Synthesis of polycyclic structures by the Diels-Alder reaction of inner-outer-ring 1,3-bis(trimethylsilyloxy)dienes

Article abstract of DOI:10.1021/jo0015319

A Diels-Alder reaction of novel inner-outer-ring 1,3-silyloxydienes 5-8 with a variety of dienophiles to afford highly functionalized polycyclic structures is reported. The inner-outer-ring 1,3-silyloxydienes 5-8 containing five- to seven-membered carbocyclic and heterocyclic rings were prepared in a single reaction vessel from 2-acetylcyclocarbonyls in quantitative yields. The Diels-Alder reaction with 1,4-benzoquinone (BQ), dimethyl acetylenedicarboxylate (DMAD), and methyl vinyl ketone (MVK) proceeded smoothly at room temperature, affording functionalized polycyclic naphthols, phenols, and enones with high regioselectivity and good yields (39-75%). Moreover, dienes 5-8 also reacted in a hetero-Diels-Alder reaction with benzaldehyde (BA) and N-benzylideneaniline (NBA) in the presence of catalytic amounts of ZnCI₂, affording substituted polycyclic pyranones and pyridinones in good yields (40-93%). Overall, our synthetic strategy provides straightforward access to an interesting set of polycyclic structures useful for natural and nonnatural product synthesis.

Full text of DOI:10.1021/jo0015319

J . Org. Chem. 2001, 66, 1395-1402
1395
Syn th esis of P olycyclic Str u ctu r es by th e Diels-Ald er Rea ction of
In n er -Ou ter -Rin g 1,3-Bis(tr im eth ylsilyloxy)d ien es
J ose´ Pe´rez Sestelo,* Mar´ıa del Mar Real, and Luis A. Sarandeses*
Departamento de Quı´mica Fundamental, Universidade da Corun˜a, E-15071 A Corun˜a, Spain
sestelo@udc.es
Received October 27, 2000
A Diels-Alder reaction of novel inner-outer-ring 1,3-silyloxydienes 5-8 with a variety of dienophiles
to afford highly functionalized polycyclic structures is reported. The inner-outer-ring 1,3-
silyloxydienes 5-8 containing five- to seven-membered carbocyclic and heterocyclic rings were
prepared in a single reaction vessel from 2-acetylcyclocarbonyls in quantitative yields. The Diels-
Alder reaction with 1,4-benzoquinone (BQ), dimethyl acetylenedicarboxylate (DMAD), and methyl
vinyl ketone (MVK) proceeded smoothly at room temperature, affording functionalized polycyclic
naphthols, phenols, and enones with high regioselectivity and good yields (39-75%). Moreover,
dienes 5-8 also reacted in a hetero-Diels-Alder reaction with benzaldehyde (BA) and N-
benzylideneaniline (NBA) in the presence of catalytic amounts of ZnCl2, affording substituted
polycyclic pyranones and pyridinones in good yields (40-93%). Overall, our synthetic strategy
provides straightforward access to an interesting set of polycyclic structures useful for natural
and nonnatural product synthesis.
In tr od u ction
The oxygenated dienes are an important family of
dienes recognized by their high reactivity, selectivity, and
usefulness in natural product synthesis. Soon after the
discovery of the Diels-Alder reaction, the high reactivity
of alkoxydienes was revealed,7 but the difficulty of their
preparation limited their synthetic applications. The
development of efficient methods to prepare silyl enol
ethers from ketones,8 led to the extensive employment
of silyloxydienes in the Diels-Alder reaction.9 A particu-
larly useful subgroup is constituted by the 1,3-dioxygen-
ated dienes, due to their increased reactivity with
dienophiles, produced from the synergism between the
two oxygen substituents, and the ease with which the
cycloadducts may be selectively converted to enones and
aromatic compounds. The most representative member
of this group is 1-methoxy-3-trimethylsilyloxy-1,3-buta-
diene (3), the so-called Danishefsky’s diene.10
The Diels-Alder reaction is one of the most funda-
mental and useful reactions in organic synthesis.1 Since
its discovery over 70 years ago, the synthetic potential
of this reaction has been greatly expanded through
modifications of the diene and dienophile components.2
Dienes where the olefins form part of a cyclic structure,
such as inner-outer-ring dienes (1),3 are particularly
useful for the synthesis of polycyclic structures, since they
allow the incorporation of additional rings in the six-
membered ring formed in the Diels-Alder reaction (eq
1). Despite this interesting synthetic feature, inner-outer-
After our participation in the synthesis of furaquinocin
C,11 where the key step was a Diels-Alder reaction
between a quinone and an inner-outer-ring 1,3-bis-
ring dienes have strong synthetic limitations due to their
low reactivity and poor regioselectivity,4 a problem that
can sometimes be overcome by the introduction of sub-
stituents5 in the inner-outer-ring dienes or in the
dienophiles.2e,6
(5) (a) Woodward, R. B.; Hoffmann, R. The Conservation of Orbital
Symmetry; Verlag Chemie: Weinheim, 1970. (b) Fleming, I. Frontier
Orbitals and Organic Chemical Reactions; Wiley: London, 1976. (c)
Herndon, W. C. Chem. Rev. 1972, 72, 157. (d) Sauer, J .; Sustmann, R.
Angew. Chem., Int. Ed. Engl. 1980, 19, 779. (e) Houk, K. N.; Gonza´lez,
J .; Li, Y. Acc. Chem. Res. 1995, 28, 81.
(6) Some recent examples: (a) Schuster, T.; Bauch, M.; Du¨rner, G.;
Go¨bel, M. W. Org. Lett. 2000, 1, 279. (b) Ge, M.; Stoltz, B. M.; Corey,
E. J . Org. Lett. 2000, 1, 1927. (c) Carren˜o, M. C.; Garc´ıa Ruano, J . L.;
Toledo, M. A. Chem. Eur. J . 2000, 6, 288. (d) Woo, S.; Legoupy, S.;
Parra, S.; Fallis, A. G. Org. Lett. 1999, 1, 1013.
(7) (a) J ohnson, J . R.; J obling, W. H.; Bodamer, G. W. J . Am. Chem.
Soc. 1941, 63, 131. (b) McElvian, S. M.; Morris, L. R. J . Am. Chem.
Soc. 1952, 74, 2657.
(8) (a) House, H. O.; Czuba, L. J .; Gall, M.; Olmstead, H. D. J . Org.
Chem. 1969, 34, 2324. (b) Stork, G.; Hudrlik, P. F. J . Am. Chem. Soc.
1968, 90, 4462.
(1) (a) Oppolzer W. In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 5;
Chapter 4.1. (b) Carruthers, W. Cycloaddition Reactions in Organic
Synthesis; Pergamon Press: Oxford, U.K., 1990.
(2) (a) Kloetzel, M. C. Org. React. 1948, 4, 1. (b) Holmes, H. C. Org.
React. 1948, 4, 60. (c) Butz, L. W.; Rytina, A. W. Org. React. 1949, 5,
136. (d) Onishenko, A. S. Diene Synthesis; Daniel Davy & Co.: New
York, 1964. (e) Fringuelli, F.; Taticchi, A. Dienes in the Diels-Alder
Reaction; Wiley: New York, 1990. (f) Boger, D. L.; Weinreb, S. M.
Hetero Diels-Alder Methodology in Organic Synthesis; Academic
Press: New York, 1987.
(3) March, J . Advanced Organic Chemistry, 4th ed.; Wiley-Inter-
science: New York, 1992; p 840.
(4) (a) Markgraf, J . H.; Greeno, E. W.; Miller, M. D.; Zaks, W. J .;
Lee, G. A. Tetrahedron Lett. 1983, 24, 241. (b) Tanis, S. P.; Abdallah,
Y. M. Synth. Commun. 1986, 16, 251. (c) Ireland, R. E.; Thompson,
W. J .; Mandel, N. S.; Mandel, G. S. J . Org. Chem. 1979, 44, 3583.
(9) (a) Petrzilka, M.; Grayson, J . I. Synthesis 1981, 753. (b) Dan-
ishefsky, S. Acc. Chem. Res. 1981, 14, 400. (c) Brownbridge, P.
Synthesis 1983, 85. (d) Danishefsky, S.; DeNinno, M. P. Angew. Chem.,
Int. Ed. Engl. 1987, 26, 15. (e) Danishefsky, S. Chemtracts: Org. Chem.
1989, 2, 273.
10.1021/jo0015319 CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/17/2001

1396 J . Org. Chem., Vol. 66, No. 4, 2001
Pe´rez Sestelo et al.
step following a modified procedure (eq 1).18 Other
reaction conditions and other acylating reagents, such
as acetic anhydride or acetyl chloride, gave either lower
yields, or mixtures of C- and O-acylation products that
were difficult to separate.
(silyloxy)diene, we became interested in further exploring
the Diels-Alder reactivity of this type of diene with
dienophiles. Hitherto, the use of 1,3-bis(silyloxy)dienes
has been limited to linear dienes12 and one example of
inner-outer ring dienes.13 In this, a full account,14 we
report on the Diels-Alder reaction of novel inner-outer-
ring 1,3-bis(silyloxy)dienes prepared from 2-acetylcyclo-
carbonyls (4) with several types of dienophiles directed
to the synthesis of polycyclic structures of interest.
With the 2-acetylcyclocarbonyls in hand, we proceeded
to study the preparation of the corresponding dienes.
Some years ago, Molander and Cameron19 prepared some
1,3-bis(trimethylsilyloxy)dienes,20 including diene 5, in
a two-step process using Et3N and TMSCl, to prepare the
silyl enol ether intermediate, followed by the addition of
LDA/TMSCl to synthesize the 1,3-bis(trimethylsilyloxy)-
dienes (70% overall yield). In our procedure, diene 5 was
obtained in a quantitative yield in a one-pot/two-step
process using LDA as a base at low temperature, followed
by TMSCl addition (Scheme 1).21 When the reaction was
interrupted after the first addition of LDA and TMSCl,
the silyl enol ether 15 intermediate was isolated. The
structure of 15 was inferred from the observed homoal-
lylic 1H NMR coupling constant (J ) 2.0 Hz) between the
methyl group and the methylene hydrogen at the â-posi-
tion. Silyl enol ether 15 can be transformed into diene 5
by addition of LDA and TMSCl at -78 °C in a quantita-
tive yield. Following the same experimental procedure,
2-acetyl-δ-valerolactone (12) was converted to diene 6 in
a quantitative yield. The structure of the silyl enol ether
intermediate 16 was also assigned based on the data from
Resu lts a n d Discu ssion
P r ep a r a tion of th e Dien es. Our research focused on
dienes 5-8 containing heterocyclic and carbocyclic rings
of five to seven members, with the purpose of studying
the effect that the ring size and components had on the
Diels-Alder reactivity, and to exploit this to incorporate
furane, pyrane, cyclohexane, and medium-sized rings into
a polycyclic structure. For the preparation of the dienes,
we used 2-acetylcyclocarbonyl compounds that could be
prepared by acetylation of the corresponding cyclocarbo-
nyls in one or two steps.15
1
its H NMR spectra.
Sch em e 1
2-Acetylbutyrolactone (11) and 2-acetylcyclohexanone
(13) are commercially available, while 2-acetyl-δ-valero-
lactone (12)16 and 2-acetylcycloheptanone (14)17 were
prepared in 45% and 67% yields from δ-valerolactone (9)
and cycloheptanone (10), respectively, by treatment with
LDA at -78 °C, and acetylation with pyruvonitrile in one
The preparation of carbocyclic dienes 7 and 8 from
2-acetylcyclohexanone and 2-acetylcycloheptanone re-
quires a regioselective deprotonation. Literature prece-
dents22 have shown that the treatment of 2-acetylcyclo-
hexanone with Et3N and TMSCl, gives a mixture of
dienes 19 and 7 in a ratio of 9:1, 7 being the minor
regioisomer (Scheme 2). Following the experimental
procedure described for 5 and 6, we found that treatment
of commercial 2-acetylcyclohexanone with LDA at low
temperature (-78 °C), followed by addition of TMSCl,
resulted in the formation of a single product which was
assigned as silyl enol ether 17, based on the methyl
(10) (a) Danishefsky, S.; Kitahara, T. J . Am. Chem. Soc. 1974, 96,
7807. (b) Danishefsky, S.; Kitahara, T. J . Org. Chem. 1975, 40, 538.
(c) Danishefsky, S.; Kitahara, T.; Yan, C. F.; Morris, J . J . Am. Chem.
Soc. 1979, 101, 6996. (d) Danishefsky, S.; Kitahara, T.; Singh, R. K. J .
Am. Chem. Soc. 1979, 101, 7008.
(11) (a) Smith, A. B., III; Pe´rez Sestelo, J .; Dormer, P. G. J . Am.
Chem. Soc. 1995, 117, 10755. (b) Smith, A. B., III; Pe´rez Sestelo, J .;
Dormer, P. G. Heterocycles 2000, 53, 1315.
(12) (a) Ibuka, T.; Mori, Y.; Inubushi, Y. Tetrahedron Lett. 1976,
3169. (b) Ibuka, T.; Mitsui, Y.; Hayashi, K.; Minakata, H.; Inubushi,
Y. Tetrahedron Lett. 1981, 22, 4425. (c) Cameron, D. W.; Fetrill, G. I.;
Perlmutter, P. Tetrahedron Lett. 1981, 22, 3273. (d) Krohn, K.;
Ostermeyer, H.-H.; Tolkiehn, K. Chem. Ber. 1979, 112, 2640. (e)
Brisson, C.; Brassard, P. J . Org. Chem. 1981, 40, 1810.
(13) Tsuge, O.; Kanemasa, S.; Sakoh, H.; Wada, E. Bull. Chem. Soc.
J pn. 1984, 57, 3234.
(14) For a previous communication, see: Pe´rez Sestelo, J .; Real, M.
M.; Mourin˜o, A.; Sarandeses, L. A. Tetrahedron Lett. 1999, 40, 985.
(15) (a) House, H. O. Modern Synthetic Reactions, 2nd ed.; Benjamin/
Cummings: Menlo Park, 1972; pp 734-765. (b) Caine, D. In Carbon-
Carbon Bond Formation; Augustine, R. L., Ed.; Marcel Dekker: New
York, 1979; pp 250-258. (c) Black, T. H. Org. Prep. Proc. Int. 1989,
21, 179. (d) Stork, G.; Brizzolara, A.; Landesman, H.; Szmuszkovicz,
J .; Terrel, R. J . Am. Chem. Soc. 1963, 85, 207.
(16) Raulins, N. R.; Berdahl, D. R.; Bury, T. G. J . Org. Chem. 1980,
45, 920.
(17) Martins, M. A. P.; Bastos, G. P.; Sinhorin, A. P.; Flores, A. F.
C.; Bonacorso, H. G.; Zanatta, N. Synlett 1999, 789.
(18) Tang, Q.; Sen, S. E. Tetrahedron Lett. 1998, 39, 2249.
(19) Molander, G. A.; Cameron, K. O. J . Am. Chem. Soc. 1993, 115,
830.
(20) While this manuscript was in preparation, the synthesis of new
1,3-bis(trimethylsilyloxy)dienes was reported: Langer, P.; Schneider,
T.; Stoll, M. Chem. Eur. J . 2000, 6, 3204.
(21) Other experimental conditions, such as the addition of LDA/
TMSCl (2.2 equiv) gave lower yields, and at many times gave mixtures
of silyl enol ethers.
(22) (a) Babot, O.; Cazeau, P.; Duboudin, F. J . Organomet. Chem.
1987, 326, C27. (b) Hansson, L.; Carlston, R. Acta Chem. Scand. 1989,
43, 304.

Synthesis of Polycyclic Structures
J . Org. Chem., Vol. 66, No. 4, 2001 1397
Ta ble 1. Resu lts of th e Diels-Ald er Rea ction of 1,3-Bis(tr im eth ylsilyloxy)d ien es 5-8 w ith Dien op h ilesa
a
BQ: 1,4-benzoquinone. DMAD: dimethyl acetylenedicarboxylate. MVK: methyl vinyl ketone. BA: benzaldehyde. NBA: N-
benzylideneaniline.
1
singlet observed by H NMR. Kinetic deprotonation of
argon after distillation and kept for at least 1 week under
refrigeration (4-5 °C). The carbocyclic dienes 7 and 8
showed a higher stability than 5 and 6. Attempts to
increase the diene stability by preparing the less labile
tert-butyldimethylsilyl enol ethers failed.
Diels-Ald er Rea ctivity. The Diels-Alder reaction
of the inner-outer-ring 1,3-bis(trimethylsilyloxy)dienes
5-8 was studied with some of the most common dieno-
philes with the purpose to access to a diverse array of
polycyclic structures and to explore the reactivity of these
novel dienes. We assayed the reaction with 1,4-benzo-
quinone (BQ), dimethyl acetylenedicarboxylate (DMAD),
methyl vinyl ketone (MVK), benzaldehyde (BA), and
N-benzylideneaniline (NBA).
17 with LDA, and enolate trapping with TMSCl, led to
the desired diene 7,23 as the only diene observed by H
1
NMR, as a distillable colorless oil in a quantitative yield.
In this way, diene 7 was prepared for the first time in a
pure form by a new regioselective one-pot procedure. The
novel diene 8 was also obtained following the same
experimental procedure in a quantitative yield from
2-acetylcycloheptanone. The structure of the silyl enol
1
ether intermediate 18 was also determined by H NMR.
Sch em e 2
(a ) Rea ction w ith 1,4-Ben zoqu in on e (BQ). The
Diels-Alder reaction of silyloxydienes with quinones has
been very useful for the synthesis of several natural
products.9 The inner-outer-ring 1,3-bis(silyloxy)dienes
5-8 reacted with 1,4-benzoquinone at room-temperature
exothermically, in short reaction times (3-5 h) and good
yields (70-75%). Trihydroxy naphthalenes 20 were di-
rectly obtained from this reaction, following a general
reaction pattern (Scheme 3). However, they proved to be
Although 1,3-bis(trimethylsilyloxy)dienes 5-8 are mois-
ture-sensitive liquids or oils, they can be stored under
(23) Krageloh, K.; Simchen, G.; Schweiker, K. Liebigs Ann. Chem.
1985, 2352.

1398 J . Org. Chem., Vol. 66, No. 4, 2001
Pe´rez Sestelo et al.
Sch em e 3
Sch em e 5
significant in the preparation of heterocyclic com-
pounds.1,2 Only highly reactive dienes react with hetero-
dienophiles with the assistance of Lewis acids.2f For this
reason, we decided to explore the hetero-Diels-Alder
reaction of the inner-outer-ring 1,3-bis(silyloxy)dienes
5-8 with aldehydes and imines. The hetero-Diels-Alder
reaction of silyloxydienes with aldehydes and imines has
been very useful in the synthesis of pyranes in carbohy-
drate chemistry and also for other heterocyclic struc-
tures.9,24 Despite the scant reporting of the use of inner-
outer-ring silyloxydienes, they should allow for the
construction of interesting polyheterocyclic structures.25
The Diels-Alder reaction of 1,3-bis(silyloxy)dienes 5-8
with benzaldehyde (BA) proceeded smoothly at room
temperature in THF and catalytic amounts of ZnCl2 to
give interesting bicyclic pyranones (33-36) in moderate
yields (40-60%) (see Scheme 5, and Table 1, entries 4,
8, 13, and 17).26 The yields were moderate mainly because
the 1,3-bis(trimethylsilyloxy)dienes were partially hy-
drolyzed in the reaction conditions. A considerable quan-
tity of the corresponding 2-acetylcyclocarbonyl compound
was recovered (40%). As seen in the reactions with MVK,
in the reactions with BA, a single regioisomer was
Sch em e 4
unstable in air and were transformed in situ into the
acetylated derivatives (21-24). In this way, novel naph-
thofuran, naphthopyran, and phenanthrene structures
(see Table 1, entries 1, 5, 10, and 14) were prepared in
two steps from the 2-acetylcyclocarbonyls.
(b) Rea ction w ith Dim eth yl Acetylen ed ica r boxy-
la te (DMAD). DMAD is an electron-deficient alkyne
often used in cycloadditions.2 The Diels-Alder reaction
of DMAD with 1,3-dioxygenated dienes has allowed the
preparation of various functionalized phenols.9 The reac-
tion of dienes 5-8 with DMAD proceeded at room
temperature to give moderate yields (39-70%) (Scheme
4). While diene 5 affords the benzofurane 25 directly (see
Table 1, entry 2), the reaction with other dienes needed
acidic conditions to give phenols 26-28 (see Table 1,
entries 6, 11, and 15). The reaction times were similar
for all dienes, but the lowest yields were obtained with
diene 8 containing the cycloheptane ring (Table 1, entry
15).
(c) Rea ction w ith Meth yl Vin yl Keton e (MVK). As
an asymmetric dienophile, MVK allows for the study of
the regioselectivity of dienes in the Diels-Alder reaction.
On the other hand, the reaction of 1,3-oxygenated dienes
with MVK has afforded synthetically useful enones.9
Dienes 5 and 6 react with MVK at room temperature to
give enones 29 and 30 in 62% and 40% yields, respec-
1
detected by H NMR.
The reactivity of the inner-outer-ring silyloxydienes
5-8 with a nonactivated imine, N-benzylideneaniline
(NBA), was also studied.24 The Diels-Alder reaction of
dienes 7 and 8 took place in THF with catalytic amounts
of ZnCl2 to give the pyridinone derivatives 37 and 38 in
yields of 93% and 69%, respectively (Table 1, entries 9
and 18). The Diels-Alder reaction of dienes 5 and 6 did
not afford the corresponding pyridinones, the structure
of the new products is still under investigation.
Con clu sion s
In summary, we have shown that the inner-outer-ring
1,3-bis(trimethylsilyloxy)dienes 5-8 containing carbocy-
clic or heterocyclic rings with different ring sizes can be
efficiently prepared from 2-acetylcyclocarbonyls. Dienes
5-8 react smoothly with 1,4-benzoquinone, dimethyl
acetylenecarboxylate, and methyl vinyl ketone in a
efficient and regioselective Diels-Alder reaction. The
dienes also participate in a hetero-Diels-Alder reaction
with aldehydes such as benzaldehyde, and imines such
as N-benzylideneaniline. Overall, the Diels-Alder reac-
tivity of 5-8 is comparable to other Danishefsky’s type
dienes, with low dependence on the ring size and diene
components used. Our synthetic strategy provides a
straightforward access to an interesting set of highly
1
tively, as the only regioisomers detected by H NMR (see
Table 1, entries 3 and 12). Dienes 7 and 8 containing the
carbocyclic six- and-seven membered rings showed a
lower reactivity. Diene 7 needed to be heated with MVK
in benzene at 90 °C to give the unstable enone 31 in a
50% yield after 24 h (Table 1, entry 7). The reaction of
diene 8 with MVK at 90 °C gave enone 32 in only a 10%
yield, but in the presence of catalytic amounts of ZnCl2,
the reaction proceeded at room temperature to give a 46%
yield after 24 h (Table 1, entry 16). For all the dienes, a
(24) (a) Kerwin, J . F.; Danishefsky, S. Tetrahedron Lett. 1982, 23,
3739. (b) Danishefsky, S.; Langer, M. E.; Vogel, C. Tetrahedron Lett.
1985, 26, 5983.
(25) Veyrat, C.; Wartski, L.; Seyden-Penne, J . Tetrahedron Lett.
1986, 27, 2981.
1
single regioisomer was detected by H NMR (Scheme 4).
(d ) Heter o-Diels-Ald er Rea ction . The Diels-Alder
reaction of dienes and/or dienophiles containing heteroa-
toms inserted in the olefins (hetero-Diels-Alder) is
(26) The use of other Lewis acids gave similar results.

Synthesis of Polycyclic Structures
J . Org. Chem., Vol. 66, No. 4, 2001 1399
as a yellow oil: 1H NMR (CDCl3) δ 0.26 (s, 9 H), 2.32 (t, J )
2.0 Hz, 3 H), 2.80 (dt, J ) 7.8, 2.0 Hz, 2 H), 4.23 (t, J ) 7.8
Hz, 2 H); 13C NMR (CDCl3) δ 1.0 (3 × CH3), 18.6 (CH3), 26.1
(CH2), 64.3 (CH2), 104.6 (C), 162.5 (C), 172.4 (C); MS (FAB)
m/z 201 (M+ + 1, 43), 181 (100).
functionalized polycyclic structures present in natural
and nonnatural products with good yields (39-93%).
Exp er im en ta l Section
2-Acet yl-1-(t r im et h ylsilyloxy)-5,6-d ih yd r o-4H -p yr a n
(16). Following the same experimental procedure described
for 15, the title compound 16 [94 mg, 85%, Rf ) 0.80 (20%
EtOAc/hexanes)] was prepared from 3-acetyltetrahydropyran-
2-one (74 mg, 0.52 mmol): 1H NMR (CD2Cl2) δ 0.27 (s, 9 H),
1.78 (m, 2 H), 2.31 (t, J ) 1.7 Hz, 3 H), 2.38 (m, 2 H), 4.14 (t,
J ) 5.4 Hz, 2 H); 13C NMR (CD2Cl2) δ 0.9 (3 × CH3), 21.8 (CH3),
23.0 (CH2), 23.5 (CH2), 68.4 (CH2), 107.3 (C), 165.1 (C), 168.1
(C).
2-Acetyl-1-(tr im eth ylsilyloxy)-1-cycloh exen e (17). Fol-
lowing the same experimental procedure described for 15, the
title compound 17 [302 mg, 99%, Rf ) 0.57 (40% EtOAc/
hexanes)] was prepared from 2-acetylcyclohexanone (185 µL,
1.42 mmol): 1H NMR (CDCl3) δ 0.29 (s, 9 H), 1.61 (m, 4 H),
2.23 (t, J ) 5.4 Hz, 2 H), 2.26 (t, J ) 5.4 Hz, 2 H), 2.37 (s, 3
H); 13C NMR (CDCl3) δ 1.2 (3 × CH3), 22.2 (CH2), 22.9 (CH2),
24.1 (CH2), 32.2 (CH2), 32.5 (CH3), 118.4 (C), 161.4 (C), 199.2
(C); MS (FAB) m/z 197 (M+ - CH3, 30), 181 (100).
Gen er al Mater ials an d Meth ods. Unless otherwise stated,
all reactions were conducted in flame-dried glassware under
a positive pressure of argon. Reaction temperatures refer to
external bath temperatures. All dry solvents were distilled
under argon immediately prior to use. Tetrahydrofuran (THF),
ether (Et2O), and benzene were distilled from the sodium ketyl
of benzophenone. Dichloromethane (CH2Cl2) and acetic anhy-
dride were distilled from P2O5. Trimethylsilyl chloride and
i-Pr2NH were distilled from CaH2 prior use. Pyridine was
distilled from KOH. Methyl vinyl ketone and benzaldehyde
were distilled under vacuum prior use. Lithium diisopropy-
lamine (LDA) was prepared as a 0.5-1.0 M solution in THF
by addition of i-Pr2NH to a solution of n-BuLi in hexanes at
-78 °C dilution by adding THF and warming to 0 °C.27 Organic
extracts were dried over anhydrous MgSO4, filtered, and
concentrated using a rotary evaporator at aspirator pressure
(20-30 mmHg). Thin-layer chromatography was effected on
silica gel 60 F254 (layer thickness 0.2 mm), and components
were located by observation under UV light and/or by treating
the plates with a phosphomolybdic acid or p-anisaldehyde
reagent followed by heating. Flash column chromatography
was performed on silica gel 60 (230-400 mesh) by Still’s
2-Acetyl-1-(tr im eth ylsilyloxy)-1-cycloh ep ten e (18). Fol-
lowing the same experimental procedure described for 15, the
title compound 18 [242 mg, 98%, Rf ) 0.65 (40% EtOAc/
hexanes)] was prepared from 2-acetylcycloheptanone (168 mg,
0.64 mmol): 1H NMR (CD2Cl2) δ 0.23 (s, 9 H), 1.60 (m, 6 H),
2.15 (s, 3 H), 2.38 (m, 2 H), 2.50 (m, 2 H).
method.28 Bulb-to-bulb distillations were performed in
a
Kugelrohr apparatus, and bp corresponds to the external air
bath temperature. 1H NMR spectra were recorded on a 200
MHz spectrometer and 13C NMR spectra at 50 MHz. DEPT
was used to assign carbon types. Melting points are uncor-
rected.
Gen er a l Exp er im en ta l P r oced u r e for P r ep a r a tion of
1,3-Bis(tr im eth ylsilyloxy)d ien es. To a cooled (-78 °C)
solution of the 2-acetylcycloalkanone or 2-acetyllactone (3
mmol) in THF was added via syringe a previously prepared
solution of LDA in THF (1.2 equiv). The mixture was stirred
for 30 min and TMSCl (1.5 equiv) was added over 10 min. The
reaction mixture was warmed to room temperature and
recooled to -78 °C. Then, a solution of LDA in THF (1.2 equiv)
was slowly added via syringe dropwise over 5 min. After 40
min, TMSCl (1.5 equiv) was added over 10 min, and the
reaction mixture was allowed to reach room temperature for
1 h. The solvent was evaporated at reduced pressure, the
residue was dissolved in Et2O (25 mL) and filtered, and the
filtrate was concentrated to afford the desired diene in
quantitative yield.
2-Acetyl-δ-va ler ola cton e (12). To a solution of δ-valero-
lactone (400 µL, 4.32 mmol) in THF (15 mL) at -78 °C was
added a solution of LDA in THF (9.2 mL, 5.06 mmol, 0.55 M)
dropwise via syringe. After 1 h of stirring, pyruvonitrile (370
µL, 5.18 mmol) was added dropwise over a 10 min period. After
20 min, the reaction mixture was quenched by addition of a
few drops of water. The solvent was evaporated and the
residue purified by column chromatography (30% AcOEt/
hexanes) to give 250 mg of 2-acetyl-δ-valerolactone [12, 45%,
Rf ) 0.35 (30% AcOEt/hexanes)] as a yellow solid: mp 46-48
°C; 1H NMR (CDCl3) δ 1.93 (m, 2 H), 2.01 (s, 3 H), 2.42 (t, J )
6.6 Hz, 2 H), 4.29 (t, J ) 5.1 Hz, 2 H), 13.70 (s, 1 H); 13C NMR
(CDCl3) δ 18.7 (CH3), 22.5 (CH2), 22.6 (CH2), 68.9 (CH2), 93.2
(C), 172.7 (C), 175.8 (C); MS (EI, 70 eV) m/z 143 (M+ + 1, 23),
142 (M+, 92), 99 (100).
2-Acetylcycloh ep ta n on e (14). Following the same experi-
mental procedure as for 12, reaction of cycloheptanone (300
µL, 2.53 mmol) with LDA in THF (6.4 mL, 0.47 M, 3.04 mmol)
and pyruvonitrile (215 µL, 3.04 mmol) afforded after column
chromatography (20% AcOEt/hexanes) 263 mg of 2-acetylcy-
cloheptanone [67%, Rf ) 0.58 (40% AcOEt/hexanes)] as a
yellow oil: 1H NMR (CDCl3) δ 1.67 (m, 6 H), 2.12 (s, 3 H),
2.37 (m, 2 H), 2.54 (m, 2 H), 16.48 (s, 1 H); 13C NMR (CDCl3)
δ 22.2 (CH3), 24.7 (CH2), 26.8 (CH2), 28.7 (CH2), 31.6 (CH2),
40.5 (CH2), 111.7 (C), 185.6 (C), 200.4 (C); MS (EI, 70 eV) m/z
154 (M+, 94), 111 (100), 139 (82).
1-Tr im et h ylsilyloxy-2-[1-(t r im et h ylsilyloxy)et h ylid e-
n yl]-4,5-d ih yd r ofu r a n (5).19 Following the general experi-
mental procedure described previously, diene 5 was obtained
from 2-acetylbutyrolactone (500 µL, 4.64 mmol) as a liquid in
quantitative yield [1.26 g, Rf ) 0.49 (40% AcOEt/hexanes)]:
1
bp (bulb-to-bulb) 129-131 °C (0.5 mmHg); H NMR (CD2Cl2)
δ 0.19 (s, 9 H), 0.25 (s, 9 H), 2.69 (t, J ) 8.8 Hz, 2 H), 3.86 (s,
1 H), 3.92 (s, 1 H), 4.21 (t, J ) 8.8 Hz, 2 H); 13C NMR (CD2Cl2)
δ 0.2 (3 × CH3), 0.5 (3 × CH3), 30.6 (CH2), 66.5 (CH2), 82.2
(C), 87.1 (CH2), 153.7 (C), 155.4 (C); MS (EI, 70 eV) m/z 273
(M+ + 1, 2), 73 (100).
2-Tr im et h ylsilyloxy-3-[1-(t r im et h ylsilyloxy)et h ylid e-
n yl]-5,6-d ih yd r o-4H-p yr a n (6). Following the general ex-
perimental procedure, diene 6 was obtained from 2-acetyl-δ-
valerolactone (12, 260 mg, 1.83 mmol) as a liquid in quantitative
yield [519 mg, Rf ) 0.81 (50% AcOEt/hexanes)]: bp (bulb-to-
1
3-[1-[(Tr im eth ylsilyl)oxy]eth yliden yl]-4,5-dih ydr ofu r an -
2-on e (15). To a cooled (-78 °C) solution of 2-acetylbutyro-
lactone (170 µL, 1.6 mmol) in THF (5 mL) was slowly added
via syringe a solution of LDA in THF (3.7 mL, 1.89 mmol, 0.51
M). The reaction mixture was stirred for 30 min, and TMSCl
(300 µL, 2.37 mmol) was added via syringe dropwise. The
mixture was warmed to room temperature, the solvent was
evaporated at reduced pressure, the residue was dissolved in
Et2O (25 mL) and filtered, and the filtrate was concentrated
to afford 315 mg of 15 [99%, Rf ) 0.30 (40% EtOAc/hexanes)]
bulb) 124-126 °C (0.7 mmHg); H NMR (CDCl3) δ 0.20 (s, 9
H), 0.22 (s, 9 H), 1.79 (m, 2 H), 2.17 (t, J ) 6.6 Hz, 2 H), 4.00
(t, J ) 5.4 Hz, 2 H), 4.21 (s, 1 H), 4.41 (s, 1 H); 13C NMR
(CDCl3) δ 0.1 (3 × CH3), 0.5 (3 × CH3), 22.3 (CH2), 22.7 (CH2),
66.9 (CH2), 90.4 (CH2), 105.0 (C), 152.9 (C), 155.2 (C); MS (EI,
70 eV) m/z 286 (M+, 5), 271 (11), 73 (100).
1-Tr im et h ylsilyloxy-2-[1-(t r im et h ylsilyloxy)et h ylid e-
n yl]-1-cycloh exen e (7).23 Following the general experimental
procedure, diene 7 was obtained from 2-acetylcyclohexanone
(550 µL, 4.23 mmol) as a yellow oil in quantitative yield (1.2
g, Rf ) 0.71 (40% AcOEt/hexanes)]: bp (bulb-to-bulb) 119-
1
121 °C (0.1 mmHg); H NMR (CDCl3) δ 0.20 (s, 9 H), 0.21 (s,
(27) Vedejs, E.; Engler, D. A.; Telschow, J . E. J . Org. Chem. 1978,
43, 188.
(28) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
9 H), 1.60 (m, 4 H), 2.08 (t, J ) 6.5 Hz, 2 H), 2.14 (t, J ) 6.5
Hz, 2 H), 4.36 (s, 1 H), 4.53 (s, 1 H); 13C NMR (CDCl3) δ 0.1

1400 J . Org. Chem., Vol. 66, No. 4, 2001
Pe´rez Sestelo et al.
(3 × CH3), 0.9 (3 × CH3), 22.7 (CH2), 23.1 (CH2), 26.3 (CH2),
31.2 (CH2), 93.9 (CH2), 114.3 (C), 147.1 (C), 154.9 (C); MS (EI,
70 eV) m/z 285 (M+ + 1, 9), 284 (M+, 36), 269 (90), 73 (100).
pyridine (1 mL) and Ac2O (250 µL, 2.64 mmol) were added.
Purification by column chromatography (30% AcOEt/hexanes)
afforded 230 mg of 24 [70%, Rf ) 0.33 (30% AcOEt/hexanes)]
as a brown solid: mp 165-167 °C (CH2Cl2/hexanes); 1H NMR
(CDCl3) δ 1.76 (m, 6 H), 2.38 (s, 3 H), 2.39 (s, 3 H), 2.44 (s, 3
H), 2.88 (m, 2 H), 3.44 (m, 2 H), 7.07 and 7.20 (2 d, AB system,
J ) 8.3 Hz, 2 H), 7.43 (s, 1 H). 13C NMR (CDCl3) δ 20.9 (CH3),
21.1 (CH3), 21.4 (CH3), 25.9 (CH2), 26.4 (CH2), 26.7 (CH2), 30.8
(CH2), 31.4 (CH2), 111.5 (CH), 117.0 (CH), 119.6 (CH), 125.4
(C), 127.9 (C), 137.7 (C), 140.9 (C), 144.3 (C), 144.5 (C), 147.4
(C), 169.1 (C), 169.5 (2 × C); MS (EI, 70 eV) m/z 370 (M+, 8),
328 (19), 244 (100); HRMS (EI) calcd for C21H22O6 370.1416
(M+), found 370.1426.
1-Tr im et h ylsilyloxy-2-[1-(t r im et h ylsilyloxy)et h ylid e-
n yl]-1-cycloh ep ten e (8). Following the general experimental
procedure, diene 8 was obtained from 2-acetylcycloheptanone
(209 mg, 1.36 mmol) as a liquid in quantitative yield [402 mg,
Rf ) 0.74 (30% AcOEt/hexanes)]: bp (bulb-to-bulb) 129-131
°C (0.7 mmHg); 1H NMR (CDCl3) δ 0.18 (s, 9 H), 0.20 (s, 9 H),
1.54 (m, 4H), 1.66 (m, 2H), 2.17 (m, 2 H), 2.31 (m, 2 H), 4.30
(s, 1 H), 4.39 (s, 1 H); 13C NMR (CDCl3) δ 0.2 (3 × CH3), 0.8 (3
× CH3), 25.0 (CH2), 27.0 (CH2), 28.6 (CH2), 32.1 (CH2), 36.1
(CH2), 93.5 (CH2), 119.5 (C), 152.5 (C), 155.3 (C); MS (EI, 70
eV) m/z 299 (M+ + 1, 14), 298 (M+, 6), 283 (18), 73 (100).
Dim eth yl 2,3-Dih yd r o-4-h yd r oxyben zofu r a n -6,7-d ica r -
boxyla te (25). Dimethyl acetylenedicarboxylate (77 µL, 0.26
mmol) was added to diene 5 (509 mg, 1.87 mmol) at room
temperature. After 12 h, the reaction mixture was directly
purified by column chromatography (50% AcOEt/hexanes) to
give 108 mg of 25 [69%, Rf ) 0.23 (40% AcOEt/hexanes)] as a
white solid: mp 138-140 °C (Et2O/hexanes); IR (KBr) 3390,
1730, 1700, 1600, 1280, 1250 cm-1; 1H NMR (CDCl3) δ 3.17 (t,
J ) 8.8 Hz, 2 H), 3.85 (s, 3H), 3.88 (s, 3H), 4.69 (t, J ) 8.8 Hz,
2 H), 6.80 (s, 1 H), 6.89 (s, 1 H); 13C NMR (CDCl3) δ 26.5 (CH2),
52.6 (CH3), 52.8 (CH3), 72.9 (CH2), 107.4 (C), 110.2 (CH), 117.5
(C), 132.0 (C), 154.6 (C), 160.6 (C), 167.1 (C), 168.1 (C); MS
(EI, 70 eV) m/z 253 (M+ + 1, 12), 252 (M+, 83), 221 (100). Anal.
Calcd for C12H12O6: C, 57.0; H, 4.8. Found: C, 57.20; H, 4.53.
Dim eth yl 2,3-Dih yd r o-5-h yd r oxyben zo[b]-4H-p yr a n -
7,8-d ica r boxyla te (26). Dimethyl acetylenedicarboxylate (60
µL, 0.49 mmol) was added to diene 6 (220 mg, 0.77 mmol) at
room temperature. After the mixture was stirred for 20 h, CH2-
Cl2 (6 mL) and HCl (10 mL, 18%) were added and the resulting
mixture stirred for 5 h. The organic phase was extracted, dried,
and filtered, and the filtrate was concentrated. The residue
was purified by column chromatography (30% AcOEt/hexanes)
to give 90 mg of 26 [66%, Rf ) 0.18 (60% AcOEt/hexanes)] as
a white solid: mp 137-139 °C (Et2O/hexanes); 1H NMR
(CDCl3) δ 2.02 (m, 2 H), 2.69 (t, J ) 6.6 Hz, 2 H), 3.83 (s, 3 H),
3.91 (s, 3 H), 4.18 (t, J ) 5.1 Hz, 2 H), 6.41 (br s, 1 H), 6.97 (s,
1 H); 13C NMR (CDCl3) δ 19.3 (CH2), 20.9 (CH2), 52.5 (CH3),
52.7 (CH3), 66.6 (CH2), 107.8 (CH), 115.3 (C), 116.6 (C), 126.5
(C), 153.2 (C), 154.9 (C), 166.1 (C), 168.8 (C); MS (EI, 70 eV)
m/z 267 (M+ + 1, 6), 266 (M+, 41), 235 (100); HRMS (EI) calcd
for C13H14O6 266.0790 (M+), found 266.0799.
Dim eth yl 4-Hyd r oxy-5,6,7,8-tetr a h yd r on a p h th o-1,2-d i-
ca r boxyla te (27). Following the same experimental procedure
as for 26, reaction of dimethyl acetylenedicarboxylate (90 µL,
0.73 mmol) and diene 7 (304 mg, 1.07 mmol) afforded after
purification by column chromatography (50% AcOEt/hexanes)
128 mg of 27 [66%, Rf ) 0.28 (40% AcOEt/hexanes)] as a white
solid: mp 132-134 °C (Et2O/hexanes); 1H NMR (CDCl3) δ 1.80
(m, 4 H), 2.68 (t, J ) 6.4 Hz, 2 H), 2.72 (t, J ) 6.4 Hz, 2 H),
3.87 (s, 3 H), 3.91 (s, 3 H), 5.12 (s, 1 H), 7.23 (s, 1 H); 13C NMR
(CDCl3) δ 21.7 (CH2), 22.1 (CH2), 23.4 (CH2), 26.5 (CH2), 52.4
(CH3), 52.5 (CH3), 113.0 (CH), 125.5 (C), 127.8 (C), 129.7 (C),
136.3 (C), 154.1 (C), 166.4 (C), 170.6 (C); MS (EI, 70 eV) m/z
264 (M+, 3), 233 (46), 174 (100). Anal. Calcd for C14H16O5: C,
63.63; H, 6.10. Found: C, 63.67; H, 6.03.
4,6,9-Tr ia cetoxy-2,3-d ih yd r on a p h th o[1,2-b]fu r a n (21).
1,4-Benzoquinone (114 mg, 1.05 mmol) was added to neat
diene 5 (430 mg, 1.58 mmol) in portions at room temperature
during 15 min. The exothermic mixture was stirred for 2 h,
and CH2Cl2 (2 mL), pyridine (2 mL), and Ac2O (600 µL, 6.35
mmol) were successively added. After the mixture was stirred
overnight, the solvent was evaporated and the residue was
purified by column chromatography (40% AcOEt/hexanes) to
give 270 mg of 21 [75%, Rf ) 0.45 (60% AcOEt/hexanes)] as a
light brown solid: mp 160-162 °C (CH2Cl2/hexanes); IR (KBr)
1770-1750, 1610, 1590, 1525, 1210, 1190, 1170 cm-1; 1H NMR
(CDCl3) δ 2.35 (s, 3 H), 2.37 (s, 3 H), 2.43 (s, 3 H), 3.21 (t, J )
9.0 Hz, 2 H), 4.78 (t, J ) 9.0 Hz, 2 H), 7.00 and 7.19 (2 d, AB
system, J ) 7.8 Hz, 2 H), 7.14 (s, 1 H); 13C NMR (CDCl3) δ
20.9 (2 × CH3), 21.1 (CH3), 27.8 (CH2), 72.6 (CH2), 105.4 (CH),
114.5 (C), 117.3 (CH), 117.5 (C), 118.4 (CH), 129.4 (C), 143.2
(C), 144.2 (C), 146.7 (C), 156.3 (C), 168.5 (C), 169.0 (C), 170.1
(C); MS (EI, 70 eV) m/z 345 (M+ + 1, 1), 344 (M+, 7), 218 (100).
Anal. Calcd for C18H16O7: C, 62.79; H, 4.68. Found: C, 62.81;
H, 4.67.
5,7,10-Tr ia cet oxy-2,3-d ih yd r on a p h t h o[1,2-b]-4H -p yr -
a n (22). Following the same experimental procedure as for
21, 1,4-benzoquinone (55 mg, 0.56 mmol) was added to diene
6 (240 mg, 0.84 mmol) and stirred for 5 h. Pyridine (1 mL)
and Ac2O (160 µL, 1.69 mmol) were added. Purification by
column chromatography (30% AcOEt/hexanes) afforded 145
mg of 22 [72%, Rf ) 0.27 (50% AcOEt/hexanes)] as a yellow
1
solid: mp 145-147 °C (CH2Cl2/hexanes); H NMR (CDCl3) δ
2.05 (m, 2 H), 2.34 (s, 3 H), 2.36 (s, 3 H), 2.42 (s, 3 H), 2.69 (t,
J ) 6.6 Hz, 2 H), 4.27 (t, J ) 5.4 Hz, 2 H), 6.99 and 7.21 (2 d,
AB system, J ) 8.3 Hz, 2 H), 7.15 (s, 1 H); 13C NMR (CDCl3)
δ 19.9 (CH2), 20.78 (CH2), 20.82 (CH3), 20.9 (CH3), 21.1 (CH3),
66.5 (CH2), 105.2 (CH), 113.2 (C), 118.2 (CH), 118.3 (CH), 127.7
(C), 143.9 (C), 144.0 (2 × C), 148.6 (C), 151.6 (C), 168.9 (C),
169.0 (C), 170.1 (C); MS (EI, 70 eV) m/z 359 (M+ + 1, 5), 358
(M+, 24), 232 (100); HRMS calcd for C19H18O7 358.1053 (M+),
found 358.1060.
1,4,9-Tr ia cetoxy-5,6,7,8-tetr a h yd r op h en a n th r en e (23).
Following the same experimental procedure as for 21, 1,4-
benzoquinone (109 mg, 1.01 mmol) was added to a solution of
diene 7 (431 mg, 1.52 mmol) in CH2Cl2 (1 mL). After the
mixture was stirred for 4 h, pyridine (1 mL) and Ac2O (290
µL, 3.07 mmol) were added. Purification by column chroma-
tography (50% AcOEt/hexanes) afforded 247 mg of 23 [70%,
Rf ) 0.29 (40% AcOEt/hexanes)] as a brown solid: mp 186-
188 °C (CH2Cl2/hexanes); IR (neat) 1760, 1610, 1200 cm-1; 1H
NMR (CDCl3) δ 1.82 (m, 4 H), 2.37 (s, 3 H), 2.39 (s, 3 H), 2.44
(s, 3 H), 2.70 (m, 2 H), 3.27 (m, 2 H), 7.06 and 7.21 (2 d, AB
system, J ) 8.3 Hz, 2 H), 7.42 (s, 1 H); 13C NMR (CDCl3) δ
20.9 (CH3), 21.1 (CH3), 21.2 (CH2), 21.6 (CH3), 23.1 (CH2), 24.7
(CH2), 29.0 (CH2), 111.1 (CH), 117.4 (CH), 119.8 (CH), 126.1
(C), 127.4 (C), 130.8 (C), 134.7 (C), 144.3 (C), 144.8 (C), 148.5
(C) 169.1 (C), 169.3 (C), 169.8 (C); MS (EI, 70 eV) m/z 357 (M+
+ 1, 1), 356 (M+, 7), 272(53), 230 (100). Anal. Calcd for
Dim eth yl 4-Hyd r oxycycloh ep ta [a ]ben zen e-1,2-d ica r -
boxyla te (28). Following the same experimental procedure
as for 26, reaction of dimethyl acetylenedicarboxylate (120 µL,
0.98 mmol) and diene 8 (171 mg, 0.57 mmol) afforded after
purification by column chromatography (15% AcOEt/hexanes)
62 mg of 28 [39%, Rf ) 0.70 (30% AcOEt/hexanes), white solid]
and 37 mg of 2-acetylcycloheptanone (14, 41%). 28: mp 155-
157 °C (Et2O/hexanes); 1H NMR (CDCl3) δ 1.61 (m, 6 H), 1.79
(m, 4 H), 2.72 (t, J ) 5.7 Hz, 2 H), 2.90 (t, J ) 5.6 Hz, 2 H),
3.85 (s, 3 H), 3.91 (s, 3 H), 5.60 (s, 1 H), 7.29 (s, 1 H); 13C NMR
(CDCl3) δ 25.7 (CH2), 26.7 (CH2), 27.1 (CH2), 31.97 (CH2), 32.02
(CH2), 52.4 (CH3), 52.5 (CH3), 114.7 (CH), 125.5 (C), 127.5 (C),
135.7 (C), 143.1 (C), 152.8 (C), 166.2 (C), 170.8 (C); MS (EI,
70 eV) m/z 278 (M+, 4), 247 (12), 160 (16), 71 (100); HRMS
(EI) calcd for C15H18O5 278.1154 (M+), found 278.1152.
7-Acetyl-2,3,4,5,6,7-h exa h yd r oben zofu r a n -4-on e (29).
Methyl vinyl ketone (55 µL, 0.65 mmol) was added to diene 5
C
20H20O6: C, 67.41; H, 5.66. Found: C, 67.16; H, 5.68.
1,4,6-Tr ia cetoxycycloh ep ta [a ]n a p h th a len e (24). Fol-
lowing the same experimental procedure as for 21, 1,4-
benzoquinone (95 mg, 0.88 mmol) was added to diene 8 (400
mg, 1.34 mmol). After the mixture was stirred for 20 h,

Synthesis of Polycyclic Structures
J . Org. Chem., Vol. 66, No. 4, 2001 1401
(529 mg, 1.94 mmol) via syringe, and the reaction mixture was
stirred for 24 h and purified by column chromatography (60%
AcOEt/hexanes) to afford 74 mg of 29 [62%, Rf ) 0.20 (60%
) 0.23 (50% AcOEt/hexanes), yellow oil] and 35 mg of 2-acetyl-
δ-valerolactone (12, 40%). 34: 1H NMR (CDCl3) δ 1.95 (m, 2
H), 2.34 (m, 2 H), 2.66 (dd, J ) 17.1, 3.6 Hz, 1 H), 2.80 (dd, J
) 17.1, 13.4 Hz, 1 H), 4.18 (m, 1 H), 4.41 (m, 1H), 5.48 (dd, J
) 13.4, 3.6 Hz, 1 H), 7.40 (m, 5 H); 13C NMR (CDCl3) δ 17.3
(CH2), 21.6 (CH2), 42.3 (CH2), 69.6 (CH2), 80.3 (CH), 91.3 (C),
126.1 (2 × CH), 128.6 (CH), 128.7 (CH), 128.8 (CH), 137.6 (C),
169.9 (C), 190.5 (C); MS (EI, 70 eV) m/z 230 (M+, 10), 212 (7),
104 (100); HRMS (EI) calcd for C14H14O3 230.0943 (M+), found
230.0935.
AcOEt/hexanes)] as a yellow oil: IR (neat) 1715, 1660 cm-1
;
1H NMR (CDCl3) δ 2.10-2.50 (m, 4 H), 2.26 (s, 3 H), 2.81 (dt,
J ) 8.8, 2.0 Hz, 2 H), 3.49 (t, J ) 4.6 Hz, 1H), 4.58 (t, J ) 9.8
Hz, 2 H); 13C NMR (CDCl3) δ 24.4 (CH2), 25.7 (CH2), 29.5 (CH),
34.4 (CH2), 47.9 (CH3), 73.4 (CH2), 114.7 (C), 173.0 (C), 194.6
(C), 203.6 (C); MS (EI, 70 eV) m/z 181 (M+ + 1, 5), 180 (M+,
33), 137 (100); HRMS (EI) calcd for C10H12O3 180.0786 (M+),
found 180.0788.
8-Ace t yl-2,3,5,6,7,8-h e xa h yd r ob e n zo[b]-4H -p yr a n -5-
on e (30). Following the same experimental procedure as for
29, reaction of diene 6 (67 mg, 0.24 mmol) with methyl vinyl
ketone (30 µL, 0.36 mmol) for 24 h gave after purification by
column chromatography (35-40% AcOEt/hexanes) 18 mg of
30 [40%, Rf ) 0.35 (80% AcOEt/hexanes)] as a colorless oil:
1H NMR (CDCl3) δ 1.86 (m, 2 H), 2.10-2.52 (m, 6 H), 2.26 (s,
3 H), 3.41 (t, J ) 5.6 Hz, 1 H), 4.13 (t, J ) 5.4 Hz, 2 H). 13C
NMR (CDCl3) δ 17.5 (CH2), 21.2 (CH2), 23.5 (CH2), 29.1 (CH),
33.9 (CH2), 51.9 (CH3), 67.7 (CH2), 113.4 (C), 167.2 (C), 196.9
(C), 205.6 (C); MS (EI, 70 eV) m/z 195 (M+ + 1, 6), 194 (M+,
39), 152 (100); HRMS (EI) calcd for C11H14O2 194.0943 (M+),
found 194.0942.
2-P h en yl-2,3-dih ydr ocycloh exa[b]-4H-pyr an -4-on e (35).
Following the experimental procedure described for 33, diene
7 (430 mg, 1.51 mmol) reacted with benzaldehyde (230 µL, 2.26
mmol) during 21 h in the presence of a catalytic amount of
ZnCl2 to give, after purification by column chromatography
(20% AcOEt/hexanes), 207 mg of 35 [60%, Rf ) 0.30 (30%
AcOEt/hexanes)] as a white solid (mp 56-57 °C): IR (neat)
1660, 1610, 1400, 1295 cm-1 1H NMR (CDCl3) δ 1.65 (m, 4
;
H), 2.32 (m, 4 H), 2.64 (dd, J ) 16.6, 3.4 Hz, 1 H), 2.72 (dd, J
) 16.6, 14.2 Hz, 1 H), 5.35 (dd, J ) 14.2, 3.4 Hz, 1 H), 7.39
(m, 5 H); 13C NMR (CDCl3) δ 20.7 (CH2), 21.9 (CH2), 22.1 (CH2),
28.6 (CH2), 43.1 (CH2), 79.8 (CH), 112.4 (C), 126.1 (2 × CH),
128.6 (CH), 128.7 (2 × CH), 138.7 (C), 171.3 (C), 191.9 (C);
MS (EI, 70 eV) m/z 229 (M+ + 1, 8), 228 (M+, 22), 151 (14),
104 (100); HRMS (EI) calcd for C15H16O2 228.1150 (M+), found
228.1148.
5-Acetylbicyclo[4.4.0]d ec-1(6)-en -2-on e (31). A solution
of methyl vinyl ketone (60 µL, 0.72 mmol) and diene 7 (284
mg, 1.00 mmol) in benzene (1 mL) was heated at 90 °C in a
sealed tube for 24 h. The reaction mixture was purified by
column chromatography (40% AcOEt/hexanes), affording 69
mg of 31 [50%, Rf ) 0.37 (60% AcOEt/hexanes)] as a yellow
2-P h en yl-2,3-dih ydr ocycloh epta[b]-4H-pyr an -4-on e (36).
Following the same experimental procedure as for 33, diene 8
(200 mg, 0.67 mmol) reacted with benzaldehyde (110 µL, 1.08
mmol) during 48 h, in the presence of a catalytic amount of
ZnCl2, to give, after purification by column chromatography
(5-15% AcOEt/hexanes), 67 mg of 36 [41%, Rf ) 0.18 (5%
AcOEt/hexanes), white solid] and 42 mg of 2-acetylcyclohep-
tanone (14, 40%). 36: mp 45-47 °C; IR (neat) 1660, 1610, 1400
cm-1; 1H NMR (CDCl3) δ 1.52 (m, 2 H), 1.73 (m, 4 H), 2.55 (m,
5 H), 2.83 (dd, J ) 16.6, 14.2 Hz, 1 H), 5.32 (dd, J ) 14.2, 3.9
Hz, 1 H), 7.38 (m, 5 H); 13C NMR (CDCl3) δ 22.0 (CH2), 24.9
(CH2), 26.9 (CH2), 31.7 (CH2), 34.9 (CH2), 42.3 (CH2), 80.1 (CH),
116.8 (C), 126.1 (2 × CH), 128.6 (CH), 128.7 (2 × CH), 138.6
(C), 177.0 (C), 190.9 (C); MS (EI, 70 eV) m/z 243 (M+ + 1, 16),
242 (M+, 23), 104 (100); HRMS (EI) calcd for C16H18O2 242.1307
(M+), found 242.1305.
1
oil: IR (neat) 1705, 1660 cm-1; H NMR (CDCl3) δ 1.60 (m, 4
H), 2.18 (m, 4 H), 2.25 (s, 3 H), 2.32 (m, 4 H), 3.31 (t, J ) 4.9
Hz, 1 H); 13C NMR (CDCl3) δ 21.8 (CH2), 21.9 (CH2), 22.2 (CH2),
25.4 (CH2), 29.4 (CH), 31.0 (CH2), 34.4 (CH2), 54.3 (CH3), 134.6
(C), 152.3 (C), 197.6 (C), 207.7 (C); MS (EI, 70 eV) m/z 193
(M+ + 1, 3), 192 (M+, 12), 149 (100); HRMS (EI) calcd for
C
12H16O2 192.1150 (M+), found 192.1142.
11-Acet ylbicyclo[5.4.0]u n d ec-1(7)-en -8-on e (32). Fol-
lowing the same experimental procedure as for 29, reaction
of diene 8 (130 mg, 0.44 mmol) and methyl vinyl ketone (55
µL, 0.66 mmol) afforded after purification by column chroma-
tography (30% AcOEt/hexanes) 41 mg of the diketone 32 [46%,
Rf ) 0.53 (30% AcOEt/hexanes)] as a yellow oil: 1H NMR
(CDCl3) δ 1.65 (m, 6 H), 2.17-2.33 (m, 6 H), 2.27 (s, 3 H), 2.55
(t, J ) 5.6 Hz, 2 H), 3.49 (t, J ) 4.6 Hz, 1 H); 13C NMR (CDCl3)
δ 24.2 (CH2), 25.2 (CH2), 25.4 (CH2), 25.7 (CH2), 29.4 (CH3),
32.1 (CH2), 33.8 (CH2), 36.5 (CH2), 56.2 (CH), 140.6 (C), 157.8
(C), 196.9 (C), 207.4 (C); MS (EI, 70 eV) m/z 206 (M+, 13), 164
(100); HRMS (EI) calcd for C13H18O2 206.1307 (M+), found
206.1314.
6-P h en yl-2,3,5,6-t et r a h yd r ofu r a n [2,3-b]-4H -p yr a n -4-
on e (33). To a solution of diene 5 (475 mg, 1.74 mmol) in THF
(2 mL) at room temperature were added benzaldehyde (120
µL, 1.18 mmol) and a catalytic amount of ZnCl2. After the
mixture was stirred for 20 h, the reaction mixture was diluted
with CH2Cl2 (30 mL) and washed with a solution of HCl (10
mL, 5%). The organic layer was dried and filtered, and the
filtrate was concentrated. The residue was purified by column
chromatography (50% AcOEt/hexanes), affording 112 mg of 33
[44%, Rf ) 0.25 (80% AcOEt/hexanes), white solid] and 176
mg of 2-acetylbutyrolactone (44%). 33: mp 123-125 °C (CH2-
Cl2); 1H NMR (CD3OD) δ 2.58 (dd, J ) 17.1, 3.9 Hz, 1 H), 2.89
(m, 2 H), 3.30 (m, 1 H), 4.67 (m, 2 H), 5.74 (dd, J ) 12.7, 3.9
Hz, 1 H), 7.42 (m, 5 H); 13C NMR (CD3OD) δ 26.1 (CH2), 43.2
(CH2), 74.6 (CH2), 86.3 (CH), 91.3 (C), 128.6 (2 × CH), 130.9
(2 × CH), 131.2 (CH), 139.7 (C), 179.9 (C), 189.9 (C); MS (EI,
70 eV) m/z 216 (M+, 27), 188 (11), 131 (100); HRMS (EI) calcd
for C13H12O3 216.0786 (M+), found 216.0795.
N,2-Dip h en yl-1,2,3,4,5,6,7,8-oct a h yd r oq u in olin -4-on e
(37). To diene 7 (380 mg, 1.34 mmol) were added at room
temperature N-benzylideneaniline (136 mg, 0.75 mmol) and
a catalytic amount of ZnCl2 in THF (2 mL). After being stirred
for 20 h, the reaction mixture was diluted with AcOEt (40 mL)
and washed with water (20 mL). The organic layer was dried,
filtered, and concentrated. The residue was purified by column
chromatography (30% AcOEt/hexanes), affording 215 mg of
ketone 37 [93%, Rf ) 0.28 (50% AcOEt/hexanes)] as a white
solid: mp 160-162 °C (CH2Cl2/hexanes); IR (neat) 1630, 1560,
1
1280 cm-1; H NMR (CDCl3) δ 1.63 (m, 4 H), 2.07 (m, 2 H),
2.37 (m, 2 H), 2.84 (dd, J ) 16.4, 7.1 Hz, 1 H), 3.12 (dd, J )
16.4, 6.1 Hz, 1 H), 4.91 (t, J ) 6.6 Hz, 1 H), 7.03 (m, 2 H), 7.21
(m, 8 H); 13C NMR (CDCl3) δ 21.7 (CH2), 22.1 (CH2), 22.7 (CH2),
30.0 (CH2), 43.3 (CH2), 65.4 (CH), 110.0 (C), 126.7 (CH), 127.1
(2 × CH), 127.5 (CH), 127.6 (2 × CH), 128.5 (2 × CH), 129.0
(2 × CH), 139.9 (C), 144.1 (C), 158.4 (C), 189.9 (C); MS (EI, 70
eV) m/z 304 (M+ + 1, 14), 303 (M+, 44), 226 (15), 77 (100).
Anal. Calcd for C21H21NO: C, 83.13; H, 6.98; N, 4.62. Found:
C, 83.04; H, 7.13; N, 4.73.
N,2-Dip h en yl-1,2,3,4-tetr a h yd r ocycloh ep ta [b]p yr id in -
4-on e (38). Following the same experimental procedure as for
37, reaction of diene 8 (138 mg, 0.46 mmol) with N-benzylide-
neaniline (60 mg, 0.33 mmol) and a catalytic amount of ZnCl2
in THF (2 mL) at room temperature during 20 h afforded, after
purification by column chromatography (40% AcOEt/hexanes)
72 mg of 38 [69%, Rf ) 0.26 (40% AcOEt/hexanes)] as a white
solid: mp 122-124 °C (CH2Cl2/hexanes); IR (neat) 1625, 1550,
2-P h en yl-2,3,6,7-tetr ah ydr o-4H-pyr an e[2,3-b]-4H-pyr an -
4-on e (34). Following the experimental procedure described
for 33, diene 6 (180 mg, 0.63 mmol) reacted with benzaldehyde
(100 µL, 0.98 mmol) in the presence of a catalytic amount of
ZnCl2 to give, after 24 h of stirring and purification by column
chromatography (50% AcOEt/hexanes), 58 mg of 34 [40%, Rf
1
1185 cm-1; H NMR (CDCl3) δ 1.46 (m, 2 H), 1.66 (m, 4 H),
2.43 (m, 2 H), 2.67 (m, 1 H), 2.80 (dd, J ) 16.1, 4.4 Hz, 1 H),
3.20 (dd, J ) 16.4, 6.6 Hz, 1 H), 4.98 (dd, J ) 6.6, 4.4 Hz,

1402 J . Org. Chem., Vol. 66, No. 4, 2001
Pe´rez Sestelo et al.
1 H), 7.03 (m, 2 H), 7.27 (m, 8 H); 13C NMR (CDCl3) δ 23.3
(CH2), 26.1 (CH2), 27.5 (CH2), 31.9 (CH2), 33.0 (CH2), 41.6
(CH2), 65.0 (CH), 116.8 (C), 125.9 (2 × CH), 126.1 (CH), 126.6
(2 × CH), 127.5 (CH), 128.5 (2 × CH), 129.3 (2 × CH), 139.6
(C), 145.3 (C), 163.5 (C), 188.3 (C); MS (EI, 70 eV) m/z 318
(M+ + 1, 13), 317 (M+, 46), 289 (11), 77 (100). Anal. Calcd for
C22H23NO: C, 83.24; H, 7.30; N, 4.41. Found: C, 83.27; H, 7.54;
N, 4.54.
Ack n ow led gm en t. This work was supported by the
University of A Corun˜a and Xunta de Galicia (XUGA
10305A98).
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR for all new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
J O0015319