Carbohydrate carbocyclization by a zinc-mediated tandem reaction and ring-closing enyne metathesis

Article abstract of DOI:10.1021/jo0200062

Methyl 5-deoxy-5-iodo-pentofuranosides are reductively ring-opened and propargylated in a tandem fashion in the presence of zinc. The 1,7-enynes thus obtained are subjected to ring-closing enyne metathesis with catalyst B to produce functionalized 1-vinyl cyclohexenes. By adding BnNH₂ to the tandem reaction, an amino group can be introduced in the 1,7-enyne products. Addition of 2-TMS-ethynylcerium(III) chloride after the reductive ring-opening produces the corresponding 1,6-enynes. Further annulation of the product 1,3-dienes can be achieved through a Diels - Alder reaction with good control of stereochemistry. These procedures constitute efficient methods for rapid carbocyclization and annulation of carbohydrates to produce a variety of functionalized five- and six-membered ring systems.

Full text of DOI:10.1021/jo0200062

J . Org. Chem. 2002, 67, 4441-4449
4441
Ca r boh yd r a te Ca r bocycliza tion by a Zin c-Med ia ted Ta n d em
Rea ction a n d Rin g-Closin g En yn e Meta th esis
Carina Storm Poulsen and Robert Madsen*
Department of Chemistry, Building 201, Technical University of Denmark, DK-2800 Lyngby, Denmark
rm@kemi.dtu.dk
Received J anuary 2, 2002
Methyl 5-deoxy-5-iodo-pentofuranosides are reductively ring-opened and propargylated in a tandem
fashion in the presence of zinc. The 1,7-enynes thus obtained are subjected to ring-closing enyne
metathesis with catalyst B to produce functionalized 1-vinyl cyclohexenes. By adding BnNH2 to
the tandem reaction, an amino group can be introduced in the 1,7-enyne products. Addition of
2-TMS-ethynylcerium(III) chloride after the reductive ring-opening produces the corresponding 1,6-
enynes. Further annulation of the product 1,3-dienes can be achieved through a Diels-Alder reaction
with good control of stereochemistry. These procedures constitute efficient methods for rapid
carbocyclization and annulation of carbohydrates to produce a variety of functionalized five- and
six-membered ring systems.
Sch em e 1
In tr od u ction
A polyhydroxylated carbocyclic ring is found in many
biologically important molecules and natural products,1
such as glycosidaseinhibitors,2a aminoglycosideantibiotics,2b
inositol phosphates,2c and carbanucleosides.2d Synthetic
approaches to these compounds from the chiral pool often
commence with the carbocyclization of a suitable carbo-
hydrate. Indeed, chemical synthesis of carbocyclic rings
from carbohydrates has been the subject of numerous
studies for more than two decades.3 Significant contribu-
tions include the Ferrier II reaction and similar rear-
rangements, cycloadditions, radical cyclizations, ring-
contractions with organometallic reagents, and carbanion
cyclizations.3 Some of these methods, however, do require
a significant number of steps for preparation of the
starting materials or employ toxic metal reagents for the
cyclization event.
for preparation of the diene precursors in one step from
methyl ω-iodo glycosides (Scheme 1).6 Subsequent ring-
closing olefin metathesis forms the carbocyclic ring and
all ring-sizes from five- to eight-membered rings have
been prepared by the combination of these two reac-
tions.6,7
During the last five years ring-closing olefin metathesis
has been developed for converting sugars into car-
bocycles.4,5 This is a very versatile method which can be
applied to a wide variety of sugars and ring-sizes. We
have recently introduced a zinc-mediated domino reaction
An alternative metathesis reaction involves ring-
closure of enynes to produce 1-vinyl cycloalkenes.8,9
A
* To whom correspondence should be addressed. Fax: (+45) 4593
3968.
variety of different late transition metal catalysts have
been shown to mediate the enyne metathesis reaction.8
In general, ring-closing enyne metathesis is more difficult
to achieve than ring-closing olefin metathesis particularly
when forming ring-sizes larger than five.10 Only a few
examples exist where enyne metathesis has been applied
in carbohydrate chemistry.11 We envisioned that our zinc-
mediated reactions could also be employed for the forma-
tion of enynes (Scheme 1). Zinc would serve a dual
(1) Ogawa, S. In Carbohydrates in Drug Design; Witczak, Z. J .,
Nieforth, K. A., Eds.; Dekker: New York, 1997; p 433.
(2) (a) Berecibar, A.; Grandjean, C.; Siriwardena, A. Chem. Rev.
1999, 99, 779. (b) Mingeot-Leclercq, M.-P.; Glupczynski, Y.; Tulkens,
P. M. Antimicrob. Agents Chemother. 1999, 43, 727. (c) J enkins, D. J .;
Riley, A. M.; Potter, B. V. L. In Carbohydrate Mimics - Concepts and
Methods; Chapleur, Y., Ed.; Wiley-VCH: Weinheim, 1998; p 171. (d)
Crimmins, M. T. Tetrahedron 1998, 54, 9229.
(3) (a) Dalko, D. I.; Sinay¨, P. Angew. Chem., Int. Ed. 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) Lope´z, J . C.;
Fraser-Reid, B. Chem. Commun. 1997, 2251. (e) Ferrier, R. J .;
Middleton, S. Chem. Rev. 1993, 93, 2779.
(4) For recent reviews, see: J ørgensen, M.; Hadwiger, P.; Madsen,
R.; Stu¨tz, A. E.; Wrodnigg, T. M. Curr. Org. Chem. 2000, 4, 565. Roy,
R.; Das, S. K. Chem. Commun. 2000, 519.
(5) For general reviews on ring-closing olefin metathesis, see: Trnka,
T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18. Fu¨rstner, A. Angew.
Chem., Int. Ed. 2000, 39, 3012. Schrock, R. R. Tetrahedron 1999, 55,
8141.
(6) (a) Hyldtoft, L.; Madsen, R. J . Am. Chem. Soc. 2000, 122, 8444.
(b) Hyldtoft, L.; Poulsen, C. S.; Madsen, R. Chem. Commun. 1999, 2101.
(7) (a) Skaanderup, P. R.; Madsen, R. Chem. Commun. 2001, 1106.
(b) Boyer, F.-D.; Hanna, I. Tetrahedron Lett. 2001, 42, 1275. (c) Boyer,
F.-D.; Hanna, I.; Nolan, S. P. J . Org. Chem. 2001, 66, 4094.
(8) Mori, M. Top. Organomet. Chem. 1998, 1, 133.
(9) For a review covering different enyne cycloisomerization reac-
tions, see: Aubert, C.; Buisine, O.; Malacria, M. Chem. Rev. 2002, 102,
813.
10.1021/jo0200062 CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/22/2002

4442 J . Org. Chem., Vol. 67, No. 13, 2002
Poulsen and Madsen
Ta ble 1. Zin c-Med ia ted Ta n d em Rea ction a
purpose in this process. First, it would mediate the
fragmentation of the iodoglycoside, and second, it would
activate an alkynyl bromide species for the Barbier
alkylation. The enyne thus formed would be directly set
up for metathesis to form a carbocyclic 1,3-diene product.
This, on the other hand, can undergo further synthetic
transformations, especially cycloaddition reactions to
generate additional rings.
Herein, we report a full account on synthesis of
carbohydrate-derived enynes by a zinc-mediated tandem
reaction and subsequent metathesis of these to form
carbocycles. We also demonstrate that the obtained
dienes can be further annulated in a Diels-Alder reac-
tion.
Resu lts a n d Discu ssion
Ta n d em Rea ction . We have previously established
general reaction conditions for the zinc-mediated reduc-
tive ring-opening-allylation of methyl 5-deoxy-5-iodo-
pentofuranosides.6 With these procedures in hand, we
then decided to probe the tandem reaction with propargyl
bromide on isopropylidene 5-iodo-ribofuranoside 1.12 It
was soon realized that the mode of addition of propargyl
bromide played a major role. Carrying out the tandem
reaction on 1 with 5 equiv of propargyl bromide all added
from the start of the reaction gave a modest 37% yield of
the desired 1,7-enyne 7 together with the intermediate
unsaturated aldehyde. However, shifting to dropwise
addition of the propargyl bromide over 5 h by syringe
pump led to an improved 73% yield with no unsaturated
aldehyde remaining (Table 1, entry 1). Enyne 7 was
formed in an excellent 9:1 diastereomeric ratio. The
stereochemistry at the newly generated stereogenic
center was assigned after Lindlar reduction to the
corresponding diene which have been prepared earlier.6a
Several other conditions were investigated in an at-
tempt to further improve the yield of 7 in the tandem
reaction. Anhydrous conditions with an added Lewis acid
to promote the reaction has been shown to work very well
with several alkylating agents.6a However, carrying out
the ring-opening and propargylation of 1 in anhydrous
THF with added MgBr2‚OEt2 led mainly to decomposi-
tion. Additional studies with other substrates have shown
that the generated enynes are usually unstable toward
acidic conditions. As a result, several experiments were
conducted with added base instead. We have previously
shown that if Et3N is added to the tandem reaction in
aqueous THF the rate of the overall transformation is
decreased while the diastereoselectivity in some cases is
improved.6a In this case added Et3N would mainly serve
as an acid scavenger to improve the yield. In fact,
utilizing the optimized conditions for 1 the addition of
0.5 equiv of Et3N did cause a slight improvement in the
a
b
All reactions were carried out by sonication at 40 °C. 0.5
equiv. of Et3N was also added.
yield of 7 (entry 2). However, increasing the amount of
Et3N to 2 equiv gave rise to a very slow transformation
and only a low yield of the desired enyne 7 was obtained
together with a significant amount of the intermediate
aldehyde and unreacted 1. Utilizing propargyl chloride
instead of the bromide under the optimized conditions
gave a 50% yield of enyne 7. As a result, the following
studies with other pentofuranosides were carried out
with propargyl bromide in THF-H2O mixture.
Unprotected 5-iodo-ribofuranoside 2 did not afford any
enyne product in the tandem reaction (entry 3). The
reductive ring-opening of 2 with zinc proceeded smoothly,6a
but the propargylation of the resulting enal led only to
decomposition. The same result has been observed with
other substrates containing a free hydroxyl group (e.g.,
613 in entry 7). Consequently, the iodopentofuranosides
were protected, and the triethylsilyl (TES) group has
previously been shown to be a convenient hydroxyl-
protecting group in these reactions.6 Hereby, substrates
3, 4, and 5 were prepared6 and subjected to zinc and
propargyl bromide. In all three cases the desired enynes
(10) For recent examples, see: Fu¨rstner, A.; Ackermann, L.; Gabor,
B.; Goddard, R.; Lehmann, C. W.; Mynott, R.; Stelzer, F.; Thiel, O. R.
Chem. Eur. J . 2001, 7, 3236. Timmer, M. S. M.; Ovaa, H.; Filippov, D.
V.; van der Marel, G. A.; van Boom, J . H. Tetrahedron Lett. 2001, 42,
8231. Yao, Q. Org. Lett. 2001, 3, 2069. Mori, M.; Kitamura, T.; Sato,
Y. Synthesis 2001, 654.
(11) Marco-Contelles, J .; Arroyo, N.; Ruiz-Caro, J . Synlett 2001, 652.
Boyer, F.-D.; Hanna, I.; Ricard, L. Org. Lett. 2001, 3, 3095. Leeuwen-
burgh, M. A.; Appeldoorn, C. C. M.; van Hooft, P. A. V.; Overkleeft, H.
S.; van der Marel, G. A.; van Boom, J . H. Eur. J . Org. Chem. 2000,
873. Clark, J . S.; Hamelin, O. Angew. Chem., Int. Ed. 2000, 39, 372.
Leeuwenburgh, M. A.; Kulker, C.; Duynstee, H. I.; Overkleeft, H. S.;
van der Marel, G. A.; van Boom, J . H. Tetrahedron 1999, 55, 8253.
(12) Lerner, L. M. Carbohydr. Res. 1977, 53, 177.
(13) Aly, Y. L.; Abdel-Megied, A. E.-S.; Pedersen, E. B.; Nielsen, C.
Liebigs Ann. Chem. 1992, 127.

Carbohydrate Carbocyclization
J . Org. Chem., Vol. 67, No. 13, 2002 4443
Sch em e 2
were formed in satisfying yields (entries 4-6). For these
compounds, no improvement in yields were observed on
addition of Et3N and even small amounts of Et3N (0.5
equiv) led to a significant decrease in the rate of the
reaction. Enynes 8 and 9 are enantiomers. They were
both formed in a 7:3 diastereomeric ratio favoring the
erythro relationship between the newly generated ste-
reogenic center and the center at C-2 in the starting
pentose. The stereochemistry was assigned after hydro-
genation of the enynes with Lindlar catalyst to produce
the corresponding dienes which have been prepared
previously.6a The stereochemical outcome of the pro-
pargylations with 1, 3, and 4 can all be rationalized based
on the predictions in the Felkin-Anh model.14 With
2-deoxyribose substrate 5, however, the diastereoselec-
tivity was low15 (entry 6). The structure of the main
product 10â was assigned after conversion into the
corresponding MEM-protected enyne,16 which has been
used earlier for synthesis of the A-ring in 1R-hydroxy
vitamin D3 by enyne carbopalladation.17 In fact, all the
hydroxylated enynes in Table 1 are useful for synthesis
of vitamin D analogues by this carbopalladation tech-
nique.18 At last, it should be noticed that the formation
of allenes has never been observed in any of the experi-
ments in Table 1. Usually, the zinc-mediated propargy-
lation of aldehydes gives rise to various amounts of the
corresponding allene.19 However, it should also be noted
that very little allene product has been observed in
previous zinc-mediated propargylations of carbohydrate-
derived aldehydes.20 Maybe allenes are indeed formed in
the experiments in Table 1, but are not stable under the
reaction conditions, which would account for the slightly
lower yields in these propargylation reactions as com-
pared to the corresponding allylation reactions.6a
In the tandem reactions with allyl bromide it has
previously been possible to intercept the intermediate
aldehyde with BnNH2 prior to the allylation.6,7a This is
a very attractive method for the introduction of an amino
group in these reactions. Generally, this protocol is
carried out in anhydrous THF with slow addition of the
alkylating agent in order to ensure imine formation and
prevent alkylation of the intermediate aldehyde. How-
ever, dropwise addition of propargyl bromide to a mixture
of 1, zinc, and BnNH2 in THF under sonication did not
provide any enyne product, but instead led to Wurtz-type
homocoupling of 1 as the only identifiable product. This
dimerization of 1 is known to occur with other zinc
sources,21 but has not been observed before in our
reactions. Attempts with added Lewis acids to facilitate
the reductive ring-opening led to complex mixtures of
products. Although zinc-mediated propargylation of imi-
nes is known22 it appears that propargyl bromide requires
other conditions than allyl bromide in these reactions.
As a result, it was decided to analyze the individual steps
more carefully (Scheme 2). First, treatment of 1 with zinc
gave cleanly enal 11 which was isolated by extraction.23
Second, treatment of this with BnNH2 in anhydrous THF
containing 3 Å molecular sieves gave complete conversion
into the corresponding imine. To this solution zinc was
added, and the mixture was sonicated for 3 h during
which time propargyl bromide was added dropwise. This
now gave a mixture of products from which enyne 12
could be isolated in about 20% yield. Like the enynes in
Table 1, enyne 12 also appears to be unstable to acidic
conditions. In an attempt to improve the yield, Et3N was
added to the reaction mixture based on the result in
Table 1, entry 2. Hereby, the following one-pot procedure
was developed with no isolation of the intermediate
components: furanoside 1 was sonicated with zinc in
THF for 30 min followed by addition of BnNH2 and
continued sonication for 2 h. Then Et3N was added
followed by dropwise addition of propargyl bromide over
2.5 h with continuous sonication. Workup gave the
desired enyne 12 in 48% yield as a single diastereomer.
The stereochemistry was verified by hydrogenation over
Lindlar catalyst to produce known diene 13.6a
Finally, it was investigated whether a two-carbon
nucleophile could be employed in the tandem reaction.
Several experiments were carried out with various ethy-
nylmetal species and ribofuranoside 1. First, furanoside
1 was fragmented with zinc to afford unsaturated alde-
hyde 11. Direct addition of HCtCMgBr24 after the
fragmentation gave a complex mixture of products.
Instead, the zinc salts were allowed to precipitate and
the solution of 11 was then cannulated into a solution of
HCtCMgBr in THF. Hereby, 1,6-enyne 14 was isolated
in 26% yield as a 2:1 mixture of diastereomers after
standard acetylation in the workup (Scheme 3). Several
byproducts were also formed, but were not identified. In
an attempt to optimize this reaction magnesium was
replaced by a number of other metals. However, only
(14) Che´rest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968,
2199. Anh, N. T. Top. Curr. Chem. 1980, 88, 145.
(15) A comparable diastereoselectivity was obtained in the pro-
pargylation of the corresponding TBS-protected aldehyde, see: Vri-
elynck, S.; Vandewalle, M.; Garcı´a, A. M.; Mascaren˜as, J . L.; Mourin˜o,
A. Tetrahedron Lett. 1995, 36, 9023.
(16) Moriarty, R. M.; Kim, J .; Brumer, H., III. Tetrahedron Lett.
1995, 36, 51.
(17) Trost, B. M.; Dumas, J .; Villa, M. J . Am. Chem. Soc. 1992, 114,
9836.
(18) Kittaka, A.; Suhara, Y.; Takayanagi, H.; Fujishima, T.; Kuri-
hara, M.; Takayama, H. Org. Lett. 2000, 2, 2619. Furishima, T.; Konno,
K.; Nakagawa, K.; Kurobe, M.; Okano, T.; Takayama, H. Bioorg. Med.
Chem. 2000, 8, 123. Moriarty, R. M.; Brumer, H., III Tetrahedron Lett.
1995, 36, 9265.
(19) Yi, X.-H.; Meng, Y.; Hua, X.-G., Li, C.-J . J . Org. Chem. 1998,
63, 7472. Bieber, L. W., da Silva, M. F.; da Costa, R. C.; Silva, L. O. S.
Tetrahedron Lett. 1998, 39, 3655.
(20) Chattopadhyay, A.; Dhotare, B. Tetrahedron: Asymmetry 1998,
9, 2715. Pakulski, Z.; Zamojski, A. Tetrahedron 1997, 53, 2653. Wu,
W.-L.; Yao, Z.-J .; Li, Y.-L.; Li, J .-C.; Xia, Y.; Wu, Y.-L. J . Org. Chem.
1995, 60, 3257.
(21) Blanchard, P.; Da Silva, A. D.; El Kortbi, M. S.; Fourrey, J .-L.;
Robert-Ge´ro, M. J . Org. Chem. 1993, 58, 6517.
(22) Moreau, J .-L.; Gaudemar, M. Bull. Soc. Chim. Fr. 1973, 2549.
Gourtois, G.; Miginiac, L. J . Organomet. Chem. 1989, 376, 235.
(23) Kobori, Y.; Myles, D. C.; Whitesides, G. M. J . Org. Chem. 1992,
57, 5899.
(24) Suzuki, M.; Kimura, Y.; Terashima, S. Chem. Pharm. Bull.
1986, 34, 1531.

4444 J . Org. Chem., Vol. 67, No. 13, 2002
Poulsen and Madsen
Sch em e 3
Ch a r t 1
at room temperature, and at 50 °C only decomposition
of 16 was observed. A variety of other complexes did not
react with 16 at 50 °C, including PtCl2(COD), PdCl2-
(PhCN)2, PdCl2(PPh3)2, and [Rh(CO)2Cl]2. With these
somewhat disappointing results in hand, attention was
then shifted toward the metal carbene complexes.
complex mixtures of products were obtained when the
crude fragmentation product was treated with HCtCLi,24
(HCtC)3Ce,24 or HCtCZnOTf.25 When HCtCCeCl2 or
24
HCtCZnBr26 were employed for the addition, reduction
of the intermediate aldehyde 11 to alcohol occurred as
the main reaction. As a result, the corresponding TMS-
protected ethynylmetal reagents were also investigated.
Interestingly, TMSCtCMgBr,24 TMSCtCCeCl2,24 and
(TMSCtC)2Zn27 all gave rise to various amounts of the
desired enyne 15. To prevent reduction of aldehyde 11
to the alcohol, it appeared important to remove the zinc
salts from the fragmentation prior to the addition of the
alkylating agent. The best result was obtained with
TMSCtCCeCl228 giving rise to a 68% yield of 15 as a 7:3
mixture of diastereomers. The stereochemistry was veri-
fied after removal of the TMS group and Lindlar reduc-
tion to the corresponding 1,6-diene, which have been
prepared previously.6a
Ruthenium carbene complexes A and B commonly
employed in olefin metathesis will also catalyze enyne
metathesis. With terminal alkynes these reactions are
best carried out under an atmosphere of ethylene gas to
ensure better turnover of the active catalyst.30 Treatment
of enyne 7R with 10% of A in CH2Cl2 at 40 °C led to
decomposition while virtually no reaction occurred at
room temperature. Carrying out the same reaction with
TBS-protected enyne 16 and A gave now for the first time
significant conversion into the desired diene 17 with some
unreacted 16 remaining. Encouraged by this result focus
now shifted toward the more reactive catalyst B. Treat-
ment of unprotected 7R with this catalyst still led to
decomposition. However, when 16 was reacted with 8%
of B at room temperature in CH2Cl2 under an ethylene
atmosphere a gratifying 66% yield (72% based on recov-
ered 16) of 17 was obtained. Interestingly, if the same
reaction was run under an argon atmosphere the dimer
18 was formed as a significant byproduct in 29% yield.
En yn e Meta th esis. Ring-closing metathesis of enynes
to produce 1-vinyl cyclohexenes has been known for more
than a decade.8 In general, there are two catalyst systems
for this reaction operating by different mechanisms. A
variety of low-valent late transition metal complexes will
catalyze the rearrangement by an oxidative addition-
reductive elimination pathway.8 On the other hand,
several metal carbene complexes will catalyze the same
rearrangement by a series of [2 + 2] cycloadditions-
retrocycloadditions, as in olefin metathesis.8 We decided
to use enyne 7R and the corresponding TBS-protected
compound 16 as test substrates for these cyclization
experiments (Chart 1).
Complexes [Ru(CO)3Cl2]2 (with CO atm), PtCl2, and
PtCl4 have been some of the most effective catalysts for
metathesis of simple enynes in toluene at 60-80 °C.29
However, with enynes 7R and 16 only decomposition was
observed under these conditions with no sign of the cyclic
1,3-diene product. Several similar complexes were also
investigated, but only with 16, which appeared to be more
stable. Zeise’s dimer [PtCl2(C2H4)]2 caused rapid decom-
position of 16 already at room temperature. Other Pt(II)
complexes PtCl2(PhCN)2 and PtCl2(MeCN)2 did not react
1
The structure of 18 was confirmed by H and 13C NMR
as well as mass spectroscopy. This clearly shows the
importance of the ethylene atmosphere in these reactions.
With this protocol in hand, the enynes from the tandem
reactions could now be transformed into cyclic 1,3-dienes
with catalyst B (Table 2). Free hydroxyl and amino
groups had to be protected in order for the enyne
metathesis to take place. The acetyl group was here
chosen as a convenient blocking group. In addition, we
have previously experienced in the ring-closing olefin
metathesis reaction that acetyl protection was superior
to benzyl or silyl protection.6a,31 Standard acetylation of
enyne 7R gave acetate 19, which was cyclized in good
yield into the corresponding 1,3-diene (entry 1). A similar
result was obtained for the acetylated epimer 20 and
TBS-protected 21 (entries 2 and 3). The triethylsilyl
protected enynes in Table 1 would not undergo the
metathesis reaction and were converted into fully acety-
lated substrates 22-24 by a one-pot reaction involving
treatment with TBAF in THF followed by addition of
Ac2O, Et3N, and DMAP. These triacetates turned out to
(25) Sasaki, H.; Boyall, D.; Carreira, E. M. Helv. Chim. Acta 2001,
84, 964.
(26) Negishi, E.; Kotora, M.; Xu, C. J . Org. Chem. 1997, 62, 8957.
(27) Niwa, S.; Soai, K. J . Chem. Soc., Perkin Trans. 1 1990, 937.
(28) For a recent review on organocerium reagents, see: Liu, H.-J .;
Shia, K.-S.; Shang, X.; Zhu, B.-Y. Tetrahedron 1999, 55, 3803.
(29) Chatani, N.; Furukawa, N.; Sakurai, H.; Murai, S. Organo-
metallics 1996, 15, 901. Chatani, N.; Morimoto, T.; Muto, T.; Murai,
S. J . Am. Chem. Soc. 1994, 116, 6049.
(30) Mori, M.; Sakakibara, N.; Kinoshita, A. J . Org. Chem. 1998,
63, 6082.
(31) J ørgensen, M.; Iversen, E. H.; Paulsen, A. L.; Madsen, R. J .
Org. Chem. 2001, 66, 4630.

Carbohydrate Carbocyclization
J . Org. Chem., Vol. 67, No. 13, 2002 4445
Ta ble 2. Rin g-Closin g En yn e Meta th esis w ith Ca ta lyst
Ba
F igu r e 1. 2D-NOESY for 37. Arrows show observed enhance-
ments.
Sch em e 4
Acetylated 1,6-enyne 27 was prepared directly from
15R by the same one-pot desilylation-acetylation protocol
as employed above. When 27 was subjected to 10% of
catalyst B only a 32% yield was obtained of the desired
1,3-diene 36 together with several byproducts (entry 9).
Interestingly, when less reactive catalyst A was used for
this cyclization the yield increased to 70% (entry 10). In
general, five-membered rings are formed more readily by
enyne metathesis than six-membered rings,10 which
allows for the use of the weaker catalyst A in this case.
Diels-Ald er Rea ction . The cyclic 1,3-dienes thus
prepared are perfect substrates for a subsequent Diels-
Alder reaction. This would give rise to highly function-
alized decalins which are important subunits in a number
of biologically significant compounds.33 We decided to
investigate this possibility, and particularly whether the
regioselectivity could be controlled with unsymmetrical
dienophiles.34 Indeed, warming 17 in an acrolein solution
at 60 °C for 24 h gave mainly one Diels-Alder adduct
which was isolated in 69% yield (Scheme 4). The 1H NMR
spectrum was fully assigned by selective decoupling
experiments. The 9.4 Hz coupling constant between H6
and H7 is noteworthy. Subsequent 2D-NOESY studies
verified the structure to be that of 37 (Figure 1). This is
the product of endo addition from the face opposite the
isopropylidene group. The regioselectivity is in line with
earlier observations in similar systems.34 Interestingly,
this cycloaddition reaction can give eight possible prod-
ucts, and only trace amounts were observed of some of
the other isomers.
a
All reactions were carried out in CH2Cl2 at room temperature
b
under an atmosphere of ethylene. Yields in parentheses are
Subjecting acetate protected diene 28 to warm acrolein
also gave one main product 38 in 56% yield. Analysis of
based on recovered starting material. c Catalyst A was used
instead of B.
1
the H NMR revealed that the coupling constants were
be good substrates for the enyne metathesis reaction
(entries 4-6). Attempted metathesis of aminoenyne 12
in the presence of TsOH to protonate the amine led to
decomposition. Instead, 12 was converted into acetamide
25 and trifluoroacetamide 26, the latter being easier to
deprotect. Both compounds could be transformed into the
vinyl cyclohexenes (entries 7 and 8). All in all, these
enyne metathesis reactions proceeded well with catalyst
B and ethylene atmosphere. We did not observe other
carbocyclic ring isomers in any of the metathesis reac-
tions as recently reported for other substrates.32
(32) Kitamura, T.; Sato, Y.; Mori, M. Chem. Commun. 2001, 1258.
(33) For some recent syntheses of functionalized decalins, see:
Go¨ssinger, E.; Schwartz, A.; Sereining, N. Tetrahedron 2001, 57, 3045.
Labadie, G. R.; Cravero, R. M.; Conza´lez-Sierra, M. Tetrahedron Lett.
2001, 42, 1811. Mehta, G.; Ramesh, S. S. Chem. Commun. 2000, 2429.
J arosz, S.; Sko´ra, S. Tetrahedron: Asymmetry 2000, 11, 1433. Tsai,
Y.-F.; Peddinti, K.; Liao, C.-C. Chem. Commun. 2000, 475.
(34) Very good regioselectivity has recently been reported in Diels-
Alder reactions with similar 1,3-diene systems, see: Ling, T.;
Chowdhury, C.; Kramer, B. A.; Vong, B. G.; Palladino, M. A.; The-
odorakis, E. A. J . Org. Chem. 2001, 66, 8843. Pai, C.-C.; Liu, R.-S.
Org. Lett. 2001, 3, 1295. Bentz, D.; Laschat, S. Synthesis 2001, 1766.
Renaud, J .; Graf, C.-D.; Oberer, L. Angew. Chem., Int. Ed. 2000, 39,
3101.

4446 J . Org. Chem., Vol. 67, No. 13, 2002
Poulsen and Madsen
(4S,5S,6S)-5,6-Bis[(t r iet h ylsilyl)oxy]-7-oct en -1-yn -4-
virtually identical to those found in the spectrum of 37.
Accordingly, 38 was also assigned to be the product of
endo addition from the face opposite the isopropylidene
group.
In conclusion, carbohydrates have been converted into
functionalized 1-vinyl cyclopentenes and -hexenes by the
combination of a zinc-mediated tandem reaction and ring-
closing enyne metathesis. Further annulation can be
achieved by a Diels-Alder reaction, which provides
functionalized decalins in very few steps from carbo-
hydrates. These methods complement our previously
developed carbocyclization method using ring-closing
olefin metathesis.6a
ol (8R) a n d (4R,5S,6S)-5,6-Bis[(tr ieth ylsilyl)oxy]-7-octen -
25
1-yn -4-ol (8â). For 8R. Rf ) 0.63 (pentane/Et2O ) 9:1). [R]D
:
-61.5 (c 1.64, CHCl3). 1H NMR (300 MHz, CDCl3): δ 6.06 (ddd,
J ) 17.2, 10.7, 4.4 Hz, 1H), 5.36 (dt, J ) 17.2, 1.8 Hz, 1H),
5.26 (dt, J ) 10.7, 1.8 Hz, 1H), 4.38 (m, 1H), 4.06 (s, 1H), 3.82
(m, 1H), 3.70 (dd, J ) 8.6, 4.3 Hz, 1H), 2.55 (dt, J ) 16.7, 2.6
Hz, 1H), 2.35 (ddd, J ) 16.7, 6.4, 2.6 Hz, 1H), 2.01 (t, J ) 2.6
Hz, 1H), 0.98 (t, J ) 8.1 Hz, 18H), 0.71-0.55 (m, 12H). 13C
NMR (75 MHz, CDCl3): δ 135.2, 116.2, 81.4, 76.2, 74.0, 71.0,
69.8, 23.6, 6.8, 6.6, 5.0, 4.6. Anal. Calcd for C20H40O3Si2: C,
62.44; H, 10.48. Found: C, 62.23; H, 10.60. Hydrogenation over
Lindlar catalyst and removal of the silyl groups with TBAF
gave the corresponding octadiene triol with NMR data in
accordance with literature values.6a
For 8â. Rf ) 0.63 (pentane/Et2O ) 9:1). 1H NMR (300 MHz,
CDCl3): δ 6.01 (ddd, J ) 17.3, 10.5, 5.7 Hz, 1H), 5.27 (ddd, J
) 17.3, 1.8, 1.5 Hz, 1H), 5.16 (ddd, J ) 10.5, 1.8, 1.5 Hz, 1H),
4.19 (ddt, J ) 5.7, 4.9, 1.5 Hz, 1H), 3.91 (dddd, J ) 7.4, 6.8,
6.4, 2.8 Hz, 1H), 3.81 (dd, J ) 4.9, 2.8 Hz, 1H), 2.56 (d, J )
6.8 Hz, 1H), 2.43 (ddd, J ) 16.7, 6.4, 2.8 Hz, 1H), 2.36 (ddd, J
) 16.7, 7.4, 2.8 Hz, 1H), 1.97 (t, J ) 2.8 Hz, 1H), 1.05-0.92
(m, 18H), 0.74-0.55 (m, 12H). 13C NMR (75 MHz, CDCl3): δ
137.2, 115.5, 81.2, 74.9 (2C), 69.8, 68.2, 24.8, 6.8, 6.8, 5.1, 4.8.
Compounds 9R/â are the enantiomers of 8â/R.
(4R,6S)-6-[(Tr ieth ylsilyl)oxy]-7-octen -1-yn -4-ol (10â) an d
(4S,6S)-6-[(Tr ieth ylsilyl)oxy]-7-octen -1-yn -4-ol (10R). For
10â. Rf ) 0.36 (pentane/Et2O ) 9:1). 1H NMR (300 MHz,
CDCl3): δ 5.89 (ddd, J ) 17.1, 10.4, 5.6 Hz, 1H), 5.26 (dt, J )
17.2, 1.4 Hz, 1H), 5.14 (dq, J ) 10.4, 1.4 Hz, 1H), 4.54 (m,
1H), 4.06 (m, 1H), 3.53 (s, 1H), 2.45-2.27 (m, 2H), 2.01 (t, J )
2.8 Hz, 1H), 1.81-1.75 (m, 2H), 0.96 (t, J ) 8.0 Hz, 9H), 0.63
(q, J ) 8.0 Hz, 6H). 13C NMR (75 MHz, CDCl3): δ 139.8, 114.6,
80.9, 72.2, 70.2, 67.0, 42.1, 27.2, 6.7, 4.7. Removal of the silyl
group with TBAF and subsequent protection with MEMCl
provided (4R,6S)-4,6-bis[(2-methoxyethoxymethyl)oxy]-7-octen-
1-yne with NMR data in accordance with literature values.16
For 10R. Rf ) 0.36 (pentane/Et2O ) 9:1). 1H NMR (300 MHz,
CDCl3): δ 5.84 (ddd, J ) 17.1, 10.3, 7.2 Hz, 1H), 5.26 (dt, J )
17.2, 1.4 Hz, 1H), 5.08 (dq, J ) 10.3, 1.4 Hz, 1H), 4.38 (m,
1H), 3.96 (m, 1H), 3.52 (s, 1H), 2.45-2.27 (m, 2H), 2.02 (t, J )
2.8 Hz, 1H), 1.81-1.75 (m, 2H), 0.96 (t, J ) 8.0 Hz, 9H), 0.63
(q, J ) 8.0 Hz, 6H). 13C NMR (75 MHz, CDCl3): δ 140.8, 114.8,
80.9, 74.7, 70.2, 69.3, 43.1, 27.2, 6.7, 4.9. Anal. Calcd for
Exp er im en ta l Section
Gen er a l P r oced u r es. All sonications were performed 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 20
min, and then filtered and washed with H2O and Et2O. Finally,
the zinc was dried under high vacuum with a heat gun.
Propargyl bromide was prepared according to literature pro-
cedures35 and occasionally redistilled (note: distillations should
be carried out behind a safety shield. Neat propargyl bromide
has been reported to be shock-sensitive). Thin-layer chroma-
tography was performed on aluminum plates precoated with
silica gel (Merck 1.05554). Compounds were visualized by
heating after dipping in a solution of Ce(SO4)2 (2.5 g) and
(NH4)6Mo7O24 (6.25 g) in 10% aqueous H2SO4 (250 mL) or in a
solution of KMnO4 (3 g) and K2CO3 (20 g) in 1% aqueous NaOH
(300 mL). Flash chromatography was performed using silica
gel 60. Microanalyses were conducted by the Department of
Chemistry at the University of Copenhagen.
Gen er a l P r oced u r e for Ta n d em Rea ction . Zinc (2.5 g)
was added to a solution of the methyl 5-iodo-furanoside (1 g)
in THF:H2O (20 mL). The mixture was sonicated at 40 °C
under an argon atmosphere during which time propargyl
bromide (5 equiv) was added dropwise by syringe pump over
5-8 h. Zinc salts were removed by filtration through Celite.
The Celite was washed with CH2Cl2. The filtrate was diluted
with more CH2Cl2 and washed with saturated aqueous NaH-
CO3. The aqueous phase was extracted with CH2Cl2. The
combined organic phases were dried and concentrated, and the
residue was purified by flash chromatography eluting with a
pentane:Et2O mixture containing 0.5% Et3N.
C
14H26O2Si: C, 66.09; H, 10.30. Found: C, 66.31; H, 10.39.
(4S,5S,6R)-4-[(N-Ben zyl)a m in o]-5,6-(isop r op ylid en e-
d ioxy)-7-octen -1-yn e (12). A mixture of furanoside 1 (500
mg, 1.6 mmol) and zinc (2 g) in dry THF (15 mL) was sonicated
under an argon atmosphere at 40 °C for 30 min. BnNH2 (0.52
mL, 4.8 mmol) was added and the mixture sonicated for an
additional 2 h at 40 °C. Et3N (0.7 mL, 4.8 mmol) was then
added and the sonication continued for 2.5 h during which time
propargyl bromide (1.1 mL, 14.4 mmol) was added dropwise
by syringe pump. The mixture was filtered through Celite. The
Celite was rinsed with Et2O and the filtrate washed with H2O.
The organic phase was dried and concentrated, and the residue
was purified by flash chromatography (CH2Cl2/MeOH/Et3N )
98:1:1) to afford 217 mg (48%) of 12 as a colorless syrup. Rf )
(4S,5S,6R)-5,6-(Isop r op ylid en ed ioxy)-7-oct en -1-yn -4-
ol (7R) a n d (4R,5S,6R)-5,6-[(Isop r op ylid en e)d ioxy]-7-
octen -1-yn -4-ol (7â). For 7R. Rf ) 0.57 (pentane/Et2O ) 4:1).
[R]D26: -14.3 (c 1.21, CHCl3). 1H NMR (300 MHz, CDCl3): δ
5.98 (ddd, J ) 17.3, 10.4, 6.9 Hz, 1H), 5.40 (ddd, J ) 17.3, 1.5,
0.8 Hz, 1H), 5.25 (ddd, J ) 10.4, 1.4, 0.8 Hz, 1H), 4.66 (ddd, J
) 6.9, 6.5, 0.8 Hz, 1H), 4.03 (dd, J ) 8.7, 6.5 Hz, 1H), 3.73 (m,
1H), 2.61 (ddd, J ) 16.9, 3.6, 2.7 Hz, 1H), 2.42 (ddd, J ) 16.9,
7.2, 2.7 Hz, 1H), 2.04 (t, J ) 2.7 Hz, 1H), 2.10 (s, 1H), 1.42 (s,
3H), 1.32 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 133.7, 118.1,
108.8, 80.2, 79.2, 78.4, 70.9, 67.9, 27.7, 25.2, 24.3. EI (positive
mode) m/z calcd for C10H13O3 ((M - CH3)+) 181.0865. Found
181.0867. A solution of 7R (200 mg) in EtOH (15 mL) was
hydrogenated over Lindlar catalyst (18 mg) under 1 atm of
H2 at room temperature for 7 h. The catalyst was removed by
filtration and the filtrate concentrated. The residue was
dissolved in MeOH (10 mL) and stirred with acidic ion-
exchange resin (2 mL) for 2 h at 40 °C. Filtration, concentra-
tion, and purification by flash chromatography (Et2O) gave
1
0.71 (hexane/EtOAc ) 3:1). [R]D24: +79.6 (c 1.07, CHCl3). H
NMR (300 MHz, CDCl3): δ 7.35-7.20 (m, 5H), 5.98 (ddd, J )
17.0, 10.5, 6.5 Hz, 1H), 5.37 (ddd, J ) 17.0, 2.0, 1.4 Hz, 1H),
5.20 (ddd, J ) 10.5, 2.0, 1.2 Hz, 1H), 4.69 (m, 1H), 4.13 (dd, J
) 9.3, 6.2 Hz, 1H), 3.89 (d, J ) 12.5 Hz, 1H), 3.62 (d, J ) 12.5
Hz, 1H), 2.82 (ddd, J ) 9.3, 4.0, 3.9 Hz, 1H), 2.70 (ddd, J )
17.1, 4.0, 2.6 Hz, 1H), 2.57 (ddd, J ) 17.1, 3.9, 2.6 Hz, 1H),
2.00 (t, J ) 2.6 Hz, 1H), 1.47 (s, 3H), 1.37 (s, 3H). 13C NMR
(75 MHz, CDCl3): δ 140.0, 134.6, 128.2, 128.1, 126.9, 116.8,
108.1, 80.3, 78.7, 78.3, 70.8, 54.4, 50.7, 27.7, 25.3, 19.9. Anal.
Calcd for C18H23NO2: C, 75.76; H, 8.12; N, 4.91. Found: C,
75.21; H, 8.22; N, 4.95. Hydrogenation over Lindlar catalyst
in the presence of 2 equiv of AcOH gave 13 with NMR data in
accordance with previous values.6a
1
(3R,4S,5S)-1,7-octadiene-3,4,5-triol with H and 13C NMR data
in accordance with previous values.6a
For 7â. Rf ) 0.57 (pentane/Et2O ) 4:1). 13C NMR (75 MHz,
CDCl3): δ 133.6, 119.7, 108.5, 80.7, 78.9, 78.5, 70.4, 68.2, 27.1,
24.8, 24.1.
Acetylation of 12 with Ac2O and Et3N in CH2Cl2 gave 25 as
an almost equal mixture of two rotamers by NMR: Rf ) 0.37
(hexane/EtOAc ) 2:1). [R]D23: +21.0 (c 0.73, CHCl3). Mp: 69-
(35) Gaudemar, M. Ann. Chim., 13. Ser. 1956, 1, 161.

Carbohydrate Carbocyclization
J . Org. Chem., Vol. 67, No. 13, 2002 4447
70 °C. 1H NMR (300 MHz, CDCl3): δ 7.40-7.20 (m, 10H), 5.93
(ddd, J ) 17.2, 10.4, 7.0 Hz, 1H), 5.75 (m, 1H), 5.39 (bd, J )
17.2 Hz, 1H), 5.34 (bd, J ) 10.4 Hz, 1H), 5.50 (bs, 1H), 5.25
(bd, J ) 6.3 Hz, 1H), 5.08 (m, 1H), 5.02 (d, J ) 15.0 Hz, 1H),
4.70 (d, J ) 17.6 Hz, 1H), 4.57 (d, J ) 17.6 Hz, 1H), 4.49 (m,
1H), 4.27 (m, 1H), 4.23-4.15 (m, 2H), 4.07 (m, 1H), 3.88 (dd,
J ) 7.3, 6.8 Hz, 1H), 2.63-2.56 (m, 2H), 2.56-2.50 (m, 2H),
2.30 (s, 3H), 2.03 (t, J ) 2.6 Hz, 1H), 2.03 (s, 3H), 1.95 (t, J )
2.6 Hz, 1H), 1.44 (bs, 6H), 1.22 (s, 3H), 1.20 (s, 3H). 13C NMR
(75 MHz, CDCl3): δ 172.4, 172.2, 138.8, 137.9, 133.5, 133.3,
128.5, 128.3 (2C), 128.0, 127.1, 126.1, 119.1, 118.8, 108.4 (2C),
81.1, 79.9, 78.8 (2C), 78.7, 78.3, 71.7, 70.2, 56.6, 52.2, 48.8,
44.9, 27.3, 27.0, 24.7, 24.6, 22.7, 22.4, 20.5, 18.9. Anal. Calcd
for C20H25NO3: C, 73.37; H, 7.70; N, 4.28. Found: C, 73.19;
H, 7.76; N, 4.30.
Trifluoroacetylation of 12 with TFAA and Et3N in CH2Cl2
gave 26 as an almost equal mixture of two rotamers by NMR:
Rf ) 0.60 (hexane/EtOAc ) 2:1). [R]D23: -52.1 (c 0.95, CHCl3).
1H NMR (300 MHz, CDCl3): δ 7.40-7.20 (m, 10H), 5.81 (ddd,
J ) 17.0, 10.3, 6.9 Hz, 1H), 5.73 (ddd, J ) 17.6, 10.4, 7.0 Hz,
1H), 5.44 (bd, J ) 17.0 Hz, 1H), 5.41 (bd, J ) 10.3 Hz, 1H),
5.28 (bd, J ) 10.4 Hz, 1H), 5.25 (bd, J ) 17.6 Hz, 1H), 4.80 (d,
J ) 15.3 Hz, 1H), 4.73 (d, J ) 7.4 Hz, 1H), 4.68 (d, J ) 15.3
Hz, 1H), 4.63 (d, J ) 7.4 Hz, 1H), 4.58 (m, 1H), 4.36 (bd, J )
8.0 Hz, 1H), 4.33-4.17 (m, 4H), 2.62 (m, 1H), 2.59 (m, 1H),
2.45 (m, 1H), 2.32 (dt, J ) 17.9, 3.0 Hz, 1H), 1.99-1.94 (m,
2H), 1.49 (s, 3H), 1.39 (s, 3H), 1.27 (s, 3H), 1.14 (s, 3H). 13C
NMR (75 MHz, CDCl3): δ 158.1 (q, J ) 35.6 Hz), 157.9 (q, J
) 35.3 Hz), 136.6, 135.7, 133.0, 132.0, 128.6, 128.2, 128.1,
127.9, 127.6, 127.3, 119.9, 119.5, 116.6 (q, J ) 288.3 Hz), 116.5
(q, J ) 288.5 Hz), 109.2, 108.5, 80.0 (2C), 79.0, 78.7, 78.5, 77.9,
71.5, 70.7, 56.8, 55.8, 49.5, 47.3, 27.0, 26.3, 24.5, 24.2, 18.6,
18.5. Anal. Calcd for C20H22F3NO3: C, 62.98; H, 5.81; N, 3.67.
Found: C, 63.04; H, 5.85; N, 3.70.
62.0, 27.6, 25.2, -0.4. Anal. Calcd for C13H22O3Si: C, 61.38;
H, 8.72. Found: C, 61.36; H, 8.51. Removal of the silyl groups
with TBAF followed by hydrogenation over Lindlar catalyst
and cleavage of the isopropylidene acetal gave the correspond-
ing heptadiene triols. These could be separated by flash
chromatography and the major isomer was identified as
1,2,6,7-tetradeoxy-ribo-hept-1,6-dienitol by comparison with
literature data.6a
(4S,5R,6R)-5,6-(Isop r op ylid en ed ioxy)-4-[(ter t-bu tyld i-
m eth ylsilyl)oxy]-7-octen -1-yn e (16) a n d (4R,5R,6R)-5,6-
(Isop r op ylid en ed ioxy)-4-[(ter t-bu tyld im eth ylsilyl)oxy]-
7-octen -1-yn e (21). The crude product from the tandem
fragmentation-propargylation of 1 was dried azeotropically
with toluene. The residue (consisting of 7R and 7â) was
dissolved in CH2Cl2 and 2,6-lutidine (2 equiv). TBSOTf (1.2
equiv) was added dropwise over 1 h at 0 °C, and the mixture
was then allowed to stir at room temperature for an additional
1 h. The solution was diluted with CH2Cl2 and washed with
saturated aqueous NaHCO3, dried, and concentrated. The title
compounds 16 and 21 were separated by flash chromatography
(pentane/Et2O ) 98:2 with 0.5% Et3N) in a combined yield of
57% starting from 1.
For 16. Rf ) 0.54 (pentane/Et2O ) 95:5). [R]D24: +40.1 (c
1.23, CHCl3). 1H NMR (300 MHz, CDCl3): δ 5.98 (ddd, J )
17.2, 10.3, 7.1 Hz, 1H), 5.36 (ddd, J ) 17.2, 1.5, 0.6 Hz, 1H),
5.23 (ddd, J ) 10.3, 1.5, 0.6 Hz, 1H), 4.62 (m, 1H), 4.26 (dd, J
) 7.2, 6.8 Hz, 1H), 3.89 (ddd, J ) 7.2, 4.6, 4.5 Hz, 1H), 2.56
(ddd, J ) 17.2, 4.5, 2.7 Hz, 1H), 2.48 (ddd, J ) 17.2, 4.6, 2.7
Hz, 1H), 1.98 (t, J ) 2.7 Hz, 1H), 1.46 (s, 3H), 1.38 (s, 3H),
0.90 (s, 9H), 0.13 (s, 3H), 0.08 (s, 3H). 13C NMR (75 MHz,
CDCl3): δ 134.4, 117.8, 108.2, 80.6, 79.1, 78.5, 70.4, 69.0, 27.7,
25.9, 25.3, 24.5, 18.1, -3.9, -4.5. Anal. Calcd for C17H30O3Si:
C, 65.76; H, 9.74. Found: C, 65.63; H, 9.89.
For 21. Rf ) 0.50 (pentane/Et2O ) 95:5). [R]D24: +15.5 (c
0.73, CHCl3). 1H NMR (300 MHz, CDCl3): δ 5.90 (ddd, J )
17.3, 10.0, 8.4 Hz, 1H), 5.31 (ddd, J ) 17.3, 1.5, 1.0 Hz, 1H),
5.26 (ddd, J ) 10.0, 1.5, 0.8 Hz, 1H), 4.48 (dddd, J ) 8.4, 6.1,
1.0, 0.8 Hz, 1H), 4.19 (dd, J ) 7.1, 6.1 Hz, 1H), 3.82 (ddd, J )
7.1, 6.1, 4.6 Hz, 1H), 2.43 (ddd, J ) 16.9, 4.6, 2.7 Hz, 1H),
2.33 (ddd, J ) 16.9, 6.1, 2.7 Hz, 1H), 1.97 (t, J ) 2.7 Hz, 1H),
1.50 (s, 3H), 1.37 (s, 3H), 0.91 (bs, 9H), 0.12 (s, 3H), 0.11 (s,
3H). 13C NMR (75 MHz, CDCl3): δ 134.7, 119.2, 108.8, 81.3,
80.6, 79.1, 77.4, 70.3, 28.1, 26.2, 25.7, 24.1, 18.6, -4.1, -4.2.
Anal. Calcd for C17H30O3Si: C, 65.76; H, 9.74. Found: C, 65.41;
H, 9.53.
(4S,5R,6R)-4-(Acetyloxy)-5,6-(isop r op ylid en ed ioxy)-7-
octen -1-yn e (19) a n d (4R,5R,6R)-4-(Acetyloxy)-5,6-(iso-
p r op ylid en ed ioxy)-7-octen -1-yn e (20). The crude product
from the fragmentation-propargylation of 1 was dried azeo-
tropically with toluene. The residue was dissolved in CH2Cl2
and treated with Ac2O (1.5 equiv), Et3N (2 equiv) and a
catalytic amount of DMAP overnight. The mixture was washed
with H2O, dried and concentrated. The title compounds 19 and
20 were separated by flash chromatography (pentane/Et2O )
4:1 with 0.5% Et3N) in a combined yield of 75% starting from
1.
(3S,4S,5R)-4,5-(Isopr opyliden edioxy)-1-(tr im eth ylsilyl)-
6-h ep t en -1-yn -3-ol (15R) a n d (3R,4S,5R)-4,5-(Isop r op -
ylid en ed ioxy)-1-(tr im eth ylsilyl)-6-h ep ten -1-yn -3-ol (15â).
A suspension of anhydrous CeCl3 (2.4 g, 9.6 mmol, dried at
225 °C under high vacuum overnight) in anhydrous THF (15
mL), was stirred at room temperature for 1 day and then
cooled to -78 °C followed by addition of a 0.6 M solution of
trimethylsilylethynylmagnesium chloride in THF (16 mL, 9.6
mmol). The mixture was stirred at -78 °C for 1 h and then
allowed to warm to 0 °C and stirred for an additional 1 h at
this temperature. In the meantime, a solution of furanoside 1
(750 mg, 2.4 mmol) in THF (15 mL) was sonicated with
activated zinc dust (1.8 g) and TMSCl (0.15 mL, 1.2 mmol) at
40 °C for 2 h. The mixture was then filtered through Celite,
and the Celite was rinsed with CH2Cl2. The filtrate was
washed with saturated aqueous NaHCO3, dried, and concen-
trated. The crude aldehyde 11 thus obtained was dissolved in
dry THF (5 mL) and added to the freshly prepared solution of
trimethylsilylethynylcerium chloride (9.6 mmol) at 0 °C. This
mixture was stirred at 0 °C for 10 min and then at room
temperature for 45 min. TLC (pentane/Et2O ) 2:1) indicated
full conversion of the aldehyde. Excess alkylating agent was
quenched by stirring with H2O (25 mL) for 5 min. The mixure
was diluted with CH2Cl2, and the phases were separated. The
aqueous phase was extracted with CH2Cl2, and the combined
organic phases were dried and concentrated. The residue was
purified by flash chromatography (CH2Cl2/Et3N ) 99:1, Rf )
0.20) to afford 415 mg (68%) of enynes 15R and 15â as an
inseparable mixture in a 7:3 ratio. Rf ) 0.66 (hexane/EtOAc
) 2:1).
For 19. Rf ) 0.58 (pentane/Et2O ) 4:1). [R]D26: +36.1 (c 1.25,
CHCl3). 1H NMR (300 MHz, CDCl3): δ 5.78 (ddd, J ) 17.3,
10.4, 7.0 Hz, 1H), 5.37 (ddd, J ) 17.3, 1.5, 1.0 Hz, 1H), 5.22
(ddd, J ) 10.4, 1.5, 1.0 Hz, 1H), 4.86 (ddd, J ) 8.8, 4.8, 4.0
Hz, 1H), 4.67 (ddd, J ) 7.0, 6.3, 1.0 Hz, 1H), 4.39 (dd, J ) 8.8,
6.3 Hz, 1H), 2.71 (ddd, J ) 17.4, 4.0, 2.7 Hz, 1H), 2.61 (ddd, J
) 17.4, 4.8, 2.7 Hz, 1H), 2.03 (s, 3H), 1.99 (t, J ) 2.7 Hz, 1H),
1.48 (s, 3H), 1.39 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 169.5,
132.5, 118.1, 108.9, 79.1, 78.3, 76.5, 70.4, 68.9, 27.6, 25.2, 21.1,
20.9. Anal. Calcd for C13H18O4: C, 65.53; H, 7.61. Found: C,
65.55; H, 7.60.
For 15R. 1H NMR (300 MHz, CDCl3): δ 6.14 (ddd, J ) 17.4,
10.4, 7.2 Hz, 1H), 5.42 (bd, J ) 17.4 Hz, 1H), 5.30 (bd, J )
10.4 Hz, 1H), 4.70 (m, 1H), 4.33 (d, J ) 4.1 Hz, 1H), 4.23 (dd,
J ) 7.2, 4.1 Hz, 1H), 1.56 (bs, 3H), 1.39 (bs, 3H), 0.17 (bs, 9H).
13C NMR (75 MHz, CDCl3): δ 133.1, 119.0, 109.1, 103.6, 91.8,
80.4, 78.2, 62.9, 26.9, 25.1, -0.4.
For 20. Rf ) 0.50 (pentane/Et2O ) 4:1). [R]D25: -42.0 (c 0.93,
CHCl3). 1H NMR (300 MHz, CDCl3): δ 5.78 (ddd, J ) 17.3,
10.1, 7.3 Hz, 1H), 5.37 (dt, J ) 17.3, 1.4 Hz, 1H), 5.28 (dt, J )
10.1, 1.4 Hz, 1H), 4.88 (ddd, J ) 7.2, 5.6, 4.0 Hz, 1H), 4.66 (bt,
J ) 7.3 Hz, 1H), 4.43 (dd, J ) 6.8, 4.0 Hz, 1H), 2.57 (ddd, J )
16.7, 7.2, 2.8 Hz, 1H), 2.49 (ddd, J ) 16.7, 5.6, 2.8 Hz, 1H),
2.06 (s, 3H), 2.00 (t, J ) 2.8 Hz, 1H), 1.50 (s, 3H), 1.38 (s, 3H).
13C NMR (75 MHz, CDCl3): δ 170.2, 133.0, 119.5, 109.5, 79.3,
For 15â. 1H NMR (300 MHz, CDCl3): δ 5.95 (ddd, J ) 17.4,
10.4, 7.0 Hz, 1H), 5.39 (bd, J ) 17.4 Hz, 1H), 5.28 (bd, J )
10.4 Hz, 1H), 4.67 (m, 1H), 4.25 (d, J ) 6.6 Hz, 1H), 4.25 (m,
1H), 1.52 (bs, 3H), 1.40 (bs, 3H), 0.16 (bs, 9H). 13C NMR (75
MHz, CDCl3): δ 132.7, 119.0, 109.3, 102.8, 91.5, 80.6, 78.3,

4448 J . Org. Chem., Vol. 67, No. 13, 2002
Poulsen and Madsen
78.5, 77.5, 71.1, 70.0, 27.2, 25.8, 21.4 (2C). Anal. Calcd for
(3R,4R,5S)-5-(Acetyloxy)-3,4-(isop r op ylid en ed ioxy)-1-
vin ylcycloh exen e (28). Rf ) 0.40 (pentane/Et2O ) 4:1).
[R]D23: +25.7 (c 1.59, CHCl3). Mp: 111-113 °C. 1H NMR (300
MHz, CDCl3): δ 6.34 (dd, J ) 17.5, 10.8 Hz, 1H), 5.62 (m, 1H),
5.24 (d, J ) 17.5 Hz, 1H), 5.12 (d, J ) 10.8 Hz, 1H), 5.10 (ddd,
J ) 10.5, 5.8, 5.3 Hz, 1H), 4.75 (m, 1H), 4.43 (bdd, J ) 5.4, 5.3
Hz, 1H), 2.51 (dd, J ) 15.5, 5.8 Hz, 1H), 2.40 (ddt, J ) 15.5,
10.5, 2.2 Hz, 1H), 2.15 (s, 3H), 1.39 (s, 3H), 1.36 (s, 3H). 13C
NMR (75 MHz, CDCl3): δ 170.5, 137.6, 134.8, 125.9, 114.4,
110.2, 74.2, 73.9, 69.6, 27.6, 26.8, 23.7, 21.2. Anal. Calcd for
C
13H18O4: C, 65.53; H, 7.61. Found: C, 65.30; H, 7.48.
(4R,5R,6R)-4,5,6-Tr is(a cetyloxy)-7-octen -1-yn e (23) a n d
(4S,5R,6R)-4,5,6-Tr is(a cet yloxy)-7-oct en -1-yn e (24). The
diastereomeric mixture of triethylsilyl-protected enynes 9â and
9R (437 mg, 1.14 mmol, ratio 7:3) was dissolved in anhydrous
THF (10 mL). A 1.0 M solution of TBAF in THF (2.5 mL, 2.5
mmol) was added, and the mixture was stirred at room
temperature for 30 min. At this point TLC indicated full
desilylation of 9â/R. Ac2O (0.43 mL, 4.5 mmol), Et3N (0.71 mL,
5.1 mmol), and a catalytic amount of DMAP were then added,
and the solution was stirred for an additional 2 h at room
temperature. The mixture was diluted with CH2Cl2 and
washed with water. The organic layer was dried and concen-
trated, and the residue was purified by flash chromatography
(hexane/EtOAc ) 4:1) to yield 214 mg (67%) of 23 and 81 mg
C
13H18O4: C, 65.53; H, 7.61. Found: C, 65.47; H, 7.62.
(3R,4R,5R)-5-(Acetyloxy)-3,4-(isop r op ylid en ed ioxy)-1-
vin ylcycloh exen e (29). Rf ) 0.41 (pentane/Et2O ) 4:1).
[R]D22:-14.0 (c 0.56, CHCl3). 1H NMR (300 MHz, CDCl3): δ
6.38 (dd, J ) 17.5, 10.8 Hz, 1H), 5.80 (m, 1H), 5.23 (d, J )
17.5 Hz, 1H), 5.14 (d, J ) 10.8 Hz, 1H), 5.10 (dt, J ) 8.2, 5.0
Hz, 1H), 4.71 (m, 1H), 4.18 (dd, J ) 8.2, 6.2 Hz, 1H), 2.68 (dd,
J ) 16.6, 5.0 Hz, 1H), 2.11 (m, 1H), 2.09 (s, 3H), 1.46 (s, 3H),
1.29 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 170.4, 137.5, 136.8,
123.8, 115.0, 109.5, 75.2, 72.7, 70.9, 27.9, 26.9, 26.0, 21.2. EI
(positive mode) m/z calcd for C12H15O4 ((M - CH3)+) 223.0970.
Found 223.0976.
(25%) of 24.
26
For 23. Rf ) 0.48 (hexane/EtOAc ) 2:1). [R]D
: +40.9
1
(c 1.01, CHCl3). Mp: 60-61 °C. H NMR (300 MHz, CDCl3):
δ 5.77 (ddd, J ) 17.2, 10.4, 5.6 Hz, 1H), 5.57 (dddd, J ) 5.6,
3.9, 1.4, 1.2 Hz, 1H), 5.38 (dd, J ) 7.7, 3.9 Hz, 1H), 5.33 (ddd,
J ) 17.2, 1.4, 1.2 Hz, 1H), 5.29 (dt, J ) 10.4, 1.2 Hz, 1H), 5.17
(ddd, J ) 7.7, 6.3, 4.8 Hz, 1H), 2.61 (ddd, J ) 17.3, 4.8, 2.7
Hz, 1H), 2.50 (ddd, J ) 17.3, 6.3, 2.7 Hz, 1H), 2.12 (s, 3H),
2.12 (s, 3H), 2.10 (s, 3H), 2.03 (t, J ) 2.7 Hz, 1H). 13C NMR
(75 MHz, CDCl3): δ 169.6 (3C), 131.9, 118.5, 78.4, 72.2, 71.5,
70.8, 68.3, 20.8, 20.7 (2C), 20.6. Anal. Calcd for C14H18O6: C,
59.57; H, 6.43. Found: C, 59.66; H, 6.34.
(3R,4R,5R)-3,4-(Isop r op ylid en ed ioxy)-5-[(ter t-bu tyld i-
m eth ylsilyl)oxy]-1-vin ylcycloh exen e (30). Rf ) 0.38 (pen-
tane/Et2O ) 95:5). [R]D22: -17.7 (c 0.55, CHCl3). 1H NMR (300
MHz, CDCl3): δ 6.38 (dd, J ) 17.4, 10.7 Hz, 1H), 5.74 (m, 1H),
5.24 (d, J ) 17.3 Hz, 1H), 5.10 (d, J ) 10.7 Hz, 1H), 4.70 (m,
1H), 4.01 (t, J ) 6.6 Hz, 1H), 3.94 (dt, J ) 7.4, 4.5 Hz, 1H),
2.43 (dd, J ) 16.7, 4.5 Hz, 1H), 2.09 (dd, J ) 16.7, 7.4 Hz,
1H), 1.42 (s, 3H), 1.38 (s, 3H), 0.89 (s, 9H), 0.10 (s, 3H), 0.08
(s, 3H). 13C NMR (75 MHz, CDCl3): δ 138.3, 136.7, 124.3,
114.1, 108.8, 78.3, 73.1, 69.6, 30.1, 28.1, 26.1, 25.8, 18.0, -4.5,
-4.8.
For 24. Rf ) 0.39 (hexane/EtOAc ) 2:1). [R]D24: +19.3 (c
1.73, CHCl3). 1H NMR (300 MHz, CDCl3): δ 5.75 (ddd, J )
16.8, 10.7, 6.4 Hz, 1H), 5.48-5.27 (m, 4H), 5.12 (dt, J ) 6.1,
4.4 Hz, 1H), 2.50 (dd, J ) 6.1, 2.8 Hz, 2H), 2.10 (s, 3H), 2.09
(s, 3H), 2.07 (s, 3H), 2.03 (t, J ) 2.8 Hz, 1H). 13C NMR (75
MHz, CDCl3): δ 169.7 (2C), 169.5, 131.4, 119.8, 77.8, 72.7, 72.3,
71.3, 69.3, 20.9, 20.8, 20.7, 20.6. Anal. Calcd for C14H18O6: C,
59.57; H, 6.43. Found: C, 59.69; H, 6.37.
(3S,4S,5S)-3,4,5-Tr is(acetyloxy)-1-vin ylcycloh exen e (31).
Rf ) 0.40 (pentane/Et2O ) 2:1). [R]D23: +181.9 (c 1.59, CHCl3).
1
Mp: 72-74 °C. H NMR (300 MHz, CDCl3): δ 6.36 (dd, J )
Compound 22 is the enantiomer of 23 and was prepared
from 8R by the same procedure as described for 23.
17.5, 10.8 Hz, 1H), 5.65 (m, 1H), 5.56 (m, 1H), 5.43 (ddd, J )
5.3, 5.2, 2.4 Hz, 1H), 5.23 (dd, J ) 17.5, 0.5 Hz, 1H), 5.18-
5.13 (m, 2H), 2.62 (m, 1H), 2.46 (bdd, J ) 17.7, 5.6 Hz, 1H),
2.07 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H). 13C NMR (75 MHz,
CDCl3): δ 170.3, 170.2, 170.1, 137.2, 136.3, 123.5, 115.0, 70.8,
69.5, 68.0, 27.7, 21.0 (2C), 20.8. Anal. Calcd for C14H18O6: C,
59.57; H, 6.43. Found: C, 59.52; H, 6.37.
(3S,4R,5R)-3-(Acetyloxy)-4,5-(isop r op ylid en ed ioxy)-6-
h ep ten -1-yn e (27). The diastereomeric mixture of trimeth-
ylsilyl protected enynes 15R and 15â was desilylated with
TBAF and acetylated with Ac2O as described above. The title
enyne 27 was isolated diastereomerically pure by flash chro-
matography (pentane/Et2O ) 4:1). Rf ) 0.67 (hexane/EtOAc
) 2:1). [R]D22: -26.6 (c 1.11, CHCl3). 1H NMR (300 MHz,
CDCl3): δ 5.93 (ddd, J ) 17.2, 10.3, 7.4 Hz, 1H), 5.42 (bd, J )
17.2 Hz, 1H), 5.30 (bd, J ) 10.3 Hz, 1H), 5.30 (dd, J ) 5.2, 2.2
Hz, 1H), 4.72 (dd, J ) 7.4, 6.4 Hz, 1H), 4.33 (dd, J ) 6.4, 5.2
Hz, 1H), 2.50 (dd, J ) 2.2, 0.5 Hz, 1H), 2.08 (d, J ) 0.4 Hz,
3H), 1.56 (bs, 3H), 1.41 (bs, 3H). 13C NMR (75 MHz, CDCl3):
δ 169.0, 131.8, 119.3, 109.5, 78.7, 78.3, 78.0, 75.0, 63.0, 27.1,
25.0, 20.7. Anal. Calcd for C12H16O4: C, 64.27; H, 7.19.
Found: C, 63.83; H, 7.36.
Compound 32 is the enantiomer of 31.
(3R,4R,5S)-3,4,5-Tr is(acetyloxy)-1-vin ylcycloh exen e (33).
Rf ) 0.37 (pentane/Et2O ) 4:1). [R]D23: -62.0 (c 1.32, CHCl3).
1H NMR (300 MHz, CDCl3): δ 6.34 (dd, J ) 17.5, 10.9 Hz,
1H), 5.62-5.53 (m, 2H), 5.31 (dd, J ) 10.6, 7.3 Hz, 1H), 5.22
(bd, J ) 17.5 Hz, 1H), 5.17 (bd, J ) 10.9 Hz, 1H), 5.15 (ddd, J
) 10.6, 10.3, 5.8 Hz, 1H), 2.85 (dd, J ) 16.8, 5.8 Hz, 1H), 2.29
(ddd, J ) 16.8, 10.3, 2.4 Hz, 1H), 2.06 (s, 3H), 2.06 (s, 3H),
2.05 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 170.3, 170.0 (2C),
136.6, 135.6, 124.3, 115.4, 72.3, 72.0, 68.9, 29.0, 20.9, 20.8, 20.7.
Anal. Calcd for C14H18O6: C, 59.57; H, 6.43. Found: C, 59.10;
H, 6.28.
Gen er a l P r oced u r e for En yn e Meta th esis (Ta ble 2).
The enyne (0.3 mmol, dried azeotropically with toluene) was
dissolved in CH2Cl2 (6 mL), and ethylene gas was passed
through the solution for 20 min. Ruthenium catalyst B (or
catalyst A) was then added, and the solution was degassed
again with ethylene for 20 min. The mixture was stirred under
an atmosphere of ethylene at room temperature until TLC
revealed full conversion or that the reaction had stopped (3-
24 h). Silica gel was then added and the solvent removed in
vacuo. The cyclized product was obtained after flash chroma-
tography.
(3R,4S,5S)-5-(N-Acet yl-N-b en zyla m in o)-3,4-(isop r op -
ylid en ed ioxy)-1-vin ylcycloh exen e (34). NMR shows the
product as a 9:1 mixture of rotamers. NMR data are given for
27
the major rotamer. Rf ) 0.52 (hexane/EtOAc ) 1:1). [R]D
:
-11.7 (c 0.58, CHCl3). 1H NMR (300 MHz, CDCl3): δ 7.40-
7.20 (m, 5H), 6.30 (dd, J ) 17.6, 10.8 Hz, 1H), 5.50 (bs, 1H),
5.19-4.97 (m, 3H), 4.83 (bs, 2H), 4.70 (m, 1H), 4.28 (bd, J )
4.9 Hz, 1H), 2.29-2.22 (m, 2H), 2.12 (s, 3H), 1.26 (s, 3H), 1.11
(s, 3H). 13C NMR (75 MHz, CDCl3): δ 170.5, 138.8, 138.0,
135.9, 128.5, 126.8, 126.0, 125.5, 113.6, 109.6, 75.0, 74.8, 49.9,
48.7, 27.8, 26.4, 22.5, 22.1. Anal. Calcd for C20H25NO3: C,
73.37; H, 7.70; N, 4.28. Found: C, 72.84; H, 7.61; N, 4.15.
(3R,4S,5S)-5-[N-Ben zyl-N-(tr iflu or oa cetyl)a m in o]-3,4-
(isop r op ylid en ed ioxy)-1-vin ylcycloh exen e (35). NMR
shows the product as an almost equal mixture of rotamers. Rf
) 0.77 (hexane/EtOAc ) 3:1). [R]D24: -25.8 (c 1.23, CHCl3).
1H NMR (300 MHz, CDCl3): δ 7.44-7.19 (m, 10H), 6.40-6.24
(m, 2H), 5.59-5.50 (m, 2H), 5.16-4.88 (m, 8H), 4.75 (m, 2H),
4.39 (bd, J ) 4.7 Hz, 2H), 4.35-4.24 (m, 2H), 2.66-2.53 (m,
2H), 2.30-2.18 (m, 2H), 1.36 (s, 3H), 1.30 (s, 3H), 1.26 (s, 3H),
(3R,4R,5S)-3,4-(Isop r op ylid en ed ioxy)-5-[(ter t-bu tyld i-
m eth ylsilyl)oxy]-1-vin ylcycloh exen e (17). Rf ) 0.39 (pen-
tane/Et2O ) 95:5). [R]D26: +17.5 (c 1.20, CHCl3). 1H NMR (300
MHz, CDCl3): δ 6.31 (dd, J ) 17.5, 10.8 Hz, 1H), 5.48 (m, 1H),
5.23 (d, J ) 17.5 Hz, 1H), 5.07 (d, J ) 10.8 Hz, 1H), 4.63 (m,
1H), 4.29 (m, 1H), 3.86 (ddd, J ) 9.7, 6.2, 2.1 Hz, 1H), 2.38
(dt, J ) 15.6, 2.1 Hz, 1H), 2.29 (dd, J ) 15.6, 5.9 Hz, 1H), 1.35
(s, 3H), 1.31 (s, 3H), 0.95 (s, 9H), 0.10 (s, 6H). 13C NMR (75
MHz, CDCl3): δ 138.5, 135.9, 126.4, 114.1, 110.0, 76.9, 74.8,
69.3, 28.1, 27.8, 27.1, 26.2, 18.7, -4.1, -4.3. Anal. Calcd for
C
17H30O3Si: C, 65.76; H, 9.74. Found: C, 65.85; H, 10.00.

Carbohydrate Carbocyclization
J . Org. Chem., Vol. 67, No. 13, 2002 4449
1.10 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 158.4 (q, J ) 34.1
Hz), 157.5 (q, J ) 33.3 Hz), 137.6 (2C), 137.4, 137.3, 135.6,
135.4, 128.3 (2C), 127.2, 127.0, 126.8 (2C), 125.8 (2C), 116.7
(q, J ) 286.6 Hz), 116.5 (q, J ) 292.4 Hz), 114.4, 114.0, 110.5,
110.0, 75.5, 74.9, 74.7, 73.6, 54.7, 53.3, 48.2, 47.9, 27.7 (2C),
26.6, 26.4, 24.1, 22.3. Anal. Calcd for C20H22F3NO3: C, 62.98;
H, 5.81; N, 3.67. Found: C, 63.30; H, 5.35; N, 3.66.
H-8), 3.87 (dd, J ) 9.4, 5.4 Hz, 1H, H-7), 3.80 (ddd, J ) 10.5,
5.1, 4.0 Hz, 1H, H-9), 2.85 (m, 1H, H-6), 2.68 (m, 1H, H-5),
2.46 (dt, J ) 12.2, 1.4 Hz, 1H, H-10), 2.22 (dd, J ) 12.2, 5.1
Hz, 1H, H-10′), 2.10-1.94 (m, 2H), 1.85 (m, 1H), 1.52 (m, 1H),
1.55 (s, 3H), 1.30 (s, 3H), 0.90 (s, 9H), 0.10 (s, 3H), 0.09 (s,
3H). 13C NMR (75 MHz, CDCl3): δ 203.4, 132.0, 124.1, 109.2,
77.4, 75.4, 70.8, 49.4, 40.9, 38.9, 28.3, 25.9 (4C), 24.1, 18.3,
17.8, -4.6, -4.7. Anal. Calcd for C20H34O4Si: C, 65.53; H, 9.35.
Found: C, 65.48; H, 9.52.
(5S,6R,7R,8R,9S)-9-(Acetyloxy)-5-for m yl-7,8-(isop r op -
ylid en ed ioxy)bicyclo[4.4.0]d ec-1-en e (38). Prepared from
28 using the same procedure as described above. Rf ) 0.50
(hexane/EtOAc ) 2:1). [R]D22: -100.8 (c 0.61, CHCl3). Mp:
121-123 °C. 1H NMR (500 MHz, CDCl3): δ 9.88 (d, J ) 1.5
Hz, 1H), 5.68 (bdd, J ) 5.0, 0.5 Hz, 1H, H-2), 4.92 (ddd, J )
10.5, 5.5, 3.9 Hz, 1H, H-9), 4.32 (m, 1H, H-8), 3.97 (dd, J )
9.3, 4.9 Hz, 1H, H-7), 2.83 (m, 1H, H-6), 2.68 (dddd, J ) 12.1,
5.4, 2.9, 1.5 Hz, 1H, H-5), 2.47 (m, 1H, H-10), 2.38 (dd, J )
12.3, 5.5 Hz, 1H, H-10′), 2.11 (s, 3H), 2.10-1.94 (m, 2H), 1.92
(m, 1H), 1.55 (s, 3H), 1.53 (m, 1H), 1.31 (s, 3H). 13C NMR (75
MHz, CDCl3): δ 203.1, 170.2, 130.3, 125.7, 109.8, 75.6, 74.6,
70.7, 49.4, 40.9, 35.0, 28.2, 26.1, 24.2, 21.2, 17.6. Anal. Calcd
for C16H22O5: C, 65.29; H, 7.53. Found: C, 65.33; H, 7.53.
(3R,4R,5S)-5-(Acetyloxy)-3,4-(isop r op ylid en ed ioxy)-1-
vin ylcyclop en ten e (36). Rf ) 0.67 (hexane/EtOAc ) 2:1).
[R]D22: -175.7 (c 1.17, CHCl3). Mp: 62-63 °C. H NMR (300
1
MHz, CDCl3): δ 6.41 (dd, J ) 17.6, 11.0 Hz, 1H), 5.99 (m, 1H),
5.54 (d, J ) 17.6 Hz, 1H), 5.28 (d, J ) 11.0 Hz, 1H), 5.04 (dd,
J ) 6.0, 2.3 Hz, 1H), 4.91 (dd, J ) 6.0, 5.8 Hz, 1H), 2.11 (s,
3H), 1.40 (s, 3H), 1.37 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
170.4, 142.6, 131.2, 130.3, 118.6, 112.9, 82.1, 76.9, 74.0, 27.1,
26.4, 20.7. Anal. Calcd for C12H16O4: C, 64.27; H, 7.19.
Found: C, 64.33; H, 7.31.
(5S,6R,7R,8R,9S)-5-F or m yl-7,8-(isop r op ylid en ed ioxy)-
9-[(ter t-bu tyldim eth ylsilyl)oxy]bicyclo[4.4.0]dec-1-en e (37).
A solution of diene 17 (50 mg, 0.16 mmol) in acrolein (5 mL)
was heated to 60 °C in a sealed pressure tube for 24 h. At this
point, TLC showed almost complete consumption of 17 and
the formation of one major product and a few minor products.
The mixture was concentrated and the residue purified by
flash chromatography (hexane/EtOAc ) 9:1) to afford 41 mg
(69%) of 37. Rf ) 0.50 (hexane/EtOAc ) 4:1). [R]D22: -71.1 (c
Ack n ow led gm en t. We thank the Danish Natural
Science Research Council for financial support.
1
1.01, CHCl3). Mp: 55-56 °C. H NMR (500 MHz, CDCl3): δ
9.89 (bs, 1H), 5.59 (m, 1H, H-2), 4.18 (dd, J ) 5.4, 4.4 Hz, 1H,
J O0200062