Synthesis of furo[3,4-c]furans using a rhodium(II)-catalyzed cyclization/Diels - Alder cycloaddition sequence

Article abstract of DOI:10.1021/jo020413d

A series of 2-alkynyl 2-diazo-3-oxobutanoates, when treated with a catalytic quantity of rhodium(II) acetate, afforded furo[3,4-c]furans in good yield. The reaction proceeds by addition of a rhodium-stablilized carbenoid onto the acetylenic π-bond to give a vinyl carbenoid that subsequently cyclizes onto the neighboring carbonyl group to produce the furan ring. These furo[3,4-c]furans react with various dienophiles, furnishing anisole derivatives derived by loss of water from the initially formed Diels - Alder cycloadducts. The Rh(II)-catalyzed cyclization reaction was quite versatile with regard to the nature of the interacting carbonyl group. The methodology was applied to the synthesis of several oxa-polyheterocyclic systems by first generating a 2-alkoxy-substituted furan and then allowing it to undergo a subsequent intramolecular Diels - Alder cycloaddition. Ring opening of the resulting cycloadduct is followed by deprotonation to furnish a rearranged keto lactone. The potential use of this method for the synthesis of the alkaloid strychnine was probed using suitable model diazo compounds. To establish the viability of this approach, the Rh(II)-catalyzed cyclization/cycloaddition sequence of α-diazo amides 64 and 68 were studied. Both compounds underwent the sequential process in good overall yield, leading to novel pentacyclic products. The structural features of the resultant products present numerous opportunities for postcycloaddition manipulations that could be exploited to synthetic advantage.

Full text of DOI:10.1021/jo020413d

Syn th esis of F u r o[3,4-c]fu r a n s Usin g a Rh od iu m (II)-Ca ta lyzed
Cycliza tion /Diels-Ald er Cycloa d d ition Sequ en ce
Albert Padwa* and Christopher S. Straub
Department of Chemistry, Emory University, Atlanta, Georgia 30322
chemap@emory.edu
Received J une 17, 2002
A series of 2-alkynyl 2-diazo-3-oxobutanoates, when treated with a catalytic quantity of rhodium(II)
acetate, afforded furo[3,4-c]furans in good yield. The reaction proceeds by addition of a rhodium-
stablilized carbenoid onto the acetylenic π-bond to give a vinyl carbenoid that subsequently cyclizes
onto the neighboring carbonyl group to produce the furan ring. These furo[3,4-c]furans react with
various dienophiles, furnishing anisole derivatives derived by loss of water from the initially formed
Diels-Alder cycloadducts. The Rh(II)-catalyzed cyclization reaction was quite versatile with regard
to the nature of the interacting carbonyl group. The methodology was applied to the synthesis of
several oxa-polyheterocyclic systems by first generating a 2-alkoxy-substituted furan and then
allowing it to undergo a subsequent intramolecular Diels-Alder cycloaddition. Ring opening of
the resulting cycloadduct is followed by deprotonation to furnish a rearranged keto lactone. The
potential use of this method for the synthesis of the alkaloid strychnine was probed using suitable
model diazo compounds. To establish the viability of this approach, the Rh(II)-catalyzed cyclization/
cycloaddition sequence of R-diazo amides 64 and 68 were studied. Both compounds underwent the
sequential process in good overall yield, leading to novel pentacyclic products. The structural features
of the resultant products present numerous opportunities for postcycloaddition manipulations that
could be exploited to synthetic advantage.
The chemistry of transition metal carbene complexes
has been the subject of intense activity over the past 2
decades.1-20 Current interest in this area stems from the
role of metal carbenes in alkene metathesis,21 in alkene
and alkyne polymerization,22 in cyclopropanation chem-
istry,23 and as intermediates in an impressive array of
synthetic methodologies.24,25 Many transition metal car-
bene complexes react readily with alkynes to form vinyl
carbene complexes.1-4 The product distribution has been
found to vary considerably depending on the metal
employed and the nature of the functionality present on
the enyne substrate. Of special interest is the intra-
molecular reaction of carbene complexes with alkynes,
which has inspired many variations.20 Earlier work by
our group showed that the rhodium(II)-catalyzed reaction
of R-diazo ketones bearing tethered alkyne units repre-
sents a powerful method for the construction of a variety
of polycyclic skeletons.26 Exposure of the starting R-diazo
ketone to a rhodium(II) catalyst results in cyclization of
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10.1021/jo020413d CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/11/2002
J . Org. Chem. 2003, 68, 227-239
227

Padwa and Straub
erocyclic chemistry.31-35 Several different synthetic ap-
proaches to alkenone carbenes have been developed over
the years, producing intermediates that display common
trends in their reactivity.36-42 The utility of this transition
metal catalyzed cyclization approach to ring construction
would be significantly expanded if the resulting bicyclic
furan was to undergo a subsequent [4 + 2]-cycloaddition,
since a cyclohexane annulation would then result. Since
synthetic methods that combine transformations of dif-
ferent reaction types are extremely useful for organic
synthesis, we decided to extend our earlier studies toward
more complex ring systems. In this paper, we detail our
recent observations dealing with the cyclization/cyclo-
addition sequence of bicyclic furans derived from the
Rh(II)-catalyzed reaction of R-diazo carbonyls tethered
to alkynyl groups as a method for the synthesis of
polycyclic ring systems.
SCHEME 1
SCHEME 2
Resu lts a n d Discu ssion
Preparation of the propargyl diazo malonic ester
system was straightforward and high-yielding. Silyl
propargyl alcohol was acylated with Meldrum’s acid and
then allowed to react with DCC in the presence of an
appropriately substituted alcohol to give the alkynyl ester
derivative. Diazo transfer was readily accomplished using
p-nitrobenzenesulfonyl azide and triethylamine.43 2-Diazo
malonic ester 9 was efficiently converted to furan 10 in
high yield (95%) by treatment with a catalytic amount
of rhodium(II) acetate in benzene at 80 °C (Scheme 3).
Interestingly, the simpler propargyl ester 11, which
possesses a terminal hydrogen, underwent the cyclization
reaction in low yield (19%), producing 12 along with other
unidentifiable products. We suspect that some of these
products may be formed via a 6-endo cyclization pathway,
as had been previously encountered with related keto
carbenoids derived from terminal alkynes.26,27 Exposure
of the methoxy silyl substituted furan 10 to TBAF in THF
cleanly furnished the desilylated furan 12 in 94% yield.
Related cyclizations occurred with both the carbomethoxy
and bromo-substituted alkynes 13 and 15, producing
furans 14 and 16 in 73% and 90% yield, respectively.
Attempts to induce a [4 + 2]-cycloaddition of the silylated
furan 10 with various dienophiles failed to give any
cycloadducts, and only starting material was obtained,
even after prolonged heating. On the other hand, the
sterically less encumbered furan 12 was found to react
the R-keto carbenoid to an intermediate in which carbene-
like reactivity has been transferred to one of the original
alkyne carbon atoms. A neighboring functional group
present on the backbone then traps the cyclized inter-
mediate 3 via known carbenoid chemistry to give various
products (Scheme 1).27
During the course of our studies in this area, we
reported on a novel construction of bicyclic furans by
coupling a metal carbenoid cyclization onto a tethered
alkyne with an electrocyclization reaction (Scheme 2).28
Transformations of this type are of considerable synthetic
utility, since the vast majority of furano-sesquiterpenes
are functionalized at the C3 and C4 position of the furan
ring.29,30 Use of an ester group (R1dOEt) also allows for
transformation of 5 to the corresponding butenolide
system 6. Formation of five-membered rings by 6π-
electrocyclization is a well-precedented process in het-
(26) Padwa, A.; Krumpe, K. E.; Gareau, Y.; Chiacchio, U. J . Org.
Chem. 1991, 56, 2523. Padwa, A.; Xu, S. L. J . Am. Chem. Soc. 1992,
114, 5881. Padwa, A.; Kassir, J . M.; Xu, S. L. J . Org. Chem. 1991, 56,
6971. Baird, M. S.; Buxton, S. R.; Whitley, J . S. Tetrahedron Lett. 1984,
25, 1509. Padwa, A.; Fryxell, G. E.; Zhi, L. J . Org. Chem. 1988, 53,
2875. Padwa, A.; Krumpe, K. E.; Zhi, L. Tetrahedron Lett. 1989, 30,
2633. Padwa, A.; Chiacchio, U.; Garreau, Y.; Kassir, J . M.; Krumpe,
K. E.; Schoffstall, A. M. J . Org. Chem. 1990, 55, 414. Padwa, A.; Austin,
J . A.; Xu, S. L. J . Org. Chem. 1992, 57, 1330. Padwa, A.; Krumpe, K.
E.; Kassir, J . M. J . Org. Chem. 1992, 57, 4940. Padwa, A.; Austin, D.
J .; Xu, S. L. Tetrahedron Lett. 1991, 32, 4103. Padwa, A.; Chiacchio,
U.; Fairfax, D. J .; Kassir, J . M.; Litrico, A.; Semones, M. A.; Xu, S. L.
J . Org. Chem. 1993, 58, 6429. Padwa, A.; Kassir, J . M.; Semones, M.
A.; Weingarten, M. D. J . Org. Chem. 1995, 60, 53. Padwa, A.; Austin,
D. J .; Chiacchio, U.; Kassir, J . M.; Rescifina, A.; Xu, S. L. Tetrahedron
Lett. 1991, 32, 5923.
(27) For a brief review, see: Padwa, A. J . Organometallic Chem.
2001, 617, 3.
(28) Kinder, F. R.; Padwa, A. Tetrahedron Lett. 1990, 31, 6835.
Padwa, A.; Kinder, F. R. J . Org. Chem. 1993, 58, 21.
(29) Rigby, J . H.; Wilson, J . Z. J . Org. Chem. 1987, 52, 34. Rigby, J .
H.; Senanayake, C. J . Am. Chem. Soc. 1987, 109, 3147.
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Am. Chem. Soc. 1981, 103, 4643.
(34) Visser, G. W.; Verboom, W.; Benders, P. H.; Reinhoudt, D. N.
J . Chem. Soc., Chem. Commun. 1982, 669.
(35) Padwa, A.; Bakulev, V. A.; Kappe, C. O. Organic Synthesis:
Theory and Applications; J AI Press: 1996; Vol 3, pp 149-229.
(36) Padwa, A.; Akiba, M.; Chou, C. S.; Cohen, L. J . Org. Chem.
1982, 47, 7, 183.
(37) Eberbach, W.; Roser, J . Tetrahedron Lett. 1987, 28, 2685.
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hedron Lett. 1988, 29, 2045.
(39) Hamaguchi, M.; Ibata, T. Chem. Lett. 1976, 287.
(40) Maier, M. E.; Schoeffling, B. Chem. Ber. 1989, 122, 1081.
(41) Davies, H. M. L.; Romines, K. R. Tetrahedron 1988, 44, 3343.
(42) Padwa, A.; Straub, S. S. Org. Lett. 2000, 2, 2093.
(43) Regitz, M. Chem. Ber. 1966, 99, 3128. Regitz, M.; Hocker, J .;
Liedhegener, A. Organic Synthesis; Wiley: New York, 1973; Collect
Vol. V, pp 179-183. Sundberg, R. J .; Pearce, B. C. J . Org. Chem. 1985,
50, 425.
228 J . Org. Chem., Vol. 68, No. 2, 2003

Synthesis of Furo[3,4-c]furans
SCHEME 3
SCHEME 4
required for cyclization to the pyrrolidino-substituted
furo[3,4-c]furan 24 (Scheme 4). The success achieved with
the Rh(II)-catalyzed cyclization of 23f24 was extended
to the simpler dimethylamido system 25. In this case,
however, decomposition under standard conditions
(Rh2OAc4/CH2Cl2) afforded a mixture of products from
which only a low yield (ca. 2%) of the dimethylamino-
substituted furan 26 was obtained. The major product
isolated in 80% yield was azetidinone 27, derived by C-H
insertion into one of the amino methyl groups.45 Interest-
ingly, the product distribution was found to be markedly
dependent on the solvent used.46 Thus, when rhodium(II)
acetate [or rhodium(II) octanoate] in hexane was used,
a clean transformation was observed and furan 26 was
isolated in 98% yield, with no detectable quantities of
â-lactam 27 being formed. The Rh(II)-catalyzed reaction
of the closely related N-phenyl-N-methyl diazoamide 28
was also examined. In this case only azetidinone 30 (80%)
was formed using either of the above sets of conditions.
Furan 29 could not be detected in the crude reaction
mixtures.
We also discovered that the Rh(II)-catalyzed decom-
position of 25 is ligand dependent, thereby suggesting
that a metalated species is involved in the product-
determining step. Similar observations have been made
previously.47 Changing the catalyst from Rh2OAc4 to
Rh2(pfb)4 (pfb ) perfluorobutyrate) in CH2Cl2 resulted
in the exclusive formation of furan 26. The more electron-
withdrawing perfluorobutyrate ligand favors electro-
cyclization with the tethered alkynyl group, while 1,4-
insertion is favored by the more electron-donating acetate
ligand. The initially formed rhodium carbenoid derived
from the starting diazo compound is highly electron
deficient at the carbon center and is further destabilized
with both N-phenylmaleimide and maleic anhydride at
145 °C, furnishing the expected anisole derivatives 17
and 18 in 88% and 65% yield, respectively. The Diels-
Alder reaction of 12 also occurred with both dimethyl
acetylenedicarboxylate (DMAD) and dimethyl fumarate,
giving rise to the anisole derivatives 19 and 20, which
are derived by rearrangement or loss of water from the
initially formed cycloadducts.
Furan 12, however, could not be induced to react with
mono-activated dienophiles (e.g. methyl vinyl ketone)
under a range of conditions (refluxing xylene, 10 kbar in
toluene, trityl perchlorate in CH2Cl2, lithium perchlorate
in ether, TiCl4 in CH2Cl2, etc). Interestingly, the [4 + 2]
cycloaddition reaction of 12 with methyl vinyl ketone
occurred at 25 °C when nitromethane/methanol was used
as the solvent and gave the ring-opened ketal 21 in
quantitative yield. An analogous reaction pathway was
followed by phenyl vinyl sulfone, which furnished ketal
22 in 89% yield upon treatment with 12 in nitromethane
at 25 °C.44
The Rh(II)-catalyzed cyclization reaction was quite
versatile with regard to the nature of the interacting
carbonyl group. Thus, when the cyclization reaction was
carried out with the pyrrolidinyl amido system 23, there
was no notable difference in yield (90%) or reaction time
(45) Doyle, M. P.; Shanklin, M. S.; Oon, S. M.; Pho, H. Q.; van der
Heide, F. R.; Veal, W. R. J . Org. Chem. 1988, 53, 3384.
(46) Davies, H. M. L.; Saikali, E.; Clark, T. J .; Chee, E. H.
Tetrahedron Lett. 1990, 31, 6299. Davies, H. M. L.; Saikali, E.; Young,
W. B. J . Org. Chem. 1991, 56, 5696. Davies, H. M. L.; Clark, T. J .;
Kimmer, G. J . Org. Chem. 1991, 56, 6440. Padwa, A.; Krumpe, K. E.;
Kassir, J . M. J . Org. Chem. 1992, 57, 4940.
(44) Nitromethane is known to facilitate the Diels-Alder reaction
at low temperature with related systems, see: Konopelski, J . P.;
Sa´nchez, A. J . J . Org. Chem. 1994, 59, 5445.
(47) For a review of ligand effects on the Rh(II)-catalyzed reaction
of R-diazo carbonyls, see: Padwa, A.; Austin, D. J . Angew. Chem., Int.
Ed. Engl. 1994, 33, 1797.
J . Org. Chem, Vol. 68, No. 2, 2003 229

Padwa and Straub
SCHEME 5
SCHEME 6
by an electron-withdrawing ligand. With this more reac-
tive intermediate, interaction with the acetylenic π-bond
is preferred over the entropically more demanding 1,4-
insertion pathway. The observed solvent effect can be
rationalized in a similar manner. A nonpolar solvent such
as hexane apparently facilitates interaction of the rho-
dium carbenoid with the electron rich acetylenic π-bond
thereby favoring furan formation.
in an equilibrated mixture of the two cyclopenta[a]-
naphthalenone isomers (i.e., 34:35 ) 2:1). This mecha-
nistic description is further complicated, however, by the
possibility of a thermally allowed 1,5-H shift that inter-
converts 38 and 39 and ultimately results in a higher
percentage of benzopyran 33 in the equilibrating mixture.
Indeed, heating a sample of 34 (or 35) with p-TsOH for
several hours at 120 °C in toluene furnished benzopyran
33 as the major product of the mixture.
To access synthetically more valuable targets, we
focused our attention on an intramolecular variation of
the Rh(II)-catalyzed cyclization/Diels-Alder cycloaddition
sequence. In this regard, we first investigated the IMDAF
(intramolecular Diels-Alder of furans) chemistry48 of
furan 32, which was readily formed by the Rh(II)-
catalyzed reaction of 31 followed by protiodesilylation
with TBAF (Scheme 5). Thermolysis of a sample of 32 in
xylene at 145 °C in the presence of a trace of p-TsOH
afforded a mixture of three compounds, which were
separated by silica gel chromatography and assigned as
cyclopenta[a]naphthalenones 33 (46%), 34 (28%), and 35
(15%). The relative stereochemistry about the ring junc-
ture for compounds 34 and 35 was established by NOESY
NMR experiments. A reasonable mechanism for the
formation of the IMDAF products is outlined below
(Scheme 6). The initial step proceeds by the expected
[4 + 2]-cycloaddition of the furan across the tethered
π-bond to give cycloadduct 36. Following opening of the
oxybridge, proton loss (Ha) (route A) is accompanied by
a subsequent dehydration of 38 to give the aromatic
dihydrobenzopyran 33. Loss of proton Hb (route B) from
the initially formed oxonium ion 37 can compete with
route A and furnishes dienol 39, which rapidly tautomer-
izes to give 34 (28%). The protonation of enol 39 occurs
from the bottom face of this slightly cupped diene, leading
to the observed stereoisomer. Once 34 is formed, it is
partially equilibrated to 35 (15%) via enol 40. Again,
protonation of the enol (i.e., 40) occurs from the sterically
less crowded R-face.49 In support of this mechanistic
proposal, we noted that heating a pure sample of 34 (or
35) for 1 h at 80 °C in the presence of p-TsOH resulted
To further illustrate the viability of the Rh(II)-cycliza-
tion/cycloaddition/rearrangement sequence as a strategy
for the synthesis of complex polycyclic systems, we
studied the Rh(II)-catalyzed behavior of diazo esters 41
and 42. Synthesis of both these compounds proceeded
uneventfully using an analogous procedure to that em-
ployed for 31. Cyclization with Rh2OAc4 followed by
protiodesilylation afforded furans 43 and 44 in good yield.
Thermolysis of 43 at 145 °C in xylene afforded a 1:2-
mixture of dihydrobenzofuran 45 and 1,7-dioxa-indacene
dione 46 as the two major products in 51% overall yield
(Scheme 7). In a similar manner, the related styryl-
substituted furo[3,4-c]furan 44 was easily prepared by
the Rh(II)-catalyzed reaction of diazo malonic ester 42.
Heating a sample of 42 afforded the related indacene
dione 47, but now as the minor component (36%) of the
reaction mixture. The major product (63%) corresponded
to the dienol-substituted lactone 48. Both of these
products can be rationalized by a mechanism similar to
that outlined above. When a phenyl group resides at the
bridgehead carbon (i.e., 51), the deprotonation step is now
required to occur from the alternate γ-positions, thereby
resulting in the formation of compounds 47 and 48 as
shown in Scheme 8. A related pathway seemingly occurs
with oxonium ion 50, producing keto lactone 46 via enol
52 (R ) H). An alternative possibility to rationalize the
formation of 46 would involve proton loss from the
R-position of 50 followed by a rapid 1,5-sigmatropic
(48) Kappe, C. O.; Murphree, S. S.; Padwa, A. Tetrahedron 1997,
53, 14179.
(49) Ab initio MO calculations using the 6-31G* basis set also
indicate that the cis-ring juncture present in 35 is preferred over the
trans-isomer by 8 kcal/mol.
230 J . Org. Chem., Vol. 68, No. 2, 2003

Synthesis of Furo[3,4-c]furans
SCHEME 7
SCHEME 9
SCHEME 8
from an endo sidearm transition state were neither
detected nor isolated. This result is not so surprising
since, in these mobile cycloaddition equilibria, the transi-
tion state leading to the exo-adduct is sterically less
encumbered and the resulting adduct is the thermo-
dynamically most stable isomer. The initially formed
Diels-Alder adduct 55 rearranges to the observed prod-
ucts by the same general pathway as that outlined in
Scheme 6.
To demonstrate the viability of our sequential process
as a practical strategy for the synthesis of complex
heterocycles, we have explored the feasibility of this
approach in the context of the total synthesis of strych-
nine (61).52 The key step in our plan involves a sequential
cyclization/IMDAF reaction of diazo amide 58 to furnish
the rearranged cycloadduct 59 by a process similar to
those outlined in Schemes 7-9. Lactone 59 would even-
tually be transformed into compound 60, which had
previously been converted into strychnine by Kuehne and
Xu.53 Thus, the formation of 60 from diazo amide 58
would constitute a formal synthesis of this challenging
alkaloid (Scheme 10).
hydrogen shift of the initially formed hydroxy-cyclohexa-
diene to give enol 52 (R ) H).
Extension of the carbenoid cyclization/cycloaddition
sequence to the related cyclopentenyl diazo ester 53 was
also carried out. In this case, diazo ester 53 was converted
to furan 54 in 68% overall yield for the two-step sequence.
Heating a sample of 54 at 145 °C in xylene afforded a
2:1-mixture of 56 and 57 in 91% yield (Scheme 9). The
stereochemical centers in both compounds were assigned
on the basis of their NMR spectral data. In 56, a strong
To establish the viability of this approach, the Rh(II)-
catalyzed cyclizations of two model substrates (i.e., 64
and 68) were examined. Easily prepared N-phenyl-N-
prop-2-ynyl-malonamic acid methyl ester (62) was hy-
drolyzed to the corresponding carboxylic acid 63 which,
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Eichberg, M. J .; Dorta, R. L.; Grotjahn, D. B.; Lamottke, K.; Schmidt,
M.; Vollhardt, K. P. C. J . Am. Chem. Soc. 2001, 123, 9324.
(53) Kuehne, M. E.; Xu, F. J . Org. Chem. 1993, 58, 7490.
NOE was observed between H3 and H4 as well as H14
.
Additionally, protons H4 and H14 exhibited a strong NOE,
as did protons H9 and H14. An analogous set of NOE
enhancements helped to elucidate the stereochemistry
of compound 57. The formation of these products is
consistent with a preferred exo-orientation of the tether
in the Diels-Alder cycloaddition reaction and is analo-
gous with that reported by others for related furanyl
systems possessing short tethers.50,51 Products resulting
J . Org. Chem, Vol. 68, No. 2, 2003 231

Padwa and Straub
SCHEME 10
SCHEME 12
SCHEME 11
at the terminal alkyne carbon. Further heating of 65 at
145 °C in xylene afforded a 1:1-mixture of lactams 66
and 67 in 90% yield, presumably by a mechanism similar
to that outlined in Scheme 8.
An analogous cyclization occurred with diazo â-amido
ester 68. Thus, treatment of 68 with a catalytic quantity
of rhodium(II) perfluorobutyrate afforded furan 69 in 94%
isolated yield. Further heating of this furan at 145 °C
furnished the novel pentacyclic product 72 as a single
stereoisomer in 68% yield (Scheme 12). The structure and
stereochemistry of 72 was confirmed by 1H NMR and
NOE experiments. Each of the bond-forming events is
assumed to occur by the pathway outlined in Scheme 12.
In conclusion, the Rh(II)-catalyzed cyclization/IMDAF
sequence of diazo malonate esters affords structurally
elaborated polycyclic products with good to excellent
efficiency. The structural features of the resulting prod-
ucts present numerous opportunities for postcycloaddi-
tion manipulations that could be exploited to synthetic
advantage. Efforts in our laboratory directed toward a
formal total synthesis of strychnine using this approach
are currently underway and our results will be reported
in due course.
in turn, was subjected to a DCC coupling with the
appropriate phenol. Diazo transfer to the activated
methylene group of the â-amido ester gave the starting
R-diazoamides 64 and 68, which possess the necessary
functionalities required for the planned sequence. The
rhodium(II)-catalyzed reaction of 64 furnished the ex-
pected furan 65 in 81% yield (Scheme 11). An interesting
point worth noting is that whereas diazo â-alkoxy esters
such as 41 and 42 require the presence of a trimethylsilyl
group on the alkyne carbon for efficient cyclization to
occur, diazo amido esters 64 and 68 undergo efficient
reorganization to 2-alkoxy-substituted furans (i.e., 65 and
69) without the need to incorporate a silyl substituent
Exp er im en ta l Section
Melting points are uncorrected. Mass spectra were deter-
mined at an ionizing voltage of 70 eV. Unless otherwise noted,
all reactions were performed in flame dried glassware under
an atmosphere of dry argon. Solutions were evaporated under
reduced pressure with a rotary evaporator and the residue was
chromatographed on a silica gel column using a 5% ethyl
acetate/hexane mixture as the eluent unless specified other-
wise. All solids were recrystallized from 3% ethyl acetate/
hexane for analytical data.
232 J . Org. Chem., Vol. 68, No. 2, 2003

Synthesis of Furo[3,4-c]furans
Gen er a l P r oced u r e for th e P r ep a r a tion of Dia zo
Ma lon ic a n d Ma lon a m ic Acid Ester s. To a solution con-
taining 42 mmol of the appropriate carboxylic acid in 250 mL
of CH2Cl2 at 0 °C under argon was added 4.2 mmol of DMAP,
83 mmol of the appropriate alcohol, and 46 mmol of 1,3-
dicyclohexylcarbodiimide. The reaction mixture was allowed
to stir at room temperature for 3 h. The resulting suspension
was filtered, the filtrate concentrated under reduced pressure,
and the crude residue was subjected to silica gel chromatog-
raphy.
and 161.3. Anal. Calcd for C7H6N2O4: C, 46.16; H, 3.32; N,
15.38. Found: C, 45.93; H, 3.29; N, 15.38.
6-Meth oxy-3H-fu r o[3,4-c]fu r a n -1-on e (12). To a solution
of 0.5 g (0.26 mmol) of diazo ester 11 in 5 mL of dry benzene
at 80 °C was added 0.12 g of Rh2(OAc)4. The reaction mixture
was heated for 10 min, the solvent was removed under reduced
pressure, and the residue was subjected to silica gel chroma-
tography to give 0.46 g (19%) of 12 as a white solid: mp 88-
89 °C; IR (film) 1758, 1756, 1632, 1619, 1443, and 1393 cm-1
;
1H NMR (300 MHz, CDCl3) δ 4.31 (s, 3H), 5.16 (d, 2H, J ) 1.8
Hz), and 6.70 (t, 1H, J ) 1.8 Hz); 13C NMR (75 MHz, CDCl3)
δ 60.9, 64.8, 90.9, 122.2, 131.2, 157.6, and 163.8. Anal. Calcd
for C7H6O4: C, 54.54; H, 3.93. Found: C, 54.32; H, 3.89.
A sample of furanone 12 was also prepared in 80% yield by
treating a 0.84 g (3.7 mmol) sample of furan 10 in 45 mL of
THF with a 1.0 M solution of TBAF in THF at 0 °C for 15
min.
To a solution containing 2.1 mmol of the above malonic or
malonamic acid ester and 3.1 mmol of 4-nitrobenzenesulfonyl
azide54 in 20 mL of CH2Cl2 at 0 °C under argon was added 6.7
mmol of triethylamine. After stirring of the solution for 12 h,
the solvent was removed under reduced pressure and the
residue was subjected to flash silica gel chromatography.
2-Dia zom a lon ic Acid Meth yl Ester 3-Tr im eth ylsila n yl-
p r op -2-yn yl Ester (9). A solution of 4.0 g (28 mmol) of 2,2-
dimethyl-1,3-dioxane-4,6-dione and 3.6 g (28 mmol) of 3-(tri-
methylsilyl)-2-propyn-1-ol55 in 100 mL of toluene was heated
at 110 °C for 4 h. The solvent was removed under reduced
pressure to give 6.1 g (100%) of malonic acid mono(3-tri-
methylsilanyl-prop-2-ynyl) ester as a yellow oil: IR (neat) 2307,
2-Dia zom a lon ic Acid 3-Meth oxyca r bon ylp r op -2-yn yl
Ester Meth yl Ester (13). Esterification of malonic acid
monomethyl ester with 4-hydroxybut-2-ynoic acid methyl
ester57 gave malonic acid 3-methoxycarbonylprop-2-ynyl ester
methyl ester (36%) as a yellow oil: IR (neat) 2250, 1764, 1742,
1719, and 1438 cm-1 1H NMR (300 MHz, CDCl3) δ 3.46 (s,
;
1756, 1723, 1422, 1266, and 849 cm-1 1H NMR (300 MHz,
;
2H), 3.77 (s, 3H), 3.80 (s, 3H), and 4.87 (s, 2H); 13C NMR
(75 MHz, CDCl3) δ 41.1, 52.4, 53.0, 53.2, 78.3, 80.5, 153.2,
165.5, and 166.3; HRMS calcd for C9H10O6 214.0477, found
214.0476.
CDCl3) δ 0.19 (s, 9H), 3.50 (s, 2H), 4.78 (s, 2H), and 10.40 (brs,
1H); 13C NMR (75 MHz, CDCl3) δ -0.1, 40.8, 54.3, 93.4, 98.0,
165.9, and 171.3. The acid was used in the next step without
further purification.
Diazo transfer of the above compound afforded diazo ester
13 (24%) as a pale yellow oil: IR (neat) 2250, 2146, 1764, 1742,
Esterification of the above compound with methanol fur-
nished malonic acid methyl ester 3-trimethylsilanylprop-2-ynyl
ester (94%) as a colorless liquid: IR (neat) 2188, 1762, 1744,
1721, and 1438 cm-1 1H NMR (300 MHz, CDCl3) δ 3.80 (s,
;
3H), 3.86 (s, 3H), and 4.96 (s, 2H); 13C NMR (100 MHz, CDCl3)
δ 52.1, 52.9, 53.1, 78.3, 80.6, 153.3, 160.0, and 161.1; HRMS
calcd for C9H8N2O6: 240.0382, found 240.0384.
1439, and 1372 cm-1 1H NMR (300 MHz, CDCl3) δ 0.19 (s,
;
9H), 3.45 (s, 2H), 3.76 (s, 3H), and 4.75 (s, 2H); 13C NMR (75
MHz, CDCl3) δ 0.1, 41.4, 52.9, 54.0, 93.0, 98.3, 165.8, and
166.6; HRMS calcd for C10H16O4Si 228.0818, found 228.0816.
Diazo transfer of the above compound gave diazo ester 9
(97%) as a yellow oil: IR (neat) 2140, 1767, 1742, 1700, 1439,
and 1327 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.18 (s, 9H), 3.85
(s, 3H), and 4.84 (s, 2H); 13C NMR (100 MHz, CDCl3) δ -0.2,
52.8, 53.6, 93.0, 98.4, 160.2, and 161.5. Anal. Calcd for
3-Me t h oxy-4-oxo-4H ,6H -fu r o[3,4-c]fu r a n -1-ca r b ox-
ylic Acid Meth yl Ester (14). To a solution of 0.4 g (1.6 mmol)
of diazo ester 13 in 20 mL of dry benzene at 80 °C was added
20 mg of Rh2(OAc)4. The reaction mixture was heated for 5
min, the solvent was removed under reduced pressure, and
the residue was subjected to silica gel chromatography to give
0.25 g (73%) of 14 as a white solid: mp 156-158 °C; IR (film)
C
10H14N2O4Si: C, 47.23; H, 5.55; N, 11.02. Found: C, 47.40;
1
1773, 1708, 1650, 1598, 1443, and 1032 cm-1; H NMR (300
H, 5.47; N, 11.06.
MHz, CDCl3) δ 3.87 (s, 3H), 4.39 (s, 3H), and 5.31 (s, 2H); 13
C
6-Met h oxy-4-t r im et h ylsila n yl-3H -fu r o[3,4-c]fu r a n -1-
on e (10). To a solution of 0.37 g (1.4 mmol) of diazo ester 9 in
15 mL of dry benzene at 80 °C was added 2 mg of Rh2(OAc)4.
The reaction mixture was heated for 10 min, then the solvent
was removed under reduced pressure, and the residue was
subjected to silica gel chromatography to give 0.31 g (95%) of
10 as a white solid: mp 35-37 °C; IR (film) 1766, 1621, 1590,
1451, 1316, and 1252 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.21
(s, 9H), 4.28 (s, 3H), and 5.12 (s, 2H); 13C NMR (75 MHz,
CDCl3) δ -1.7, 60.9, 65.3, 91.1, 139.6, 142.5, 160.7, and 163.9.
Anal. Calcd for C10H14O4Si: C, 53.07; H, 6.24. Found: C, 53.01;
H, 6.19.
NMR (75 MHz, CDCl3) δ 52.3, 61.5, 65.6, 94.4, 124.6, 141.9,
157.4, 158.2, and 162.4. Anal. Calcd for C9H8O6: C, 50.94; H,
3.80. Found: C, 50.88; H, 3.74.
2-Dia zom a lon ic Acid 3-Br om o-1,1-d im et h ylp r op -2-
yn yl Ester Meth yl Ester (15). A solution of 2.5 g (15 mmol)
of 2,2-dimethyl-1,3-dioxane-4,6-dione and 2.2 g (15 mmol) of
4-bromo-2-methylbut-3-yn-2-ol58 in 50 mL of toluene was
heated at 110 °C for 4 h. The solvent was removed under
reduced pressure to give 3.9 g (100%) of malonic acid mono-
(3-bromo-1,1-dimethylprop-2-ynyl) ester as a yellow oil, which
was used in the next step without further purification: IR
(neat) 2209, 1746, 1329, 1252, 1194, and 1125 cm-1; 1H NMR
(300 MHz, CDCl3) δ 1.70 (s, 6H), 3.42 (s, 2H), and 10.8 (brs,
1H); 13C NMR (100 MHz, CDCl3) δ 28.8, 41.7, 46.3, 74.8, 80.1,
165.0, and 172.0.
2-Dia zom a lon ic Acid Meth yl Ester P r op -2-yn yl Ester
(11). Esterification of malonic acid monomethyl ester56 with
propargyl alcohol afforded malonic acid methyl ester prop-2-
ynyl ester (82%) as a light yellow liquid, which was used in
the next step without further purification: IR (neat) 2130,
Esterification of the above carboxylic acid with methanol
gave 0.57 g (77%) of malonic acid 3-bromo-1,1-dimethyl-
prop-2-ynyl ester methyl ester as a colorless oil, which was
used in the next step without further purification: IR (neat)
1
1755, 1739, 1439, 1337, and 1150 cm-1; H NMR (300 MHz,
CDCl3) δ 2.54 (t, 1H, J ) 2.4 Hz), 3.46 (s, 2H), 3.77 (s, 3H),
and 4.76 (d, 2H, J ) 2.4 Hz); 13C NMR (75 MHz, CDCl3) δ
41.1, 52.8, 53.0, 75.6, 77.0, 165.8, and 166.6.
Diazo transfer of the above compound furnished diazo ester
11 as a yellow solid: mp 54-56 °C; IR (film) 2143, 1760, 1739,
1700, 1439, and 1328 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.55
(t, 1H, J ) 2.4 Hz), 3.86 (s, 3H), and 4.84 (d, 2H, J ) 2.4 Hz);
13C NMR (100 MHz, CDCl3) δ 52.7, 52.8, 75.8, 75.9, 77.1, 160.2,
1
2211, 1758, 1740, 1438, and 1339 cm-1; H NMR (300 MHz,
CDCl3) δ 1.68 (s, 6H), 3.36 (s, 2H), and 3.76 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 28.8, 42.2, 45.9, 52.7, 74.2, 80.3, 164.8, and
167.
Diazo transfer in the standard manner gave diazo ester 15
(98%) as a yellow solid: mp 39-40 °C; IR (film) 2207, 2138,
1766, 1740, 1698, and 1337 cm-1; 1H NMR (300 MHz, CDCl3)
δ 1.73 (s, 6H), and 3.84 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
(54) Bollinger, F. W.; Tuma, L. D. Synlett. 1996, 407.
(55) Hwu, J . R.; Furth, P. S. J . Am. Chem. Soc. 1989, 111,
8834.
(57) Earl, R. A.; Townsend, L. B. Can. J . Chem. 1980, 58, 2550.
(58) Colonge, C. Bull. Soc. Chim. Fr. 1947, 842.
(56) Grakauskas, V.; Guest, A. M. J . Org. Chem. 1978, 43, 3485.
J . Org. Chem, Vol. 68, No. 2, 2003 233

Padwa and Straub
29.2, 46.3, 52.7, 74.9, 80.2, 159.1, and 161.8. Anal. Calcd for
C9H9BrN2O4: C, 37.39; H, 3.14; N, 9.69. Found: C, 37.47; H,
3.11; N, 9.71.
(400 MHz, CDCl3) δ 2.16 (ddd, 1H, J ) 14.0, 6.8 and 4.0 Hz),
2.30 (s, 3H), 2.36 (ddd, 1H, J ) 14.0, 7.2 and 5.6 Hz), 3.34 (s,
3H), 3.35 (s, 3H), 3.44 (dd, 1H, 7.2 and 4.0 Hz), 3.45 (brs, 1H),
4.63 (dd, 1H, J ) 6.8 and 5.6 Hz), 4.82 (d, 1H, J ) 18.4 and
0.8 Hz), and 5.04 (d, 1H, J ) 18.4 Hz); 13C NMR (100 MHz,
CDCl3) δ 31.1, 32.1, 50.6, 51.2, 52.1, 62.3, 69.9, 98.3, 125.5,
168.7, 171.5, and 207.3. Anal. Calcd for C12H16O6: C, 56.23;
H, 6.30. Found: C, 56.15; H, 6.28.
6-Ben zen esu lfon yl-4-h yd r oxy-7,7-d im et h oxy-4,5,6,7-
tetr a h yd r o-3H-isoben zofu r a n -1-on e (22). A solution of 0.1
g (0.7 mmol) of furan 12, 0.33 g (2.0 mmol) of phenyl vinyl
sulfone, and 0.03 g (1.0 mmol) of methanol in 5 mL of
nitromethane was stirred at 25 °C for 5 days. The solution
was concentrated under reduced pressure and the residue was
subjected to silica gel chromatography to give 0.2 g (89%) of
12 as a white solid: mp 124-126 °C; IR (neat) 1738, 1457,
1377, 1305, 1131, and 1081 cm-1; 1H NMR (400 MHz, acetone-
d6) δ 2.37 (ddd, 1H, J ) 14.0, 8.8 and 4.0 Hz), 2.65 (ddd, 1H,
J ) 14.0, 5.6 and 5.6 Hz), 2.84 (s, 1H), 2.88 (s, 3H), 3.20 (s,
3H), 4.19 (dd, 1H, J ) 5.6 and 4.0 Hz), 4.81 (dd, 1H, J ) 18.0
and 0.8 Hz), 4.90 (dd, 1H, J ) 8.8 and 5.6 Hz), 4.98 (d, 1H, J
) 18.0 Hz), 7.63-7.67 (m, 2H), 7.72-7.76 (m, 1H), and 7.95-
7.97 (m, 2H); 13C NMR (100 MHz, acetone-d6) δ 32.2, 50.1, 51.4,
62.4, 66.0, 70.0, 98.2, 125.1, 129.8, 130.0, 134.5, 141.7, 169.9,
and 170.6. Anal. Calcd for C16H18O7S: C, 54.23; H 5.12.
Found: C, 53.97; H, 5.13.
4-Br om o-6-m eth oxy-3,3-d im eth yl-3H-fu r o[3,4-c]fu r a n -
1-on e (16). To a solution of 0.1 g (0.35 mmol) of diazo ester
15 in 5 mL of dry benzene at 80 °C was added 2 mg of
Rh2(OAc)4. The reaction mixture was heated for an additional
30 min, and the solvent was removed under reduced pressure
to give 90% yield of 16 as a pale yellow oil: IR (C6D6) 2361,
1765, and 812 cm-1; 1H NMR (300 MHz, C6D6) δ 1.24 (s, 6H),
and 3.68 (s, 3H); 13C NMR (75 MHz, C6D6) δ 26.4, 60.8, 81.0,
98.1, 118.7, 138.6, 157.5, and 165.3. Anal. Calcd for C9H9-
BrO4: C, 41.54; H, 3.49. Found: C, 41.38; H, 3.51.
8-Met h oxy-6-p h en yl-3H -2-oxa -6-a za -s-in d a cen e-1,5,7-
tr ion e (17). A solution of 0.09 g (0.6 mmol) of furan 12 and
0.1 g (0.6 mmol) of N-phenylmaleimide in 5 mL of xylene was
heated at 145 °C in a thick-walled sealed tube for 15 h. The
solution was concentrated under reduced pressure, and the
residue was recrystallized from EtOAc to give 0.15 g (88%) of
17 as a yellow solid: mp 233-235 °C; IR (KBr) 1767, 1717,
1461, 1378, and 1100 cm-1; 1H NMR (300 MHz, CDCl3) δ 4.49
(s, 3H), 5.38 (s, 2H), 7.41-7.56 (m, 5H), and 7.67 (s, 1H); 13C
NMR (75 MHz, CDCl3) δ 63.6, 69.3, 112.3, 120.2, 121.7, 127.5,
128.3, 128.9, 131.6, 139.3, 156.0, 157.4, 164.2, 165.5, and 166.8.
Anal. Calcd for C17H11NO5: C, 66.01; H, 3.59; N, 4.53. Found:
C, 65.97; H, 3.61; N, 4.48.
3-Oxo-3-p yr r olid in -1-ylp r op ion ic Acid . To a solution of
2.0 g (14 mmol) of 2,2-dimethyl-1,3-dioxane-4,6-dione in 20 mL
of dry CH2Cl2 at 0 °C was slowly added 5.5 g (38 mmol) of
1-(trimethylsilyl)pyrrolidine.59 The reaction mixture was stirred
for 48 h and slowly warmed to room temperature, and 20 mL
of an aqueous saturated NaHCO3 solution was added. The
layers were separated, and the organic layer was extracted
with 20 mL portions of aqueous saturated NaHCO3 solution.
The aqueous layers were combined, acidified with concentrated
HCl, and extracted with CHCl3. The combined extracts were
dried over MgSO4, filtered, and concentrated under reduced
pressure to give 1.1 g (50%) of the titled compound, which was
used in the next step without further purification: 1H NMR
(400 MHz, CDCl3) δ 1.95-2.07 (m, 4H), 3.33 (s, 2H), 3.46 (t,
2H, J ) 8.8 Hz), and 3.55 (t, 2H, J ) 8.8 Hz).
4-Meth oxy-7H-ben zo[1,2-c;4,5-c′]difu r an -1,3,5-tr ion e (18).
A solution of 0.13 g (0.9 mmol) of furan 12 and 0.08 g (0.9
mmol) of maleic anhydride in 5 mL of dry xylene was heated
at 145 °C in a thick-walled sealed tube for 15 h. The solution
was concentrated under reduced pressure and the residue was
triturated in ether to give 0.13 g (65%) of 18 as a yellow solid:
mp 191-193 °C; IR (KBr) 1848, 1788, 1760, 1610, and 1460
1
cm-1; H NMR (400 MHz, acetone-d6) δ 4.42 (s, 3H), 5.54 (s,
2H), and 7.93 (s, 1H); 13C NMR (100 MHz, acetone-d6) δ 68.9,
74.4, 118.7, 128.1, 144.1, 163.4, 164.5, 165.2, 167.6, and 171.3.
Anal. Calcd for C11H6O6: C, 56.42; H, 2.58. Found: C, 56.26;
H, 2.70.
4-Hydr oxy-7-m eth oxy-1-oxo-1,3-dih ydr oisoben zofu r an -
5,6-d ica r boxylic Acid Dim eth yl Ester (19). A solution of
0.1 g (0.7 mmol) of furan 12 and 0.19 g (1.3 mmol) of dimethyl
acetylenedicarboxylate in 5 mL of dry xylene was heated at
145 °C in a thick-walled sealed tube for 15 h. The solution
was concentrated under reduced pressure and the residue was
triturated in ether to give 0.17 g (90%) of 19 as a yellow solid:
mp 143-145 °C; IR (Nujol) 1761, 1731, 1684, 1462, 1337, and
1232 cm-1; 1H NMR (400 MHz, CDCl3) δ 3.95 (s, 3H), 3.98 (s,
3H), 4.02 (s, 3H), 5.31 (s, 2H), and 10.93 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 53.1, 53.9, 64.1, 67.8, 113.8, 124.4, 130.8,
138.1, 147.7, 152.2, 166.4, 167.2, and 168.5. Anal. Calcd for
2-Dia zo-3-oxo-3-p yr r olid in -1-ylp r op ion ic Acid 3-Tr i-
m eth ylsila n yl-p r op -2-yn yl Ester (23). Esterification of the
above carboxylic acid with 3-(trimethylsilyl)-2-propyn-1-ol gave
3-oxo-3-pyrrolidin-1-yl-propionic acid 3-trimethylsilanylprop-
2-ynyl ester (75%) as a yellow solid: mp 52-54 °C; IR (film)
1
2188, 1752, 1647, 1436, and 1246 cm-1; H NMR (300 MHz,
CDCl3) δ 0.18 (s, 9H), 1.84-2.03 (m, 4H), 3.42-3.53 (m, 4H),
3.45 (s, 2H), and 4.75 (s, 2H); 13C NMR (75 MHz, CDCl3) δ
0.1, 24.7, 26.4, 42.6, 46.3, 47.4, 53.8, 92.7, 98.7, 163.9, and
166.8. Anal. Calcd for C13H21NO3Si: C, 58.39; H, 7.92; N, 5.24.
Found: C, 58.35; H, 7.88; N, 5.24.
C
13H12O8: C, 52.71; H, 4.08. Found: C, 52.44; H, 4.01.
7-Meth oxy-1-oxo-1,3-d ih yd r oisoben zofu r a n -5,6-d ica r -
Diazo transfer of the above compound gave diazo ester 23
(100%) as a yellow oil: IR (neat) 2186, 2136, 1719, 1625, 1414
boxylic Acid Dim eth yl Ester (20). A solution of 0.06 g (0.4
mmol) of furan 12 and 0.11 g (0.8 mmol) of dimethyl maleate
in 3 mL of xylene was heated at 145 °C in a thick-walled sealed
tube for 15 h. The solution was concentrated under reduced
pressure and the residue was subjected to silica gel chroma-
tography to give 0.08 g (78%) of 20 as a white solid: mp 134-
and 1287 cm-1 1H NMR (300 MHz, CDCl3) δ 0.19 (s, 9H),
;
1.87-1.93 (m, 4H), 3.50-3.55 (m, 4H), and 4.80 (s, 2H); 13C
NMR (75 MHz, CDCl3) δ 0.0, 24.8, 26.2, 47.6, 48.8, 53.4, 92.9,
98.6, 159.3, and 161.3. Anal. Calcd for C13H19N3O3Si: C, 53.22;
H, 6.53; N, 14.32. Found: C, 53.10; H, 6.50; N, 14.21.
135 °C; IR (film) 1771, 1733, 1458, 1323, 1287, and 1241 cm-1
;
1H NMR (400 MHz, CDCl3) δ 3.94 (s, 3H), 3.98 (s, 3H), 4.19
(s, 3H), 5.33 (s, 2H), and 7.79 (s, 1H); 13C NMR (75 MHz,
CDCl3) δ 53.2, 53.4, 64.3, 69.2, 118.2, 120.6, 130.8, 134.7, 149.7,
156.9, 164.7, 166.7, and 167.1. Anal. Calcd for C13H12O7: C,
55.72; H, 4.32. Found: C, 55.99; H, 4.40.
6-P yr r olid in -1-yl-4-t r im e t h ylsila n yl-3H -fu r o[3,4-c]-
fu r a n -1-on e (24). To a solution of 0.08 g (0.3 mmol) of diazo
ester 23 in 6 mL of dry benzene at 80 °C was added 2 mg of
Rh2(OAc)4. The reaction mixture was heated at reflux for 30
min, the solvent was removed under reduced pressure, and
the residue was subjected to silica gel chromatography to give
0.07 g (90%) of 24 as a yellow oil: IR (neat) 1750, 1627, 1461,
6-Acetyl-4-h yd r oxy-7,7-d im eth oxy-4,5,6,7-tetr a h yd r o-
3H-isoben zofu r a n -1-on e (21). A solution of 0.1 g (0.65 mmol)
of furan 12, 0.14 g (2.0 mmol) of methyl vinyl ketone, and 0.03
g (1.0 mmol) of methanol in 5 mL of nitromethane was stirred
at 25 °C for 48 h. The solution was concentrated under reduced
pressure and the residue was subjected to silica gel chroma-
tography to give 0.17 g (100%) of 21 as a pale yellow oil: IR
(neat) 1760, 1710, 1671, 1443, 1362, and 1057 cm-1; 1H NMR
1349, and 1148 cm-1 1H NMR (300 MHz, CDCl3) δ 0.20 (s,
;
9H), 1.96-2.01 (m, 4H), 3.65-3.71 (m, 4H), and 5.06 (s, 2H);
13C NMR (75 MHz, CDCl3) δ -1.5, 25.7, 48.5, 64.5, 88.8, 137.0,
(59) Brill, W. K. D.; Nielsen, J .; Caruthers, M. H. J . Am. Chem. Soc.
1991, 113, 3972.
234 J . Org. Chem., Vol. 68, No. 2, 2003

Synthesis of Furo[3,4-c]furans
144.4, 156.5, and 165.2. Anal. Calcd for C13H19NO3Si: C, 58.84;
H, 7.22; N, 5.28. Found: C, 58.75; H, 7.04; N, 5.17.
2-Dia zo-N,N-d im et h ylm a lon a m ic Acid 3-Tr im et h yl-
sila n ylp r op -2-yn yl E st er (25). Esterification of N,N-di-
methylmalonamic acid60 with 3-(trimethylsilyl)-2-propyn-1-ol
gave N,N-dimethylmalonamic acid 3-trimethylsilanylprop-2-
ynyl ester (93%) as a pale yellow oil: IR (neat) 2186, 1750,
1657, 1399, 1252, and 1160 cm-1; 1H NMR (400 MHz, CDCl3)
δ 0.18 (s, 9H), 2.99 (s, 3H), 3.02 (s, 3H), 3.52 (s, 2H), and 4.76
(s, 2H); 13C NMR (100 MHz, CDCl3) δ -0.2, 35.7, 38.0, 41.4,
53.7, 92.7, 98.6, 165.7, and 167.0. Anal. Calcd for C11H19NO3-
Si: C, 54.74; H, 7.93; N, 5.80. Found: C, 54.66; H, 5.77; N,
7.99.
°C was added 4 mg of Rh2(OAc)4. The reaction mixture was
heated for 1.5 h, the solvent was removed under reduced
pressure, and the residue was subjected to silica gel chroma-
tography to give 0.15 g (77%) of 30 as a light yellow oil: IR
1
(film) 1767, 1740, 1602, 1503, 1158, and 845 cm-1; H NMR
(300 MHz, CDCl3) δ 0.19 (s, 9H), 3.81 (dd, 1H, J ) 5.7 and 5.7
Hz), 3.99 (dd, 1H, J ) 5.7 and 3.0 Hz), 4.26 (dd, 1H, J ) 5.7
and 3.0 Hz), 4.76 (d, 1H, J ) 15.9 Hz), 4.87 (d, 1H, J ) 15.9
Hz), 7.12-7.18 (m, 1H), and 7.36 (d, 4H, J ) 4.2 Hz); 13C NMR
(75 MHz, CDCl3) δ 0.1, 41.6, 53.2, 54.3, 93.2, 98.2, 116.6, 124.7,
129.4, 137.8, 158.3, and 166.2. Anal. Calcd for
C16H19-
NO3Si: C, 63.76; H, 6.35; N, 4.65. Found: C, 63.94; H, 6.37;
N, 4.71.
2-Dia zom a lon ic Acid P en t-4-en yl Ester 3-Tr im eth yl-
sila n ylp r op -2-yn yl Ester (31). Esterification of malonic acid
mono(3-trimethylsilanylprop-2-ynyl) ester with 4-penten-1-ol
gave malonic acid pent-4-enyl ester 3-trimethylsilanylprop-2-
ynyl) ester (88%) as a colorless liquid: IR (neat) 2187, 1758,
1740, 1642, 1330, and 1252 cm-1; 1H NMR (400 MHz, CDCl3)
δ 0.18 (s, 9H), 1.76 (tt, 2H, J ) 7.2 and 6.4 Hz), 2.13 (td, 2H,
J ) 7.6 and 7.2 Hz), 3.43 (s, 2H), 4.17 (t, 2H, J ) 6.4 Hz), 4.75
(s, 2H), 4.99-5.08 (m, 2H), and 5.74-5.85 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ -0.2, 27.8, 30.1, 41.5, 53.9, 65.2, 93.0,
98.3, 115.7, 137.4, 166.0, and 166.3. Anal. Calcd for C14H22O4-
Si: C, 59.54; H, 7.85. Found: C, 59.78; H, 7.74.
Diazo transfer of the above compound gave diazo ester 25
(100%) as a yellow oil: IR (neat) 2186, 2128, 1717, 1638, and
1295 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.19 (s, 9H), 3.01 (s,
6H), and 4.80 (s, 2H); 13C NMR (100 MHz, CDCl3) δ -0.2, 38.0,
53.4, 92.9, 98.6, 161.4, and 161.5. Anal. Calcd for C11H17N3O3-
Si: C, 49.42; H, 6.41; N, 15.72. Found: C, 49.55; H, 6.54; N,
15.62.
6-Dim et h yla m in o-4-t r im et h ylsila n yl-3H -fu r o[3,4-c]-
fu r a n -1-on e (26). To a solution of 0.5 g (1.8 mmol) of diazo
ester 30 in 20 mL of dry hexane at 80 °C was added 8 mg of
Rh2(OAc)4. The reaction mixture was heated for 3 h and the
solvent was removed under reduced pressure to give 0.5 g (98%
yield) of 26 as an pale yellow oil: IR (neat) 1743, 1631, 1443,
Diazo transfer of the above compound afforded diazo ester
1
1250, 1002, and 845 cm-1; H NMR (400 MHz, CDCl3) δ 0.20
31 (98%) as a yellow oil: IR (neat) 2141, 1764, 1740, 1696,
(s, 9H), 3.23 (s, 6H), and 5.06 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ -1.6, 38.6, 64.3, 88.7, 136.8, 144.6, 158.7, and 165.3.
Anal. Calcd for C11H17NO3Si: C, 55.21; H, 7.17; N, 5.86.
Found: C, 55.16; H, 7.24; N, 5.60.
1642, and 1317 cm-1 1H NMR (300 MHz, CDCl3) δ 0.18 (s,
;
9H), 1.80 (tt, 2H, J ) 6.9 and 6.6 Hz), 2.14 (td, 2H, J ) 7.8
and 6.9 Hz), 4.27 (t, 2H, J ) 6.6 Hz), 4.84 (s, 2H), 4.98-5.09
(m, 2H), and 5.73-5.87 (m, 1H); 13C NMR (75 MHz, CDCl3) δ
-0.2, 27.9, 30.1, 53.6, 65.3, 93.0, 98.4, 115.7, 137.3, 160.3, and
161.0. Anal. Calcd for C14H20N2O4Si: C, 54.52; H, 6.54; N, 9.08.
Found: C, 54.63; H, 6.55; N, 9.15.
1-Meth yl-2-oxoa zetid in e-3-ca r boxylic Acid 3-Tr im eth -
ylsila n ylp r op -2-yn yl Ester (27). To a solution of 0.12 g (0.43
mmol) of diazo ester 25 in 4 mL of dry CH2Cl2 at 50 °C was
added 2 mg of Rh2(OAc)4. The reaction mixture was heated
for 1 h, the solvent was removed under reduced pressure, and
the residue was subjected to silica gel chromatography to give
0.08 g (80%) of â-lactam 27 as a yellow oil: IR (neat) 2186,
6-P en t-4-en yloxy-3H-fu r o[3,4-c]fu r a n -1-on e (32). To a
solution of 1.4 g (4.4 mmol) of diazo ester 31 in 50 mL of dry
benzene at 80 °C was added 8 mg of Rh2(OAc)4. The reaction
mixture was heated for 1 h, the solvent was removed under
reduced pressure, and the residue was subjected to silica gel
chromatography to give 1.0 g (83%) of 6-pent-4-enyloxy-4-
trimethylsilanyl-3H-furo[3,4-c]furan-1-one as a light yellow
1
1772, 1740, 1667, 1370, and 1252 cm-1; H NMR (400 MHz,
CDCl3) δ 0.18 (s, 9H), 2.89 (s, 3H), 3.40 (dd, 1H, 7.2 and 7.2
Hz), 3.58 (dd, 1H, J ) 7.2 and 3.6 Hz), 4.10 (dd, 1H, J ) 7.2
and 3.6 Hz), 4.72 (d, 1H, J ) 18.2 Hz), and 4.84 (d, 1H, J )
18.2 Hz); 13C NMR (100 MHz, CDCl3) δ -0.2, 29.2, 44.0, 54.0,
54.5, 92.9, 98.4, 162.0, and 166.9. Anal. Calcd for C11H17NO3-
Si: C, 55.21; H, 7.17; N, 5.86. Found: C, 55.05; H, 7.04; N,
5.93.
oil: IR (neat) 1766, 1619, 1588, 1373, 1314, and 1252 cm-1
;
1H NMR (300 MHz, CDCl3) δ 0.24 (s, 9H), 1.88-1.97 (m, 2H),
2.21-2.28 (m, 2H), 4.64 (t, 2H, J ) 6.6 Hz), 5.00-5.11 (m, 2H),
5.14 (s, 2H), and 5.77-5.90 (m, 1H); 13C NMR (75 MHz, CDCl3)
δ -1.7, 28.5, 29.7, 65.3, 73.6, 90.9, 115.8, 137.3, 139.5, 142.6,
160.3, and 164.1; HRMS calcd for C14H20O4Si 280.1131, found
280.1130.
2-Diazo-N-m eth yl-N-ph en ylm alon am ic Acid 3-Tr im eth -
ylsila n ylp r op -2-yn yl Ester (28). Esterification of N-methyl-
N-phenylmalonamic acid61 with 3-(trimethylsilyl)-2-propyn-1-
ol gave 2-diazo-N-methyl-N-phenylmalonamic acid 3-trimeth-
ylsilanylprop-2-ynyl ester (98%) as a light yellow oil: IR (neat)
A solution of 1.0 g (3.6 mmol) of the above furan in 50 mL
of THF was cooled in an ice bath. A 1.0 M solution of TBAF in
THF (3.9 mmol) was added dropwise to the reaction mixture
and the solution was stirred at 0 °C for 20 min. The mixture
was poured into 30 mL of a saturated aqueous NH4Cl solution
and extracted with ether. The organic layer was dried over
MgSO4 and filtered, and the solvent was removed under
reduced pressure. The residue was subjected to silica gel
chromatography to give 0.56 g (76%) of 32 as a yellow oil: IR
(neat) 1758, 1627, 1611, 1384, 1307, and 1168 cm-1; 1H NMR
(400 MHz, CDCl3) δ 1.89-1.95 (m, 2H), 2.21-2.27 (m, 2H),
4.63 (t, 2H, J ) 6.4 Hz), 5.00-5.10 (m, 2H), 5.15 (d, 2H, J )
1.6 Hz), 5.78-5.88 (m, 1H), and 6.69 (t, 1H, J ) 1.6 Hz); 13C
NMR (100 MHz, CDCl3) δ 28.3, 29.7, 64.7, 73.5, 90.6, 115.8,
122.0, 131.1, 137.2, 156.9, and 163.8. Anal. Calcd for
1
2186, 1752, 1669, 1598, 1497, and 1385 cm-1; H NMR (400
MHz, CDCl3) δ 0.18 (s, 9H), 3.26 (s, 2H), 3.31 (s, 3H), 4.68 (s,
2H), and 7.23-7.44 (m, 5H); 13C NMR (100 MHz, CDCl3) δ
-0.2, 37.6, 41.5, 53.6, 92.6, 98.6, 127.4, 128.5, 130.1, 143.5,
165.7, and 167.0. Anal. Calcd for C16H21NO3Si: C, 63.33; H,
6.98; N, 4.62. Found: C, 63.09; H, 6.97; N, 4.66.
Diazo transfer of the above compound furnished diazo ester
28 (92%) as a yellow solid: mp 57-59 °C; IR (film) 2186, 2128,
1727, 1638, 1596, and 1420 cm-1; 1H NMR (300 MHz, CDCl3)
δ 0.17 (s, 9H), 3.39 (s, 3H), 4.54 (s, 2H), and 7.20-7.42 (m,
5H); 13C NMR (75 MHz, CDCl3) δ -0.1, 39.0, 53.4, 92.7, 98.4,
125.9, 127.1, 129.5, 143.8, 160.6, and 161.0. Anal. Calcd for
C
16H19N3O3Si: C, 58.34; H, 5.81; N, 12.76. Found: C, 58.24;
C
11H12O4: C, 63.44; H, 5.81. Found: C, 63.40; H, 5.73.
H, 5.78; N, 12.57.
3,6,7,8-Tetr a h yd r o-2,9-d ioxa cyclop en ta [a ]n a p h th a len -
2-Oxo-1-p h en yla zetid in e-3-ca r boxylic Acid 3-Tr im eth -
ylsila n ylp r op -2-yn yl Ester (30). To a solution of 0.2 g (0.65
mmol) of diazo ester 28 in 10 mL of methylene chloride at 80
1-on e (33). A solution of 0.22 g (1.0 mmol) of furan 32 in 8
mL of xylene was heated at 145 °C in a thick-walled sealed
tube for 15 h. The solution was concentrated under reduced
pressure, and the residue was subjected to silica gel chroma-
tography. The first fraction isolated from the column contained
0.09 g (46%) of 33 as a white solid: mp 87-89 °C; IR (film)
(60) Gardner, R. R.; Gellman, S. H. Tetrahedron 1997, 53, 9881.
(61) Manandhar, M. D.; Hussaini, F. A.; Kapil, R. S.; Shoeb, A.
Phytochemistry 1985, 24, 199.
1
1752, 1597, 1490, 1303, and 1072 cm-1; H NMR (400 MHz,
J . Org. Chem, Vol. 68, No. 2, 2003 235

Padwa and Straub
CDCl3) δ 2.05-2.11 (m, 2H), 2.85 (t, 2H, J ) 6.4 Hz), 4.40 (t,
2H, J ) 5.6 Hz), 5.19 (s, 2H), 6.87 (d, 1H, J ) 7.6 Hz), and
7.32 (d, 1H, J ) 7.6 Hz); 13C NMR (100 MHz, CDCl3) δ 21.8,
24.8, 67.6, 68.9, 112.9, 112.9, 123.0, 136.7, 147.3, 154.4, and
169.6. Anal. Calcd for C11H10O3: C, 69.45; H, 5.30. Found: C,
69.33; H, 5.24.
Hz), 5.11-5.22 (m, 2H), 5.15 (d, 2H, J ) 2.0 Hz), 5.81-5.91
(m, 1H), and 6.70 (t, 1H, J ) 2.0 Hz); 13C NMR (100 MHz,
CDCl3) δ 33.5, 64.7, 73.0, 90.7, 118.2, 122.0, 131.0, 133.1, 156.7,
and 163.8. Anal. Calcd for C10H10O4: C, 61.84; H, 5.19.
Found: C, 61.62; H, 5.08.
3,6-Dih yd r o-2H-1,7-d ioxa -a s-in d a cen -8-on e (45). A solu-
tion of 0.22 g (1.1 mmol) of furan 43 in 5 mL of xylene was
heated at 145 °C in a thick-walled sealed tube for 13 h. The
solution was concentrated under reduced pressure, and the
residue was subjected to silica gel chromatography. The first
fraction isolated from the column contained 0.03 g (14%) of
45 as a yellow solid: mp 138-139 °C; IR (KBr) 1754, 1482,
3,3a ,6,7,8,9b -H exa h yd r o-5H -2,9-d ioxa cyclop en t a [a ]-
n a p h th a len e-1,4-d ion e (34). The second fraction isolated
from the silica gel column contained 0.06 g (28%) of 34 as a
yellow oil: IR (neat) 1774, 1721, 1301, 1151, and 1046 cm-1
;
1H NMR (400 MHz, CDCl3) δ 1.90-2.02 (m, 4H), 2.88 (d, 1H,
J ) 18.6 Hz), 3.01 (d, 1H, J ) 18.6 Hz), 3.39 (ddd, 1H, J )
10.0, 6.8 and 2.4 Hz), 3.65 (d, 1H, J ) 10.0 Hz), 4.07-4.17 (m,
2H), 4.25 (dd, 1H, J ) 9.6 and 6.8 Hz), and 4.91 (dd, 1H, J )
9.6 and 2.4 Hz); 13C NMR (100 MHz, CDCl3) δ 22.1, 25.0, 41.5,
44.1, 47.4, 66.0, 66.8, 104.3, 140.3, 173.2, and 203.9. Anal.
Calcd for C11H12O4: C, 63.44; H, 5.81. Found: C, 63.22; H,
5.69.
1
1459, 1248, and 982 cm-1; H NMR (400 MHz, CDCl3) δ 3.28
(t, 2H, J ) 8.8 Hz), 4.83 (t, 2H, J ) 8.8 Hz), 5.27 (d, 2H, J )
1.2 Hz), 6.89 (d, 1H, J ) 7.2 Hz), and 7.46 (td, 1H, J ) 7.2
and 1.2 Hz); 13C NMR (100 MHz, CDCl3) δ 28.7, 70.1, 73.8,
108.7, 113.4, 128.9, 131.0, 147.0, 158.3, and 169.3. Anal. Calcd
for C10H8O3: C, 68.16; H, 4.58. Found: C, 68.07; H, 4.49.
2,3,3a ,4,5a ,6-H e xa h yd r o-1,7-d ioxa -a s-in d a ce n e -5,8-
d ion e (46). The second fraction isolated from the column
contained 0.07 g (37%) of 46 as a white solid: mp 98-100 °C;
IR (film) 1748, 1713, 1686, 1187, and 945 cm-1; 1H NMR (400
MHz, CDCl3) δ 1.74-1.95 (m, 1H), 2.20 (dd, 1H, J ) 18.4 and
10.0 Hz), 2.57-2.64 (m, 1H), 2.95 (dd, 1H, J ) 18.4 and 7.6
Hz), 3.36-3.46 (m, 1H), 3.67 (ddd, 1H, J ) 9.6, 8.0 and 2.4
Hz), 4.39 (dd, 1H, J ) 9.6 and 8.0 Hz), 4.46 (ddd, 1H, J )
12.0, 9.2, and 2 Hz), 4.57 (dd, 1H, J ) 9.6 and 9.6 Hz), and
4.76 (ddd, 1H, J ) 9.2, 9.2 and 0.8 Hz); 13C NMR (100 MHz,
CDCl3) δ 31.2, 39.9, 42.0, 46.4, 66.4, 75.5, 89.4, 167.3, 167.4,
and 207.1. Anal. Calcd for C10H10O4: C, 61.84; H, 5.19.
Found: C, 61.73; H, 5.10.
3,3a ,5a ,6,7,8-H exa h yd r o-5H -2,9-d ioxa cyclop en t a [a ]-
n a p h th a len e-1,4-d ion e (35). The third fraction isolated from
the column contained 0.03 g (15%) of 35 as a white solid: mp
139-142 °C; IR (film) 1742, 1719, 1642, 1175, and 1067 cm-1
;
1H NMR (400 MHz, CDCl3) δ 1.48-1.58 (m, 1H), 1.91-2.01
(m, 2H), 2.14-2.22 (m, 1H), 2.26 (dd, 1H, J ) 18.4 and 10.8
Hz), 2.71 (dd, 1H, J ) 18.4 and 6.0 Hz), 2.98-3.07 (m, 1H),
3.72-3.77 (m, 1H), 4.11-4.17 (m, 1H), and 4.39-4.55 (m, 3H);
13C NMR (100 MHz, CDCl3) δ 23.0, 25.8, 34.1, 42.9, 48.2, 65.1,
69.6, 95.3, 163.9, 167.2, and 206.1. Anal. Calcd for C11H12O4:
C, 63.44; H, 5.81. Found: C, 63.34; H, 5.77.
2-Dia zom a lon ic Acid Bu t -3-en yl E st er 3-Tr im et h yl-
sila n ylp r op -2-yn yl Ester (41). Esterification of malonic acid
mono(3-trimethylsilanylprop-2-ynyl) ester with 3-buten-1-ol
gave malonic acid but-3-enyl ester 3-trimethylsilanylprop-2-
ynyl ester (85%) as a colorless oil: IR (neat) 2186, 1759, 1738,
2-Dia zom a lon ic Acid 3-P h en ylbu t-3-en yl Ester 3-Tr i-
m eth ylsila n ylp r op -2-yn yl Ester (42). Esterification of ma-
lonic acid mono(3-trimethylsilanylprop-2-ynyl) ester with
3-phenyl-3-buten-1-ol62 gave malonic acid 3-phenyl-but-3-enyl
ester 3-trimethylsilanylprop-2-ynyl ester (58%) as a pale yellow
oil: IR (neat) 2186, 1756, 1740, 1494, and 1326 cm-1; 1H NMR
(300 MHz, CDCl3) δ 0.18 (s, 9H), 2.86 (dt, 2H, J ) 7.2 and 0.9
Hz), 3.37 (s, 2H), 4.26 (t, 2H, J ) 7.2 Hz), 4.76 (s, 2H), 5.14
(dd, 1H, J ) 0.9 and 0.9 Hz), 5.38 (d, 1H, J ) 0.9 Hz), and
7.25-7.42 (m, 5H); 13C NMR (75 MHz, CDCl3) δ -0.2, 34.5,
41.4, 53.9, 64.4, 93.0, 98.4, 114.9, 126.2, 127.9, 128.6, 140.4,
144.1, 165.9, and 166.2. Anal. Calcd for C19H24O4Si: C, 66.25;
H, 7.02. Found: C, 65.98; H, 7.10.
1638, and 1325 cm-1 1H NMR (400 MHz, CDCl3) δ 0.19 (s,
;
9H), 2.39-2.44 (m, 2H), 3.43 (s, 2H), 4.21 (t, 2H, J ) 7.2 Hz),
4.75 (s, 2H), 5.07-5.15 (m, 2H), and 5.73-5.83 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ -0.2, 33.0, 41.5, 53.9, 64.8, 93.0,
98.4, 117.8, 133.8, 166.0, and 166.3. Anal. Calcd for C13H20O4-
Si: C, 58.18; H, 7.51. Found: C, 58.36; H, 7.46.
Diazo transfer of the above compound gave diazo ester 41
(100%) as a yellow oil: IR (neat) 2185, 2140, 1766, 1740, 1700,
and 1374 cm-1 1H NMR (300 MHz, CDCl3) δ 0.18 (s, 9H),
;
2.41-2.48 (m, 2H), 4.30 (t, 2H, J ) 6.9), 4.84 (s, 2H), 5.07-
5.17 (m, 2H), and 5.72-5.86 (m, 1H); 13C NMR (75 MHz,
CDCl3) δ -0.2, 33.3, 53.6, 64.8, 93.0, 98.4, 117.9, 133.6, 160.3,
and 160.8. Anal. Calcd for C13H18N2O4Si: C, 53.04; H, 6.16;
N, 9.52. Found: C, 52.94; H, 6.10; N, 9.35.
Diazo transfer of the above compound gave diazo ester 42
(98%) as a light yellow oil: IR (neat) 2142, 1764, 1738, 1698,
and 1322 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.18 (s, 9H), 2.91
(t, 2H, J ) 6.8 Hz), 4.35 (t, 2H, J ) 6.8 Hz), 4.832 (s, 2H), 5.15
(d, 1H, J ) 0.8), 5.39 (d, 1H, J ) 0.8), and 7.25-7.42 (m, 5H);
13C NMR (100 MHz, CDCl3) δ -0.1, 34.8, 53.6, 64.5, 93.0, 98.4,
115.1, 126.2, 128.0, 128.7, 140.4, 144.2, 160.3, and 160.7;
HRMS calcd for C19H22N2O4Si 370.1349, found 370.1348.
6-(3-P h en ylb u t -3-en yloxy)-3H -fu r o[3,4-c]fu r a n -1-on e
(44). To a solution of 0.22 g (0.6 mmol) of diazo ester 42 in 8
mL of dry benzene at 80 °C was added 2 mg of Rh2(OAc)4. The
reaction mixture was heated at 80 °C for 30 min, the solvent
was removed under reduced pressure, and the residue was
subjected to silica gel chromatography to give 0.16 g (76%) of
6-(3-phenylbut-3-enyloxy)-4-trimethylsilanyl-3H-furo[3,4-c]-
furan-1-one as a light yellow oil: IR (neat) 1766, 1619, 1588,
6-Bu t-3-en yloxy-3H-fu r o[3,4-c]fu r a n -1-on e (43). To a
solution of 0.14 g (0.5 mmol) of diazo ester 41 in 4 mL of dry
benzene at 80 °C was added 2 mg of Rh2(OAc)4. The reaction
mixture was heated for 30 min, the solvent was removed under
reduced pressure, and the residue was subjected to silica gel
chromatography to give 0.12 g (92%) of 6-but-3-enyloxy-4-
trimethylsilanyl-3H-furo[3,4-c]furan-1-one as a white solid; mp
28-30 °C; IR (film) 1769, 1619, 1588, 1372, 1252, and 843
cm-1 1H NMR (300 MHz, CDCl3) δ 0.23 (s, 9H), 2.57-2.60
;
(m, 2H), 4.67 (t, 2H, J ) 6.3 Hz), 5.11-5.23 (m, 2H), 5.14 (s,
2H), and 5.81-5.94 (m, 2H); 13C NMR (75 MHz, CDCl3) δ -1.8,
33.6, 65.3, 73.2, 91.0, 118.2, 133.2, 139.6, 142.5, 160.1, and
164.1; HRMS calcd for C13H18O4Si: 266.0974. Found 266.0974.
1
1372, 1030, and 845 cm-1; H NMR (300 MHz, CDCl3) δ 0.2
(s, 9H), 3.03 (t, 2H, J ) 6.6 Hz), 4.74 (t, 2H, J ) 6.6 Hz), 5.11
(s, 2H), 5.23 (d, 1H, J ) 0.9 Hz), 5.43 (d, 1H, J ) 0.9 Hz), and
7.24-7.43 (m, 5H); 13C NMR (75 MHz, CDCl3) δ -1.8, 34.9,
65.2, 72.2, 91.1, 115.2, 126.2, 127.8, 128.6, 139.5, 140.3, 142.5,
143.4, 159.9, and 163.9; HRMS calcd for C19H22O4Si 342.1287,
found 342.1287.
A solution of 1.1 g (3.1 mmol) of the above furan in 50 mL
of THF was cooled in an ice bath. A 1.0 M solution of TBAF in
THF (3.4 mmol) was added dropwise to the reaction mixture
A solution of 0.12 g (0.5 mmol) of the above furan in 6 mL
of THF was cooled in an ice bath. A 1.0 M solution of TBAF in
THF (0.5 mmol) was added dropwise to the reaction mixture
and the solution was stirred at 0 °C for 15 min. The mixture
was poured into 10 mL of an aqueous saturated NH4Cl solution
and extracted with ether. The organic layer was dried over
MgSO4 and filtered, and the solvent was removed under
reduced pressure. The residue was subjected to silica gel
chromatography to give 0.08 g (95%) of 43 as a clear oil: IR
1
(film) 1762, 1629, 1611, 1308, 1171, and 1019 cm-1; H NMR
(400 MHz, CDCl3) δ 2.55-2.61 (m, 2H), 4.66 (t, 2H, J ) 6.4
(62) Maercker, A.; Weber, K. J ustus Liebigs Ann. Chem. 1972, 20.
236 J . Org. Chem., Vol. 68, No. 2, 2003

Synthesis of Furo[3,4-c]furans
and the solution was stirred at 0 °C for 20 min. The mixture
was poured into 30 mL of an aqueous saturated NH4Cl solution
and extracted with ether. The organic layer was dried over
MgSO4 and filtered, and the solvent was removed under
reduced pressure. The residue was subjected to silica gel
chromatography to give 0.68 g (82%) of 44 as a pale yellow
solid: mp 28-30 °C; IR (neat) 1760, 1629, 1611, 1308, 1167,
and 1017 cm-1; 1H NMR (400 MHz, CDCl3) δ 3.03 (t, 2H, J )
6.4 Hz), 4.73 (t, 2H, J ) 6.4 Hz), 5.12 (d, 2H, J ) 1.6 Hz), 5.22
(d, 1H, J ) 1.2 Hz), 5.42 (d, 1H, J ) 1.2 Hz), 6.66 (t, 1H, J )
1.6 Hz), and 7.26-7.42 (m, 5H); 13C NMR (100 MHz, CDCl3)
δ 34.9, 64.7, 72.2, 90.8, 115.4, 122.0, 126.3, 127.9, 128.6, 131.1,
140.4, 143.4, 156.7, and 163.7. Anal. Calcd for C16H14O4: C,
71.09; H, 5.22. Found: C, 70.88; H, 5.14.
3a -P h e n y l-2,3,3a ,4,5a ,6-h e x a h y d r o -1,7-d i o x a -a s -
in d a cen e-5,8-d ion e (47). A solution of 0.09 g (1.1 mmol) of
furan 44 in 5 mL of dry xylene was heated at 145 °C in a thick-
walled sealed tube for 13 h. The solution was concentrated
under reduced pressure and the residue was subjected to silica
gel chromatography. The first fraction isolated from the
column contained 0.03 g (36%) of 47 as a yellow solid: mp
172-174 °C; IR (film) 1746, 1665, 1449, 1225, 1048, and 942
cm-1; 1H NMR (400 MHz, CDCl3) δ 2.39-2.47 (m, 1H), 2.51-
2.55 (m, 1H), 2.67 (d, 1H, J ) 18.4 Hz), 3.33 (dd, 1H, J ) 9.6
and 8.0 Hz), 3.41 (d, 1H, J ) 18.4 Hz), 4.31 (dd, 1H, J ) 9.6
and 8.0 Hz), 4.35 (ddd, 1H, J ) 11.6, 9.2 and 5.2 Hz), 4.52
(dd, 1H, J ) 9.6 and 9.6 Hz), 4.70 (ddd, 1H, J ) 9.2, 9.2 and
0.8 Hz), and 7.32-7.43 (m, 5H); 13C NMR (100 MHz, CDCl3)
δ 41.8, 45.9, 51.0, 54.7, 66.6, 73.8, 91.7, 126.2, 128.5, 129.8,
138.5, 167.7, 168.5, and 207.3. Anal. Calcd for C16H14O4: C,
71.09; H, 5.22. Found: C, 71.04; H, 5.03.
The reaction mixture was heated for 25 min, the solvent was
removed under reduced pressure, and the residue was sub-
jected to silica gel chromatography to give 1.7 g (95%) of 6-(2-
cyclopent-2-enylethoxy)-4-trimethylsilanyl-3H-furo[3,4-c]furan-
1-one as a colorless oil: IR (neat) 1765, 1619, 1588, 1372, 1313,
and 1251 cm-1 1H NMR (400 MHz, CDCl3) δ 0.23 (s, 9H),
;
1.45-1.54 (m, 1H), 1.76-1.85 (m, 1H), 1.90-1.99 (m, 1H),
2.07-2.16 (m, 1H), 2.24-2.43 (m, 2H), 2.84-2.92 (m, 1H),
4.63-4.72 (m, 2H), 5.14 (s, 2H), 5.70-5.73 (m, 1H), and 5.75-
5.79 (m, 1H); 13C NMR (100 MHz, CDCl3) δ -1.7, 29.9, 32.1,
35.2, 42.1, 65.3, 73.4, 90.9, 131.4, 134.1, 139.4, 142.6, 160.3,
and 164.1; HRMS calcd for C16H22O4Si: 306.1287, found
306.1288.
A solution of 1.7 g (5.4 mmol) of the above furan in 50 mL
of THF was cooled in an ice bath. A 1.0 M solution of TBAF in
THF (5.9 mmol) was added dropwise to the reaction mixture
and the solution was stirred at 0 °C for 20 min. The mixture
was poured into 30 mL of aqueous saturated NH4Cl and
extracted with ether. The organic layer was dried over MgSO4
and filtered, and the solvent was removed under reduced
pressure. The residue was subjected to silica gel chromatog-
raphy to give 0.91 g (72%) of 54 as a pale yellow oil: IR (neat)
1
1758, 1626, 1614, 1467, 1384, and 1306 cm-1; H NMR (400
MHz, CDCl3) δ 1.45-1.53 (m, 1H), 1.76-1.85 (m, 1H), 1.90-
1.98 (m, 1H), 2.07-2.15 (m, 1H), 2.24-2.43 (m, 2H), 2.82-
2.91 (m, 1H), 4.62-4.71 (m, 2H), 5.15 (d, 2H, J ) 2.0 Hz),
5.69-5.72 (m, 1H), 5.75-5.79 (m, 1H), and 6.69 (t, 1H, J )
2.0 Hz); 13C NMR (100 MHz, CDCl3) δ 29.9, 32.1, 35.1, 42.1,
64.7, 73.3, 90.6, 121.9, 131.1, 131.4, 134.0, 157.0, and 163.8.
Anal. Calcd for C13H14O4: C, 66.64; H, 6.03. Found: C, 66.60;
H, 5.92.
5-Hyd r oxy-3a -p h en yl-3,3a ,4,5-tetr a h yd r o-2H-1,7-d ioxa -
a s-in d a cen -8-on e (48). The second fraction isolated from the
column contained 0.05 g (63%) of 48 as a yellow solid: mp 84-
3,3a ,4,5,5a ,6a ,7,9a -Octa h yd r o-2H-1,8-d ioxa cyclop en ta -
[e]a cen a p h th ylen e-6,9-d ion e (56). A solution of 0.22 g (0.9
mmol) of furan 54 in 8 mL of xylene was heated at 145 °C in
a thick-walled sealed tube for 15 h. The solution was concen-
trated under reduced pressure and the residue was subjected
to silica gel chromatography. The first fraction isolated from
the column contained 0.14 g (63%) of 56 as a yellow oil: IR
86 °C; IR (film) 1746, 1665, 1449, 1225, and 1048 cm-1 1H
;
NMR (400 MHz, CDCl3) δ 1.99 (dd, 1H, J ) 11.6 and 11.6 Hz),
2.32 (ddd, 1H, J ) 12.4, 12.4 and 8.4 Hz), 2.40 (brs, 1H), 2.48
(dd, 1H, J ) 12.4 and 4.8 Hz), 2.79 (dd, 1H, J ) 11.6 and 4.8
Hz), 4.18 (ddd, 1H, J ) 12.4, 9.2 and 4.8 Hz), 4.24 (ddd, 1H, J
) 11.6, 4.8 and 2.4 Hz), 4.65 (dd, 1H, J ) 9.2 and 8.8 Hz),
6.65 (d, 1H, J ) 2.4 Hz), and 7.24-7.39 (m, 5H); 13C NMR
(100 MHz, CDCl3) δ 39.5, 46.8, 55.2, 63.0, 74.1, 98.6, 122.3,
126.3, 128.2, 129.4, 132.2, 139.8, 166.0, and 171.5. Anal. Calcd
for C16H14O4: C, 71.09; H, 5.22. Found: C, 71.24; H, 5.06.
2-Dia zom a lon ic Acid 2-Cyclop en t-2-en yl Eth yl Ester
3-Tr im eth ylsila n ylp r op -2-yn yl Ester (53). Esterification of
malonic acid mono(3-trimethylsilanylprop-2-ynyl) ester with
2-cyclopent-2-enylethanol63 gave malonic acid 2-cyclopent-2-
enylethyl ester 3-trimethylsilanylprop-2-ynyl ester (100%) as
a colorless oil: IR (neat) 2187, 1758, 1640, 1251, and 1147
(film) 1775, 1724, 1463,1156, and 1058 cm-1 1H NMR (400
;
MHz, CDCl3) δ 0.92-1.03 (m, 1H), 1.31-1.41 (m, 1H), 1.70-
1.80 (m, 1H), 1.99-2.06 (m, 1H), 2.06-2.13 (m, 1H), 2.30-
2.37 (m, 1H), 2.44-2.53 (m, 1H), 3.41-3.46 (m, 1H), 3.60 (ddd,
1H, J ) 9.6, 7.2 and 2.8 Hz), 3.88 (ddd, 1H, J ) 14.4, 10.8 and
2.0 Hz), 3.96 (ddd, 1H, J ) 9.6, 3.6 and 2.4 Hz), 4.26 (dd, 1H,
J ) 9.2 and 7.2 Hz), 4.38 (ddd, 1H, J ) 10.8, 3.6 and 2.4 Hz),
and 4.92 (dd, 1H, J ) 9.2 and 2.8 Hz); 13C NMR (100 MHz,
CDCl3) δ 24.0, 28.6, 32.3, 37.3, 44.5, 47.1, 47.6, 65.0, 66.8,
115.0, 138.7, 172.2, and 202.3. Anal. Calcd for C13H14O4: C,
66.64; H, 6.03. Found: C, 66.51; H, 5.88.
3,3a ,4,5,5a ,6a ,7,9c-Octa h yd r o-2H-1,8-d ioxa cyclop en ta -
[e]a cen a p h th ylen e-6,9-d ion e (57). The minor fraction iso-
lated from the silica gel column contained 0.06 g (28%) of 57
as a yellow oil: IR (film) 1744, 1719, 1644, 1188, and 1048
cm-1; 1H NMR (400 MHz, CDCl3) δ 1.22-1.31 (m, 1H), 1.43-
1.53 (m, 1H), 1.73-1.82 (m, 1H), 1.89-1.97 (m, 1H), 2.10-
2.27 (m, 2H), 2.47-2.58 (m, 1H), 3.05 (ddd, 1H, J ) 10.0, 5.6
and 3.2 Hz), 3.63 (ddd, 1H, J ) 10.0, 10.0 and 3.2 Hz), 3.95
(ddd, 1H, J ) 9.6, 9.6 and 3.2 Hz), 4.10 (dt, 1H, J ) 11.2 and
2.0 Hz), 4.36 (dd, 1H, J ) 9.6 and 9.6 Hz), 4.39 (dt, 1H, J )
11.2 and 3.6 Hz), and 4.57 (dd, 1H, J ) 9.6 and 9.6 Hz); 13C
NMR (100 MHz, CDCl3) δ 26.3, 28.2, 32.4, 37.0, 42.6, 46.4,
51.0, 64.3, 66.9, 96.3, 163.6, 167.1, and 203.7; HRMS calcd for
cm-1 1H NMR (300 MHz, CDCl3) δ 0.19 (s, 9H), 1.32-1.48
;
(m, 1H), 1.54-1.70 (m, 1H), 1.72-1.84 (m, 1H), 2.04-2.13 (m,
1H), 2.22-2.42 (m, 2H), 2.68-2.79 (m, 1H), 3.43 (s, 2H), 4.18-
4.23 (m, 2H), 4.75 (s, 2H), 5.64-5.68 (m, 1H), and 5.73-5.78
(m, 1H); 13C NMR (75 MHz, CDCl3) δ -0.2, 29.9, 32.1, 34.6,
41.5, 42.4, 53.9, 64.9, 92.9, 98.3, 131.3, 134.1, 166.0, and 166.4.
Anal. Calcd for C16H24O4Si: C, 62.30; H, 7.84. Found: C, 62.15;
H, 7.82.
Diazo transfer of the above compound gave 53 (94%) as a
yellow oil: IR (neat) 2184, 2140, 1764, 1740, and 1696 cm-1
;
1H NMR (400 MHz, CDCl3) δ 0.18 (s, 9H), 1.40-1.49 (m, 1H),
1.64-1.72 (m, 1H), 1.77-1.86 (m, 1H), 2.04-2.13 (m, 1H),
2.24-2.41 (m, 2H), 2.71-2.79 (m, 1H), 4.25-4.36 (m, 2H), 4.84
(s, 2H), 5.52-5.68 (m, 1H), and 5.74-5.77 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ -0.2, 29.8, 32.1, 34.8, 42.5, 53.6, 65.0,
93.0, 98.4, 131.4, 134.1, 160.3, and 161.0; HRMS calcd for
C
13H14O4 234.0892, found 234.0890.
2-Diazo-N-ph en yl-N-pr op-2-yn ylm alon am ic Acid 2-P r o-
p en ylp h en yl Ester (64). To a solution of 4.5 g (38 mmol) of
malonic acid monomethyl ester in 70 mL of CH2Cl2 at 0 °C
under an argon atmosphere was added 0.14 g (1.1 mmol) of
DMAP, 5.0 g (38 mmol) of N-phenyl-N-propynylamine, and 8.7
g (42 mmol) of 1,3-dicyclohexylcarbodiimide. The reaction
mixture was allowed to stir at room temperature for 24 h. The
resulting suspension was filtered, the filtrate concentrated
under reduced pressure, and the crude residue was subjected
C
16H22N2O4Si 334.1349, found 334.1348.
6-(2-Cyclop en t -2-en ylet h oxy)-3H -fu r o[3,4-c]fu r a n -1-
on e (54). To a solution of 1.9 g (5.7 mmol) of diazo ester 53 in
50 mL of dry benzene at 80 °C was added 8 mg of Rh2(OAc)4.
(63) Irwin, A. J .; J ones, J . B. J . Am. Chem. Soc. 1977, 99, 1625.
J . Org. Chem, Vol. 68, No. 2, 2003 237

Padwa and Straub
to silica gel chromatography to give 8.2 g (92%) of N-phenyl-
N-prop-2-ynylmalonamic acid methyl ester (62) as a yellow
8.1 Hz), 7.89 (d, 1H, J ) 8.7 Hz), and 8.05 (d, 1H, J ) 7.5 Hz);
13C NMR (75 MHz, CDCl3/CD3OD) δ 20.7, 51.4, 112.6, 115.5,
118.3, 119.7, 122.2, 123.5, 123.7, 124.0, 124.6, 127.3, 129.3,
139.0, 139.5, 140.4, 151.2, 156.8, and 165.9. Anal. Calcd for
liquid: IR (neat) 2120, 1743, 1666, 1595, 1494, and 1397 cm-1
;
1H NMR (300 MHz, CDCl3) δ 2.23 (t, 1H, J ) 1.8 Hz), 3.22 (s,
2H), 3.67 (s, 3H), 4.52 (d, 2H, J ) 1.8 Hz), and 7.31-7.48 (m,
5H); 13C NMR (75 MHz, CDCl3) δ 38.7, 41.5, 52.5, 72.7, 78.6,
128.5, 129.2, 130.1, 141.1, 165.7, and 167.9; HRMS calcd for
C
21H15NO2: C, 80.48; H, 4.83; N, 4.47. Found: C, 80.26; H,
4.95; N, 4.39.
5-Met h yl-2-p h en yl-3,3a ,5,5a -t et r a h yd r o-2H -10-oxa -2-
a za cyclop en ta [a ]flu or en e-1,4-d ion e (67). The second frac-
tion isolated from the silica gel column contained 0.08 g (43%)
of 67 as a colorless oil: IR (film) 1713, 1702, 1598, 1499, and
C
13H13NO3 231.0895, found 231.0892.
To a solution of 4.1 g (18 mmol) of the above compound in
20 mL of methanol at 0 °C was added a solution of 1.4 g (25
mmol) of potassium hydroxide in 2 mL of methanol. The
reaction mixture was allowed to stir for 72 h, concentrated
under reduced pressure, taken up in 50 mL of water, and
washed with CHCl3. The aqueous layer was acidified with
concentrated HCl and extracted with CHCl3. The combined
organic layers were dried over MgSO4 and filtered, and the
solvent was removed under reduced pressure to give 3.9 g
(100%) of N-phenyl-N-prop-2-ynylmalonamic acid (63) as a
white solid: mp 85-86 °C; IR (film) 2123, 1739, 1661, 1630,
1
1395 cm-1; H NMR (400 MHz, CDCl3) δ 1.60 (d, 3H, J ) 7.2
Hz), 3.66-3.70 (m, 1H), 3.80-3.88 (m, 1H), 3.98-4.08 (m, 1H),
4.54-4.57 (m, 2H), and 7.15-7.62 (m, 9H); 13C NMR (100 MHz,
CDCl3) δ 14.8, 40.5, 40.9, 44.5, 46.9, 112.2, 112.3, 119.3, 120.3,
120.4, 123.1, 125.0, 125.5, 129.1, 138.7, 144.7, 156.3, 168.4,
and 207.1. Anal. Calcd for C21H17NO3: C, 76.11; H, 5.17; N,
4.23. Found: C, 76.03; H, 5.22; N, 4.08.
2-Dia zo-N-p h en yl-N-p r op -2-yn ylm a lon a m ic Acid 2-
Cyclop en t -1-en ylp h en yl E st er (68). Esterification of N-
phenyl-N-prop-2-ynylmalonamic acid (63) with 2-cyclo-
pentenylphenol64 gave N-phenyl-N-prop-2-ynylmalonamic acid
2-cyclopent-1-enylphenyl ester (98%) as a yellow oil: IR (neat)
1592, and 1494 cm-1 1H NMR (300 MHz, CDCl3) δ 2.30 (t,
;
1H, J ) 2.1 Hz), 3.15 (s, 2H), 4.53 (d, 2H, J ) 2.1 Hz), 7.27-
7.30 (m, 2H), 7.48-7.51 (m, 3H) and 10.60 (s, 1H); 13C NMR
(75 MHz, CDCl3) δ 37.9, 39.1, 73.4, 77.7, 128.0, 129.9, 130.5,
139.6, 168.2, and 169.3. Anal. Calcd for C12H11NO3: C, 66.34;
H, 5.11; N, 6.45. Found: C, 66.17; H, 5.11; N, 6.32.
1
2122, 1764, 1669, 1596, and 1493 cm-1; H NMR (300 MHz,
CDCl3) δ 1.85-1.92 (m, 2H), 2.23 (t, 1H, J ) 1.8 Hz), 2.39-
2.43 (m, 2H), 2.55-2.60 (m, 2H), 3.44 (s, 2H), 4.55 (d, 2H, J )
1.8 Hz), 5.93-5.95 (m, 1H), 7.01-7.03 (m, 1H), and 7.16-7.50
(m, 8H); 13C NMR (75 MHz, CDCl3) δ 23.4, 33.8, 35.4, 38.9,
41.7, 72.8, 78.6, 123.0, 126.3, 127.8, 128.6, 129.1, 129.3, 130.2,
130.5, 130.8, 138.7, 141.2, 147.8, 165.2, and 166.1; HRMS calcd
for C23H21NO3 359.1521, found 359.1518.
Esterification of the above carboxylic acid with 2-propenyl-
phenol gave N-phenyl-N-prop-2-ynylmalonamic acid 2-pro-
penylphenyl ester (100%), as a 8:1-mixture of trans and cis
isomers: IR (neat) 2122, 1763, 1667, 1595, 1493, and 1396
cm-1; 1H NMR (300 MHz, CDCl3) trans isomer δ 1.87 (dd, 3H,
J ) 6.6 and 1.2 Hz), 2.23 (t, 1H, J ) 2.4 Hz), 3.47 (s, 2H), 4.56
(d, 2H, J ) 2.4 Hz), 6.21 (qd, 1H, J ) 15.6 and 6.6 Hz), 6.40
(dd, 1H, J ) 15.9 and 1.5 Hz), and 6.97-7.52 (m, 4H); cis
isomer δ 1.74 (dd, 3H, J ) 6.9 and 1.8 Hz), 2.23 (m, 1H), 3.43
(s, 2H), 4.54 (d, 2H, J ) 2.4 Hz), 5.80 (qd, 1H, J ) 11.7 and
7.5 Hz), 6.40 (m, 1H), and 6.97-7.52 (m, 4H); 13C NMR (75
MHz, CDCl3) trans isomer δ 19.1, 38.8, 41.6, 72.8, 78.6, 122.5,
124.3, 126.0, 126.4, 126.5, 127.8, 128.6, 129.3, 130.2, 130.6,
141.2, 147.4, 165.3, and 166.0; HRMS calcd for C21H19NO3
333.1365, found 333.1366.
Diazo transfer of the above compound gave diazo ester 68
(71%) as a yellow oil: IR (neat) 2126, 1738, 1702, 1641, 1593,
1
and 1492 cm-1; H NMR (300 MHz, CDCl3) δ 1.88-1.96 (m,
2H), 2.24 (t, 1H, J ) 1.8 Hz), 2.44-2.49 (m, 2H), 2.50-2.55
(m, 2H), 4.56 (d, 2H, J ) 1.8 Hz), 5.87-5.89 (m, 1H), 6.63-
6.67 (m, 1H), and 7.10-7.43 (m, 8H); 13C NMR (75 MHz,
CDCl3) δ 23.5, 33.8, 35.4, 40.7, 72.9, 78.6, 123.1, 126.4, 127.3,
127.7, 128.0, 129.1, 129.7, 130.7, 130.8, 138.7, 141.8, 147.0,
159.9, and 161.1; HRMS calcd for C23H19N3O3 385.1426, found
385.1424.
3-(2-Cyclop en t-1-en ylp h en oxy)-5-p h en yl-5,6-d ih yd r o-
fu r o[3,4-c]p yr r ol-4-on e (69). To a solution of 0.1 g (0.27
mmol) of diazo ester 68 in 8 mL of dry benzene at 25 °C was
added 2 mg of Rh2(pfb)4. The reaction mixture was stirred for
10 min, the solvent was removed under reduced pressure, and
the residue was subjected to silica gel chromatography to give
0.09 g (94%) of 69 as a white solid: mp 108-110 °C; IR (film)
Diazo transfer of the major E-isomer gave 64 in 79% yield:
IR (neat) 2127, 1739, 1703, 1642, and 1594 cm-1; 1H NMR (400
MHz, CDCl3) δ 1.86 (d, 3H, J ) 4.8 Hz), 2.25 (t, 1H, J ) 2.4
Hz), 4.57 (d, 2H, J ) 2.4 Hz), 6.09-6.20 (m, 2H), 6.61-6.66
(m, 1H), and 7.10-7.43 (m, 8H); 13C NMR (100 MHz, CDCl3)
δ 19.1, 40.6, 72.8, 78.5, 122.5, 123.9, 126.5, 126.6, 127.2, 127.7,
127.8, 127.9, 128.8, 129.5, 129.5, 141.8, 146.6, 159.8, and 161.1;
HRMS calcd for C21H17N3O3 359.1270, found 359.1268.
1
1703, 1657, 1593, 1500, and 1376 cm-1; H NMR (300 MHz,
CDCl3) δ 1.89-1.97 (m, 2H), 2.46-2.51 (m, 2H), 2.73-2.78 (m,
2H), 4.68 (d, 2H, J ) 1.2 Hz), 6.29-6.31 (m, 1H), 6.86 (t, 1H,
J ) 1.2 Hz), 7.09-7.39 (m, 6H), and 7.64-7.66 (m, 2H); 13C
NMR (75 MHz, CDCl3) δ 23.3, 34.0, 35.4, 45.5, 101.0, 119.6,
119.7, 124.3, 124.7, 125.3, 125.7, 127.9, 129.1, 129.2, 129.4,
131.8, 138.2, 140.1, 151.3, 152.4, and 160.8. Anal. Calcd for
5-P h en yl-3-(2-p r op en ylp h en oxy)-5,6-d ih yd r ofu r o[3,4-
c]p yr r ol-4-on e (65). To a solution of 1.0 g (2.7 mmol) of diazo
ester 64 in 50 mL of benzene at 25 °C was added 8 mg of
Rh2(pfb)4. The reaction mixture was stirred for 2 h, the solvent
was removed under reduced pressure, and the residue was
subjected to silica gel chromatography to give 0.71 g (81%) of
65 as a clear oil: IR (neat) 1703, 1657, 1593, 1500, and 1376
cm-1; 1H NMR (400 MHz, CDCl3) δ 1.89 (dd, 3H, J ) 6.4 and
1.6 Hz), 4.70 (d, 2H, J ) 1.6 Hz), 6.30 (qd, 1H, J ) 16.0 and
6.4 Hz), 6.73 (dd, 1H, J ) 16.0 and 1.6 Hz), 6.88 (t, 1H, J )
1.6 Hz), and 7.09-7.67 (m, 9H); 13C NMR (100 MHz, CDCl3)
δ 19.1, 45.6, 119.3, 119.9, 124.3, 124.4, 124.4, 124.5, 124.8,
125.2, 125.9, 126.9, 128.0, 128.7, 129.2, 140.1, 151.4, 151.8,
160.8; HRMS calcd for C21H17NO3 331.1208, found 331.1206.
5-Me t h y l-2-p h e n y l-2,3-d ih y d r o -10-o x a -2-a za c y c lo -
p en ta [a ]flu or en -1-on e (66). A solution of 0.2 g (0.6 mmol)
of 65 in 8 mL of xylene was heated at 145 °C in a thick-walled
sealed tube for 15 h. The solution was concentrated under
reduced pressure and the residue was subjected to silica gel
chromatography. The first fraction isolated from the column
contained 0.09 g (47%) of 66 as a yellow solid: mp 247-248
°C; IR (film) 1689, 1595, 1490, 1362, and 1201 cm-1; 1H NMR
(300 MHz, CDCl3/CD3OD) δ 2.90 (s, 3H), 4.96 (s, 2H), 7.20-
7.24 (m, 2H), 7.31 (s, 1H), 7.40-7.56 (m, 4H), 7.78 (d, 1H, J )
C
23H19NO3: C, 77.28; H, 5.36; N, 3.92. Found: C, 77.14; H,
5.30; N, 3.99.
8-Aza-4-oxa-8-ph en yltetr acyclo[10.3.0.01,5.06,10]pen tadec-
5(6)-en e-7,11-d ion e (72). A solution of 0.15 g (0.4 mmol) of
furan 69 in 6 mL of xylene was heated at 145 °C in a thick-
walled sealed tube for 13 h. The solution was concentrated
under reduced pressure, and the residue was subjected to silica
gel chromatography to give 0.1 g (68%) of 72 as a yellow oil:
IR (film) 1714, 1681, 1597, 1495, and 1389 cm-1; 1H NMR (400
MHz, CDCl3) δ 1.99-2.05 (m, 1H), 2.07-2.15 (m, 2H), 2.17-
2.25 (m, 1H), 2.32-2.44 (m, 1H), 2.52-2.61 (m, 1H), 2.91 (dd,
1H, J ) 10.0 and 4.8 Hz), 3.92 (dd, 1H, J ) 10.0 and 6.0 Hz),
4.00 (t, 1H, J ) 10.0 Hz), 4.27 (dd, 1H, J ) 10.0 and 6.0 Hz)
and 7.06-7.76 (m, 9H); 13C NMR (100 MHz, CDCl3) δ 25.7,
31.5, 40.8, 41.0, 46.4, 54.1, 58.5, 101.7, 111.4, 119.4, 122.7,
(64) Casiraghi, G.; Casnati, G.; Satori, G.; Bolzoni, L. J . Chem. Soc.,
Perkin Trans. 1 1979, 2027.
238 J . Org. Chem., Vol. 68, No. 2, 2003

Synthesis of Furo[3,4-c]furans
124.0, 124.6, 129.1, 129.4, 133.1, 139.6, 157.4, 163.5, 163.6,
and 209.4. Anal. Calcd for C23H19NO3: C, 77.28; H, 5.36; N,
3.92. Found: C, 77.22; H, 5.25; N, 3.79.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for new compounds lacking elemental analyses. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Ack n ow led gm en t. This research was supported by
the National Science Foundation (grant CHE-0132651).
J O020413D
J . Org. Chem, Vol. 68, No. 2, 2003 239