On the synthesis of vinyl and phenyl C-furanosides by stereospecific debenzylative cycloetherification

Article abstract of DOI:10.1016/j.tet.2009.01.014

Open-chain benzyl-ether-protected polyols in which one of the alcohols is either allylic or benzylic are synthesised by addition of organometallic vinyl or phenyl reagents to benzyl-ether-protected carbohydrate hemiacetals. The diastereoselectivity of add

Full text of DOI:10.1016/j.tet.2009.01.014

Tetrahedron 65 (2009) 2022–2031
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On the synthesis of vinyl and phenyl C-furanosides by stereospecific
debenzylative cycloetherification
*
`
Riccardo Cribiu, K. Eszter Borbas, Ian Cumpstey
Organic Chemistry, Stockholm University, Arrhenius Laboratory, 106 91 Stockholm, Sweden
a r t i c l e i n f o
a b s t r a c t
Article history:
Open-chain benzyl-ether-protected polyols in which one of the alcohols is either allylic or benzylic are
synthesised by addition of organometallic vinyl or phenyl reagents to benzyl-ether-protected carbohy-
drate hemiacetals. The diastereoselectivity of addition is dependent on whether a Grignard reagent or
a trialkylzincate reagent is used. The open-chain compounds undergo a stereospecific cyclisation re-
action on treatment with catalytic strong Brønsted acid with heating to form tetrahydrofurans with
inversion of configuration at the allylic or benzylic carbon (C-1) and loss of hydroxyl from this position. A
Received 29 September 2008
Received in revised form 12 December 2008
Accepted 5 January 2009
Available online 10 January 2009
short synthesis of the starting material, 1,2,4,6-tetra-O-benzyl-D-galactose, from lactose is described.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
BnO
TFA,
HO
OH
4
O
MeCN,
PhMe
BnO
BnO
1
HO
Polyhydroxylated tetrahydrofuran (THF) derivatives occur in
nature as substructures of various natural products. C-Furanosides
are polyhydroxylated THFs and are hydrolytically stable bio-
isosteres of furanosides, which are widespread in bacterial poly-
saccharides,1 hence such compounds may be relevant for the
development of new antibacterial treatments.2 Among the many
methods reported for the synthesis of THFs3 are the acid-catalysed
dehydrative ring-closure of activated (e.g., benzylic) diols, often
under equilibrating conditions and via carbocationic intermediates
to give a thermodynamically stable diastereomer.4 Alternatively,
intramolecular nucleophilic attack onto a good leaving group (e.g.,
a sulfonate) can give a stereospecific cyclisation with inversion of
configuration at the reacting carbon atom to give a single di-
astereomer of product derived from a single diastereomer of the
starting material. Benzyl ethers5 and alcohols6 have both been
reported as intramolecular nucleophiles in this latter process. Re-
lated to this are other diastereoselective debenzylative cyclo-
etherifications that may operate under kinetic control, but that rely
on, for example, activation of a diastereotopic C]C double bond to
initiate ring-closure.7
OBn
OBn
BnO
OBn
Scheme 1.
phenyl-substituted carbohydrate derivatives react in the same way
to give phenyl C-furanosides, also stereospecifically. The stereo-
specific nature of the cyclisation reaction drives the requirement
for diastereoselectivity in synthesis to the previous step: formation
of the activated diol by organometallic addition to a carbohydrate
hemiacetal. With this in mind, we also give the results of our in-
vestigation into zinc-modified organometallic additions, which can
influence the diastereoselectivity of these reactions. Finally, we also
give a short synthesis of the required galactose hemiacetal 2
starting from lactose.
2. Results and discussion
2.1. Synthesis of galactose hemiacetal (2)
We recently reported a Brønsted acid (TFA) induced stereospe-
cific debenzylative cyclisation reaction of vinyl-substituted carbo-
hydrate derivatives to give THFs (Scheme 1). The reaction is
stereospecific with inversion of configuration at allylic C-1 and loss
of OH, OAc or OCH2Ar as leaving groups.8 In this paper, we describe
a modification using catalytic strong acid, and also show that the
For this study, we needed gram quantities of the galacto hemi-
acetal 2. While the easily crystallised gluco compound 1 may be
prepared on a hundred-gram scale starting from cheap a-methyl
glucoside in two steps (benzylation and hydrolysis),9 the higher
price of the galactose methyl glycosides makes this approach less
attractive.10 A very cheap galactoside is available in lactose 3, and
we investigated a benzylation–hydrolysis route starting from this
disaccharide. A synthesis of benzylated sugar hemiacetals derived
* Corresponding author. Tel.: þ46 (0)8 16 2481; fax: þ46 (0)8 15 4908.
E-mail address: cumpstey@organ.su.se (I. Cumpstey).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.014

R. Cribiu` et al. / Tetrahedron 65 (2009) 2022–2031
2023
HO
HO
BnO
BnO
2.2. Organometallic additions
OH
O
OBn
O
OH
O
OBn
O
(i)
O
O
OBn
Next, we examined organometallic addition to hemiacetals 1
and 2: introducing activating groups, vinyl and phenyl, renders the
resulting C-1 alcohols allylic or benzylic, respectively. Using vinyl-
magnesium bromide, diastereomeric product ratios of 1:2 (7a/7b)15
and 2:1 (8a/8b)8 were obtained from gluco 1 and galacto 2 hemi-
acetals, respectively, in good overall yields. We have already
reported the results of some attempts to influence the stereo-
selectivity of the addition to gluco hemiacetal 1.15 Nicotra found
that divinylzinc adds to benzylated pentofuranose hemiacetals
with excellent diastereoselectivity in favour of the 1,2-chelate
product,16 but we found that this reagent gave no reaction with
either of hemiacetals 1 and 2. More reactive organozinc derivatives
have been described: triorganozincates have been shown to add to
BnO
4b
HO
3
OH
BnO
OH
OBn
OH
(ii)
BnO
BnO
BnO
BnO
OBn
O
OBn
O
OBn
O
(iii)
(iv)
+
HO
OH
OAc
BnO
OBn
5
OBn
BnO OH
6
2
Scheme 2. Reagents and conditions: (i) BnBr, NaH, DMF, 0 ꢀC/rt, 46%; (ii) H2SO4(aq)
AcOH, 85 ꢀC, 5, 29%; (iii) Ac2O, Et3N, 62% from 4b; (iv) NaOMe, MeOH, 97%.
,
a,b
-unsaturated carbonyl derivatives17 diastereoselectively,18 and
from the non-reducing disaccharide, sucrose, has recently been
published.11 Benzylation of reducing monosaccharides gives mainly
-pyranosides, but for galactose, the a-furanoside is the major
to sulfinylimines diastereoselectively.19 A procedure using catalytic
zinc was also reported.20 We prepared triorganozincates from
vinylmagnesium bromide and either a dialkylzinc or zinc bro-
mide.17–19 These reagents reacted with gluco 1 and galacto 2
hemiacetals to give the addition products (i.e., 7a,b and 8a,b, re-
spectively) in good yield, and changes in the diastereoselectivity of
the reaction were seen compared to the reaction with the Grignard
reagent. Indeed, for the galacto hemiacetal, the change from
vinylmagnesium bromide to a triorganozincate reagent resulted in
a reversal of diastereoselectivity in the reaction (Table 1, cf. entries
8–10). The vinyl group was transferred in preference to both ethyl
(only tested for hemiacetal 1) and methyl groups in these addition
reactions; while traces of a diol derived from ethyl transfer to 1
could be detected when ZnEt2 was used as zinc source (Table 1,
entry 3), we could not see any evidence of methyl transfer when
b
product making this direct route to the galacto hemiacetal 2 un-
feasible;12 Schmidt has described alkylation of minimally protected
carbohydrate hemiacetals to give
attempted perbenzylation of lactose 3 under standard conditions
(Scheme 2), we were able to isolate a major perbenzylated -di-
b
-glycosides.13 When we
b
saccharide 4b after chromatography and recrystallisation. Hydro-
lysis of disaccharide 4b gave the two hemiacetals 2 and 5, which
were easily separable by chromatography. However, both hemi-
acetals were contaminated by traces of inseparable by-products.
The gluco compound was recrystallised to give pure 5 (29%), while
the galacto compound must be acetylated and recrystallised (6,
b
only, 62% from 4b),14 and finally deacetylated (97%) to give the
pure galacto hemiacetal 2.
Table 1
Organometallic additions to gluco 1 and galacto 2 hemiacetals
HO
R
HO
R
O
OH
OH
OH
BnO
BnO
BnO
BnO
[RM]
+
BnO
OBn
1
OBn
OBn
BnO
OBn
OBn
OBn
7a, R = CH=CH2
9a, R = Ph
7b, R = CH=CH2
9b, R = Ph
HO
HO
R
R
OH
OH
BnO
O
OH
BnO
BnO
[RM]
+
OBn
BnO
OBn
BnO
BnO
OBn
OBn
OBn
8b, R = CH=CH2
10b, R = Ph
OBn
2
8a, R = CH=CH2
10a, R = Ph
sm
R
Conditions
dr
Product/yielda
1
2
3
4
5
6
7
8
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
CH]CH2
CH]CH2
CH]CH2
CH]CH2
Ph
Ph
Ph
CH]CH2
CH]CH2
CH]CH2
Ph
VinylMgBr (4), THF, 0 ꢀC/rt, 22 h
VinylMgBr (10), ZnBr2 (2.5), THF
7a/7b, 1:2.5
7a/7b, 1:4
7a/7b, 1:4
7a/7b, 1:4
9a/9b, 1:2
9a/9b, <1:6
9a/9b, 1:7
8a/8b, 2:1
8a/8b, 1:2
8a/8b, 1:2
10a/10b, 1:1.7
10a/10b, 1:3
10a/10b, 1:3
10a/10b, 1:3
10a/10b, 1:3
7a/29%; 7b/65%15
7a/10%; 7b/57%
7a,b/60%b,c
VinylMgBr (5), ZnEt2 (5.5), THF, hexane
VinylMgBr (5), ZnMe2 (5.5), THF, toluene
PhMgBr (3), Et2O, THF
PhMgBr (10), ZnBr2 (2.5), Et2O
PhMgBr (5), ZnMe2 (5.5), Et2O, toluene
VinylMgBr (2.5), THF
VinylMgBr (10), ZnBr2 (2.5), THF
VinylMgBr (5), ZnMe2 (5.5), THF, toluene
PhMgBr (10), Et2O, THF
PhMgBr (9), Et2O
PhMgBr (10), Et2O, toluene
PhMgBr (10), ZnBr2 (2.5), Et2O, toluene
PhMgBr (5), ZnMe2 (5.5), Et2O, toluene
7a/10%; 7b/53%
9a/25%; 9b/48%
9a/9%; 9b/75%
9a/7%; 9b/47%
8a/53%; 8b/31%
8a/17%; 8b/40%
8a/24%; 8b/48%
10a/28%; 10b/48%
10a,b/80%c
9
10
11
12
13
14
15
Ph
Ph
Ph
Ph
10a,b/67%c
10a,b/47%c
10a/19%; 10b/46%
a
Isolated yields.
b
c
A small amount of a compound resulting from ethyl transfer was also seen.
Diastereomers not separated.

2024
R. Cribiu` et al. / Tetrahedron 65 (2009) 2022–2031
ZnMe2 was used, which is in agreement with reported results that
methyl is a less transferrable group than ethyl.19
Ph
HO
BnO
HO
OH
BnO
BnO
+ H+
O
To introduce a phenyl group, hemiacetals 1 and 2 were treated
with phenylmagnesium bromide to give the respective diols 9a,b,
and 10a,b. Both pairs of diastereomers could be separated by
chromatography. Phenyl-substituted triorganozincates prepared as
for the vinyl derivatives gave the gluco-derived diol 9b with a much
enhanced diastereoselectivity over that seen with the Grignard
reagent (cf. Table 1, entries 5–7). For the galactose case, little change
in diastereoselectivity was seen (entries 11–15).
OH2
OBn
OBn
OBn
O
BnO
–H2O
Ph
O
BnO
HO
BnO
HO
The stereochemical assignment of the diastereomeric diols
resulting from phenyl Grignard addition could be made as fol-
lows: Marco-Contelles has used empirical trends in H-1 1H NMR
chemical shifts and J1,2 coupling constants to assign the stereo-
chemistry of pairs of diastereomers resulting from organometallic
addition (methyl21 or phenylethynyl substituents) to tetrabenzyl
glucose 1.22 It is to be expected that glucose and galactose de-
rivatives should follow similar trends, as the compounds are iso-
structural around C-1. Indeed, our own data for vinyl derivatives
7a,b,23 8a,b (whose stereochemistry we have assigned pre-
viously)8 fits these trends, as do Vasella’s data for glucose- and
galactose-derived trimethylsilylethynyl and bromoethynyl com-
pounds:24 1R compounds invariably have a lower chemical shift
for H-1 (by 0.1–0.2 ppm) than do the corresponding 1S com-
pounds. The vicinal 1H–1H coupling J1,2 for the 1R compounds is
2.7–3.3 Hz, while for the 1S epimers J1,2 is bigger, in the range 4.6–
5.3 Hz. We found that the phenyl-substituted glucose derivatives
also fitted these trends, and 9a (H-1 5.08 ppm, J1,2 5.8 Hz) was
assigned with the 1S configuration, and 9b (H-1 4.92 ppm, J1,2
2.8 Hz) was assigned as 1R. For the galactose phenyl derivatives
also, 10a (H-1 5.00 ppm, J1,2 6.4 Hz) was assigned as 1S, and 10b
(H-1 4.94 ppm, J1,2 2.3 Hz) was assigned as 1R.25
This means that for most of the examples we tested, the tri-
organozincate reagents give more of the product predicted from
a 1,2-chelation model26 than do the Grignard reagents. This is
manifested in a selectivity enhancement for the gluco cases (7b/7a;
2.5:1/4:1) and (9b/9a; 2:1/6:1), while for the galacto vinyl
system, it gives a reversal of diastereoselectivity (8b/8a; 1:2/2:1).
But for the galacto phenyl reactions, (formation of 10a,b) little
change in diastereoselectivity was seen in changing between
Grignard and zinc reagents.
BnO
OBn
OBn
BnO
Bn+
H+
XH
XBn
Scheme 3. A reasonable mechanism for the cyclisation reaction, illustrated for the
formation of 11b from 7b. XH represents a scavenger, e.g., toluene, water, OH-5, or
MeCN–H2O or acetone–H2O.
cyclisation of 7a with 0.1 equiv DNBSA in acetonitrile was complete
after 21 h (Table 2, entry 1), giving clean conversion to the two
products 11a and 12a (obtained as single diastereomers) without
formation of impurities due to benzylation of the benzyl ether
protecting groups (SEAr) as we had seen earlier.8 We tested differ-
ent solvents (Table 2, entries 3–5): the reaction could be carried out
in acetone (60 ꢀC) with a comparable yield of the major product
11a, but the reaction was much less clean than for acetonitrile, the
mixture quickly turned dark brown, whereas for acetonitrile only
a very slight colouration was seen. The reaction in acetone was
somewhat faster than that in acetonitrile however. In dichloro-
methane (40 ꢀC), more of the benzylated by-product 12a was seen,
while in toluene (80 ꢀC), we found that the reaction was not ste-
reospecific: traces of the C-1 epimer 11b were found to contami-
nate the major product 11a. Microwave heating could be used to
accelerate the reaction (Table 2, entries 2 and 6). Heating diol 7a in
acetone gave complete conversion and a major cyclised product 11a
after a very short reaction time (15 min) in a sealed tube at 100 ꢀC.
In acetonitrile, the reaction was slower (1 h), but cleaner conver-
sion to THFs 11a and 12a was seen.
The glucose- and galactose-derived vinyl-substituted diols 7a,b
and 8a,b were heated (conventional heating and/or microwave
heating) in acetonitrile and in acetone using 0.1 equiv DNBSA as
catalytic activator, and in all cases, vinyl C-glycosides 11a,b and
13a,b were formed as major products, along with the perbenzyl by-
products 12a,b and 14a,b, which were easily isolated when aceto-
nitrile was used as solvent (Table 2, entries 1, 2, 5–14). In each case,
a single diastereomer of the starting material gave a single di-
astereomer of product. Reactions in acetonitrile were cleaner than
those in acetone, and isolation of the products was invariably
easier; when acetone was used as solvent, some formation of the
perbenzylated by-products 12a,b and 14a,b was seen but these
were not obtained pure, and the major products 11a,b and 13a,b
were still contaminated after chromatography by benzyl alcohol,
which must be removed by high vacuum. The cyclisations of both of
the galactose-derived diols 8a and 8b were somewhat slower than
those of the glucose-derived compounds 7a and 7b, and some
starting material still remained after longer reaction times. We also
showed that the perbenzylated open-chain derivative 15a
(obtained by benzylation of diol 7a, NaH, BnBr, THF, 93%) cyclised
under microwave heating with DNBSA to give the perbenzylated
THF 12a (Table 2, entries 15, 16). Perbenzylated 15a cyclised more
slowly than did diol 7a under the same reaction conditions in both
acetonitrile and acetone, presumably due to a sterically more
congested transition state.
2.3. Debenzylative cyclisations
We have previously described a stereospecific debenzylative
cyclisation reaction of the vinyl-substituted diols 7a,b and 8a,b to
give C-glycosides with retention of configuration at C-4 and in-
version at C-1.8 A likely mechanism involves protonation of the
allylic alcohol, converting it into a better leaving group, which can
then undergo an intramolecular substitution by O-4 with Walden
inversion to give the heterocycle (Scheme 3). A benzyl group is lost
from O-4, and this may be quenched either by an external scav-
enger, or by nucleophiles from within the molecule (e.g., OH-5),
resulting in the formation of by-products. In any case, a proton may
be regenerated, implying that the reaction could be run with cat-
alytic acid. Sanz has recently reported Brønsted acid catalysed
nucleophilic substitution reactions of activated alcohols.27
When 7a was treated with a catalytic quantity (0.5 equiv) of
TsOH in acetonitrile, some product formation (11a) could be
detected by TLC, but even after heating at 50 ꢀC for 6 days, only
a low conversion of the starting material was seen. With a stronger
sulfonic acid, 2,4-dinitrobenzenesulfonic acid (DNBSA, 0.5 equiv)28
some starting material still remained after 48 h at rt, but heating
the mixture drove the reaction to completion, and diol 7a was
converted into two major products, THFs 11a and 12a. Subsequent
reactions were therefore all carried out with heating. The

R. Cribiu` et al. / Tetrahedron 65 (2009) 2022–2031
2025
The phenyl-substituted diols 9a,b and 10a,b also each cyclised
stereospecifically on heating with DNBSA in either acetone or
acetonitrile to give phenyl C-glycosides 16a,b and 17a,b as single
diastereomers (Table 2, entries 17–26). Just as in the vinyl series, we
found that the reactions were cleaner in acetonitrile than in ace-
tone, and that when acetonitrile was used, the perbenzyl de-
rivatives 18a,b and 19a,b were easily isolated in addition to the
major products 16a,b and 17a,b. We confirmed that the stereo-
chemistry of the benzylated by-products 18a,b and 19a,b was the
same as the respective major reaction products 16a,b and 17a,b in
each case by standard benzylation (NaH, BnBr, DMF, 67–95%).
We assigned the stereochemistry of the phenyl-substituted
THFs by comparison of the 13C NMR chemical shifts of 16a,b and
17a,b with those of compounds of similar constitution and known
configuration, i.e., the vinyl C-hexofuranosides 11a,b and 13a,b, and
also the previously described benzyl-ether-protected vinyl C-pen-
Table 2
Debenzylative cycloetherification with catalytic DNBSA
BnO
R'O
R
OR'
O
R
BnO
R'O
BnO
OBn
BnO
OBn
OBn
11a, R = CH=CH2, R' = H
12a, R = CH=CH2, R' = Bn
16a, R = Ph, R' = H
7a, R = CH=CH2, R' = H
9a, R = Ph, R' = H
15a, R = CH=CH2, R' = Bn
18a, R = Ph, R' = Bn
BnO
O
R
HO
R
OH
R'O
BnO
BnO
BnO
OBn
OBn
tofuranosides.29 Significant differences between
were seen in the shifts for C-1 and C-2: these carbons appear at
higher chemical shift in C-furanosides with a (gluco or galacto)
configuration than in those with an (gluco or galacto) configura-
a- and b-epimers
11b, R = CH=CH2, R' = H
12b, R = CH=CH2, R' = Bn
16b, R = Ph, R' = H
OBn
7b, R = CH=CH2
9b, R = Ph
b
18b, R = Ph, R' = Bn
a
tion.30 Glucose and galactose epimers were distinguished by dif-
ferences in the shifts of C-4: this carbon resonates at higher
chemical shift in C-furanosides with a galacto configuration than in
those with a gluco configuration. These trends were clearly fol-
lowed by our compounds, which allowed an assignment of the
stereochemistry.31 This means that the cyclisation reactions of
the phenyl derivatives had the same stereochemical outcome as for
the vinyl derivatives: retention of configuration at C-4 and in-
version at C-1. It is well known that in SN2-type reactions, allylic
and benzylic secondary carbons are substituted more quickly than
other secondary carbons.32,33
Schmidt has reported a similar cyclisation of glucose-derived
benzylic alcohols. A diastereomeric mixture of open-chain alcohols
cyclised under mildly acidic conditions to give a diastereomeric
mixture of aryl C-furanosides.34 The highly oxygenated aryl groups
used by Schmidt would be more able to stabilise a carbocationic
intermediate, making an SN1-type cyclisation more likely, and also
enabling the subsequent observed isomerisation to the thermo-
BnO
HO
R
O
R
OH
BnO
BnO
R'O
BnO
OBn
OBn
OBn
13a, R = CH=CH2, R' = H
14a, R = CH=CH2, R' = Bn
17a, R = Ph, R' = H
8a, R = CH=CH2
10a, R = Ph
19a, R = Ph, R' = Bn
BnO
HO
R
O
R
OH
BnO
BnO
R'O
BnO
OBn
OBn
13b, R = CH=CH2, R' = H
14b, R = CH=CH2, R' = Bn
17b, R = Ph, R' = H
OBn
8b, R = CH=CH2
10b, R = Ph
19b, R = Ph, R' = Bn
Entry
sm
Solvent
T/ꢀC
t
Products/yielda
dynamically more stable b-C-pyranosides. A very similar acid-cat-
1
2
3
4
5
6
7
8
7a
7a
7a
7a
7a
7a
7b
7b
7b
7b
8a
8a
8b
8b
15a
15a
9a
9a
9a
9b
9b
9b
MeCN
MeCN
DCM
Toluene
Acetone
Acetone
MeCN
80
100b
40
21 h
1 h
24 h
24 h
4 h
11a/72%; 12a/23%
11a/67%; 12a/23%
11a/54%; 12a/33%
Not stereospecific
11a/65%
alysed cyclisation of phenyl-substituted carbohydrate-derived diols
in benzene has also been reported,35 but here the reaction does not
appear to be stereospecific as the authors describe the formation of
more than one furanoside product from a single diastereomer of
starting material. The origin of the difference between this report
and our results is not clear, but it is possible that a different solvent
is the cause (as we have seen, Table 2, entry 4), or simply that the
dominance of the stereospecific reaction pathway over other non-
stereospecific cyclisation mechanisms is substrate dependent.
A similar report of acid-catalysed cyclisation of open-chain
carbohydrate-derived compounds to give vinyl C-pentofuranosides
has been published.36
80
60
100b
80
15 min
20 h
15 min
20 h
30 min
38 h
24 h
23 h
22 h
3.5 h
2 h
11a/69%
11b/60%; 12b/13%
11b/67%; 12b/12%
11b/58%
MeCN
100b
60
9
Acetone
Acetone
MeCN
Acetone
MeCN
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
100b
80
11b/68%c
13a/69%; 14a/19%
13a/31%
13b/43%; 14b/16%
13b/51%
12a/75%
12a/73%
16a/58%; 18a/21%
16a/65%
16a/66%
16b/70%; 18b/13%
16b/65%
16b/78%
60
80
60
Acetone
MeCN
100b
100b
80
Acetone
MeCN
Acetone
Acetone
MeCN
Acetone
Acetone
MeCN
Acetone
MeCN
21 h
3. Conclusions
60
26 h
15 min
23 h
20 h
15 min
26 h
24 h
21 h
100b
80
We have shown that the stereospecific debenzylative cyclo-
etherification reaction of some C-1-activated carbohydrate de-
rivatives with inversion of configuration at C-1 and loss of OH as
a leaving group to give THF derivatives may be run under catalytic
Brønsted acidic conditions. The reaction is stereospecific for both
vinyl- and phenyl-substituted derivatives under the reported re-
action conditions, and it may be valuable in stereocontrolled syn-
theses of vinyl or aryl C-furanosides or other polyhydroxylated THF
derivatives. We may also conclude that triorganozincates add to
benzyl-protected carbohydrate hemiacetals giving addition prod-
ucts with altered diastereoselectivity compared to Grignard re-
agents, and hence may be a useful alternative reagent.
60
100b
80
10a
10a
10b
10b
17a/63%; 19a/16%
60
80
60
17a/30%d
17b/51%; 19b/19%
17b/37%
Acetone
36 h
Reactions carried out with 0.1 equiv DNBSA unless otherwise stated.
a
Isolated yields.
b
Microwave heating.
Used 0.02 equiv DNBSA.
Used 0.3 equiv DNBSA.
c
d

2026
R. Cribiu` et al. / Tetrahedron 65 (2009) 2022–2031
4. Experimental section
concentrated in vacuo. The residue was partially purified by dry
flash column chromatography (pentane/EtOAc 15:1 (1 L)/pen-
tane/EtOAc 10:1 (500 mL)/pentane/EtOAc 4:1 (1.5 L)) to give
a pale yellow oil (19 g), which was then recrystallised from EtOAc
4.1. General methods
Melting points were recorded on a Gallenkamp melting point
apparatus and are uncorrected. Proton nuclear magnetic resonance
(1H) spectra were recorded on Bruker Avance II 400 (400 MHz),
Bruker Avance II 500 (500 MHz) or Varian Mercury 400 (400 MHz)
spectrometers; multiplicities are quoted as singlet (s), broad singlet
(br s), doublet (d), doublet of doublets (dd), triplet (t), apparent
triplet (at), apparent triplet of doublets (atd), doublet of apparent
triplets (dat), quartet (q), apparent quartet (aq), AB quartet (ABq) or
multiplet (m). Carbon nuclear magnetic resonance (13C) spectra
were recorded on Bruker Avance II 400 (100 MHz), Bruker Avance II
500 (125 MHz) or Varian Mercury 400 (100 MHz) spectrometers,
and multiplicities assigned by DEPT. Spectra were assigned using
COSY, HSQC and DEPT experiments. All chemical shifts are quoted
(25 mL)/pentane (80 mL) to give perbenzylated b-lactoside 4b
(13.4 g, 46%) as white crystals. Mp 83–86 ꢀC, lit. mp 74–76 ꢀC;37
25
20
[a
]
þ0.9 (c 1.0, CHCl3), lit. [
a]
þ0.1 (CHCl3);37 1H NMR (400 MHz,
D
D
CDCl3) dH 3.37–3.41 (m, 3H, H-5I, H-5II, H-6), 3.44 (dd, J2,3 9.8 Hz, J3,4
3.0 Hz,1H, H-3II), 3.51 (dd, J1,2 7.7 Hz, J2,3 9.2 Hz,1H, H-2I), 3.56–3.60
I
II
(m, 2H, H-3 , H-60), 3.76–3.81 (m, 2H, H-2 , H-6), 3.84 (dd, J5,6
0
4.5 Hz, J6,6 11.0 Hz, 1H, H-6 ), 3.94 (d, J3,4 3.0 Hz, 1H, H-4II), 3.99 (dd,
J 8.9 Hz, J 9.8 Hz, 1H, H-4I), 4.27, 4.37 (ABq, JAB 11.8 Hz, 2H, PhCH2),
4.43 (d, J 12.1 Hz, 1H, PhCHH0), 4.47 (d, J1,2 7.7 Hz, 1H, H-1II), 4.51 (d,
J1,2 7.7 Hz, 1H, H-1I), 4.57–4.60 (m, 2H, PhCHH0, PhCHH0), 4.68 (d, J
12.0 Hz, 1H, PhCHH0), 4.72–4.80 (m, 5H, PhCH2, 3ꢁPhCHH0), 4.83 (d,
J 11.1 Hz, 1H, PhCHH0), 4.93 (d, J 10.8 Hz, 1H, PhCHH0), 4.96 (d, J
11.9 Hz, 1H, PhCHH0), 4.98 (d, J 11.3 Hz, 1H, PhCHH0), 5.05 (d, J
10.7 Hz, 1H, PhCHH0), 7.13–7.41 (m, 40H, Ar–CH); 13C NMR
(125 MHz, CDCl3) dC 68.2, 68.4 (2ꢁt, C-6I, C-6II), 71.1, 72.7, 73.2, 73.5,
74.8, 75.2, 75.4, 75.5 (8ꢁt, 8ꢁPhCH2), 73.1, 75.3 (2ꢁd, C-5I, C-5II),
73.8 (d, C-4II), 76.9 (d, C-4I), 80.1 (d, C-2II), 81.9 (d, C-2I), 82.7 (d, C-
3II), 83.2 (d, C-3I), 102.7 (C-1I), 102.9 (C-1II), 127.2, 127.5, 127.6, 127.6,
127.7, 127.7, 127.8, 127.8, 127.9, 127.9, 128.0, 128.0, 128.0, 128.1, 128.2,
128.2, 128.3, 128.3, 128.3, 128.4, 128.4, 128.5, 128.5, 128.5, 128.5
(25ꢁd, Ar–CH), 137.7, 138.2, 138.6, 138.7, 138.8, 139.0 (6ꢁs, Ar–C).
The mother liquor contains (according to NMR spectroscopy)
further 4b as the major component, along with another disaccharide
0
0
on the d-scale in parts per million (ppm). Residual solvent signals
(CHCl3, dH 7.26, dC 77.16) were used as an internal reference. Low-
and high-resolution (HRMS) electrospray (ESþ) mass spectra were
recorded using a Bruker Microtof instrument. Infra-red spectra
were recorded on a Perkin–Elmer Spectrum One FT-IR spectro-
meter using the thin film method on NaCl plates. Optical rotations
were measured on a Perkin–Elmer 241 polarimeter with a path
length of 1 dm; concentrations are given in g/100 mL. Microanal-
ysis was carried out by the Elemental Analysis Unit at the University
of Santiago de Compostela, Spain. Thin layer chromatography (TLC)
was carried out on Merck Kieselgel sheets, pre-coated with 60F254
silica. Plates were visualised with UV light and developed using 10%
sulfuric acid, or an ammonium molybdate (10% w/v) and cerium(IV)
sulfate (2% w/v) solution in 10% sulfuric acid. Flash column chro-
matography was carried out on silica gel (35–70 micron, Grace).
Acetonitrile (puriss) was bought from Riedel de Hahn, acetone
(Normapur) from VWR, and used as supplied. Dinitrobenzene-
sulfonic acid was bought from Alfa Aesar and used as supplied.
Organometallic reagents were bought from Sigma–Aldrich (phenyl-
magnesium bromide (3 M in Et2O)) or Acros (vinylmagnesium
bromide (0.7 M inTHF); dimethylzinc (1.2 M in toluene); diethylzinc
(1 M in hexane)) and used as supplied. Anhydrous zinc bromide was
from Fluka and was not purified before use. Diethyl ether was dried
over sodium. THF was distilled from sodium benzophenone ketyl
radical or purified on a Vacuum Atmospheres solvent purification
column. Toluene was purified on a Vacuum Atmospheres solvent
purification column. Reactions performed under an atmosphere of
hydrogen, nitrogen or argonwere maintained byan inflated balloon.
Characterisation data for compounds 8a,b, 11a,b–14a,b is found in
the Supplementary data of our preliminary communication (Ref. 8).
likely to be the perbenzylated
a-lactoside, with anomeric carbon
resonances at dC 96.0 and 102.9 ppm.
4.3. 2,3,4,6-Tetra-O-benzyl-
D
-galactopyranose (2), 2,3,6-tri-O-
-glucopyranose (5) and 1-O-acetyl-2,3,4,6-tetra-O-
-galactopyranose (6)
benzyl-
benzyl-
D
b-D
Benzyl lactoside 4b (6.84 g, 6.4 mmol) was suspended in a mix-
ture of acetic acid (75 mL) and H2SO4 (1 M, 10 mL), and the mixture
stirred at 85 ꢀC. After 5 h, TLC (pentane/EtOAc, 3:1) showed com-
plete consumption of the starting material (Rf 0.8) into three
products (Rf 0.6, 0.4 (1), 0.2 (5)). The reaction mixture was allowed
to cool to rt, then quenched by addition to water (250 mL). The
mixture was extracted with toluene (2ꢁ250 mL), and the organic
extracts washed with NaHCO3 (satd aq, 250 mL), dried (Na2SO4),
filtered and concentrated in vacuo. The residue was purified by
flash column chromatography (pentane/EtOAc 2:1/5:4) to give
impure galactose hemiacetal
hemiacetal 5 ( , 1:1; 1.32 g). The glucose hemiacetal 5 was
recrystallised from EtOAc/pentane to give white crystals, 5 (
7:1; 834 mg, 29%);38 1H NMR (400 MHz, CDCl3) selected data
-anomer: dH 2.40 (br s, 1H, OH), 3.03 (br s, 1H, OH), 3.55 (dd, J1,2
2 (3.24 g), and impure glucose
a/b
a/b,
4.2. Benzyl 2,3,4,6-tetra-O-benzyl-
b-D
-galactopyranosyl-
a
(1/4)-2,3,6-tri-O-benzyl- -glucopyranoside (4b)
b
-
D
3.5 Hz, J2,3 9.3 Hz, 1H, H-2), 3.60 (at, J 9.4 Hz, 1H, H-3 or H-4), 3.67–
3.68 (m, 2H, H-6, H-60), 3.79 (at, J 9.2 Hz, H-3 or H-4), 4.00 (dat, J 4.5,
9.3 Hz, 1H, H-5), 4.54, 4.59 (ABq, JAB 12.3 Hz, 2H, PhCH2), 4.69, 4.76
(ABq, JAB 11.7 Hz, 2H, PhCH2), 4.76, 4.98 (ABq, JAB 12.3 Hz, 2H,
PhCH2), 5.23 (br s, 1H, H-1), 7.27–7.37 (m, 15H, Ar–H); selected data
Lactose monohydrate 3 (10 g, 27.8 mmol) was suspended in
benzyl bromide (50 mL, 418 mmol) and DMF (250 mL), and cooled
to 0 ꢀC under N2. Sodium hydride (60% in oil, 18.9 g, 473 mmol) was
added in portions over 15 min, and the well-stirred reaction mix-
ture was left in the cooling bath and allowed to warm to rt as the ice
melted. NOTE: the reaction mixture should not be removed from
the cooling bath until after the reaction has neared completion.
Failure to follow this may result in rapid exothermic reaction. After
44 h, TLC (pentane/EtOAc 4:1) showed the presence of a major
product (Rf 0.2). The reaction mixture was cooled to 0 ꢀC, quenched
with MeOH (50 mL) and stirred for 30 min at rt. The solvent was
then removed under reduced pressure, and the residue dissolved in
EtOAc (200 mL) and washed with water (200 mL). The aqueous
phase was re-extracted with EtOAc (200 mL), and the combined
extracts were washed with brine (200 mL), dried (Na2SO4) and
b-anomer: dH 3.37 (dd, J 7.6, 9.0 Hz, 1H), 3.46 (at, J 8.7 Hz, 1H).
Impure galactose hemiacetal 2 (3.24 g) was dissolved in CH2Cl2
(70 mL), and triethylamine (21 mL) and acetic anhydride (4.2 mL)
were added. After 2 h, TLC (pentane/EtOAc, 4:1) indicated complete
conversion of starting material (Rf 0.1) into a major product (Rf 0.6).
The reaction mixture was cooled to 0 ꢀC, and MeOH (30 mL) was
slowly added, after which the mixture was concentrated in vacuo.
The residue was dissolved in EtOAc (100 mL) and washed with HCl
(1 M, 100 mL). The aqueous phase was re-extracted with EtOAc
(100 mL), and the combined extracts were dried (MgSO4), filtered
and concentrated in vacuo. The resulting yellow oil was recrystal-
lised from EtOAc/pentane to give the b-acetate 6 (2.32 g, 62% from

R. Cribiu` et al. / Tetrahedron 65 (2009) 2022–2031
2027
4b) as a white solid. Mp 98–101 ꢀC (EtOAc/pentane), lit. mp 101–
by careful addition of NH4Cl (satd aq). The mixture was diluted with
water and EtOAc. The phases were separated and the aqueous layer
was extracted twice with EtOAc. The combined organic extracts
werewashed twice with water, and then dried (Na2SO4), filtered and
concentrated in vacuo. Repeated column chromatography (pentane/
EtOAc, 3:1) gave the diols as colourless oils.
28
102 ꢀC (EtOH);39
[
a
]
D
þ2.5 (c 1.0, CHCl3), lit. þ5.3 (c 1.0, CHCl3);39
1H NMR (400 MHz, CDCl3) dH 2.03 (s, 3H, CH3), 3.54–3.63 (m, 3H, H-
3, H-6, H-60), 3.69 (m, 1H, H-5), 3.95 (dd, J1,2 8.0 Hz, J2,3 9.7 Hz, 1H,
H-2), 3.98 (m, 1H, H-4), 4.39, 4.44 (ABq, JAB 11.8 Hz, 2H, PhCH2),
4.62, 4.94 (ABq, JAB 11.6 Hz, 2H, PhCH2), 4.72–4.74 (m, 3H, PhCH2,
PhCHH0), 4.84 (d, J 11.3 Hz, 1H, PhCHH0), 5.56 (d, J1,2 8.0 Hz, 1H, H-1),
7.26–7.34 (m, 20H, Ar–H).
4.5. General methods for cyclisation with catalytic DNBSA
Acetate 6 (2.30 g, 4.0 mmol) was suspended in MeOH (50 mL),
and a solution of sodium methoxide (prepared from sodium (17 mg)
and MeOH (5 mL)) was added. After 3 h, all the starting material had
dissolved, and TLC (3:1 pentane/EtOAc) showed complete conver-
sion of starting material (Rf 0.6) into a single product (Rf 0.2). Dowex
50X 8 (Hþ) ion-exchange resin (2 mL) was added, then the mixture
was filtered and concentrated in vacuo. The residue was passed
through a pad of silica eluting with pentane/EtOAc, 1:1, to give
hemiacetal 2 (2.06 g, 97%) as a colourless oil that crystallised on
standing;40 selected data,1HNMR (400 MHz, CDCl3) dH 2.93 (br s,1H,
General procedure 4, conventional heating. The substrate (7a,b–
10a,b) was dissolved in acetone or acetonitrile. DNBSA (0.1 equiv)
was added, and the mixture was heated with a reflux condenser at
60 ꢀC or 80 ꢀC until TLC showed disappearance of the starting
material. The reaction was then quenched by addition of Et3N (ca.
1.5 mL), and the mixture was concentrated in vacuo, and the resi-
due purified by flash column chromatography to give the C-glyco-
sides (11a,b–14a,b, 16a,b–19a,b).
General procedure 5, microwave heating. The substrate (7a,b,
9a,b, 15a) was weighed into a microwave vial (2.5 mL or 5 mL as
appropriate) and dissolved in acetone or acetonitrile. DNBSA
(0.1 equiv) was added, and then the vial was sealed and heated in
the microwave apparatus (Emrys Creator) at 100 ꢀC for the stated
time (fixed hold time, normal absorption). The reaction was then
quenched by addition of triethylamine (ca. 1.5 mL), and the mixture
was concentrated in vacuo, and the residue purified by flash
column chromatography to give C-glycosides (11a,b, 12a,b, 16a,b).
OH-1
3.97 (dd, J 1.1, 2.8 Hz,1H, H-4
6.4 Hz, 1H, ), 5.28 (d, J1,2 3.5 Hz, 1H, H-1
a
), 3.14 (d, JOH,1 6.4 Hz,1H, OH-1
), 4.03 (dd, J 3.6, 9.8 Hz,1H,
).
b
), 3.76 (dd, J 7.4, 9.6 Hz,1H,
b),
a
a
), 4.15 (at, J
a
a
4.4. General methods for organometallic additions
General procedure 1, Grignard reagents. A solution of the hemi-
acetal (ca. 0.2 mM in anhydrous THF) under N2 was cooled in an ice-
water bath. The organometallic reagent (4 equiv) was added
dropwise. The reaction mixture was allowed to reach rt over ca. 1 h,
and stirring was continued for a further 20 h. The reaction was
quenched by careful addition of NH4Cl (satd aq). The mixture was
diluted with water and EtOAc. The phases were separated and the
aqueous layer was extracted twice with EtOAc. The combined or-
ganic extracts were washed with water twice, and then dried
(Na2SO4) filtered and concentrated in vacuo. The crude product was
purified by repeated column chromatography (pentane/EtOAc, 3:1)
to give the diols as colourless oils.
General procedure 2, GrignardþZnBr2. A solution of anhydrous
ZnBr2 (2.5 equiv) in anhydrous THF (vinylmagnesium bromide) or
Et2O (phenylmagnesium bromide) was cooled under N2 in an ice-
water bath. The solution was treated dropwise with the Grignard
reagent (10 equiv). After 5 min, the cooling bath was removed. If
necessary, additional solvent was added until a clear solution was
obtained. Once all the solids had dissolved, the solution was re-
cooled in an ice-water bath. The hemiacetal was added as a ca. 1 M
solution in THF (or ether) by syringe. The reaction mixture was
allowed to warm to rt over ca. 1 h, and stirring was continued for
a further 20 h. The reaction was quenched by careful addition of
NH4Cl (satd aq). The mixture was diluted with water and EtOAc.
The phases were separated and the aqueous layer was extracted
twice with EtOAc. The combined organic extracts were washed
with water twice, and then dried (Na2SO4) filtered and concen-
trated in vacuo. The crude product was purified by repeated column
chromatography (pentane/EtOAc, 3:1) to give the diols as colour-
less oils. NOTE: PhMgBr addition in Et2O resulted in a biphasic re-
action mixture, whereas a homogeneous solution was obtained
with THF. The diols were isolated in similar yields and di-
astereomeric ratios in both cases.
4.6. (2R,3R,4R,5S,6S)-1,3,4,5-Tetra-O-benzyl-oct-7-ene-
1,2,3,4,5,6-hexaol (7a) and (2R,3R,4R,5S,6R)-1,3,4,5-tetra-O-
benzyl-oct-7-ene-1,2,3,4,5,6-hexaol (7b)
Following general procedure 2, hemiacetal
1 (540 mg,
1.00 mmol) was converted into a mixture of diols 7a and 7b (1:4),
which was separated (pentane/EtOAc, 3:1) to give 7a (58 mg, 10%)
and 7b (325 mg, 57%).
Following general procedure 3, hemiacetal 1 (400 mg, 0.74 mmol)
was converted into a mixture of diols 7a and 7b (1:4), which was
separated (pentane/EtOAc, 3:1) to give 7a (40 mg, 10%) and 7b
(223 mg, 53%).
Following general procedure 3 but using Et2Zn in place of
Me2Zn, traces of a compound consistent with ethyl addition to the
hemiacetal was seen along with 7a and 7b: m/z (ESþ) 1163
(2MþNaþ, 40), 593 (MþNaþ, 100%); HRMS (ESþ) calcd for
C36H42O6Na (MNaþ) 593.2874, found 593.2889.
4.7. (2R,3S,4R,5S,6S)-1,3,4,5-Tetra-O-benzyl-oct-7-ene-
1,2,3,4,5,6-hexaol (8a) and (2R,3S,4R,5S,6R)-1,3,4,5-tetra-O-
benzyl-oct-7-ene-1,2,3,4,5,6-hexaol (8b)
Following general procedure 1, hemiacetal 2 (1.6 g, 2.9 mmol)
was converted into a mixture of diols 8a and 8b (2:1), which was
separated (toluene/EtOAc, 10:1) to give 8b (523 mg, 31%) and 8a
(884 mg, 53%).
Following general procedure 2, hemiacetal 2 (540 mg, 1.0 mmol)
was converted into a mixture of diols 8a and 8b (1:2), which was
separated to give 8b (228 mg, 40%) and 8a (98 mg, 17%).
Following general procedure 3, hemiacetal
2
(351 mg,
General procedure 3, GrignardþZnMe2. The Grignard reagent
(5.0 equiv) was added under N2 to ice-cold anhydrous THF (to afford
a ca. 0.5 mM solution). ZnMe2 (5.5 equiv) was added dropwise, and
the mixture was stirred at 0 ꢀC for 10 min. (NOTE: addition of the
reagents in any other order resulted in the spontaneous combustion
of the ZnMe2 solution.) The hemiacetal in THF (0.2–0.4 mM) was
added to this solution by syringe. The reaction mixture was allowed
to slowly warm to room temperature (approx. 1 h). Stirring was
continued for 20 h at room temperature. The reactionwas quenched
0.65 mmol) was converted into a mixture of diols 8a and 8b (1:2),
which was separated to give 8b (178 mg, 48%) and 8a (87 mg, 24%).
4.8. (1S,2S,3R,4R,5R)-2,3,4,6-Tetra-O-benzyl-1-phenyl-hexane-
1,2,3,4,5,6-hexaol (9a) and (1R,2S,3R,4R,5R)-2,3,4,6-tetra-O-
benzyl-1-phenyl-hexane-1,2,3,4,5,6-hexaol (9b)
Following general procedure 1, hemiacetal 1 (1.0 g, 1.9 mmol)
was converted into a mixture of diols 9a and 9b (1:2), which was

2028
R. Cribiu` et al. / Tetrahedron 65 (2009) 2022–2031
separated (7:2/5:2 pentane/EtOAc) to give 9a (283 mg, 25%) and
9b (545 mg, 48%).
Following general procedure 2, hemiacetal 1 (1.0 g, 1.85 mmol)
was converted into a mixture of diols 9a and 9b (<1:6), which was
separated (pentane/EtOAc, 3:1, repeated) to give 9a (97 mg, 9%) and
9b (860 mg, 75%).
C-3), 81.5 (d, C-2), 126.9, 127.7, 127.7, 127.8, 127.9, 127.9, 128.1,
128.3, 128.3, 128.4, 128.4, 128.4, 128.5 (13ꢁd, Ar–CH), 137.8, 137.9,
138.0, 138.0, 141.6 (5ꢁs, Ar–C); HRMS (ESþ) calcd for C40H43O6
(MHþ) 619.3054, found 619.3054; calcd for C40H42O6Na (MNaþ)
641.2874, found 641.2883.
25
Compound 10b, a colourless oil; [
3446 (br, OH) cmꢂ1
5.5 Hz,1H, OH-1), 3.49 (d, JOH,5 3.1 Hz,1H, OH-5), 3.54 (dd, J5,6 6.6 Hz,
a]
þ32.0 (c 1.0 CHCl3); nmax
D
Following general procedure 3, hemiacetal
1
(400 mg,
;
1H NMR (400 MHz, CDCl3) dH 3.40 (d, JOH,1
0.74 mmol) was converted into a mixture of diols 9a and 9b (1:7),
J6,6 9.4 Hz, 1H, H-6), 3.58 (dd, J5,6 5.4 Hz, J6,6 9.4 Hz, 1H, H-60), 3.86
(dd, J1,2 2.3 Hz, J2,3 6.3 Hz,1H, H-2), 3.96–3.99 (m, 2H, H-3, H-4), 4.10
(m,1H, H-5), 4.16, 4.44 (ABq, JAB 10.8 Hz, 2H, PhCH2), 4.44, 4.49 (ABq,
JAB 11.8 Hz, 2H, PhCH2), 4.55 (d, J 11.5 Hz, 1H, PhCHH0), 4.70 (d, J
11.3 Hz, 1H, PhCHH0), 4.72–4.78 (m, 2H, 2ꢁPhCHH0), 4.94 (dd, J1,2
2.3 Hz, JOH,1 5.5 Hz, 1H, H-1), 7.04–7.38 (m, 25H, Ar–H); 13C NMR
(100 MHz, CDCl3)dC 70.3 (d, C-5), 70.9 (t, C-6), 72.4 (d, C-1), 73.5, 73.7,
74.7, 75.0 (4ꢁt, 4ꢁPhCH2), 77.9, 81.1 (2ꢁd, C-3, C-4), 83.2 (d, C-2),
126.3,127.5,127.8,127.9,128.0,128.0,128.3,128.3,128.4,128.4,128.5,
128.6, 128.6 (13ꢁd, Ar–CH), 137.7, 137.9, 138.2, 138.2 (4ꢁs, 4ꢁBn-C),
142.2 (s, Ar–C); m/z (ESþ) 1259 (2MþNaþ, 100), 641 (MþNaþ, 95%);
HRMS (ESþ) calcd for C40H42O6Na (MNaþ) 641.2874, found 641.2871.
0
0
0
which was separated to give 9a (34 mg, 7%) and 9b (213 mg, 47%).
22
Compound 9a, a colourless oil, Rf 0.5 (pentane/EtOAc, 2:1); [a]
D
þ17.8 (c 1.0, CHCl3); nmax 3453 (br, OH) cmꢂ1
;
1H NMR (400 MHz,
CDCl3) dH 3.10 (br s,1H, OH), 3.63–3.64 (m, 3H, H-6, H-60, OH), 3.85–
3.87 (m, 3H, H-2, H-3, H-4), 4.04 (dat, J 4.2, 6.4 Hz, 1H, H-5), 4.39,
4.42 (ABq, JAB 11.3 Hz, 2H, PhCH2), 4.46, 4.49 (ABq, JAB 11.3 Hz, 2H,
PhCH2), 4.55, 4.61 (ABq, JAB 12.0 Hz, 2H, PhCH2), 4.57, 4.68 (ABq, JAB
11.2 Hz, 2H, PhCH2), 5.08 (d, J1,2 5.8 Hz, 1H, H-1), 7.13–7.41 (m, 25H,
Ar–H); 13C NMR (100 MHz, CDCl3) dC 71.2 (t, C-6), 71.5 (d, C-5), 72.9,
73.4, 73.6 (3ꢁt, 4ꢁPhCH2), 73.7 (d, C-1), 76.3, 78.1, 80.2 (3ꢁd, C-2,
C-3, C-4), 126.8, 127.6, 127.8, 127.9, 128.0, 128.2, 128.3, 128.4, 128.4,
128.5, 128.5, 128.6, 128.8 (13ꢁd, Ar–CH), 137.5, 137.6, 137.8, 138.3
(4ꢁs, 4ꢁBn-C), 141.8 (s, Ar–C); m/z (ESþ) 1259 (2MþNaþ, 7), 641
(MþNaþ, 100%); HRMS (ESþ) calcd for C40H42O6Na (MNaþ)
4.10. (2,3,6-Tri-O-benzyl- -glucofuranosyl)ethene (11a) and
(2,3,5,6-tetra-O-benzyl-a-D-glucofuranosyl)ethene (12a)
a-
D
641.2874, found 641.2859.
22
Compound 9b, a colourless oil, Rf 0.4 (pentane/EtOAc, 2:1); [a]
D
ꢂ12.5 (c 1.0, CHCl3); nmax 3440 (br, OH) cmꢂ1
;
1H NMR (400 MHz,
Using conventional heating (general procedure 4), diol 7a
(250 mg, 0.44 mmol) in acetone (3 mL) was converted with DNBSA
(11 mg, 0.04 mmol) into C-glycoside 11a (131 mg, 65%).
Using conventional heating (general procedure 4), diol 7a
(50 mg, 0.088 mmol) in acetonitrile (2 mL) was converted with
DNBSA (2 mg, 0.009 mmol) into C-glycosides 12a (11 mg, 23%) and
11a (29 mg, 72%).
Using microwave heating (general procedure 5), diol 7a
(575 mg, 1.0 mmol) in acetone (4 mL) was converted with DNBSA
(25 mg, 0.1 mmol) into C-glycoside 11a (322 mg, 69%).
0
CDCl3) dH 3.04 (br s, 2H, OH-1, OH-5), 3.66 (dd, J5,6 5.0 Hz, J6,6
0
0
0
9.8 Hz, 1H, H-6), 3.70 (dd, J5,6 3.6 Hz, J6,6 9.8 Hz, 1H, H-6 ), 3.81 (dd,
J3,4 3.1 Hz, J4,5 7.0 Hz, 1H, H-4), 4.02 (dd, J2,3 6.9 Hz, J3,4 3.1 Hz, 1H, H-
3), 4.05 (dd, J1,2 2.8 Hz, J2,3 6.9 Hz, 1H, H-2), 4.13–4.18 (m, 2H, H-5,
PhCHH0), 4.54–4.62 (m, 4H, PhCHH0, PhCHH0, PhCH2), 4.65 (d, J
11.4 Hz, 1H, PhCHH0), 4.70, 4.75 (ABq, JAB 11.3 Hz, 2H, PhCH2), 4.92
(d, J1,2 2.8 Hz, 1H, H-1), 7.10–7.41 (m, 25H, Ar–H); 13C NMR
(100 MHz, CDCl3) dC 71.0 (d, C-5), 71.4 (t, C-6), 73.2, 73.4, 73.6, 74.8,
75.3 (4ꢁt, d, 4ꢁPhCH2, C-1), 77.5 (d, C-4), 79.8, 83.4 (2ꢁd, C-2, C-3),
126.3, 127.5, 127.8, 127.9, 128.0, 128.0, 128.0, 128.3, 128.4, 128.4,
128.6, 128.6 (12ꢁd, Ar–CH), 137.9, 138.0, 138.1, 138.1 (4ꢁs, 4ꢁBn-C),
142.0 (s, Ar–C); m/z (ESþ) 1259 (2MþNaþ, 20), 641 (MþNaþ, 100%);
HRMS (ESþ) calcd for C40H42O6Na (MNaþ) 641.2874, found
641.2865.
Using microwave heating (general procedure 5), diol 7a (50 mg,
0.088 mmol) in acetonitrile (2 mL) was converted with DNBSA (2 mg,
0.009 mmol)intoC-glycosides12a (11 mg, 23%)and11a (27 mg, 67%).
4.11. (2,3,6-Tri-O-benzyl- -glucofuranosyl)ethene (11b) and
b-
D
(2,3,5,6-tetra-O-benzyl-b-D-glucofuranosyl)ethene (12b)
4.9. (1S,2S,3R,4S,5R)-2,3,4,6-Tetra-O-benzyl-1-phenyl-hexane-
1,2,3,4,5,6-hexaol (10a) and (1R,2S,3R,4S,5R)-2,3,4,6-tetra-O-
benzyl-1-phenyl-hexane-1,2,3,4,5,6-hexaol (10b)
Using conventional heating (general procedure 4), diol 7b
(150 mg, 0.26 mmol) in acetone (3 mL) was converted with DNBSA
(7 mg, 0.026 mmol) into C-glycoside 11b (83 mg, 68%).
Using conventional heating (general procedure 4), diol 7b
(120 mg, 0.21 mmol) in acetonitrile (2.5 mL) was converted with
DNBSA (5.2 mg, 0.021 mmol) into C-glycosides 12b (17 mg, 15%)
and 11b (64 mg, 66%).
Following general procedure 1, hemiacetal
2
(565 mg,
1.05 mmol) was converted with PhMgBr (3.2 mL, 3 M in Et2O,
9.6 mmol), in Et2O (3 mL) into a mixture of diols 10a and 10b (1:3),
which was purified (pentane/EtOAc, 3:1) togive 10a,b (519 mg, 80%).
Following general procedure 2, hemiacetal
2
(260 mg,
Using microwave heating (general procedure 5), diol 7b
(262 mg, 0.46 mmol) in acetone (2 mL) was converted with DNBSA
(2 mg, 0.009 mmol) into C-glycoside 11b (144 mg, 68%).
Using microwave heating (general procedure 5), diol 7b (50 mg,
0.088 mmol) in acetonitrile (2 mL) was converted with DNBSA
(2 mg, 0.009 mmol) into C-glycosides 12b (6 mg, 12%) and 11b
(27 mg, 67%).
0.48 mmol) was converted with ZnBr2 (285 mg, 1.3 mmol), PhMgBr
(1.6 mL, 3 M in Et2O, 4.8 mmol), in Et2O (5 mL) and toluene (3.2 mL)
into a mixture of diols 10a and 10b (1:3), which was purified
(pentane/EtOAc, 3:1) to give 10a,b (141 mg, 47%).
Following general procedure 3, hemiacetal
0.69 mmol) was converted into a mixture of diols 10a and 10b (1:3),
2
(371 mg,
which was separated togive 10b (194 mg, 46%) and 10a (80 mg,19%).
25
Compound 10a, a colourless oil; [
a
]
D
ꢂ6.3 (c 1.0 CHCl3); nmax
4.12. (2,3,6-Tri-O-benzyl- -galactofuranosyl)ethene (13a)
and (2,3,5,6-tetra-O-benzyl-a-D-galactofuranosyl)ethene (14a)
a
-
D
3430 (OH) cmꢂ1; 1H NMR (CDCl3, 400 MHz) dH 2.92 (br s, 1H, OH),
3.01 (br s, 1H, OH), 3.49–3.53 (m, 2H, H-6, H-60), 3.80 (dd, J1,2
6.4 Hz, J2,3 3.4 Hz, 1H, H-2), 3.87 (dd, J3,4 5.2 Hz, J4,5 2.0 Hz, 1H, H-
4), 3.94 (dd, J3,4 5.2 Hz, J3,2 3.4 Hz, 1H, H-3), 4.15 (dat, J5,6 6.2 Hz,
J4,5 2.0 Hz, 1H, H-5), 4.28, 4.36 (ABq, JAB 11.2 Hz, 2H, PhCH2), 4.40–
4.53 (m, 4H, 2ꢁPhCH2), 4.70, 4.74 (ABq, JAB 11.6 Hz, 2H, PhCH2),
5.00 (d, J1,2 6.4 Hz, 1H, H-1), 7.12–7.41 (m, 25H, Ar–H); 13C NMR
(CDCl3, 100 MHz) dC 69.7 (d, C-5), 71.2 (t, C-6), 73.1, 73.3 (2ꢁt,
PhCH2), 73.5 (d, C-1), 73.3, 74.0 (2ꢁt, PhCH2), 78.0 (d, C-4), 79.1 (d,
Using conventional heating (general procedure 4), diol 8a
(96 mg, 0.17 mmol) in acetone (3 mL) was converted with DNBSA
(4 mg, 0.017 mmol) into C-glycoside 13a (26 mg, 33%).
Using conventional heating (general procedure 4), diol 8a
(173 mg, 0.31 mmol) in acetonitrile (3.8 mL) was converted with
DNBSA (8 mg, 0.031 mmol) into C-glycosides 14a (26 mg, 16%) and
13a (86 mg, 61%).

R. Cribiu` et al. / Tetrahedron 65 (2009) 2022–2031
2029
4.13. (2,3,6-Tri-O-benzyl-
b-
D-galactofuranosyl)ethene (13b)
Using microwave heating (general procedure 5), diol 9b
and (2,3,5,6-tetra-O-benzyl-
b-D
-galactofuranosyl)ethene (14b)
(496 mg, 0.80 mmol) in acetone (4 mL) was converted with DNBSA
(20 mg, 0.08 mmol) into C-glycoside 16b (319 mg, 78%).
22
Using conventional heating (general procedure 4), diol 8b
(145 mg, 0.26 mmol) in acetone (3 mL) was converted with DNBSA
(6 mg, 0.025 mmol) into C-glycoside 13b (60 mg, 51%).
Using conventional heating (general procedure 4), diol 8b(131 mg,
0.23 mmol) in acetonitrile (2 mL) was converted with DNBSA (6 mg,
0.023 mmol)intoC-glycosides14b (25 mg, 20%)and13b (49 mg, 46%).
Compound 16b, a colourless oil; [
a
]
ꢂ23.9 (c 1.0, CHCl3); nmax
D
3479(br, OH) cmꢂ1; 1H NMR (400 MHz, CDCl3)dH 3.72 (dd, J5,6 6.1 Hz,
J6,6 9.8 Hz, 1H, H-6), 3.84 (dd, J5,6 3.3 Hz, J6,6 9.8 Hz, 1H, H-60), 4.02
(dd, J1,2 3.6 Hz, J2,3 1.0 Hz,1H, H-2), 4.15 (dd, J3,4 3.9 Hz, J4,5 8.0 Hz,1H,
H-4), 4.22 (dd, J2,31.0 Hz, J3,4 3.9 Hz,1H, H-3), 4.39 (ddd, J4,5 8.0 Hz, J5,6
0
0
0
0
6.1 Hz, J5,6 3.3 Hz,1H, H-5), 4.48–4.58 (m, 4H, 2 ꢁ PhCH2), 4.58, 4.63
(ABq, JAB 11.8 Hz, 2H, PhCH2), 4.88 (d, J1,2 3.6 Hz, 1H, H-1), 7.22–7.45
(m, 20H, Ar–H); 13C NMR (100 MHz, CDCl3) dC 68.8 (d, C-5), 71.8, 72.1,
72.4, 73.7 (4ꢁt, C-6, 3ꢁPhCH2), 81.4 (d, C-4), 83.4 (d, C-3), 86.5 (d, C-
1), 89.6 (d, C-2), 126.7, 127.8, 127.8, 127.9, 128.0, 128.0, 128.5, 128.5,
128.6,128.6 (10ꢁd, Ar–CH),137.7,137.8,138.3 (3ꢁs, 3ꢁBn-C),140.7 (s,
Ar–C); m/z (ESþ) 533 (MþNaþ, 100%); HRMS (ESþ) calcd for
C33H34O5Na (MNaþ) 533.2298, found 533.2293. Analysis, found: C,
78.00; H, 6.70. C33H34O5 requires C, 77.62; H, 6.71%.
4.14. (2R,3R,4R,5S,6S)-1,2,3,4,5,6-Hexa-O-benzyl-oct-7-ene-
1,2,3,4,5,6-hexaol (15a)
Diol 7a (500 mg, 0.88 mmol) was dissolved in THF (4 mL), and
BnBr (0.54 mL, 2.11 mmol) and sodium hydride (60% in oil, 100 mg,
2.11 mmol) were added. After 17 h, work-up and column chroma-
tography (pentane/EtOAc, 5:1) gave the fully protected compound
15a (614 mg, 93%) as a colourless oil. 1H NMR (CDCl3, 400 MHz) dH
3.72 (m, 1H), 3.85–3.95 (m, 5H), 4.00 (dd, J 4.5, 7.9 Hz, 1H), 4.17, 4.54
(ABq, JAB 11.8 Hz, 2H, PhCH2), 4.41 (d, J 11.8 Hz, 1H, PhCHH0), 4.50 (s,
2H, PhCH2), 4.59–4.72 (m, 6H, PhCHH0, PhCHH0, 2ꢁPhCH2), 4.80 (d, J
11.3 Hz, 1H, PhCHH0), 4.32–4.39 (m, 2H, H-1b, H-1b0), 5.97 (ddd, J1,1a
4.17. (2,3,6-Tri-O-benzyl-a-D-galactofuranosyl)benzene (17a)
Using conventional heating (general procedure 4), diol 10a
(122 mg, 0.20 mmol) in acetone (2 mL) was converted with DNBSA
(15 mg, 0.06 mmol) into C-glycoside 17a (30 mg, 30%).
0
7.9 Hz, J1a,1b 17.3 Hz, J1a,1b 10.3 Hz, 1H, H-1a), 7.23–7.32 (m, 30H, Ar–
H); 13C NMR (CDCl3, 100 MHz) dC 70.1, 70.2, 72.1, 73.4, 74.1, 74.2, 75.3
(7ꢁt, C-6, 6ꢁPhCH2), 79.3, 79.7, 79.8, 81.2, 81.9 (5ꢁd, C-1, C-2, C-3, C-
4,C-5),119.7(t, C-1b),127.4,127.4,127.5,127.6,127.6,127.7,127.7,127.8,
128.1, 128.1, 128.3, 128.3, 128.3, 128.3, 128.4, 128.4 (16ꢁd, Ar–CH),
136.0 (d, C-1a), 138.6, 138.8, 138.8, 138.9, 139.0, 139.2 (6ꢁs, 6ꢁAr–C);
HRMS (ESþ) calcd for C50H52O6Na (MNaþ) 771.3656, found 771.3654.
Using conventional heating (general procedure 4), diol 10a
(95 mg, 0.154 mmol) in acetonitrile (2 mL) was converted with
DNBSA (4 mg, 0.015 mmol) into C-glycosides 19a (15 mg, 16%) and
17a (49 mg, 63%).
25
Compound 17a, a colourless oil; [
a
]
ꢂ44.3 (c 1.0 CHCl3); nmax
D
3424 (OH) cmꢂ1; 1H NMR (CDCl3, 400 MHz) dH 3.07 (br s,1H, OH-5),
3.55–3.63 (m, 2H, H-6, H-60), 3.70 (d, J1,2 3.2 Hz, 1H, H-2), 3.93 (m,
1H, H-5), 3.97, 4.09 (ABq, JAB 12.0 Hz, 2H, PhCH2), 4.10 (d, J3,4 2.8 Hz,
1H, H-3), 4.18 (dd, J3,4 2.8 Hz, J4,5 3.2 Hz, 1H, H-4), 4.44 (s, 2H,
PhCH2), 4.50 (s, 2H, PhCH2), 5.03 (d, J1,2 3.2 Hz, 1H, H-1), 6.82–6.84
(m, 2H, Ar–H), 7.12–7.34 (m, 18H, Ar–H); 13C NMR (CDCl3, 100 MHz)
dC 70.8 (d, C-5), 71.6 (t, C-6), 71.8, 71.9, 73.4 (3ꢁt, 3ꢁPhCH2), 83.0 (d,
C-1), 83.1 (d, C-2), 84.0 (d, C-4), 84.6 (d, C-3), 127.3, 127.6, 127.7,
127.7, 127.7, 127.7, 127.8, 127.9, 128.0, 128.2, 128.3, 128.5 (12ꢁd, Ar–
CH), 136.2, 137.0, 137.5, 138.2 (4ꢁs, 4ꢁAr–C); HRMS (ESþ) calcd for
C33H34O5Na (MNaþ) 533.2298, found 533.2301.
4.15. (2,3,6-Tri-O-benzyl-a-D-glucofuranosyl)benzene (16a)
Using conventional heating (general procedure 4), diol 9a
(45 mg, 0.073 mmol) in acetone (2 mL) was converted with DNBSA
(2 mg, 0.007 mmol) into C-glycoside 16a (24 mg, 65%).
Using conventional heating (general procedure 4), diol 9a
(129 mg, 0.21 mmol) in acetonitrile (2.5 mL) was converted with
DNBSA (5 mg, 0.021 mmol) into C-glycosides 18a (30 mg, 24%) and
16a (70 mg, 66%).
Using microwave heating (general procedure 5), diol 9a
(237 mg, 0.38 mmol) in acetone (3 mL) was converted with DNBSA
4.18. (2,3,6-Tri-O-benzyl-b-D-galactofuranosyl)benzene (17b)
(10 mg, 0.04 mmol) into C-glycoside 16a (129 mg, 66%).
22
Compound 16a, a colourless oil; [
a]
ꢂ29.3 (c 1.0, CHCl3); nmax
Using conventional heating (general procedure 4), diol 10b
(194 mg, 0.31 mmol) in acetone (3.7 mL) was converted with
DNBSA (8 mg, 0.031 mmol) into C-glycoside 17b (59 mg, 37%).
Using conventional heating (general procedure 4), diol 10b
(134 mg, 0.22 mmol) in acetonitrile (2.6 mL) was converted with
DNBSA (5 mg, 0.022 mmol) into C-glycosides 19b (25 mg, 19%) and
D
3461 (br, OH) cmꢂ1 1H NMR (400 MHz, CDCl3) dH 3.70 (dd, J5,6
;
0
0
0
0
6.0 Hz, J6,6 9.8 Hz,1H, H-6), 3.81 (dd, J5,6 3.1 Hz, J6,6 9.8 Hz,1H, H-6 ),
3.95 (dd, J1,2 3.5 Hz, J2,3 0.9 Hz, 1H, H-2), 4.04, 4.12 (ABq, JAB 12.1 Hz,
0
2H, PhCH2), 4.22 (ddd, J4,5 8.6 Hz, J5,6 6.0 Hz, J5,6 3.1 Hz,1H, H-5), 4.22
(dd, J2,3 0.9 Hz, J3,4 3.7 Hz,1H, H-3), 4.35 (dd, J3,4 3.7 Hz, J4,5 8.6 Hz,1H,
H-4), 4.57 (d, J 11.8 Hz, 1H, PhCHH0), 4.60–4.63 (m, 3H, PhCHH0,
PhCH2), 5.22 (d, J1,2 3.5 Hz, 1H, H-1), 6.90–6.92 (m, 2H, Ar–H), 7.21–
7.39 (m,18H, Ar–H); 13C NMR (100 MHz, CDCl3) dC 68.9 (d, C-5), 72.2,
72.5, 72.8, 73.6 (4ꢁt, C-6, 3ꢁPhCH2), 80.8 (d, C-4), 82.9, 83.1, 83.2
(3ꢁd, C-1, C-2, C-3),127.4,127.6,127.7,127.8,127.8,127.9,128.0,128.1,
128.4, 128.6, 128.7 (11ꢁd, Ar–CH), 137.8, 137.8, 137.9, 138.4, (4ꢁs,
4ꢁAr–C); m/z (ESþ) 1043 (2MþNaþ, 55), 533 (MþNaþ,100%); HRMS
(ESþ) calcd for C33H34O5Na (MNaþ) 533.2298, found 533.2296.
17b (56 mg, 51%).
25
Compound 17b, a colourless oil; [
a
]
ꢂ27.3 (c 1.0 CHCl3); nmax
D
(OH) 3455 cmꢂ1; 1H NMR (CDCl3, 400 MHz) dH 2.70 (br s,1H, OH-5),
3.60–3.63 (m, 2H, H-6, H-60), 4.00 (aq, J 5.3 Hz,1H, H-5), 4.18 (dd, J1,2
5.2 Hz, J2,3 3.6 Hz, 1H, H-2), 4.27–4.33 (m, 2H, H-3, H-4), 4.45, 4.45
(ABq, JAB 11.6 Hz, 2H, PhCH2), 4.52 (s, 2H, PhCH2), 4.55, 4.58 (ABq,
JAB 12.0 Hz, 2H, PhCH2), 5.06 (d, J1,2 5.2 Hz, 1H, H-1), 7.17–7.42 (m,
20H, Ar–H); 13C NMR (CDCl3, 100 MHz) dC 70.5 (d, C-5), 71.5 (t, C-6),
72.0, 72.2, 73.5 (3ꢁt, 3ꢁPhCH2), 83.1 (d, C-4), 84.5 (d, C-3), 84.5 (d,
C-1), 89.7 (d, C-2), 126.3, 127.6, 127.7, 127.7, 127.7, 127.9, 128.4, 128.4,
128.4, 128.5 (10ꢁd, Ar–CH), 137.4, 137.7, 138.0, 140.4 (4ꢁs, 4ꢁAr–C);
HRMS (ESþ) calcd for C33H35O5 (MHþ) 511.2479, found 511.2480;
calcd for C33H34O5Na (MNaþ) 533.2298, found 533.2294.
4.16. (2,3,6-Tri-O-benzyl-b-D-glucofuranosyl)benzene (16b)
Using conventional heating (general procedure 4), diol 9b
(244 mg, 0.40 mmol) in acetone (4.7 mL) was converted with
DNBSA (10 mg, 0.040 mmol) into C-glycoside 16b (130 mg, 65%).
Using conventional heating (general procedure 4), diol 9b
(358 mg, 0.58 mmol) in acetonitrile (8.6 mL) was converted with
DNBSA (14 mg, 0.06 mmol) into C-glycosides 18b (47 mg, 14%) and
16b (211 mg, 71%).
4.19. (2,3,5,6-Tetra-O-benzyl-a-D-glucofuranosyl)benzene (18a)
Alcohol 16a (53 mg, 0.10 mmol) was dissolved in DMF (2 mL), and
the solution was placed under a N2 atmosphere. NaH (60%, 8 mg,

2030
R. Cribiu` et al. / Tetrahedron 65 (2009) 2022–2031
25
0.21 mmol) was added in one portion. After 30 min, the mixture was
treated with BnBr (37 mL, 0.31 mmol) and the mixture stirred over-
night. After this time, the mixture was concentrated in vacuo and the
residue dissolved in a mixture of EtOAc and water. The phases were
separated and the aqueous layer was extracted twice with EtOAc. The
combined organic extract was washed with water twice, dried
(Na2SO4), filtered and concentrated. The residue was purified by flash
(57 mg, 79%), a colourless oil. [
a
]
ꢂ29.5 (c 1.0 CHCl3); 1H NMR
D
(CDCl3, 400 MHz) dH 3.78–3.82 (m, 3H, H-6, H-60, H-4 or H-5), 4.17
(dd, J1,2 6.8 Hz, J2,3 4.0 Hz, 1H, H-2), 4.34–4.37 (m, 2H, H-3 and H-4
or H-5), 4.42–4.50 (m, 4H, 2ꢁPhCH2), 4.53 (s, 2H, PhCH2), 4.63, 4.83
(ABq, JAB 12.0 Hz, 2H, PhCH2), 5.03 (d, J1,2 6.8 Hz, 1H, H-1), 7.21–7.46
(m, 25H, Ar–H); 13C NMR (CDCl3, 100 MHz) dC 71.1 (t, C-6), 72.3,
72.4, 73.4, 73.7 (4ꢁt, 4ꢁPhCH2), 78.1, 82.7, 84.5 (3ꢁd, C-3, C-4, C-5),
84.0 (d, C-1), 90.7 (d, C-2), 126.8, 127.8, 127.9, 128.0, 128.0, 128.5,
128.6, 128.6, 128.6, 128.7 (10ꢁd, Ar–CH), 138.1, 138.2, 138.5, 138.8,
141.0 (5ꢁs, 5ꢁAr–C); HRMS (ESþ) calcd for C40H41O5 (MHþ)
601.2949, found 601.2946; calcd for C40H40O5Na (MNaþ) 623.2768,
found 623.2756.
column chromatography (pentane/ethyl acetate, 7:1) to give the
25
perbenzylated compound 18a (59 mg, 95%) as a colourless oil; [a]
D
ꢂ23.0 (c 1.0 CHCl3); 1H NMR (CDCl3, 400 MHz) dH 3.60 (dd, J5,6 5.6 Hz,
J6,6 10.6 Hz, 1H, H-6), 3.94 (d, J1,2 3.6 Hz, 1H, H-2), 4.00 (m, 1H, H-60),
0
4.01, 4.14 (ABq, JAB 12.0 Hz, 2H, PhCH2), 4.10 (m, 1H, H-5), 4.24 (d, J3,4
3.6 Hz,1H, H-3),4.50(dd, J3,4 3.6 Hz,J4,5 9.2 Hz,1H, H-4),4.54–4.65(m,
5H, 2ꢁPhCH2, PhCHH0), 4.87 (d, J 11.6 Hz, 1H, PhCHH0), 5.23 (d, J1,2
3.6 Hz, 1H, H-1), 6.88–6.90 (m, 2H, Ar–H), 7.20–7.38 (m, 23H, Ar–H);
13C NMR (CDCl3, 100 MHz) dC 71.9 (t, C-6), 72.2, 72.6, 72.7, 73.6 (4ꢁt,
4ꢁPhCH2), 76.6 (d, C-5), 80.3 (d, C-4), 82.9 (d, C-3), 83.0 (2ꢁd, C-1, C-
2),127.5,127.5,127.6,127.6,127.7,127.7,127.8,127.8,128.0,128.1,128.4,
128.5,128.5,128.7 (14ꢁd,Ar–CH),138.0,138.1,138.3,139.0,139.3(5ꢁs,
5ꢁAr–C); HRMS (ESþ) calcd for C40H41O5 (MHþ) 601.2949, found
601.2968; calcd for C40H40O5Na (MNaþ) 623.2768, found 623.2774.
Acknowledgements
The authors thank Carl Tryggers Stiftelse (research grant to I.C.
and post-doctoral fellowship to R.C.), the European Commission
(Marie Curie fellowship to K.E.B.), Vetenskapsrådet and the Ivar
Bendixsons Fond for financial support.
Supplementary data
4.20. (2,3,5,6-Tetra-O-benzyl-b-D-glucofuranosyl)
benzene (18b)
13C NMR data for stereochemical assignment of C-furanosides.
Supplementary data associated with this article can be found in the
online version, at doi:10.1016/j.tet.2009.01.014.
Prepared as described for 18a: alcohol 16b (211 mg, 0.41 mmol),
benzyl bromide (147 mL, 0.24 mmol), sodium hydride (60%, 33 mg,
0.83 mmol), DMF (2 mL) was converted into perbenzylated 18b
References and notes
25
(215 mg, 87%), a colourless oil. [
a
]
D
ꢂ24.3 (c 1, CHCl3); 1H NMR
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(CDCl3, 400 MHz) dH 3.79 (dd, J5,6 5.4 Hz, J6,6 10.6 Hz, 1H, H-6),
3.90–4.01 (m, 2H, H-2, H-60), 4.18 (d, J 3.2 Hz, 1H, H-3), 4.25–4.31
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J1,2 2.8 Hz, 1H, H-1), 7.10–7.12 (m, 2H, Ar–H), 7.21–7.41 (m, 23H, Ar–
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128.3, 128.5 (10ꢁd, Ar–CH), 137.7, 137.9, 138.7, 139.0, 140.9 (5ꢁs,
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25
(36 mg, 67%), a colourless oil. [
a
]
ꢂ11.5 (c 1, CHCl3); 1H NMR (CDCl3,
D
0
0
400 MHz) dH 3.66 (dd, J5,6 60.6 Hz, J6,6 10.4 Hz, 1H, H-6), 3.82 (dd, J5,6
0
3.6 Hz, J6,6 10.4 Hz, 1H, H-6 ), 3.94 (d, J1,2 3.6 Hz, 1H, H-2), 3.98–4.01
(m, 2H, H-5, PhCHH0), 4.10 (d, J 12.0 Hz, 1H, PhCHH0), 4.15–4.16 (m, 2H,
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2H, PhCH2),5.03(d, J1,2 3.6 Hz,1H, H-1), 6.90–6.93(m, 2H, Ar–H),7.18–
7.42 (m, 23H, Ar–H); 13C NMR (CDCl3, 100 MHz) dC 71.0 (t, C-6), 71.5,
71.6, 73.1, 73.2 (4ꢁt, 4ꢁPhCH2), 78.0(d, C-5), 82.9(d, C-1), 84.0(d, C-3,
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128.1,128.2,128.3,128.4 (12ꢁd,Ar–CH),136.5,137.8,138.4,138.8(4ꢁs,
Ar–C); HRMS (ESþ) calcd for C40H41O5 (MHþ) 601.2949, found
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