Carbohydrate carbocyclization by a novel zinc-mediated domino reaction and ring-closing olefin metathesis

Article abstract of DOI:10.1021/ja001415n

A general method for carbocyclization of carbohydrates is described using two consecutive organometallic transformations: a novel zinc-mediated domino reaction to give functionalized dienes followed by ring-closing olefin metathesis. In the first reaction

Full text of DOI:10.1021/ja001415n

8444
J. Am. Chem. Soc. 2000, 122, 8444-8452
Carbohydrate Carbocyclization by a Novel Zinc-Mediated Domino
Reaction and Ring-Closing Olefin Metathesis
Lene Hyldtoft and Robert Madsen*
Contribution from the Department of Organic Chemistry, Technical UniVersity of Denmark,
DK-2800 Lyngby, Denmark
ReceiVed April 24, 2000
Abstract: A general method for carbocyclization of carbohydrates is described using two consecutive
organometallic transformations: a novel zinc-mediated domino reaction to give functionalized dienes followed
by ring-closing olefin metathesis. In the first reaction, methyl ω-deoxy-ω-iodo glycosides undergo reductive
elimination with zinc to produce a terminal double bond. This also liberates the aldehyde which is immediately
alkylated in situ by various organozinc reagents. The alkylation occurs under Barbier conditions with methylene
iodide and several allyl bromides. Zinc plays a dual role by both promoting the reductive elimination and
activating the alkyl halide. Vinylation is carried out by adding divinylzinc. When a new stereogenic center is
generated, moderate to excellent stereocontrol is generally observed. An amino group can be introduced by
trapping the intermediate aldehyde as an imine prior to the alkylation. The reductive elimination-allylation
sequence can also be promoted by indium metal. All the alkylations produce a second double bond, and the
obtained dienes are subsequently subjected to ring-closing olefin metathesis to produce the corresponding
carbocycles. Newly developed catalyst 30 with an N-heterocyclic carbene ligand is more reactive toward these
carbohydrate-derived dienes than commercially available catalyst 18. Acetylation of the free hydroxy groups
improves the metathesis reaction significantly. Both five- and six-membered carbocycles are available by this
route, including a number of conduritols and quercitols.
Introduction
Scheme 1
Modern synthetic design demands high efficiency in terms
of minimization of synthetic steps together with maximization
of molecular complexity.1 Domino reactions are becoming a
very attractive tool in this regard.2 In these processes several
bond forming transformations take place under the same reaction
conditions, without adding additional reagent, and in which the
subsequent reactions are due to the functionality formed in the
previous step.2c The need for synthetic efficiency is particularly
acute in the area of carbohydrate chemistry. Carbohydrates are
densely functionalized molecules, and as a result their synthetic
application often requires many reaction steps, usually for
manipulation of different protecting groups. In particular the
conversion of carbohydrates into carbocycles is a major task
and has been the subject of many studies.3 This is due to the
fact that many biologically important molecules and natural
products contain a polyhydroxylated five- or six-membered
carbocycle.4 To improve the use of carbohydrates as synthetic
starting materials, we have embarked on a program to develop
more efficient transformations on carbohydrates by the use of
organometallic chemistry.5
In this regard we were interested in the zinc-mediated
reductive elimination of ω-iodo glycosides which generates an
aldehyde and a terminal double bond6 (Scheme 1). Originally
discovered by Bernet and Vasella in 1979, this transformation
has found many applications in carbohydrate chemistry.7
However, a general drawback is the instability of the liberated
aldehyde and related reproducibility problems caused by dif-
ferent zinc sources. In some applications the aldehyde has been
(1) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 259.
(2) (a) Eilbracht, P.; Ba¨rfacker, L.; Buss, C.; Hollmann, C.; Kitsos-
Rzychon, B. E.; Kranemann, C. L.; Rische, T.; Roggenbuck, R.; Schmidt,
A. Chem. ReV. 1999, 99, 3329. (b) Neuschu¨tz, K.; Velker, J.; Neier, R.
Synthesis 1998, 227. (c) Tietze, L. F. Chem. ReV. 1996, 96, 115. (d)
Denmark, S. E.; Thorarensen, A. Chem. ReV. 1996, 96, 137. (e) Parsons,
P. J.; Penkett, C. S.; Shell, A. J. Chem. ReV. 1996, 96, 195. (f) Bunce, R.
A. Tetrahedron 1995, 51, 13103. (g) Tietze, L. F.; Beifuss, U. Angew.
Chem., Int. Ed. Engl. 1993, 32, 131.
(5) (a) Hyldtoft, L.; Poulsen, C. S.; Madsen, R. Chem. Commun. 1999,
2101. (b) Beyer, J.; Madsen, R. J. Am. Chem. Soc. 1998, 120, 12137.
(6) (a) Bernet, B.; Vasella, A. HelV. Chim. Acta 1979, 62, 1990, 2400,
2411. (b) Nakane, M.; Hutchinson, C. R.; Gollman, H. Tetrahedron Lett.
1980, 21, 1213. (c) Fu¨rstner, A.; Jumbam, D.; Teslic, J.; Weidmann, H. J.
Org. Chem. 1991, 56, 2213.
(3) (a) Dalko, D. I.; Sinay¨, P. Angew. Chem., Int. Ed. Engl. 1999, 38,
773. (b) Mart´ınez-Grau, A.; Marco-Contelles, J. Chem. Soc. ReV. 1998,
27, 155. (c) RajanBabu, T. V. In PreparatiVe Carbohydrate Chemistry;
Hanessian, S., Ed.; Dekker: New York, 1997; p 545. (d) Ferrier, R. J.;
Middleton, S. Chem. ReV. 1993, 93, 2779.
(7) For some recent examples, see: (a) Dransfield, P. J.; Moutel, S.;
Shipman, M.; Sik, V. J. Chem. Soc., Perkin Trans. 1 1999, 3349. (b) Ovaa,
H.; Code´e, J. D. C.; Lastdrager, B.; Overkleeft, H. S.; van der Marel, G.
A.; van Boom, J. H. Tetrahedron Lett. 1999, 40, 5063. (c) De´sire´, J.; Prandi,
J. Tetrahedron Lett. 1997, 38, 6189. (d) Hu¨mmer, W.; Dubois, E.; Gracza,
T.; Ja¨ger, V. Synthesis 1997, 634. (e) Grove´, J. J. C.; Holzapfel, C. W.
Carbohydr. Lett. 1997, 2, 329.
(4) Ogawa, S. In Carbohydrates in Drug Design; Witczak, Z. J., Nieforth,
K. A., Eds.; Dekker: New York, 1997; p 433.
10.1021/ja001415n CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/17/2000

General Method for Carbohydrate Carbocyclization
J. Am. Chem. Soc., Vol. 122, No. 35, 2000 8445
Table 1. Zinc- and Indium-Mediated Elimination-Allylationa
trapped in situ by a nitrogen nucleophile.8 We reasoned that
carbon nucleophiles could also be used for trapping the
aldehyde, e.g., in a Barbier-type alkylation.9 Zinc would then
serve a dual function by promoting both the reductive elimina-
tion and activation of an alkyl halide for the alkylation. In
addition, if the alkyl halide contains a double bond, this
transformation would convert the ω-iodo glycosides directly into
functionalized dienes. These then can be converted into carbo-
cycles by ring-closing olefin metathesis (RCM). Since the key
catalyst development by Schrock and Grubbs, the area of olefin
metathesis has emerged as a powerful new tool for C-C bond
formation.10-12
Herein, we report a full account on a novel zinc-mediated
domino reaction that allows stereocontrolled synthesis of
carbohydrate-derived dienes from ω-iodo glycosides. These
dienes are then converted into five- and six-membered carbo-
cycles by ring-closing olefin metathesis. This sequence thus
constitutes an easy and efficient method for carbohydrate
carbocyclization by the use of two consecutive organometallic
transformations.
Results and Discussion
Elimination-Allylation. We first examined the domino
reaction with 5-iodo-ribofuranosides 1 and 2 in the presence of
zinc and allyl bromide (Table 1). A variety of zinc sources and
reaction conditions were investigated. In general, activated zinc
dust in tetrahydrofuran (THF) under sonication conditions
proved to be a very reliable procedure that consistently gave
full conversion and very high yield of the desired diene 7 (entries
1-3 and 5-7). No Wurtz coupling of the starting iodofurano-
sides was observed,13 and the conditions were sufficiently mild
to prevent the intermediate aldehyde from undergoing side
reactions before the allylation. Simple reflux instead of soni-
cation proved less reliable and sometimes caused the reaction
to stall, presumably due to precipitation of zinc(II) salts. More
reactive Rieke zinc,14 zinc graphite and zinc-silver graphite15
were found to be less convenient for general use as compared
to zinc dust. In addition, these highly reactive forms of zinc,
which are prepared from ZnCl2 and potassium, in our hands
sometimes caused base-catalyzed epimerization and decomposi-
tion of the intermediate aldehyde.
The solvent was also an important parameter in the domino
reaction. The reductive elimination of the ω-iodo glycosides
proceeded slowly in THF alone when zinc dust was used.
Enhanced reactivity could be obtained by adding a Lewis acid
a All reactions were carried out by sonication at 40 ˚C. b 2 eq of
MgBr2‚OEt2 was added instead of H2O. c 5 eq of Et3N was also added.
d Hydroxyl protecting groups were removed with ion-exchange resin
in the workup.
(8) Bernotas, R. C.; Papandreou, G.; Urbach, J.; Ganem, B. Tetrahedron
Lett. 1990, 31, 3393.
(9) Luche, J.-L.; Sarandeses, L. A. In Organozinc Reagents-A Practical
Approach; Knochel, P., Jones, P., Eds.; Oxford University Press: Oxford,
U.K., 1999; p 307.
(10) (a) Schrock, R. R. Tetrahedron 1999, 55, 8141. (b) Grubbs, R. H.;
Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28, 446.
(11) For general reviews, see: (a) Wright, D. L. Curr. Org. Chem. 1999,
3, 211. (b) Pandit, U. K.; Overkleeft, H. S.; Borer, B. C.; Biera¨ugel, H.
Eur. J. Org. Chem. 1999, 959. (c) Grubbs, R. H.; Chang, S. Tetrahedron
1998, 54, 4413. (d) Armstrong, S. K. J. Chem. Soc., Perkin Trans. 1 1998,
371. (e) Ivin, K. J. J. Mol. Catal. A 1998, 133, 1. (f) Fu¨rstner, A. Top.
Organomet. Chem. 1998, 1, 37. (e) Schuster, M.; Blechert, S. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 2036.
(12) For a recent review on olefin metathesis in carbohydrate chemistry,
see: Jørgensen, M.; Hadwiger, P.; Madsen, R.; Stu¨tz, A. E.; Wrodnigg, T.
M. Curr. Org. Chem. 2000, 4, 565.
(13) Blanchard, P.; Da Silva, A. D.; El Kortbi, M. S. Fourrey, J.-L.;
Robert-Ge´ro, M. J. Org. Chem. 1993, 58, 6517.
(14) Rieke, R. D.; Hanson, M. V. in Organozinc Reagents-A Practical
Approach; Knochel, P., Jones, P., Eds.; Oxford University Press: Oxford,
U.K., 1999; p 23.
or by using a protic solvent/cosolvent. If alcohols were used as
solvent,6a the corresponding acetal of the intermediate aldehyde
could sometimes be isolated due to the Lewis acidity of the
zinc(II) salts. However, H2O was found to be an efficient
cosolvent together with THF.9 The THF:H2O ratio influenced
the rate in the sense that more H2O generally enhanced the rate
of the overall transformation. Faster conversion could also be
achieved by adding a Lewis acid (entries 3 and 7).
The reaction with isopropylidene ribofuranoside 1 gave the
desired diene 7 in a 4:1 diastereomeric ratio (entries 1-3).16
Pure 7r could be obtained by recrystallization. This diastereo-
selectivity can be rationalized on the basis of the Felkin-Anh
model.17 It also corresponds with what has previously been
observed in zinc-mediated allylations of R-alkoxy aldehydes
(16) The stereochemistry of the products were assigned after ring-closing
olefin metathesis.
(15) Fu¨rstner, A. in ActiVe Metals-Preparation, Characterization, Ap-
plications; Fu¨rstner, A., Ed.; VCH: Weinheim, Germany, 1996; p 381.
(17) Che´rest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968, 2199.
Anh, N. T. Top. Curr. Chem. 1980, 88, 145.

8446 J. Am. Chem. Soc., Vol. 122, No. 35, 2000
Hyldtoft and Madsen
under aqueous conditions.18 However, it should be noted that
both the reductive elimination and the allylation reaction are
believed to be initiated by single electron transfer on the zinc
surface.19 As a result, the diastereoselectivity might also be
influenced by factors on this surface. Notably, when the
isopropylidene group is removed as in 2, the opposite diaste-
reomer 7â is obtained as the major product (entries 5-7). That
this reaction proceeds at all is an interesting result since we
and others20 have been unable to allylate unprotected aldoses
with zinc and allyl bromide under aqueous conditions.
Scheme 2a
Since the hydroxyl protecting group seems to have an impact
on the stereochemical outcome, we were interested in other
suitable protecting groups. Use of the isopropylidene group is
limited to glycosides with two cis oriented hydroxy groups.
Acetyl groups gave rise to complex mixtures in the elimination-
allylation reaction, presumably due to rapid decomposition of
the intermediate aldehyde. Instead, triethylsilyl (TES) groups
were found to be a convenient alternative. These are easily
introduced and then removed in the final workup. Furthermore,
the elimination-allylation with triethylsilylated ribofuranoside
3 proceeded well to give 7 in a slightly better diastereomeric
ratio than that observed in the reaction with 1 (entry 9).
Following these studies on ribofuranosides 1-3 other 5-io-
dopentofuranosides were then investigated. Unfortunately,
unprotected methyl 5-deoxy-5-iodo-D-xylo- and -D-arabinofura-
nosides turned out to be less stable and produced dienes 8 and
9 in only about 50% yield. Furthermore, the observed R:â ratio
was 1:1 in both cases. Therefore, the more stable triethylsilylated
substrates 4 and 5 were prepared and subjected to zinc and allyl
bromide (entries 10 and 12). This now gave 8 and 9 in good
yields and about 3:1 diastereoselectivity, in both cases favoring
the erythro relationship between the newly formed stereocenter
and the original stereocenter at C-2 in the starting pentose. The
2-deoxyribose substrate 6 gave diene 10 in high yield, although
the selectivity was poor (entry 13). This could, however, be
slightly improved by adding Et3N which serves as an inhibitor
slowing down the rate of the reaction (entry 14). The formation
of 10â as the major product is in accordance with the predictions
from the Evans model for 1,3-induction.21 For the other
substrates 1-5 the addition of Et3N did not produce better
results. In these cases the allylation became too slow with added
Et3N for the overall transformation to proceed at a resonable
rate.
a (a) CH2dC(CH2Br)CO2 Pr, Zn, THF:H2O (2:1), ultrasound, 40 ˚C.
(b) PhCHdCHCH2Br, Zn, THF:H2O (2:1), ultrasound, 40 ˚C. (c)
CH2dCHCH2Br, BnNH2, Zn, THF, ultrasound, 40 ˚C.
i
as with zinc (entries 1 and 4). Unprotected ribofuranoside 2,
on the other hand, gave a significantly improved 1:5 diastero-
meric ratio with indium (entries 6 and 8). These diastereo-
selectivities are in line with what has previously been observed
in indium-mediated allylation of aldoses in aqueous media.20,24,25
Isopropylidene protected aldoses give products where the
stereochemistry in the major diastereomer is erythro between
the newly generated stereocenter and the one originally present
at C-2 in the starting aldose.24 This is also observed with zinc18a
and corresponds with the Felkin-Anh model.17 Unprotected
aldoses, on the contrary, all undergo indium-mediated allylation
to give products where the stereochemistry in the major
diastereomer is threo between these stereocenters.20,25 This has
been explained on the basis of indium chelation to the R-hydroxy
group.26 Surprisingly, in the case of xylofuranoside 4 the
diastereomeric ratio was reversed when indium was used as
compared to zinc (entries 10 and 11). The reason for this change
is not immediately clear.27 However, these results do show that
besides varying the substituents in the substrates the metal can
also be used as a tool in optimizing these transformations.
Other allylating agents have also been investigated using zinc
as the metal. Reaction of 1 with isopropyl R-(bromomethyl)-
acrylate gave dienes 11r and 11â in very high yield and a 5:1
ratio (Scheme 2). Both the yield and the selectivity are similar
to the results obtained with allyl bromide in Table 1, entries
1-3. However, when 1 was reacted with cinnamyl bromide the
π-facial selectivity changed, giving 12 as the major product
isolated in 54% yield. Only minor amounts of the remaining
three diastereomers were formed. Further studies are necessary
to elucidate why the presence of a phenyl group in cinnamyl
bromide causes this crossover in π-facial discrimination as
compared to allyl bromide.28 The erythro relationship between
Besides zinc, the reductive elimination of ω-iodo glycosides
has also been accomplished with SmI2.22 Indium metal, however,
has never been used for this fragmentation. Stimulated by
previous studies on indium-mediated allylation of aldoses,23 we
decided to probe the elimination-allylation in the presence of
indium. Gratifyingly, the reaction proceeded to give the desired
dienes (Table 1, entries 4, 8, and 11). The reaction was
significantly slower with indium than with zinc, but the
stereochemical outcome is remarkable. Isopropylidene ribo-
furanoside 1 gave the same 4:1 diastereomeric ratio with indium
(18) (a) Chattopadhyay, A. J. Org. Chem. 1996, 61, 6104. (b) Chan, T.
H.; Li, C. J. Can. J. Chem. 1992, 70, 2726.
(19) (a) Marton, D.; Stivanello, D.; Tagliavini, G. J. Org. Chem. 1996,
61, 2731. (b) Fu¨rstner, A.; Baumgartner, J.; Jumbam, D. N. J. Chem. Soc.,
Perkin Trans. 1 1993, 131.
(20) Kim, E.; Gordon, D. M.; Schmid, W.; Whitesides, G. M. J. Org.
Chem. 1993, 58, 5500.
(21) Evans, D. A.; Dart, M. J.; Duffy, J. L.; Yang, M. G. J. Am. Chem.
Soc. 1996, 118, 4322.
(24) (a) Gao, J.; Ha¨rter, R.; Gordon, D. M.; Whitesides, G. M. J. Org.
Chem. 1994, 59, 3714. (b) Binder, W. H.; Prenner, R. H.; Schmid, W.
Tetrahedron 1994, 50, 749.
(25) (a) Prenner, R. H.; Binder, W. H.; Schmid, W. Liebigs Ann. Chem.
1994, 73. (b) Chan, T.-H.; Li, C.-J. J. Chem. Soc., Chem. Commun. 1992,
747.
(22) (a) Chiara, J. L.; Mart´ınez, S.; Bernabe´, M. J. Org. Chem. 1996,
61, 6488. (b) Grove´, J. J. C.; Holzapfel, C. W.; Williams, D. B. G.
Tetrahedron Lett. 1996, 37, 5817.
(23) For a general review, see: Li, C.-J.; Chan, T.-H. Tetrahedron 1999,
55, 11149.
(26) Paquette, L. A.; Mitzel, T. M. J. Am. Chem. Soc. 1996, 118, 1931.
(27) Normally, the stereochemical outcome in the aqueous Barbier-type
allylation does not depend on the metal. However, one previous exception
has been reported: Ru¨bsam, F.; Seck, S.; Giannis, A. Tetrahedron 1997,
53, 2823.

General Method for Carbohydrate Carbocyclization
J. Am. Chem. Soc., Vol. 122, No. 35, 2000 8447
Table 2. Zinc-Mediated Elimination-Vinylationa
the two newly generated stereocenters in 12 is that expected
from a chair transition state.28
Finally, it was investigated whether the intermediate aldehyde
could be intercepted with an amine prior to the allylation. This
allylation would then take place on the formed imine and result
in the introduction of an amino group. In fact, treatment of 1
with zinc, benzylamine, and allyl bromide succeeded in giving
the amino diene 13 in both good yield and diastereoselectivity.
This is an excellent example of a domino sequence: reductive
elimination followed by imine formation followed by allylation,
all in the same pot without changing conditions during the
transformation. Strictly anhydrous conditions were necessary
in order to form the intermediate imine. Only 2 equiv of
benzylamine were added. When more equivalents of benzyl-
amine were used, the amine substituted the iodide in the starting
iodofuranoside.
Elimination-Vinylation. Following the success of the
elimination-allylation sequence we then decided to investigate
the corresponding elimination-vinylation reaction. Instead of
adding a three carbon allyl group in the alkylation step, a two
carbon vinyl group would now be employed. The vinylation,
however, cannot be carried out directly under Barbier conditions
because vinyl bromide will not insert zinc under the conditions
for the reductive elimination. As a consequence29 we decided
to preform divinyl zinc prior to the reaction by magnesium-
zinc transmetalation from vinylmagnesium bromide and ZnCl2.
Divinyl zinc has previously been shown to give higher diaste-
reoselectivity in addition to sugars than vinylmagnesium
bromide.30
Indeed, treatment of isopropylidene ribofuranoside 1 with zinc
dust and divinyl zinc in THF gave diene 16 in excellent
diastereoselectivity (Table 2, entry 1). Triethylsilylated ribo-
furanoside 3 gave the same result while the reaction with
arabinofuranoside 5 was less stereoselective (entries 2 and 3).
The transformation also proceeded well for hexopyranosides,
as seen for the conversion of glucose and mannose substrates
14 and 15 (entries 4 and 5). For the latter only one diastereomer
of 19 could be observed. Unprotected ribofuranoside 2, however,
did not undergo the vinylation reaction, indicating the need for
the isopropylidene or silyl blocking groups for this transforma-
tion. The product ratios in Table 2 deserve some further
comments. For the ribose and mannose substrates 1, 3, and 15,
very high selectivity is obtained for the Felkin-Anh products
16r and 19â. This is, however, not the case for arabino and
glucose substrates 5 and 14. The vinyl addition is less selective
in these two cases, and the major products 17r and 18â are not
consistent with the predictions made by the Felkin-Anh model.
This is part of a general pattern for the addition to these
triethylsilylated substrates 3, 4, 5, 14, and 15 in Tables 1 and
2. For the substrates with 2,3-erythro configuration (3 and 15)
the addition always occurs with high selectivity for the Felkin-
Anh product. For the substrates with 2,3-threo configuration
(4, 5, and 14) the diastereoselectivity is lower and in some cases
even reverses. Chelation control is not believed to be involved
in these addition reactions. The reason for this difference must
then lie in a different steric and/or electronic influence of the
a All reactions were carried out by sonication at 40 ˚C. b Hydroxyl
protecting groups were removed with ion-exchange resin in the workup.
C-3 silyloxy group in the erythro and the threo cases. To the
best of our knowledge there has not yet been any systematic
study on additions to erythro and threo 2,3-dialkoxy aldehydes
under nonchelating conditions.31
Elimination-Olefination. Another possibility for introducing
a double bond in the alkylation step would be to add just one
carbon to form an olefin with the intermediate aldehyde. This
could potentially be done by talking advantage of the zinc-
mediated olefination with CH2I2,32 which furthermore requires
a Lewis acid that will also benefit the reductive elimination. In
fact, when glucose and mannose substrates 14 and 15 were
treated with zinc, CH2I2 and (TMS)Cl dienes 17r and 17â were
obtained, respectively (Table 3). It turned out to be important
to add a catalytic amount of PbCl2 in order to get the olefination
to proceed,33 otherwise the reaction would stop at the aldehyde
step. Since there are no stereocenters generated in this trans-
formation, it is a better method for preparing 17r and 17â than
the elimination-vinylation reaction in Table 2, entry 3.
Ring-Closing Olefin Metathesis. With the advent of efficient
catalysts, the ring-closing metathesis (RCM) reaction has
emerged as a powerful process for cyclization of dienes.11 Also
the area of carbohydrate chemistry has taken advantage of the
RCM reaction although synthesis of the diene precursors can
sometimes be cumbersome.12 The zinc-mediated domino reac-
tion provides an easy protocol for preparation of dienes, and in
the following the RCM reaction of these will be studied.
(28) For reaction of an r-siloxy aldehyde with cinnamyl bromide and
indium under aqueous conditions, see: Isaac, M. B.; Paquette, L. A. J.
Org. Chem. 1997, 62, 5333.
(29) Magnesium metal inserts vinyl bromide easily but will not perform
the reductive elimination of ω-iodo glycosides due to competing dimer-
ization by Wurtz coupling: Fu¨rstner, A.; Weidmann, H. J. Org. Chem. 1989,
54, 2307. Stout, E. I.; Doane, W. M.; Trinkus, V. C. Carbohydr. Res. 1976,
50, 282.
(31) For a recent review on 1,2- and 1,3-induction in carbonyl addition
reactions, see: Mengel, A.; Reiser, O. Chem. ReV. 1999, 99, 1191.
(32) (a) Takai, K.; Hotta, Y.; Oshima, K.; Nozaki, H. Bull. Chem. Soc.
Jpn. 1980, 53, 1698. (b) Lombardo, L. Org. Synth. 1987, 65, 81.
(33) Takai, K.; Kakiuchi, T.; Kataoka, Y.; Utimoto, K. J. Org. Chem.
1994, 59, 2668.
(30) Boschetti, A.; Nicotra, F.; Panza, L.; Russo, G. J. Org. Chem. 1988,
53, 4181.

8448 J. Am. Chem. Soc., Vol. 122, No. 35, 2000
Table 3. Zinc-Mediated Elimination-Methylenationa
Hyldtoft and Madsen
Table 4. RCM with Catalyst 18a
a All reactions were carried out by sonication at 40 ˚C. b Silyl groups
were removed with ion-exchange resin in the workup.
Previous work on RCM in carbohydrate chemistry has
concentrated on the use of commercially available Grubbs
catalyst 18.12,34
a All reactions were carried out in CH2Cl2 at room temperature.
When the major diene isomers from Table 1 were treated with
this catalyst in CH2Cl2, very high yields were obtained of the
desired cyclohexenes 21-24 (Table 4, entries 1-4). It is
noteworthy that these unprotected triols are metathesized so well.
However, there are some differences. Cyclohexenes 21, 23, and
24 all crystallized out from the reaction mixture during the
course of the reaction. Cyclohexene 22 did not crystallize, and
in this case a higher catalyst loading was necessary to force the
reaction to go to completion. Although catalyst 18 is known to
tolerate alcohols in the substrates,11 the active ruthenium-
methylene catalyst, generated after the first catalytic cycle, has
been shown to decompose rapidly in methanol.35 We speculated
that the hydroxy groups after all may inhibit the reaction in
entry 2. In fact, when 7â was acetylated to give 19, the ring
closure could be carried out with only half the amount of catalyst
(entry 5). The amino diene 13r, on the other hand, turned out
to be more difficult. Even after converting 13r into its
corresponding ammonium salt with TsOH,36 the RCM reaction
only gave about 50% conversion with 10% of 18. Full
conversion could first be achieved after conversion of the amine
into amide 20 (entry 6). The structure of the obtained cyclo-
to their close resemblance to the inositols.37,38 The dihydroxy-
lation with OsO4 occurs predominately anti to the allylic
hydroxy group to afford (+)-talo-quercitol 27 (from 21), (-)-
gala-quercitol 28 (from 22), and muco-quercitol 29 (from 23
and 24). This constitutes one of the shortest syntheses of these
quercitols in nonracemic form.
When we subsequently carried out the RCM of dienes 31 and
17r ,full conversion could not be achieved (Table 5, entries 1
and 2). If 17R was protected with benzyl groups, even lower
conversion was obtained. This prompted us to look for a more
reactive catalyst. Carbohydrate dienes are often electron deficient
and, as our results show, can sometimes be intrinsicly difficult
to metathesize. In previous RCM of carbohydrate-derived dienes
double digit percentages for the catalyst loading with 18 are
commonly employed.12 Very recently an entire new family of
more reactive metathesis catalysts has been developed, all of
which are derived from 18 by substituting one of the phosphine
1
hexene 26 was elucidated by H NMR after saturation of the
double bond. For the remaining cyclohexenes 21-24 the
structure was determined after dihydroxylation of the double
bond to give the corresponding quercitols. These cyclohexane-
pentols have previously been the target of many syntheses due
(37) Hudlicky, T.; Cebulak, M. Cyclitols and Their DeriVatiVes; VCH:
New York, 1993.
(34) Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1996,
118, 100.
(35) Kirkland, T. A.; Lynn, D. M.; Grubbs, R. H. J. Org. Chem. 1998,
63, 9904.
(36) Fu, G. C.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc. 1993,
115, 9856.
(38) For recent examples, see: (a) Maezaki, N.; Nagahashi, N.; Yoshi-
gami, R.; Iwata, C.; Tanaka, T. Tetrahedron Lett. 1999, 40, 3781. (b) Kim,
K. S.; Park, J. I.; Moon, H. K.; Yi, H. Chem. Commun. 1998, 1945. (c)
Biamonte, M. A.; Vasella, A. HelV. Chim. Acta 1998, 81, 688. (d) Maras¸,
A.; Sec¸en, H.; Su¨tbeyaz, Y.; Balci, M. J. Org. Chem. 1998, 63, 2039.

General Method for Carbohydrate Carbocyclization
J. Am. Chem. Soc., Vol. 122, No. 35, 2000 8449
Table 6. RCM with Catalyst 30a
Table 5. RCM with Catalysts 18 and 30a
a All reactions were carried out in CH2Cl2 at room temperature except
in entry 2 where 40 ˚C was used. b Acetyl groups were removed in the
workup. 51% of 17R was also obtained. c 29% of 17r was recovered.
ligands with an N-heterocyclic carbene.39 We found catalyst
30 easy to prepare without any special precautions.39a In fact,
when 17r was treated with 7% of 30, full conversion could
now be achieved and cyclopentene 32 was isolated in high yield
(entry 3). Similar results were obtained with dienes 16r and
17â (entries 4 and 5). This clearly demonstrates the increased
reactivity of 30 as compared to 18. Cyclopentene 32 has
previously been isolated from a plant of the Achariaceae
family.40
For synthesis of the corresponding cyclohexenes it turned out
to be necessary to use peracetylated dienes 35-37 (Table 6,
entries 1-3).41 The correponding unprotected dienes 12, 18â,
and 19â did not undergo the ring closure very efficiently.
Instead, treatment of 35-37 with catalyst 30 all gave high yield
of cyclohexenes 40-42. The latter two are the peracetates of
(-)-conduritol B and C which hereby are available in very few
steps from glucose and mannose, respectively. This clearly
shows the strength of the developed synthetic strategy. Numer-
ous stereocontrolled syntheses of the conduritols have been
reported,37,42 but this strategy using a zinc-mediated domino
reaction and subsequent RCM is one of the shortest.
a All reactions were carried out in CH2Cl2 at 40 ˚C. b 32% of 38
was recovered. c 25% of 39 was recovered.
reduction and acetylation gave 39 (entries 4 and 5). Treatment
of 38 and 39 with catalyst 18 gave only little conversion, while
catalyst 30 gave moderate yields of 43 and 44 in both cases
together with some recovered starting material. Deprotection
of 43 yielded the 5-epimer of shikimic acid. Although these
substituted dienes remain a problem in the RCM reaction, two
main conclusions can be drawn from these studies on carbo-
hydrate-derived dienes. First, acetylated dienes generally give
better RCM than unprotected or benzylated dienes. Second,
catalyst 30 with an N-heterocyclic carbene ligand is more
powerful for these substrates than commercially available 18.
In conclusion, we have developed an efficient method for
carbocyclization of carbohydrates by combining a novel zinc-
mediated domino reaction with the ring-closing olefin metathesis
reaction. The procedure can be used on both pentoses and
hexoses and gives rise to both five- and six-membered car-
bocycles. As a result, this technique constitutes one of the most
versatile and general methods developed so far for carbocy-
clization of sugars. Application of these reactions to short total
syntheses of biologically significant natural products is currently
in progress.
The RCM reaction is sensitive to substituents on the double
bond.43 As a consequence, ester diene 11r was expected to be
a very difficult substrate. No RCM could be achieved directly
with 11r. Acetylation was then performed to give 38 while
(39) (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999,
1, 953. (b) Weskamp, T.; Kohl, F. J.; Herrmann, W. A. J. Organomet. Chem.
1999, 582, 362. (c) Huang, J.; Schanz, H.-J.; Stevens, E. D.; Nolan, S. P.
Organometallics 1999, 18, 5375. (d) Ackermann, L.; Fu¨rstner, A.; Weskamp,
T.; Kohl, F. J.; Herrmann, W. A. Tetrahedron Lett. 1999, 40, 4787. (e)
Scholl, M.; Trnka, T. M.; Morgan, J. P.; Grubbs, R. H. Tetrahedron Lett.
1999, 40, 2247. (f) Weskamp, T.; Kohl, F. J.; Hieringer, W.; Gleich, D.;
Herrmann, W. A. Angew. Chem., Int. Ed. Engl. 1999, 38, 2416.
(40) Jensen, S. R.; Nielsen, B. J. Phytochemistry 1986, 25, 2349.
(41) The perbenzylated dienes were recently shown to require 30% of
18 for the RCM reaction: Gallos, J. K.; Koftis, T. V.; Sarli, V. C.; Litinas,
K. E. J. Chem. Soc., Perkin Trans. 1 1999, 3075.
Experimental Section
General procedures are in the Supporting Information. All sonications
were carried out in a Branson 1210 sonic bath. Zinc dust (Aldrich
20.998-8) was activated and dried immediately before use: Zinc (5 g)
in 1 M aqueous HCl (50 mL) was stirred at room temperature for 15
min, then filtered, and washed with H2O (2 × 50 mL) and Et2O (50
mL). Finally, the material was dried under high vacuum with a heatgun.
General Procedure for Elimination-Allylation (Table 1). Zinc
(8.3 g, 127 mmol) and allyl bromide (3.3 mL, 39 mmol) were added
to a deoxygenated mixture of the methyl 5-iodofuranoside (12.7 mmol)
in a THF:H2O solution (40 mL) under argon. The mixture was sonicated
at 40 °C until thin layer chromatography (TLC) revealed full conversion
of the starting material and then filtered through Celite. The Celite
(42) (a) Balci, M. Pure Appl. Chem. 1997, 69, 97. (b) Carless, H. A. J.
Tetrahedron: Asymmetry 1992, 3, 795. (c) Balci, M.; Su¨tbeyaz, Y.; Sec¸en,
H. Tetrahedron 1990, 46, 3715.
(43) Kirkland, T. A.; Grubbs, R. H. J. Org. Chem. 1997, 62, 7310.

8450 J. Am. Chem. Soc., Vol. 122, No. 35, 2000
Hyldtoft and Madsen
was washed with Et2O (20 mL). The filtrate was stirred with Amberlite
IR-120 (H+) (25 mL) for 1 h to remove hydroxyl protecting groups.
The mixture was transferred onto a column of mixed bed ion-exchange
resin consisting of Amberlite IR-120 (H+) (75 mL) and IRA-400 (OH-)
(75 mL). The column was eluted with H2O (500 mL). The eluate was
concentrated, and the residue purified by flash chromatography.
1,2,3,7,8-Pentadeoxy-D-ribo-oct-1,7-dienitol (7r). Rf ) 0.62 (Et2O).
washed with H2O (20 mL) and the aqueous phase extracted with CH2-
Cl2 (2 × 40 mL). The combined organic phases were dried and
concentrated to a syrup. 13C NMR revealed the formation of 11r and
11â in a ratio of 5:1. Flash chromatography (pentane:Et2O ) 2:1) gave
0.44 g (98%) of 11r and 11â as an inseparable mixture; Rf ) 0.35.
For 11R: 1H NMR (500 MHz, CDCl3): δ 6.25 (m, 1H), 6.04 (ddd,
J ) 6.8, 10.7, 17.1 Hz, 1H), 5.70 (m, 1H), 5.41 (ddd, J ) 1.7, 1.8,
17.1 Hz, 1H), 5.27 (dddd, J ) 1.3, 1.5, 1.6, 10.7 Hz, 1H), 5.08 (septet,
J ) 6.0 Hz, 1H), 4.68 (dt, J ) 0.9, 6.3 Hz, 1H), 3.96 (dd, J ) 6.4, 8.5
Hz, 1H), 3.77 (dt, J ) 2.6, 8.5 Hz, 1H), 2.84 (ddd, J ) 0.9, 2.6, 14.2
Hz, 1H), 2.43 (dd, J ) 9.0, 14.2 Hz, 1H), 1.50 (s, 3H), 1.37 (s, 3H),
1.30 (d, J ) 6.0 Hz, 3H), 1.29 (d, J ) 6.0 Hz, 3H). 13C NMR (50
MHz, CDCl3): δ 167.9, 137.3, 134.2, 127.9, 117.6, 108.5, 80.1, 78.7,
69.3, 68.3, 36.7, 27.7, 25.3, 21.7.
1
mp 84-85 °C (MeOH). [R]D -32.4 (c 1.0, CHCl3). H NMR (500
MHz, CDCl3): δ 6.01 (ddd, J ) 6.6, 10.5, 17.2 Hz, 1H), 5.88 (m,
1H), 5.42 (dt, J ) 1.4, 17.3 Hz, 1H), 5.33 (dt, J ) 1.4, 10.5 Hz, 1H),
5.19-5.23 (m, 2H), 4.33 (ddt, J ) 1.2, 6.1, 6.6 Hz, 1H), 3.72 (ddd, J
) 3.3, 7.2, 8.4, 1H), 3.54 (dd, J ) 5.5, 7.1 Hz, 1H), 2.60 (ddddd, J )
1.4, 1.5, 3.3, 4.7, 14.2 Hz, 1H), 2.34 (s, OH, 3H), 2.28 (ddddd, J )
1.2, 1.3, 8.3, 8.4, 14.1 Hz, 1H). 13C NMR (63 MHz, CDCl3): δ 136.6,
134.3, 118.7, 117.8, 75.1, 74.7, 71.9, 37.9. Anal. Calcd for C8H14O3:
C, 60.74; H, 8.92. Found: C, 60.72; H, 8.97.
1,2,3,7,8-Pentadeoxy-D-arabino-oct-1,7-dienitol (7â). Rf ) 0.60
(Et2O). [R]D +50 (c 0.4, MeOH). 1H NMR (500 MHz, CDCl3): δ 5.95
(ddd, J ) 5.6, 10.7, 17.5 Hz, 1H), 5.85 (m, 1H), 5.41 (dt, J ) 1.3,
17.5 Hz, 1H), 5.29 (dt, J ) 1.3, 10.7 Hz, 1H), 5.17 (dq, J ) 1.7, 11.3
Hz, 1H), 5.14 (dq, J ) 0.9, 11.3 Hz, 1H), 4.36 (dd, J ) 1.2, 5.5 Hz,
1H), 3.92 (m, 1H), 3.50 (m, 1H), 2.61 (bd, J ) 7.7 Hz, 1H), 2.54 (bd,
J ) 6.0 Hz, 1H). 13C NMR (50 MHz, CDCl3): δ 136.1, 133.8, 118.3,
117.4, 75.0, 73.6, 70.1, 37.8.
Acetylation gave 19: Rf ) 0.87 (pentane:Et2O ) 1:1). [R]D +31 (c
0.6, CHCl3). 1H NMR (500 MHz, CDCl3): δ 5.65-5.79 (m, 2H), 5.37
(dt, J ) 1.3, 17.1 Hz, 1H), 5.28-5.33 (m, 2H), 5.19-5.24 (m, 2H),
5.11 (ddd, J ) 1.3, 1.7, 7.0 Hz, 1H), 5.09 (dt, J ) 1.3, 4.7 Hz, 1H),
2.30 (m, 2H), 2.11 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H). 13C NMR (126
MHz, CDCl3): δ 170.1, 170.0, 169.5, 132.4, 132.3, 120.4, 118.6, 72.5,
72.0, 69.7, 35.5, 20.9. 20.7, 20.7. Anal. Calcd for C14H20O6: C, 59.14;
H, 7.09. Found: C, 59.60; H, 7.38.
For 11â: 13C NMR (50 MHz, CDCl3): δ 167.9, 137.3, 134.1, 127.3,
119.5, 108.5, 80.1, 79.1, 69.3, 68.3, 36.9, 27.1, 24.8, 21.7. Anal. Calcd
for C15H24O5: C, 63.36; H, 8.51. Found: C, 63.30; H, 8.53.
Compounds 11R and 11â were separated after acetylation. For 38:
Rf ) 0.81 (pentane:Et2O ) 2:1). [R]D -11.6 (c 3.0, CHCl3). 1H NMR
(500 MHz, CDCl3): δ 6.18 (m, 1H), 5.85 (dddd, J ) 2.5, 7.8, 10.3,
17.6 Hz, 1H), 5.56 (bs, 1H), 5.36 (ddd, J ) 0.8, 2.3, 17.2 Hz, 1H),
5.24 (ddd, J ) 0.8, 1.2, 10.2 Hz, 1H), 5.06-5.11 (m, 2H), 4.64 (bt, J
) 7.0 Hz, 1H), 4.17 (t, J ) 6.7 Hz, 1H), 2.97 (dd, J ) 2.1, 14.4 Hz,
1H), 2.40 (dd, J ) 8.6, 14.4 Hz, 1H), 1.92 (s, 3H), 1.54 (s, 3H), 1.39
(s, 3H), 1.30 (d, J ) 6.2 Hz, 3H), 1.29 (d, J ) 6.2 Hz, 3H). 13C NMR
(126 MHz, CDCl3): δ 169.5, 165.9, 136.7, 132.6, 127.2, 118.6, 108.9,
78.7, 78.3, 70.0, 68.0, 34.1, 27.4, 25.2, 21.6, 21.6, 20.9. Anal. Calcd
for C17H26O6: C, 62.56; H, 8.03. Found: C, 62.42; H, 7.97.
Reduction of 11R with DIBAL-H followed by acetylation gave 39:
1
Rf ) 0.65 (pentane:Et2O ) 2:1). [R]D -6.4 (c 3.0, CHCl3). H NMR
(500 MHz, CDCl3): δ 5.83 (ddd, J ) 7.3, 10.3, 17.2 Hz, 1H), 5.37
(dt, J ) 1.3, 17.2 Hz, 1H), 5.25 (dt, J ) 1.3, 10.3 Hz, 1H), 5.12 (m,
1H), 4.99-5.03 (m, 2H), 4.65 (t, J ) 7.1 Hz, 1H), 4.61 (d, J ) 13.3
Hz, 1H), 4.54 (d, J ) 13.3 Hz, 1H), 4.21 (t, J ) 6.9 Hz, 1H), 2.56
(bdd, J ) 2.2, 14.6 Hz, 1H), 2.36 (dd, J ) 8.6, 14.6 Hz, 1H), 2.09 (s,
3H), 1.98 (s, 3H), 1.51 (s, 3H), 1.38 (s, 3H). 13C NMR (50 MHz,
CDCl3): δ 170.5, 169.7, 139.4, 132.7, 118.5, 116.1, 108.9, 78.5, 78.0,
70.0, 66.5, 34.9, 27.3, 25.0, 20.9, 20.8. Anal. Calcd for C16H24O6: C,
61.52; H, 7.74. Found: C, 61.47; H, 7.72.
1,2,3,7,8-Pentadeoxy-L-lyxo-oct-1,7-dienitol (8r). Rf ) 0.59 (Et2O).
1
[R]D -22 (c 0.6, MeOH). H NMR (300 MHz, CD3OD): δ 5.79-
5.98 (m, 2H), 5.25 (dt, J ) 1.3, 15.1 Hz, 1H), 5.11 (dt, J ) 1.3, 10.0
Hz, 1H), 4.98-5.03 (m, 2H), 4.26 (ddt, J ) 1.7, 3.1, 4.5 Hz, 1H), 3.62
(dt, J ) 3.6, 9.0 Hz, 1H), 3.25 (dd, J ) 2.9, 8.6 Hz, 1H), 2.45 (m,
1H), 2.14 (m, 1H). 13C NMR (75 MHz, CD3OD): δ 139.9, 136.8, 117.2,
115.9, 77.0, 73.2, 72.2, 38.8. Anal. Calcd for C8H14O3: C, 60.74; H,
8.92. Found: C, 60.66; H, 9.41.
1,2,3,7,8-Pentadeoxy-5,6-O-isopropylidene-3-C-phenyl-D-manno-
oct-1,7-dienitol (12). Furanoside 1 (0.5 g, 1.59 mmol) was treated with
zinc (1.0 g, 15.3 mmol) and a solution of cinnamyl bromide (0.9 g,
4.6 mmol) in THF (10 mL) as described above for 11r to give after
flash chromatography 241 mg (55%) of 12, Rf ) 0.56 (pentane:Et2O
1,2,3,7,8-Pentadeoxy-L-xylo-oct-1,7-dienitol (8â). Rf ) 0.57 (Et2O).
1H NMR (500 MHz, CD3OD): δ 5.81-5.94 (m, 2H), 5.32 (ddd, J )
1.4, 1.6, 17.1 Hz, 1H), 5.18 (ddd, J ) 1.3, 2.1, 10.7 Hz, 1H), 5.10
(dddd, J ) 1.3, 1.7, 2.1, 17.1 Hz, 1H), 5.04 (dddd, J ) 1.0, 1.3, 2.1,
10.2 Hz, 1H), 4.17 (m, 1H), 3.68 (ddd, J ) 3.0, 6.0, 7.3 Hz, 1H), 3.29
(dd, J ) 3.0, 6.0 Hz, 1H), 2.28-2.38 (m, 2H). 13C NMR (75 MHz,
CD3OD): δ 139.1, 136.2, 117.2, 117.0, 76.5, 75.2, 72.3, 39.5.
Compounds 9R/â are the enantiomers of 8â/r.
1
) 4:1). [R]D +38.0 (c 1.0, CHCl3). H NMR (500 MHz, CDCl3): δ
7.31-7.34 (m, 2H), 7.21-7.25 (m, 3H), 6.24 (ddd, J ) 8.7, 10.2, 16.9
Hz, 1H), 6.09 (ddd, J ) 7.9, 10.2, 16.9 Hz, 1H), 5.34 (ddd, J ) 0.8,
1.6, 16.9 Hz, 1H), 5.33 (ddd, J ) 0.8, 1.6, 10.2 Hz, 1H), 5.19 (ddd, J
) 0.8, 2.0, 10.2 Hz, 1H), 5.10 (ddd, J ) 1.2, 2.0, 16.9 Hz, 1H), 4.50
(dd, J ) 7.1, 7.9 Hz, 1H), 3.96 (dd, J ) 3.5, 7.1 Hz, 1H), 3.47 (dd, J
) 7.3, 8.1 Hz, 1H), 2.23 (bd, J ) 6.7 Hz, 1H), 1.55 (s, 3H), 1.34 (s,
3H). 13C NMR (50 MHz, CDCl3): δ 141.3, 138.0, 134.2, 128.5, 128.0,
126.5, 119.5, 117.0, 108.4, 78.9, 77.4, 72.2, 53.3, 27.0, 24.7. Anal.
Calcd for C17H22O3: C, 74.42; H, 8.08. Found: C, 74.48; H, 8.08.
Acetylation gave 35: Rf ) 0.37 (pentane:Et2O ) 9:1). [R]D +47.7
(3S,5R)-Octa-1,7-dien-3,5-diol (10â). Rf ) 0.27 (pentane:Et2O )
1
1:1). [R]D +7.0 (c 1, CHCl3). H NMR(300 MHz, CDCl3): δ 5.93
(ddd, J ) 5.3, 10.6, 17.2 Hz, 1H), 5.82 (m, 1H), 5.30 (dt, J ) 1.5,
17.2 Hz, 1H), 5.11-5.18 (m, 3H), 4.48 (m, 1H), 4.40 (m, 1H), 2.24-
2.31 (m, 2H), 1.69-1.79 (m, 2H). 13C NMR (50 MHz, CDCl3): δ
140.5, 134.3, 118.2, 114.3, 70.4, 67.9, 42.0, 41.6. The stereochemistry
was determined after chemical correlation with the corresponding enyne;
see Table 1 in ref 5a.
1
(c 1.1, CHCl3). H NMR (300 MHz, CDCl3): δ 7.20-7.34 (m, 5H),
(3S,5S)-Octa-1,7-dien-3,5-diol (10r). Rf ) 0.29 (pentane:Et2O )
6.02 (dt, J ) 10.0, 16.8 Hz, 1H), 5.77 (ddd, J ) 7.2, 10.1, 17.0 Hz,
1H), 5.24-5.30 (m, 2H), 5.17 (dd, J ) 2.7, 9.4 Hz, 1H), 5.10 (dd, J )
1.7, 17.0 Hz, 1H), 5.06 (dd, J ) 1.8, 10.0 Hz, 1H), 4.47 (t, J ) 7.1
Hz, 1H), 3.93 (dd, J ) 2.7, 6.9 Hz, 1H), 3.69 (t, J ) 9.6 Hz, 1H), 2.02
(s, 3H), 1.57 (s, 3H), 1.31 (s, 3H). 13C NMR (50 MHz, CDCl3): δ
170.2, 140.4, 137.7, 133.0, 128.8, 128.0, 126.9, 118.8, 117.1, 108.7,
78.3, 76.4, 73.2, 52.7, 26.9, 25.5, 21.4. Anal. Calcd for C19H24O4: C,
72.13; H, 7.65. Found: C, 71.95; H, 7.57.
4-Benzylamino-1,2,3,4,7,8-hexadeoxy-5,6-O-isopropylidene-D-
ribo-oct-1,7-dienitol (13r). To a solution of furanoside 1 (1.0 g, 3.18
mmol) and benzylamine (0.7 mL, 6.41 mmol) in THF (20 mL) under
argon was added zinc (2.0 g, 30.6 mmol). The mixture was sonicated
at 40 °C for 3 h during which time allyl bromide (0.6 mL, 7.1 mmol)
was added dropwise. The sonication was continued for an additional 2
h until TLC indicated full conversion of 1, and the mixture was then
1
1:1). [R]D +5.2 (c 1, CHCl3). H NMR(300 MHz, CDCl3): δ 5.79-
5.88 (m, 2H), 5.27 (dt, J ) 1.4, 17.2 Hz, 1H), 5.10-5.19 (m, 3H),
4.39 (m, 1H), 3.95 (m, 1H), 2.24-2.31 (m, 2H), 1.58-1.76 (m, 2H).
13C NMR (50 MHz, CDCl3): δ 140.5, 134.1, 118.3, 114.5, 73.5, 71.2,
42.4, 42.4.
1,2,3,7,8-Pentadeoxy-5,6-O-isopropylidene-2-C-(isopropyloxycar-
bonyl)-D-ribo-oct-1,7-dienitol (11r). Zinc (1.00 g, 15.3 mmol) was
added to a solution of furanoside 1 (0.50 g, 1.59 mmol) in 2:1 THF:
H2O (12 mL). The mixture was sonicated at 40 °C under argon for 4
h during which time isopropyl R-(bromomethyl)acrylate (1.00 g, 4.83
mmol) was added dropwise by syringe pump. The sonication was
continued for an additional 2 h, and the mixture was then allowed to
shake at room temperature overnight and was then filtered through
Celite. The Celite was washed with Et2O (30 mL). The filtrate was

General Method for Carbohydrate Carbocyclization
J. Am. Chem. Soc., Vol. 122, No. 35, 2000 8451
filtered through Celite. The organic phase was concentrated and purified
by flash chromatography (pentane:Et2O:Et3N ) 66:33:1) through a short
column to give 745 mg (81%) of a syrup. 13C NMR revealed the
formation of 13r and 13â in a ratio of 6:1. The title product 13r was
obtained pure in a yield of 644 mg (70%) after further purification by
flash chromatography (pentane:Et2O:Et3N ) 85:15:1), Rf ) 0.5. [R]D
+53.6 (c 1.0, CHCl3).
1H NMR (500 MHz, CDCl3): δ 7.21-7.31 (m, 5H), 5.96 (ddd, J )
6.8, 10.2, 17.1 Hz, 1H), 5.87 (m, 1H), 5.34 (ddd, J ) 1.4, 1.6, 17.1
Hz, 1H), 5.21 (ddd, J ) 1.4, 1.6, 10.3 Hz, 1H), 5.11-5.16 (m, 2H),
4.63 (bt, J ) 6.6 Hz, 1H), 4.02 (dd, J ) 6.4, 9.0 Hz, 1H), 3.83 (d, J
) 12.6 Hz, 1H), 3.63 (d, J ) 12.6 Hz, 1H), 2.81 (ddd, J ) 3.8, 5.5,
8.9 Hz, 1H), 2.49 (m, 1H), 2.38 (m, 1H), 1.49 (s, 3H), 1.35 (s, 3H).
13C NMR (50 MHz, CDCl3): δ 140.4, 134.9, 134.3, 128.3, 128.2, 126.9,
118.1, 117.3, 108.1, 79.1, 78.9, 55.6, 51.0, 34.1, 27.8, 25.3. Anal. Calcd
for C18H25NO2: C, 75.22; H, 8.77; N, 4.87. Found: C, 75.20; H, 8.75;
N, 4.80.
(2C), 119.4 (2C), 73.3, 72.6 (2C), 20.8 (2C), 20.5. Anal. Calcd for
C13H18O6: C, 57.77; H, 6.71. Found: C, 57.16; H, 6.22.
1,2,7,8-Tetradeoxy-D-ido-oct-1,7-dienitol (18â). Rf ) 0.71 (ac-
1
etone). [R]D 0 (c 3.0, CHCl3). H NMR (300 MHz, CD3OD): δ 5.90
(ddd, J ) 6.4, 10.6, 17.4 Hz, 2H), 5.34 (ddd, J ) 1.4, 1.8, 17.4 Hz,
2H), 5.18 (ddd, J ) 1.1, 1.8, 10.6 Hz, 2H), 4.21 (tt, J ) 1.1, 6.4 Hz,
2H), 3.49 (bd, J ) 6.4 Hz, 2H). 13C NMR (50 MHz, CD3OD): δ 139.1
(2C), 117.0 (2C), 75.1 (4C).
Acetylation gave 36: Rf ) 0.73 (pentane:EtOAc ) 2:1). [R]D 0 (c
3.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ 5.76 (dddd, J ) 1.0, 6.2,
10.0, 17.1 Hz, 2H), 5.40 (m, 2H), 5.30 (ddd, J ) 0.9, 1.2, 17.6 Hz,
2H), 5.28 (ddd, J ) 0.8, 1.0, 10.4 Hz, 2H), 5.25 (m, 2H), 2.10 (s, 3H),
2.09 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H). 13C NMR (126 MHz, CDCl3):
δ 169.5 (2C), 167.9 (2C), 131.3 (2C), 119.9 (2C), 72.5 (2C), 70.8 (2C),
20.8 (2C), 20.6 (2C). Anal. Calcd for C16H22O8: C, 56.14; H, 6.48.
Found: C, 56.34; H, 6.48.
1,2,7,8-Tetradeoxy-D-talo-oct-1,7-dienitol (19â). Rf ) 0.65 (ac-
For 13â: 13C NMR (50 MHz, CDCl3): δ 140.6, 134.7, 133.9, 128.3,
128.2, 126.7, 118.7, 117.3, 108.3, 80.1, 79.3, 55.6, 51.2, 34.4, 28.0,
25.5.
1
etone). mp 140-141 °C. [R]D +28.6 (c 2.1, MeOH). H NMR (300
MHz, CD3OD): δ 5.94-6.06 (m, 2H), 5.31 (ddd, J ) 1.3, 1.9, 17.3
Hz, 2H), 5.15-5.21 (m, 2H), 4.36 (m, 1H), 4.26 (m, 1H), 3.71 (dd, J
) 4.6, 8.4 Hz, 1H), 3.44 (dd, J ) 2.1, 8.5 Hz, 1H). 13C NMR (50
MHz, CD3OD): δ 140.2, 138.3, 117.2, 115.7, 75.5, 75.4, 74.8, 73.0.
Acetylation of 13R gave 20 as a 1:1 mixture of two rotamers by
NMR: Rf ) 0.35 (pentane:Et2O ) 1:1). [R]D +19.2 (c 2.8, CH2Cl2).
1H NMR (500 MHz, CDCl3): δ 7.22-7.36 (m, 10H), 5.94 (ddd, J )
6.8, 10.2, 17.1 Hz, 1H), 5.64-5.78 (m, 3H), 5.38 (ddd, J ) 1.3, 1.4,
13.0 Hz, 1H), 5.31 (ddd, J ) 1.3, 1.7, 10.3 Hz, 1H), 5.26 (bs, 1H),
5.23 (bd, J ) 7.7 Hz, 1H), 4.99-5.07 (m, 4H), 4.57 (d, J ) 5.6 Hz,
2H), 4.48-4.51 (m, 2H), 4.19-4.23 (m, 4H), 3.88 (m, 1H), 3.84 (t, J
) 7.3 Hz, 1H), 2.29-2.48 (m, 4H), 2.14 (s, 3H), 1.99 (s, 3H), 1.46 (s,
3H), 1.45 (s, 3H), 1.24 (s, 3H), 1.15 (s, 3H). 13C NMR (50 MHz,
CDCl3): δ 172.1, 172.0, 138.9, 137.9, 135.1, 133.8, 133.6, 133.3, 128.3,
128.2, 127.1, 127.0, 126.0, 119.0, 118.6, 118.5, 116.5, 108.2, 79.4,
79.3, 78.8, 78.4, 58.0, 52.7, 48.2, 44.8, 34.2, 32.8, 27.2, 26.9, 24.7,
24.4, 22.4, 21.3. Anal. Calcd for C20H27NO3: C, 72.92; H, 8.26; N,
4.25. Found: C, 73.12; H, 8.26; N, 4.36.
Acetylation gave 37: Rf ) 0.74 (pentane:EtOAc ) 2:1). [R]D +13.0
1
(c 0.8, CHCl3). H NMR (500 MHz, CDCl3): δ 5.83 (ddd, J ) 7.0,
10.8, 17.4 Hz, 1H), 5.70 (ddd, J ) 5.5, 10.4, 16.9 Hz, 1H), 5.53 (m,
1H), 5.41 (m, 1H), 5.23-5.34 (m, 6H), 2.10 (s, 3H), 2.09 (s, 3H), 2.08
(s, 3H), 2.06 (s, 3H). 13C NMR (50 MHz, CDCl3): δ 169.8 (2C), 169.5
(2C), 131.8, 130.6, 119.6, 118.0, 73.0, 71.2, 70.2, 69.9, 20.8 (2C), 20.6
(2C). Anal. Calcd for C16H22O8: C, 56.14; H, 6.48. Found: C, 56.27;
H, 6.48.
General Procedure for Elimination-Methylenation (Table 3).
To a solution of the 6-iodopyranoside (500 mg, 0.77 mmol) in THF
(10 mL) under argon were added (TMS)Cl (0.28 mL, 2.2 mmol), zinc
(500 mg, 7.6 mmol), and PbCl2 (20 mg, 0.07 mmol). The mixture was
sonicated at 40 °C for 1 h while CH2I2 (0.18 mL, 2.2 mmol) was added
dropwise by syringe pump. More (TMS)Cl (0.28 mL) was added, and
the sonication was continued for an additional 4 h. The mixture was
filtered through Celite and rinsed with pentane (40 mL). The filtrate
was washed with 10% aqueous citric acid (2 × 20 mL), dried, and
concentrated. The residue was suspended in MeOH (10 mL), and
Amberlite IR-120 (H+) (7.5 mL) was added. After stirring for 2 h at
40 °C Amberlite IRA-400 (OH-) (10 mL) was added until neutral pH.
The resin was filtered off and washed with MeOH (50 mL). The filtrate
was concentrated and the residue purified by flash chromatography.
General Procedure for Elimination-Vinylation (Table 2). To a
solution of the ω-iodo glycoside (1.0 mmol) in THF (10 mL) under
argon was added zinc (660 mg, 10 mmol) (for 6-iodo glycosides 14
and 15, 15 mg of ZnCl2 was also added and the mixture sonicated for
1 h at 40 °C prior to the divinyl zinc addition). Then the mixture was
sonicated at 40 °C for 2 h while a 0.5 M divinyl zinc solution30 in
THF (6.0 mL, 3.0 mmol) was added dropwise by syringe pump. The
sonication was continued for an additional 4 h at 40 °C. The mixture
was filtered through Celite and rinsed with Et2O. To the filtrate were
added MeOH (10 mL) and Amberlite IR-120 (H+) (10 mL). After
stirring at 40 °C for 1 h, the resin was filtered off and washed with
MeOH (20 mL). The filtrate was concentrated and purified by flash
chromatography.
General Procedure for Ring-Closing Olefin Metathesis (Tables
4-6). To a deoxygenated solution of the diene (100 mg) in CH2Cl2
(10 mL) under argon was added a deoxygenated solution of 18 or 30
in CH2Cl2 (1 mL) by syringe. The solution was stirred at either room
temperature or 40 °C as indicated in the tables until TLC revealed full
conversion or that the reaction had stopped. The mixture was
concentrated (in the case of a precipitated product this was first filtered
off) and the residue purified by flash chromatography.
1,2,6,7-Tetradeoxy-ribo-hept-1,6-dienitol (16r). Rf ) 0.48 (EtOAc).
1H NMR (500 MHz, CDCl3): δ 6.03 (ddd, J ) 6.1, 10.1, 17.0 Hz,
2H), 5.40 (dt, J ) 1.6, 17.0 Hz, 2H), 5.31 (dt, J ) 1.2, 10.5 Hz, 2H),
4.26 (tt, J ) 1.4, 6.1 Hz, 2H), 3.61 (t, J ) 6.1 Hz, 1H). 13C NMR (125
MHz, CDCl3): δ 137.0 (2C), 117.5 (2C), 75.3, 74.4 (2C). Anal. Calcd
for C7H12O3: C, 58.32; H, 8.39. Found: C, 57.96; H, 8.35.
(1S,2S,3R)-Cyclohex-4-en-1,2,3-triol (21). Rf ) 0.59 (acetone). mp
1,2,6,7-Tetradeoxy-D-arabino-hept-1,6-dienitol (16â ) 17â). Rf )
0.53 (EtOAc). [R]D +66.5 (c 0.4, MeOH). 1H NMR (500 MHz,
CDCl3): δ 5.99 (ddd, J ) 5.9, 10.6, 17.1 Hz, 1H), 5.93 (ddd, J ) 5.9,
10.6, 17.1 Hz, 1H), 5.32 (dt, J ) 1.5, 17.1 Hz, 2H), 5.21-5.30 (m,
2H), 4.25 (m, 1H), 4.12 (m, 1H), 3.47 (dd, J ) 3.6, 6.6 Hz, 1H). 13C
NMR (50 MHz, CDCl3): δ 137.0, 136.4, 117.3, 117.0, 74.8, 74.6, 72.1.
Anal. Calcd for C7H12O3: C, 58.32; H, 8.39. Found: C, 58.19; H, 8.59.
1
95-96 °C (MeOH:Et2O). [R]D -69.2 (c 1.0, MeOH). H NMR (250
MHz, CD3OD): δ 5.67 (dddd, J ) 2.1, 3.0, 4.8, 10.2 Hz, 1H), 5.53
(m, 1H), 4.18 (m, 1H), 3.99 (m, 1H), 3.81 (dt, J ) 2.1, 6.0 Hz, 1H),
2.31(m, 1H), 2.22 (m, 1H). 13C NMR (50 MHz, CD3OD): δ 129.1,
126.9, 72.8, 69.8, 69.6, 30.9. Anal. Calcd for C6H10O3: C, 55.37; H,
7.74. Found: C, 55.58; H, 7.53.
(1R,2S,3R)-Cyclohex-4-en-1,2,3-triol (22). Rf ) 0.41 (acetone). mp
1,2,6,7-Tetradeoxy-xylo-hept-1,6-dienitol (17r). Rf ) 0.60 (EtOAc).
1H NMR (500 MHz, CDCl3): δ 5.98 (ddd, J ) 6.0, 10.2, 16.0 Hz,
2H), 5.41 (ddd, J ) 1.3, 2.1, 17.5 Hz, 2H), 5.29 (ddd, J ) 1.3, 2.1,
10.5 Hz, 2H), 4.27 (d, J ) 4.7 Hz, 1H), 4.29 (m, 2H). 13C NMR (50
MHz, CDCl3): δ 137.3 (2C), 117.2 (2C), 75.5, 73.4 (2C). Anal. Calcd
for C7H12O3: C, 58.32; H, 8.39. Found: C, 58.17; H, 8.37.
127-128 °C (MeOH:acetone) (Lit.:44 mp 130 °C). [R]D -167.1 (c 0.6,
1
MeOH). H NMR (500 MHz, CD3OD): δ 5.70-5.73 (m, 2H), 4.19
(m, 1H), 3.87 (ddd, J ) 5.6, 8.3, 9.2 Hz, 1H), 3.50 (dd, J ) 4.3, 9.4
Hz, 1H), 2.48 (ddd, J ) 2.1, 5.6, 17.5 Hz, 1H), 1.98 (ddd, J ) 1.0,
8.5, 17.5 Hz, 1H). 13C NMR (50 MHz, CD3OD): δ 129.0, 128.3, 74.9,
68.2, 67.9, 34.4. Anal. Calcd for C6H10O3: C, 55.37; H, 7.74. Found:
C, 55.09; H, 7.85.
1
Acetylation gave 31: Rf ) 0.41 (hexane:EtOAc ) 4:1). H NMR
(500 MHz, CDCl3): δ 5.73 (ddd, J ) 6.4, 10.7, 17.1 Hz, 2H), 5.44
(m, 2H), 5.28-5.32 (m, 4H), 5.22 (t, J ) 5.5 Hz, 1H), 2.09 (s, 6H),
2.08 (s, 3H). 13C NMR (125 MHz, CDCl3): δ 169.9, 169.5 (2C), 131.7
(44) Hudlicky, T.; Luna, H.; Olivo, H. F.; Andersen, C.; Nugent, T.;
Price, J. D. J. Chem. Soc., Perkin Trans. 1 1991, 2907.

8452 J. Am. Chem. Soc., Vol. 122, No. 35, 2000
Hyldtoft and Madsen
(1S,2S,3S)-Cyclohex-4-en-1,2,3-triol (23). Rf ) 0.63 (acetone). mp
108.8 72.5, 72.5, 71.6, 42.2, 27.4, 25.5, 20.4. Anal. Calcd for
C17H20O4: C, 70.81; H, 6.99. Found: C, 70.70; H, 7.00.
1
128-129 °C (MeOH:acetone). [R]D +509 (c 0.4, MeOH). H NMR
(500 MHz, CD3OD): δ 5.67 (ddt, J ) 1.3, 3.4, 9.8 Hz, 1H), 5.62 (ddt,
J ) 1.8, 3.4, 9.8 Hz, 1H), 4.15 (m, 1H), 4.00 (ddd, J ) 2.1, 4.7, 5.5
Hz, 1H), 3.63 (dd, J ) 2.7, 6.0 Hz, 1H), 2.31 (m, 1H), 2.22 (m, 1H).
13C NMR (126 MHz, CD3OD): δ 128.5, 127.4, 75.6, 70.8, 68.8, 32.3.
Anal. Calcd for C6H10O3: C, 55.37; H, 7.74. Found: C, 55.19; H, 7.78.
Compound 24 is the enantiomer of 23.
(-)-Conduritol B Tetraacetate (41). Rf ) 0.48 (pentane:EtOAc )
2:1). mp 117-118 °C (Lit.:47 mp 120-121 °C). [R]D -182 (c 0.7,
25
1
CHCl3) (Lit.:47 [R]D -172.4 (c 1.1, CHCl3)). H NMR (500 MHz,
CDCl3): δ 5.70 (bs, 2H), 5.59 (m, 2H), 5.53 (m, 2H), 2.06 (s, 6H),
2.04 (s, 6H). 13C NMR (50 MHz, CDCl3): δ 169.8 (4C), 127.4 (2C),
71.4 (2C), 71.2 (2C), 20.8 (4C).
(1R,2S,3R)-1,2,3-Tris(acetyloxy)cyclohex-4-ene (25). Rf ) 0.71
(-)-Conduritol C Tetraacetate (42). Rf ) 0.53 (pentane:EtOAc
) 2:1). mp 88-89 °C (Lit.:48 mp 95-97 °C). [R]D -194 (c 3.0, CHCl3)
1
(pentane:Et2O ) 1:1). [R]D -34 (c 1.0, CHCl3). H NMR (500 MHz,
(Lit.:48 [R]D -186 (c 2, CHCl3)). H NMR (500 MHz, CDCl3): δ
5.76 (ddd, J ) 1.3, 3.3, 10.7 Hz, 1H), 5.64-5.69 (m, 4H), 5.20 (dd, J
) 1.9, 7.8 Hz, 1H), 2.12 (s, 3H), 2.07 (s, 3H), 2.04 (s, 3H), 2.03 (s,
3H). 13C NMR (50 MHz, CDCl3): δ 170.4, 170.2, 169.8, 169.6, 127.4,
127.0, 70.5, 70.0, 69.4, 67.5, 20.8, 20.7 (3C).
CDCl3): δ 5.88 (ddd, J ) 3.1, 4.9, 10.2 Hz, 1H), 5.71 (m, 1H), 5.60
(bt, J ) 4.4 Hz, 1H), 5.30 (ddd, J ) 5.8, 8.0, 10.2 Hz, 1H), 5.19 (dd,
J ) 4.4, 10.2 Hz, 1H), 2.77 (m, 1H), 2.19 (m, 1H), 2.08 (s, 3H), 2.06
(s, 3H), 2.04 (s, 3H). 13C NMR (126 MHz, CDCl3): δ 170.2, 170.0,
169.9, 129.8, 123.1, 69.9, 66.8, 66.6, 30.8, 20.9, 20.8, 20.6. Anal. Calcd
for C12H16O6: C, 56.25; H, 6.29. Found: C, 56.23; H, 6.42.
25
1
(1S,2S,3R)-1-Acetyloxy-2,3-O-isopropylidene-5-isopropyloxycar-
bonylcyclohex-4-en-2,3-diol (43). Rf ) 0.41 (pentane:Et2O ) 2:1).
(1S,2S,3R)-1-(N-Benzyl)acetamido-2,3-O-isopropylidenecyclohex-
1
4-en-2,3-diol (26). Rf ) 0.67 (Et2O). [R]D -83.7 (c 2.2, CHCl3). H
1
[R]D +30.0 (c 2.1, CHCl3). H NMR (500 MHz, CDCl3): δ 6.71 (dt,
NMR (500 MHz, CDCl3): δ 7.21-7.35 (m, 5H), 5.69 (ddd, J ) 1.7,
6.0, 10.2 Hz, 1H), 5.53 (m, 1H), 5.13 (dddd, J ) 1.7, 5.5, 11.9 Hz,
1H), 4.85 (d, J ) 17.9 Hz, 1H), 4.78 (d, J ) 17.9 Hz, 1H), 4.63 (m,
1H), 4.29 (bd, J ) 5.1 Hz, 1H), 2.29 (m, 1H), 2.08 (s, 3H), 1.98 (dddd,
J ) 1.3, 4.7, 6.4, 16.2 Hz, 1H), 1.34 (s, 3H), 1.15 (s, 3H). 13C NMR
(50 MHz, CDCl3): δ 171.9, 138.6, 128.3, 127.7, 126.8, 126.6, 126.0,
125.2, 109.3, 75.3, 74.4, 49.7, 48.5, 29.4, 27.6, 23.4, 21.9. Anal. Calcd
for C18H23NO3: C, 71.73; H, 7.69; N, 4.65. Found: C, 71.61; H, 7.91;
N, 4.63.
J ) 0.9, 2.7 Hz, 1H), 5.10 (m, 1H), 5.08 (septet, J ) 6.4 Hz, 1H), 4.78
(m, 1H), 4.45 (ddd, J ) 0.9, 1.3, 5.2 Hz, 1H), 2.70 (ddd, J ) 0.9, 5.6,
16.2 Hz, 1H), 2.52 (ddt, J ) 3.0, 10.7, 16.2 Hz, 1H), 2.15 (s, 3H),
1.41 (s, 3H), 1.39 (s, 3H), 1.29 (d, J ) 6.4 Hz, 3H), 1.28 (d, J ) 6.4
Hz, 3H). 13C NMR (50 MHz, CDCl3): δ 170.4, 165.3, 134.4, 129.2,
110.6, 73.5, 73.5, 69.0, 68.5, 27.6, 26.5, 24.0, 21.7, 21.1. Anal. Calcd
for C15H22O6: C, 60.39; H, 7.43. Found: C, 60.23; H, 7.35. The
structure was confirmed by deesterification (aqueous NaOH) and acetal
1
removal (aqueous TFA) to give 5-epi-shikimic acid with H and 13C
(1r,2â,3r)-Cyclopent-4-en-1,2,3-triol (32). Rf ) 0.53 (acetone).
NMR data in accordance with literature values.49
1
mp 106-107 °C (Et2O:acetone) (Lit.:45 mp 111 °C). H NMR (250
(1S,2S,3R)-1-Acetyloxy-5-acetyloxymethyl-2,3-O-isopropylidenecy-
clohex-4-en-2,3-diol (44). Rf ) 0.64 (pentane:Et2O ) 1:1). [R]D +4.0
MHz, CD3OD): δ 5.76 (s, 2H), 4.34 (d, J ) 5.0 Hz, 2H), 3.81 (t, J )
5.1 Hz, 1H). 13C NMR (63 MHz, CD3OD): δ 134.6 (2C), 90.1 (2C),
81.0. NMR data were in accordance with literature data.40
1
(c 1.0, EtOH). H NMR (500 MHz, CDCl3): δ 5.64 (m, 1H), 5.10
(ddd, J ) 2.4, 5.6, 7.5 Hz, 1H), 4.70 (m, 1H), 4.50 (bs, 2H), 4.45
(ddd, J ) 0.9, 2.0, 5.2 Hz, 1H), 2.43 (m, 1H), 2.23 (dd, J ) 5.2, 16.0
Hz, 1H), 2.14 (s, 3H), 2.09 (s, 3H), 1.40 (s, 3H), 1.39 (s, 3H). 13C
NMR (50 MHz, CDCl3): δ 170.4, 170.4, 132.5, 123.2, 110.2, 73.8,
73.7, 69.1, 66.3, 27.6, 26.8, 25.7, 21.1, 20.7. Anal. Calcd for
C14H20O6: C, 59.14; H, 7.09. Found: C, 59.20; H, 7.20.
(1r,2r,3r)-Cyclopent-4-en-1,2,3-triol (33). Rf ) 0.56 (acetone).
1
mp 61-62 °C (Lit.:46 mp 64-65 °C). H NMR (500 MHz, CD3OD):
δ 5.93 (s, 2H), 4.40 (d, J ) 5.4 Hz, 2H), 4.01 (t, J ) 5.4 Hz, 1H). 13
C
NMR (63 MHz, CD3OD): δ 135.8 (2C), 75.1 (2C), 72.9. Anal. Calcd
for C5H8O3: C, 51.72; H, 6.94. Found: C, 51.56; H, 6.99.
(1â,2â,3r)-Cyclopent-4-en-1,2,3-triol (34). Rf ) 0.52 (acetone).
[R]D -3.7 (c 0.9, MeOH). 1H NMR (500 MHz, CD3OD): δ 5.90-
5.92 (m, 2H), 4.61 (bd, J ) 4.3 Hz, 1H), 4.59 (bd, J ) 5.4 Hz, 1H),
3.88 (dd, J ) 4.3, 5.6 Hz, 1H). 13C NMR (63 MHz, CD3OD): δ 137.4,
134.0, 81.0, 79.2, 74.2. Anal. Calcd for C5H8O3: C, 51.72; H, 6.94.
Found: C, 51.68; H, 6.57.
(1R,2R,3R,4S)-3-Acetyloxy-1,2-O-isopropylidene-4-phenylcyclo-
hex-5-en-1,2-diol (40). Rf ) 0.35 (pentane:EtOAc ) 5:1). mp 84-85
°C. [R]D -283.5 (c 0.8, CHCl3). 1H NMR (300 MHz, CDCl3): δ 7.23-
7.34 (m, 3H), 7.07-7.10 (m, 2H), 6.08 (ddd, J ) 1.6, 3.5, 10.1 Hz,
1H), 5.96 (dd, J ) 4.3, 10.1 Hz, 1H), 5.25 (dd, J ) 5.1, 7.4 Hz, 1H),
4.77 (dd, J ) 3.5, 5.8 Hz, 1H), 4.23 (dd, J ) 5.9, 7.7 Hz, 1H), 3.95
(bt, J ) 4.8 Hz, 1H), 1.95 (s, 3H), 1.50 (s, 3H), 1.40 (s, 3H). 13C NMR
(50 MHz, CDCl3): δ 169.8, 137.0, 129.9, 128.6, 127.7, 126.6, 125.4,
Acknowledgment. We thank the Danish Natural Science
Research Council for financial support.
Supporting Information Available: Experimental proce-
dure and characterization data for quercitols 27-29 as well as
proof of structure for cyclohexenes 26 and 40 (7 pages, print/
PDF). This material is available free of charge via the Internet
at http://pubs.acs.org.
JA001415N
(47) Le Drian, C.; Vionnet, J.-P.; Vogel, P. HelV. Chim. Acta 1990, 73,
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(45) Gaoni, Y. Bull. Soc. Chim. Fr. 1959, 705.
(46) Wolczunowicz, G.; Cocu, F. G.; Posternak, T. HelV. Chim. Acta
1970, 53, 2275.
(48) Le Drian, C.; Vieira, E.; Vogel, P. HelV. Chim. Acta 1989, 72, 338.
(49) Jiang, S.; McCullough, K. J.; Mekki, B.; Singh, G.; Wightman, R.
H. J. Chem. Soc., Perkin Trans. 1 1997, 1805.