranoside (27e): The activation–elimination reaction of 6e
hexane/EtOAc + 0.1% Et3N). Rf = 0.47 (6:4 hexane/EtOAc). [α]2D0
(196 mg, 0.42 mmol) was performed as described in the general
procedure and gave 25e (168 mg, 90% yield) as a clear syrup after
flash chromatography (8:2 hexane/EtOAc + 0.1% Et3N). Rf = 0.24
1
= –1.6 (c = 1.1, CHCl3). H NMR (200 MHz, CDCl3): δ = 7.38–
7.21 (m, 15 H, Ar-H), 4.92 (d, J4,5 = 1.7 Hz, 1 H, 4-H), 4.88, 4.79
Eur. J. Org. Chem. 2006, 5279–5292
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5289

E. Attolino, G. Catelani, F. D’Andrea
FULL PAPER
(8:2 hexane/EtOAc). [α]2D0 = +73.3 (c = 1.0, CHCl3). 1H NMR
system, JA,B = 11.3 Hz, 2 H, PhCH2), 4.54 (s, 2 H, PhCH2), 4.52
(dd, J1,2 = 6.4 Hz, J2,3 = 6.9 Hz, 1 H, 2-H), 4.43 (m, 1 H, 5Ј-H),
4.36 (d, 1 H, 1-H), 4.18–3.98 (m, 6 H, 2Ј-H, 3-H, 4-H, 5-H, 6a-H,
6b-H), 3.58 (dd, J6Јa,6Јb = 9.6 Hz, J5Ј,6Јa = 5.3 Hz, 1 H, 6Јa-H), 3.39
(dd, J5Ј,6Јb = 6.5 Hz, 1 H, 6Јb-H), 3.33 (s, 6 H, 2×OCH3), 1.41 [s,
(200 MHz, CDCl3): δ = 7.38–7.22 (m, 15 H, Ar-H), 4.95 (d, J1,2
=
1.0 Hz, 1 H, 1-H), 4.92 (d, J4,5 = 1.9 Hz, 1 H, 4-H), 4.76 (s, 2 H,
PhCH2), 4.74, 4.64 (AB system, JA,B = 12.1 Hz, 2 H, PhCH2), 4.64,
4.57 (AB system, JA,B = 12.0 Hz, 2 H, PhCH2), 4.45 (m, 1 H, 5-
H), 3.81 (t, J2,5 = 1.0 Hz, 1 H, 2-H), 3.68 (dd, J6a,6b = 9.8 Hz, J5,6b 3 H, C(CH3)2], 1.40 [s, 3 H, C(CH3)2], 1.39 [s, 3 H, C(CH3)2], 1.33
= 6.5 Hz, 1 H, 6b-H), 3.54 (dd, J5,6a = 5.2 Hz, 1 H, 6a-H), 3.45 (s,
[s, 3 H, C(CH3)2] ppm. 13C NMR (50 MHz, CDCl3): δ = 153.0 (C-
3Ј), 138.1 (Ar-C), 138.0 (Ar-C), 136.5 (Ar-C), 128.3–127.5 (Ar-
3 H, OCH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 150.2 (C-3),
137.9 (Ar-C), 137.8 (Ar-C), 136.2 (Ar-C), 128.0–127.1 (Ar-CH), CH), 110.2 [C(CH3)2], 108.3 [C(CH3)2], 105.0 (C-1), 102.2 (C-1Ј),
100.3 (C-1), 97.2 (C-4), 72.7 (C-2), 73.1 (PhCH2), 73.0 (PhCH2), 97.6 (C-4Ј), 78.0, 77.4 (C-3, C-5), 75.9, 74.9, 74.5 (C-2Ј, C-2, C-4),
71.0 (PhCH2), 68.4 (C-6), 67.2 (C-5), 55.3 (OCH3) ppm. C28H30O5 74.4 (PhCH2), 73.3 (PhCH2), 72.9 (PhCH2), 71.1 (C-5Ј), 69.4 (C-
(446.54): calcd. C 75.31, H 6.77; found C 75.29, H 6.78.
6Ј), 65.5 (C-6), 55.3 (OCH3), 52.8 (OCH3), 27.4 [C(CH3)2], 26.7
[C(CH3)2], 26.6 [C(CH3)2], 25.2 [C(CH3)2] ppm. C41H52O11
(720.86): calcd. C 68.31, H 7.27; found C 68.28, H 7.24.
In a repetition of the experiment, the reaction was set up as de-
scribed in the general procedure, but it was quenched after 1 h at
–30 °C and then rapidly worked up as usual. In this case, the NMR
analysis of the crude product revealed the formation of compound
27e.
Data for 26g: Clear syrup; Rf = 0.18 (2:8 hexane/EtOAc). [α]2D0
=
+10.6 (c = 1.2, CHCl3). 1H NMR (200 MHz, CDCl3): δ = 7.34–
7.25 (m, 15 H, Ar-H), 5.31 (d, J1Ј,2Ј = 6.9 Hz, 1 H, 1Ј-H), 5.07 (d,
J3Ј,4Ј = 3.1 Hz, 1 H, 4Ј-H), 4.86, 4.68 (AB system, JA,B = 11.6 Hz,
2 H, PhCH2), 4.56 (s, 2 H, PhCH2), 4.54 (s, 2 H, PhCH2), 4.46 (dd,
J1,2 = 6.3 Hz, J2,3 = 7.4 Hz, 1 H, 2-H), 4.35 (d, 1 H, 1-H), 4.30 (m,
1 H, 5-H), 4.14 (m, 3 H, 3Ј-H, 4-H, 6a-H), 4.06 (dd, J3,4 = 5.9 Hz,
1 H, 3-H), 3.98 (dd, J6a,6b = 8.8 Hz, J5,6b = 6.5 Hz, 1 H, 6b-H),
3.91 (br. s, 2 H, 6Јa-H, 6Јb-H), 3.75 (dd, J2Ј,3Ј = 5.7 Hz, 1 H, 2Ј-
H), 3.36 (s, 6 H, 2×OCH3), 1.41 [s, 3 H, C(CH3)2], 1.39 [s, 3 H,
C(CH3)2], 1.38 [s, 3 H, C(CH3)2], 1.33, [s, 3 H, C(CH3)2] ppm. 13C
NMR (50 MHz, CDCl3): δ = 149.6 (C-5Ј), 138.4 (Ar-C), 138.2 (Ar-
C), 137.9 (Ar-C), 128.3–127.4 (Ar-CH), 110.2 [C(CH3)2], 108.3
[C(CH3)2], 105.2 (C-1), 101.0 (C-1Ј), 98.7 (C-4Ј), 78.2, 77.9, 77.7
(C-2Ј, C-3, C-5), 74.9, 74.8, 74.5 (C-3Ј, C-2, C-4), 73.7 (PhCH2),
72.6 (PhCH2), 70.9 (PhCH2), 68.5 (C-6Ј), 65.3 (C-6), 55.7 (OCH3),
52.9, (OCH3), 27.3 [C(CH3)2], 26.6 [C(CH3)2], 26.5 [C(CH3)2], 25.2
[C(CH3)2] ppm. C41H52O11 (720.86): calcd. C 68.31, H 7.27; found
C 68.35, H 7.29.
Data for 27e: Clear syrup. 1H NMR (200 MHz, CD3CN): δ = 7.97
(s, 1 H, H-2Ј), 7.29–7.42 (m, 16 H, Ar-H and 4Ј-H), 6.96 (s, 1 H,
5Ј-H), 5.37 (dd, J3,4 = 3.2 Hz, J4,5 = 1.4 Hz, 1 H, 4-H), 4.83 (d, J1,2
= 1.4 Hz, 1 H, 1-H), 4.59, 4.48 (AB system, JA,B = 12.0 Hz, 2 H,
PhCH2), 4.57 (s, 2 H, PhCH2), 4.56, 4.52 (AB system, JA,B
11.4 Hz, 2 H, PhCH2), 4.10 (m, 1 H, 5-H), 3.79 (dd, 1 H, J2,3
3.8 Hz, 3-H), 3.66–3.60 (m, 3 H, H-2, 6a-H, 6b-H), 3.31 (s, 3 H,
OCH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 138.1 (C-2Ј), 138.9
(Ar-C), 138.6 (Ar-C), 137.6 (Ar-C), 130.4 (C-5Ј), 128.9–128.0 (Ar-
CH), 117.7 (C-4Ј), 100.2 (C-1), 82.7, 74.4, 72.5, 67.7 (C-2, C-3, C-
4, C-5), 73.7 (PhCH2), 73.4 (PhCH2), 71.3 (PhCH2), 68.7 (C-6),
55.4 (OCH3) ppm.
=
=
Methyl 2,3,6-Tri-O-benzyl-4-deoxy-β-
side (25f) and Methyl 2,3,6-Tri-O-benzyl-4-deoxy-α-
D
-erythro-hex-3-enopyrano-
-threo-hex-4-
L
enopyranoside (26f): Activation–elimination of 6f (283 mg,
0.61 mmol) yielded a crude residue constituted by two enol ethers
showing a single spot by TLC (Rf = 0.33, 8:2 hexane/EtOAc).
Chromatography of the residue on silica gel (8:2 hexane/EtOAc +
0.1% Et3N) gave an inseparable mixture of 25f and 26f (217 mg,
80% yield) in a 55:25 ratio, as estimated by NMR spectroscopy.
Methyl 2,3,6-Tri-O-benzyl-4-deoxy-β-
(26h) and Methyl 2,3,6-Tri-O-benzyl-4-O-(1-imidazolylsulfonyl)-α-
-galactopyranoside (27h): The activation–elimination reaction of
L-threo-hex-4-enopyranoside
D
6h (354 mg, 0.76 mmol) was set up as described in the general pro-
cedure. The reaction was quenched after 1 h at –30 °C and worked
up as usual. Chromatography (1:1 hexane/EtOAc) of the residue
gave 26h (36 mg, 10% yield) and 27h (334 mg, 74% yield).
1
Selected H NMR (200 MHz, CDCl3) signals of 25f: δ = 4.92 (d,
J4,5 = 2.3 Hz, 1 H, 4-H), 4.76 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 4.58 (m,
1 H, 5-H), 3.91 (dd, J2,5 = 1.3 Hz, 1 H, 2-H), 3.61 (dd, J6a,6b
=
Data for 26h: Clear syrup; Rf = 0.31 (75:25 hexane/EtOAc). [α]2D0
= +76.8 (c = 1.2, CHCl3); ref.[11a] [α]2D0 = +78 (c = 1.0, CHCl3). 1H
NMR (200 MHz, CDCl3): δ = 7.38–7.22 (m, 15 H, Ar-H), 5.03 (d,
J3,4 = 2.9 Hz, 1 H, 4-H), 4.85 (d, J1,2 = 2.4 Hz, 1 H, 1-H), 4.80,
4.73 (AB system, JA,B = 12.3 Hz, 2 H, PhCH2), 4.62 (s, 2 H,
PhCH2), 4.56, 4.50 (AB system, JA,B = 11.9 Hz, 2 H, PhCH2), 4.24
(ddt, J3,6a = J3,6b = 1.3 Hz, 1 H, 3-H), 3.91 (br. s, 2 H, 6a-H, 6b-
H), 3.78 (dd, J2,3 = 6.9 Hz, 1 H, 2-H), 3.50 (s, 3 H, OCH3) ppm.
13C NMR (50 MHz, CDCl3): δ = 148.6 (C-5), 138.4 (Ar-C), 138.1
(Ar-C), 137.9 (Ar-C), 128.3–127.6 (Ar-CH), 99.7, 99.6 (C-1, C-4),
76.1, 73.2 (C-2, C-3), 73.0 (PhCH2), 72.1 (PhCH2), 71.3 (PhCH2),
69.0 (C-6), 56.6 (OCH3) ppm.
9.4 Hz, J5,6b = 6.7 Hz, 1 H, 6b-H), 3.45 (s, 3 H, OCH3), 3.44 (dd,
J5,6a = 6.0 Hz, 1 H, 6a-H) ppm. Selected 13C NMR (50 MHz,
CDCl3) signals of 25f: δ = 151.4 (C-3). 102.1 (C-1), 96.9 (C-4), 74.1
(C-2), 73.6 (PhCH2), 73.2 (PhCH2), 72.7 (PhCH2), 71.0 (C-5), 69.0
(C-6), 55.9 (OCH3) ppm. Spectroscopic data for the minor product
26f completely agreed with those reported in the literature.[37]
C28H30O5 (446.54): calcd. C 75.31, H 6.77; found C 75.27, H 6.74.
4-O-(2,3,6-Tri-O-benzyl-4-deoxy-β-
2,3:5,6-di-O-isopropylidene-aldehydo-
(25g) and 4-O-(2,3,6-Tri-O-benzyl-4-deoxy-α-
anosyl)-2,3:5,6-di-O-isopropylidene-aldehydo-
D
-erythro-hex-3-enopyranosyl)-
-glucose Dimethyl Acetal
-threo-hex-4-enopyr-
-glucose Dimethyl
D
L
D
Acetal (26g): Activation–elimination of 6g (500 mg, 0.68 mmol)
gave a crude residue constituted by a 25g and 26g mixture in a
60:40 ratio, as estimated by NMR spectroscopy. Chromatography
of the crude mixture on silica gel (8:2 hexane/EtOAc + 0.1% Et3N)
allowed a complete separation of the two enol ethers 25g (225 mg,
46% yield) and 26g (147 mg, 30% yield).
Data for 27h: Clear syrup; Rf = 0.39 (1:1 hexane/EtOAc). [α]2D0
+39.3 (c = 1.4, CHCl3). H NMR (200 MHz, CDCl3): δ = 7.88 (s,
1 H, Im-H2). 7.41–7.25 (m, 16 H, 15 Ar-H, Im-H4), 6.98 (s, 1 H,
Im-H5), 5.36 (d, J3,4 = 2.8 Hz, 1 H, 4-H), 4.82, 4.69 (AB system,
JA,B = 11.1 Hz, 2 H, PhCH2), 4.79, 4.57 (AB system, JA,B
12.1 Hz, 2 H, PhCH2), 4.56 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 4.51, 4.41
(AB system, JA,B = 11.2 Hz, 2 H, PhCH2), 4.03 (m, 1 H, 5-H), 3.96
=
1
=
Data for 25g: Clear syrup; Rf = 0.18 (2:8 hexane/EtOAc). [α]2D0
=
–30.4 (c = 0.9, CHCl3). 1H NMR (200 MHz, CDCl3): δ = 7.37– (dd, J2,3 = 10.8 Hz, 1 H, 3-H), 3.60 (dd, 1 H, 2-H), 3.54 (dd, J6a,6b
7.21 (m, 15 H, Ar-H), 5.00 (d, J1Ј,2Ј = 6.2 Hz, 1 H, 1Ј-H), 4.92 (d,
= 9.0 Hz, J5,6a = 5.7 Hz, 1 H, 6a-H), 3.45 (dd, J5,6b = 8.5 Hz, 1 H,
J4Ј,5Ј = 1.2 Hz, 1 H, 4Ј-H), 4.79 (s, 2 H, PhCH2), 4.73, 4.70 (AB 6b-H), 3.35 (s, 3 H, OCH3) ppm. 13C NMR (50 MHz, CDCl3): δ
5290
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 5279–5292

Regiospecific Synthesis of 4-Deoxy--threo-hex-3-enopyranosides
FULL PAPER
[4] a) T. Tsuchiya, F. Nakamura, S. Umezawa, Tetrahedron Lett.
1979, 20, 2805–2808; b) J. D. Prugh, A. A. Deana, Tetrahedron
Lett. 1982, 23, 281–284; c) E. P. Barrette, L. Goodman, J. Org.
Chem. 1984, 49, 176–178.
[5] a) D. H. Ball, F. W. Parrish, Adv. Carbohydr. Chem. Biochem.
1969, 24, 139; b) D. H. Ball, F. W. Parrish, Adv. Carbohydr.
Chem. Biochem. 1968, 23, 223.
= 137.6 (Ar-C), 137.3 (Ar-C), 137.1 (Ar-C), 137.1 (Im-C2), 130.2
(Im-C5), 128.4–127.9 (Ar-CH), 118.2 (Im-C4), 98.6 (C-1), 83.5 (C-
4), 74.9, 74.8 (C-2, C-3), 73.6 (PhCH2), 73.5 (PhCH2), 73.4
(PhCH2), 67.2 (C-6), 66.7 (C-5), 55.6 (OCH3) ppm. C31H34N2O8S
(594.69): calcd. C 62.61, H 5.76, N 4.71, S 5.39; found C 62.53, H
5.70, N 4.69, S 5.20.
[6] K. Freudenberg, F. Brauns, Ber. Dtsch. Chem. Ges. 1922, 55,
In a repetition of the experiment, the reaction was set up as de-
scribed in the general procedure. After 1 h at –30 °C, the reacting
mixture was warmed to room temperature and stirred until the
TLC analysis revealed the complete disappearance of 27h. The mix-
ture was then quenched and worked up as usual, furnishing a syr-
upy residue constituted (TLC, 1:1 hexane/EtOAc) by 26h and other
products with Rf = 0. Chromatography of the residue gave pure
hex-4-enopyranoside 26h (43 mg, 12% yield).
3233.
[7]
a) F. Chètrien, Synth. Commun. 1989, 19, 1015; b) A. Corsaro,
G. Catelani, F. D’Andrea, S. Fisichella, M. Mariani, V. Pistarà,
Environ. Sci. Pollut. Res. 2003, 10, 325–328; c) G. Catelani, A.
Corsaro, F. D’Andrea, M. Mariani, V. Pistarà, E. Vittorino,
Carbohydr. Res. 2003, 338, 2349–2358.
[8]
K. M. Khan, S. Perveen, S. T. A. Shah, M. S. Shekhani, W. Vo-
elter, New J. Chem. 2001, 25, 896–898.
[9]
D. Horton, J. P. Roski, P. Norris, J. Org. Chem. 1996, 61, 3783–
Methyl 3,6-Di-O-benzyl-2,4-dideoxy-β-
side (25i) and Methyl 3,6-Di-O-benzyl-2,4-dideoxy-α-
D
-glycero-hex-3-enopyrano-
3793.
L-glycero-hex-
[10]
[11]
R. W. Binkley, M. G. Ambrose, J. Carbohydr. Chem. 1984, 3,
1–49.
a) A. El Nemr, T. Tsuchiya, Y. Kobayashi, Carbohydr. Res.
1996, 293, 31–59; b) A. El Nemr, T. Tsuchiya, Carbohydr. Res.
1997, 303, 267–281; c) A. El Nemr, T. Tsuchiya, Carbohydr.
Res. 2001, 330, 205–214.
a) J. M. Vatèle, S. Hanessian, Tetrahedron 1996, 52, 10557–
10568; b) S. Hanessian, Preparative Carbohydrate Chemistry,
M. Dekker, New York, 1997, pp. 127–149.
a) E. Bousquet, M. Khitri, L. Lay, F. Nicotra, L. Panza, G.
Russo, Carbohydr. Res. 1998, 311, 171–181; b) S. David, A.
Malleron, C. Dini, Carbohydr. Res. 1989, 188, 193–200.
To the best of our knowledge, only a 4Ј-O-imidazylate lactoside
affording an uncharacterised elimination product at room tem-
perature has been reported by M. Bernabe, A. Fernandez-
Mayoralas, J. Jimenez-Barbero, M. Martin-Lomas, A. Rivera,
J. Chem. Soc., Perkin Trans. 2 1989, 1867–1873.
E. Attolino, G. Catelani, F. D’Andrea, Tetrahedron Lett. 2002,
43, 1685–1688.
a) V. Moreau, J. C. Norrild, H. Driguez, Carbohydr. Res. 1997,
300, 271–277; b) J. C. McAuliffe, R. V. Stick, Aust. J. Chem.
1997, 50, 203–208.
a) E. Attolino, G. Catelani, F. D’Andrea, Tetrahedron Lett.
2002, 43, 8815–8818; b) E. Attolino, G. Catelani, F. DЈAndrea,
M. Nicolardi, J. Carbohydr. Chem. 2004, 23, 179–190.
for 4f, see a) P. L. Barili, G. Berti, G. Catelani, F. D’Andrea,
Gazz. Chim. Ital. 1992, 122, 135–142; for 4g, see b) P. L. Barili,
G. Catelani, F. D’Andrea, F. De Rensis, P. Falcini, Carbohydr.
Res. 1997, 298, 75–84; for 4h, see; c) J. Schneider, Y. C. Lee,
H. M. Flowers, Carbohydr. Res. 1974, 36, 159–166; for 4i, see;
d) V. Ferro, B. W. Skelton, R. V. Stick, A. H. White, Aust. J.
Chem. 1993, 46, 787–803.
4-enopyranoside (26i): Activation–elimination of 6i (207 mg,
0.58 mmol) gave a residue constituted by a mixture of 25i and 26i
in a 60:40 ratio, as estimated by NMR spectroscopy. Chromatog-
raphy on silica gel (8:2 hexane/EtOAc + 0.1% Et3N) of the residue
allowed only partial separation of the two enol ethers 25i (95 mg,
containing 10% of 26i, 48% yield) and 26i (63 mg, containing 10%
of 25i, 32% yield).
[12]
[13]
[14]
Data for 25i: Clear syrup; Rf = 0.32 (2:8 hexane/EtOAc). [α]2D0
=
1
–22.3 (c = 1.3, CHCl3). H NMR (200 MHz, CD3CN): δ = 7.37–
7.29 (m, 10 H, Ar-H), 4.74 (m, 3 H, 4-H, PhCH2), 4.66 (dd, J1,2ax
= 7.1 Hz, J1,2eq = 3.9 Hz, 1 H, 1-H), 4.43 (m, 1 H, 5-H), 4.55 (s, 2
H, PhCH2), 3.53 (dd, J6a,6b = 9.8 Hz, J5,6b = 6.3 Hz, 1 H, 6b-H),
3.46 (dd, J5,6a = 5.3 Hz, 1 H, 6a-H), 3.42 (s, 3 H, OCH3), 2.15–
2.26 (m, 2 H, 2ax-H, 2eq-H) ppm. 13C NMR (50 MHz, CD3CN):
δ = 152.6 (C-3). 139.6 (Ar-C), 138.0 (Ar-C), 129.3–128.4 (Ar-CH),
100.4 (C-1), 95.0 (C-4), 74.5 (PhCH2), 73.7 (PhCH2), 72.6 (C-5),
69.7 (C-6), 56.2 (OCH3), 34.6 (C-2) ppm. C21H24O5 (340.42): calcd.
C 74.09, H 7.11, found C 74.01, H 7.08.
[15]
[16]
Data for 26i: Clear syrup; Rf = 0.24 (2:8 hexane/EtOAc). [α]2D0
=
[17]
[18]
–15.2 (c = 1.1, CHCl3). 1H NMR (200 MHz, CDCl3): δ = 7.37–
7.25 (m, 10 H, Ar-H), 5.16 (d, J3,4 = 3.7 Hz, 1 H, 4-H), 5.02 (dd,
J1,2ax = 4.7 Hz, J1,2eq = 3.3 Hz, 1 H, 1-H), 4.59 (s, 2 H, PhCH2),
4.60, 4.54 (AB system, JA,B = 12.1 Hz, 2 H, PhCH2), 4.06 (m, 1 H,
3-H), 3.95 (s, 2 H, 6a-H, 6b-H), 3.51 (s, 3 H, OCH3), 2.10–2.14 (m,
2 H, 2ax-H, 2eq-H) ppm. 13C NMR (50 MHz, CDCl3): δ = 149.8
(C-5), 138.6 (Ar-C), 138.5 (Ar-C), 128.3–127.7 (Ar-CH), 100.4, 98.8
(C-1, C-4), 72.3 (PhCH2), 69.9, 69.8 (C-6, PhCH2), 66.2 (C-3), 56.6
(OCH3), 32.9 (C-2) ppm. C21H24O5 (340.42): calcd. C 74.09, H
7.11, found C 74.03, H 7.06.
[19]
For 7 and 9, see P. L. Barili, G. Berti, D. Bertozzi, G. Catelani,
F. Colonna, T. Corsetti, F. D’Andrea, Tetrahedron 1990, 46,
5365–5376; for 8, see ref.[18b]
.
[20]
[21]
[22]
[23]
P. L. Barili, G. Berti, G. Catelani, F. D’Andrea, V. Di Bussolo,
Carbohydr. Res. 1996, 290, 17–31.
S. V. Ley, W. P. Griffith, J. Norman, S. P. Marsden, Synthesis
1994, 639–666.
R. U. Lemieux, K. James, T. L. Nagabhushan, Can. J. Chem.
1973, 51, 27–32.
a) G. J. F. Chittenden, Carbohydr. Res. 1976, 52, 23–29; b) T.
Haradahira, M. Maeda, Y. Yano, M. Kojima, Chem. Pharm.
Bull. 1984, 32, 3317–3319; c) A. Burton, P. Wyatt, G.-J. Boons,
J. Chem. Soc., Perkin Trans. 1 1997, 2375–2382.
N. E. Nifant’ev, S. S. Mamyan, A. S. Shaskov, N. K. Kochet-
kov, Bioorg. Khim. 1988, 14, 187–197.
for 5f, see a) H. Paulsen, T. Hasenkamp, M. Paal, Carbohydr.
Res. 1985, 144, 45–55; for 5g, see; b) G. Catelani, F. D’Andrea,
L. Puccioni, Carbohydr. Res. 2000, 324, 204–209; for 5h, see
c) D. Saibal Kumar, N. Roy, Synth. Commun. 1995, 25, 1699–
1710.
Acknowledgments
This research was supported with funds of MIUR-Rome in the
frame of the COFIN national project. We thank Dr. Federica Balz-
ano (Dipartimento di Chimica e Chimica Industriale, Università di
Pisa) for registering high-field NMR spectra.
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Received: June 19, 2006
Published Online: October 5, 2006
5292
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 5279–5292