Studies on the oxidative addition reaction of 1,1-dibromo-1-alkenes, α-dehalopalladation, and the intramolecular bis(carbopalladation) reaction of alkenes. An efficient entry to fused bicycles

Article abstract of DOI:10.1021/jo005542d

Twenty-three examples of 1,1-dihalo-1-alkenes were synthesized by the conventional alkylation methods. The oxidative addition reactions of 1,1-dibromo-2,2-diphenylethene or 1,1-dibromo-2-phenylpropene with a stoichiometric amount of Pd(PPh₃)₄ afforded 1,2-diphenylacetylene and 1-phenylpropyne, respectively, indicating that α-dehalopalladation reaction occurred to afford vinylic carbene intermediates. However, α-dehalopalladation reaction was not observed in all 1,1-dihalo-1-alkenes containing an extra C=C bond suitable for cyclic carbopalladation under the current reaction conditions probably due to the fast cyclic carbopalladation reaction of 40A-type of palladium intermediates; A series of bicycles, i.e., fused 5,6-, 6,6-, 6,7-, and 7,7-bicyclic compounds, were prepared efficiently via this bicyclic carbopalladation protocol. Under condition A, within 0.5 h, 10 afforded the monocyclic product 37 in 79%. With prolonged reaction time, 37 was converted to bicycle 36. Even with isolated 37, the corresponding reaction under condition A afforded 36 in 92% NMR yield, indicating a stepwise oxidative addition-cyclic carbopalladation-β-elimination mechanism for this bicyclization reaction.

Full text of DOI:10.1021/jo005542d

8532
J . Org. Chem. 2000, 65, 8532-8543
Stu d ies on th e Oxid a tive Ad d ition Rea ction of
1,1-Dibr om o-1-a lk en es, r-Deh a lop a lla d a tion , a n d th e
In tr a m olecu la r Bis(ca r bop a lla d a tion ) Rea ction of Alk en es. An
Efficien t En tr y to F u sed Bicycles
Shengming Ma,* Bin Xu, and Bukuo Ni
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 354 Fenglin Lu, Shanghai 200032, People’s Republic of China
masm@pub.sioc.ac.cn
Received J une 13, 2000
Twenty-three examples of 1,1-dihalo-1-alkenes were synthesized by the conventional alkylation
methods. The oxidative addition reactions of 1,1-dibromo-2,2-diphenylethene or 1,1-dibromo-2-
phenylpropene with a stoichiometric amount of Pd(PPh3)4 afforded 1,2-diphenylacetylene and
1-phenylpropyne, respectively, indicating that R-dehalopalladation reaction occurred to afford vinylic
carbene intermediates. However, R-dehalopalladation reaction was not observed in all 1,1-dihalo-
1-alkenes containing an extra CdC bond suitable for cyclic carbopalladation under the current
reaction conditions probably due to the fast cyclic carbopalladation reaction of 40A-type of palladium
intermediates; A series of bicycles, i.e., fused 5,6-, 6,6-, 6,7-, and 7,7-bicyclic compounds, were
prepared efficiently via this bicyclic carbopalladation protocol. Under condition A, within 0.5 h, 10
afforded the monocyclic product 37 in 79%. With prolonged reaction time, 37 was converted
to bicycle 36. Even with isolated 37, the corresponding reaction under condition A afforded 36 in
92% NMR yield, indicating a stepwise oxidative addition-cyclic carbopalladation-â-elimination
mechanism for this bicyclization reaction.
Sch em e 1
In tr od u ction
Over the past several decades, dramatic advances in
organic synthesis have been witnessed due to develop-
ments in organotransition metal chemistry. Among so
many transition metals, which have provided fertile
ground for the development of chemo-, regio-, and ste-
reoselective organic transformations, palladium has been
regarded as one of the most valuable entries. Indeed,
palladium complexes can catalyze a large number of
selective transformations, such as the Heck reaction,1 the
Pd(0)-catalyzed coupling reaction of organometallic re-
agents with organic halides (or equivalents),2 and Tsuji-
Trost-type π-allylpalladium chemistry,3 etc., which would
be either difficult or impossible by conventional meth-
odologies.
only one carbon-halogen (or an appropriate leaving
group) bond was involved. Among our effort devoted to
reactions with more than one reactive centers, we became
interested in the oxidative addition reaction of 2,2-bis-
(ω-alkenyl)-1,1-dibromoethenes (Scheme 1). One formi-
dable challenge in this bicyclization paradigm is R-dehalo-
palladation, from which the formation of an alkylidene
carbene intermediate would be expected.
Normally, 1,1-dihalo-1-alkenes (X ) Cl, Br, I) are
important starting materials in organic synthesis. There
are a few reports on the Pd-catalyzed reaction of 1,1-
dihalo-1-alkenes: (1) palladium-catalyzed hydrogenolysis
of 1,1-dibromo-1-alkenes with tributyltin hydride to give
(Z)-1-bromoalkenes;5 (2) palladium-catalyzed cross cou-
pling reaction of 1,1-dihalo-1-alkenes with vinylboronic
acids,6a-e organostannanes,6f-k organoalanes,6l and organo-
zinc or Grignard reagents;6m,n (3) palladium-catalyzed
reductive reaction of 1,1-dibromo-1-alkenes with hydride
Carbopalladation of alkenes, alkynes, and allenes
provides efficient entries to stereodefined substituted
alkenes and cyclic compounds via intermolecular and
intramolecular reactions, respectively.4 In most cases,
(1) For reviews, see: (a) Heck, R. F. Acc. Chem. Res. 1979, 12, 146-
151. (b) Heck, R. F. Org. React. 1982, 27, 345-390. (c) Heck, R. F. In
Palladium Reagents in Organic Synthesis; Academic Press: New York,
1985. (d) Heck, R. F. In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 4, pp 833-863.
(e) Tsuji, J . In Palladium Reagents and Catalysts; Innovations in
Organic Synthesis; Wiley: Chichester, 1996.
(2) (a) Suzuki, A. Pure Appl. Chem. 1985, 57, 1749-1758. (b) Suzuki,
A. Pure Appl. Chem. 1991, 63, 419-422. (c) Suzuki, A. Pure Appl.
Chem. 1994, 66, 213-222. (d) Stille, J . K. Angew. Chem., Int. Ed. Engl.
1986, 25, 508-524. (e) Mitchell, T. N. Synthesis 1992, 803-815. (f)
Guram, A. S.; Buchwald, S. L. J . Am. Chem. Soc. 1994, 116, 7901-
7902. (g) Hartwig, J . F. Synlett 1997, 329-340. (h) Negishi, E. Liu, F.
In Metal-Catalyzed Cross-Coupling Reactions; Stang, P., Diederich, F.,
Eds.; VCH: Weinheim, 1998; pp 1-47.
(4) (a) Gibson, S. E.; Middleton, R. J . Contemp. Org. Synth. 1996,
3, 447-471. (b) Negishi, E.; Cope´ret, C.; Ma, S.; Liou, S.; Liu, F. Chem.
Rev. 1996, 96, 365-393. (c) Ojima, I.; Tzamarioudaki, M.; Li, Z.-Y.;
Donovan, R. J . Chem. Rev. 1996, 96, 635-662. (d) Cabri, W.; Candiani,
I. Acc. Chem. Res. 1995, 28, 2-7. (e) de Meijere, A.; Meyer, F. E. Angew.
Chem., Int. Ed. Engl. 1994, 33, 2379-2411. (f) Ma, S.; Huaxue, Y. 1991,
11, 561-573.
(5) (a) Uenishi, J .; Kawahama, R.; Shiga, Y.; Yonemitsu, O.; Tsuji,
J . Tetrahedron Lett. 1996, 37, 6759-6762. (b) Uenishi, J .; Kawahama,
R.; Yonemitsu, O.; Tsuji, J . J . Org. Chem. 1996, 61, 5716-5717. (c)
Tietze, L. F.; No¨bel, T.; Spescha, M. J . Am. Chem. Soc. 1998, 120,
8971-8977. (d) Uenishi, J .; Kawahama, R.; Yonemitsu, O.; Tsuji, J .
J . Org. Chem. 1998, 63, 8965-8975. (e) Uenishi, J .; Kawahama, R.;
Yonemitsu, O.; Wada, A.; Ito, M. Angew. Chem., Int. Ed. Engl. 1998,
37, 320-323.
(3) (a) Trost, B. M.; Cossy, J . J . Am. Chem. Soc. 1982, 104, 6881-
6882. (b) Trost, B. M. Pure Appl. Chem. 1981, 53, 2357-2370. (c) Trost,
B. M. Angew. Chem., Int. Ed. Engl. 1986, 25, 1-20. (d) Tsuji, J .;
Minami, I. Acc. Chem. Res. 1987, 20, 140-145. (e) Trost, B. M.;
VanVranken, D. L. Chem. Rev. 1996, 96, 395-422.
10.1021/jo005542d CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/21/2000

Efficient Entry to Fused Bicycles
J . Org. Chem., Vol. 65, No. 25, 2000 8533
Sch em e 2
Sch em e 3
anion;7 (4) palladium-catalyzed carbonylation reaction of
1,1-dibromo-1-alkenes under phase-transfer catalysis
(PTC) conditions.8 In all of these cases, only one of the
two carbon-halogen bonds is involved.9 So far, no
examples of a bicyclic carbopalladation reaction of 1,1-
dihalo-1-alkenes to furnish bicyclic products have been
reported.
In a preliminary communication,10 we described a
catalytic bicyclic carbopalladation reaction of 1,1-di-
bromo-1-alkenes for the efficient synthesis of fused
bicyclic compounds. By this protocol, bicyclic compounds
with different ring sizes as well as attached functional
groups can be simultaneously constructed from the
corresponding acyclic precursors in just “one shot”, which
is distinctive from the traditional “ring by ring” ap-
proach.10
In this paper, we report the possibility of R-dehalo-
palladation, the scope of this bicyclization reaction, and
a proposal for its mechanism.
Sch em e 4
Resu lts a n d Discu ssion
Syn th esis of Sta r tin g Ma ter ia ls. Generally, 1,1-di-
bromo-1-alkenes can be prepared either via the dibromo-
methylenation reaction of the corresponding ketones
11
using CBr4/PPh3 or by the reaction of an appropriate
carbonyl compound with diethyl dibromomethylphospho-
nate.12 However, these two methods are reported to be
sensitive to the steric hindrance of the starting ketones.
Thus, an efficient and convenient synthetic pathway to
1,1-dibromo-1-alkenes would be beneficial.
From the viewpoint of retrosynthetic analysis, we
reasoned that 1,1-dihalo-3-bromo-2-(bromomethyl)pro-
pene 2 could be a key building block for the synthesis of
the starting materials 1 (Scheme 2). Tetrahalide 2 could
be synthesized in large quantity from acetone with a two-
step procedure that we recently developed,13 namely, a
(6) (a) Roush, W. R.; Brown, B. B.; Drozda, S. E. Tetrahedron Lett.
1988, 29, 3541-3544. (b) Roush, W. R.; Moriarty, K. J .; Brown, B. B.
Tetrahedron Lett. 1990, 31, 6509-6512. (c) Roush, W. R.; Reilly, M.
L.; Koyama, K.; Brown, B. B. J . Org. Chem. 1997, 62, 8708-8721. (d)
Baldwin, J . E.; Chesworth, R.; Parker, J . S.; Russell, A. T. Tetrahedron
Lett. 1995, 36, 9551-9554. (e) Roush, W. R.; Koyama, K.; Curtin, M.
L.; Moriarty, K. J . J . Am. Chem. Soc. 1996, 118, 7502-7512. (f) Trost,
B. M.; Walchli, R. J . Am. Chem. Soc. 1987, 109, 3487-3488. (g) Torii,
S.; Okumoto, H.; Tadokoro, T.; Nishimura, A.; Rashid, M. A. Tetrahe-
dron Lett. 1993, 34, 2139-2142. (h) Nuss, J . M.; Rennels, R. A.; Levine,
B. H. J . Am. Chem. Soc. 1993, 115, 6991-6992. (i) Zapata, A. J .; Ruiz,
J . J . Organomet. Chem. 1994, 479, C6-C8. (j) Wang, L.; Shen, W.
Tetrahedron Lett. 1998, 39, 7625-7628. (k) Shen, W.; Wang, L. J . Org.
Chem. 1999, 64, 8873-8879. (l) Ratovelomanana, V.; Hammoud, A.;
Linstrumelle, G. Tetrahedron Lett. 1987, 1649-1650. (m) Minato, A.;
Suzuki, K.; Tamao, K. J . Am. Chem. Soc. 1987, 109, 1257-1258. (n)
Minato, A. J . Org. Chem. 1991, 56, 4052-4056.
dihalomethylenation reaction followed by radical allylic
R-bromination reaction of the resultant alkene.
The fragments containing one or two malonate unit(s)
3-7 and 9 were prepared by a simple alkylation reaction
of dimethyl malonate with the corresponding bromides
using NaH as the base (Scheme 3).
Those 1,1-dibromo-1-alkenes having two equal CdC
bond fragments, i.e., 10-13, were prepared by the
treatment of 2a with the appropriate alkyl-substituted
malonates 3-6 (Scheme 4). Similarly, 1,1-dichloro-1-
alkene 14 can be prepared from 1,1-dichloro-3-bromo-2-
(7) McAlonan, H.; Montgomery, D.; Stevenson, P. J . Tetrahedron
Lett. 1996, 37, 7151-7154.
(8) (a) Galamb, V.; Gopal, M.; Alper, H. Organometallics 1983, 2,
801-805. (b) Li, P.; Alper, H. J . Org. Chem. 1986, 51, 4354-4356.
(9) A recent example of Pd(0)-catalyzed annulation of 1,1-dihalo-1-
alkenes with alkynes to afford polycyclic compounds, see: Larock, R.
C.; Doty, M. J .; Han, X. J . Org. Chem. 1999, 64, 8770-8779.
(10) Ma, S.; Xu, B. J . Org. Chem. 1998, 63, 9156-9157.
(11) Corey, E. J .; Fuchs, P. L. Tetrahedron Lett. 1972, 3769-3772.
(12) Savignac, P.; Coutrot, P. Synthesis 1976, 197-199.
(13) Ma, S.; Xu, B.; Zhao, S. Synthesis 2000, 139-143.

8534 J . Org. Chem., Vol. 65, No. 25, 2000
Ma et al.
Sch em e 5
Sch em e 7
Sch em e 6
Sch em e 8
(bromomethyl)propene 2b13 and 3 in 75% yield. Diethers
15-17 were prepared by the reaction of 2a with the
sodium 2-alkenoxides (Scheme 4).
1,1-Dibromo-1-alkenes 21-24 with two different Cd
C bond-containing fragments were prepared by the
alkylation of 3 or 4 with 18-20, which, in turn, were
prepared from the etherification of 2a with the corre-
sponding allylic alcohols (Scheme 5).
Compound 26 was prepared by the treatment of 25
with allyl zinc chloride in DMSO/THF, which was pre-
pared from allyl chloride and zinc-copper couple (Scheme
6).14
Compounds 28-31 were easily synthesized by either
alkylation or etherification with the common starting
precursor 27 as depicted in Scheme 7. Compound 33 was
prepared by the sequential alkylation of 7 with 2a and 3
(Scheme 7).
of 3 with (S)-19, which was also derived from (S)-3-buten-
2-ol (Scheme 9).
Stu d y of th e P ossibility of R-Deh a lop a lla d a tion
a n d Op tim iza tion of th e Rea ction Con d ition s. 1,1-
Dibromo-1-alkene 10 was used as the first substrate to
test the bicyclic carbopalladation protocol under different
reaction conditions, and the results are summarized in
Table 1.
As shown in Table 1, when the reaction was catalyzed
by palladium in refluxing CH3CN, the desired bicyclic
product 36 was not formed in detectable yield (entries
1-3). Using Et3N or K2CO3 as the base and Pd(PPh3)4
as the catalyst, the reactions were low yielding and not
clean (entries 4-11). Under the catalysis of Pd(PPh3)4
using CH3CN as the solvent and Et3N as the base, 10
was cyclized to afford monocyclic product 37 cleanly; even
with prolonged reaction time, the second cyclization was
not observed (entry 12). When 10 mol % Pd2(dba)3-CHCl3
was used, only monocyclic product 37 was formed in
For use in a mechanistic study, compound 35 was
prepared from 34 and 3 (Scheme 8).13
Optically pure compound (S,S)-16 was prepared by
etherification of the corresponding optically pure (S)-3-
buten-2-ol with 2a .15 (S)-23 was synthesized by alkylation
(15) Balmer, E.; Germain, A.; J ackson, W. P.; Lygo, B. J . Chem. Soc.,
Perkin Trans. 1 1993, 399-400.
(14) LeGoff, E. J . Org. Chem. 1964, 29, 2048-2050.

Efficient Entry to Fused Bicycles
J . Org. Chem., Vol. 65, No. 25, 2000 8535
Ta ble 1. Bicyclic Ca r bop a lla d a tion Rea ction of 10 u n d er Ca ta lysis of P a lla d iu m (0) Com p lex
yield (%)
entry
catalysisa
solventb
base
time (h)
T (°C)
36
37
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
4% A
20% A
13% B
10% B
11% B
10% B
10% C
11% B
10% B
10% B
15% B
10% B
10% C
6% D
CH3CN (0.011)
CH3CN (0.045)
CH3CN (0.045)
toluene (0.045)
toluene (0.03)
xylene (0.051)
DMF (0.045)
xylene (0.03)
xylene (0.03)
xylene (0.045)
DMF e (0.045)
CH3CN (0.15)
xylene (0.045)
DMF (0.045)
xylene (0.047)
Et3N d
K2CO3
Ag2CO3
Et3N
K2CO3
Et3N
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Et3N
K2CO3
K2CO3
6
72
14
7.5
25
52
13.5
38
34
24
12
23
6.5
23.5
24
reflux
reflux
reflux
reflux
reflux
reflux
100
0
0
0
0
0
0
0
0
0
0
0
0
21
47
75
73
16
0
c,d
34
20
15
43
40
43
22
0
0
0
62
68
d
reflux f
reflux
80-85
90
d
d
56
80
95
80-85
d
10% B
K2CO3
a
b
A ) Pd(OAc)2, PPh3; B ) Pd(PPh3)4; C ) Pd2(dba)3-CHCl3, dppe; D ) Pd2(dba)3-CHCl3, PPh3. The numbers in parentheses are the
molar concentration of 10 in the solvent. c Ag2CO3 (1 equiv) was added. n-Bu4NCl was added. e EtOH (10 equiv) was added. f Before
d
refluxing, the reaction was reacted at 70-80 oC for 45 min.
Sch em e 9
F igu r e 1.
Among the many methods for generating alkylidene
carbenes,17 sR-elimination is one of the most represent-
tive approaches. Intramolecular reactions of methylene-
carbenes derived by the reaction of 1,1-dibromoalkenes
with organolithium11,18,19 or magnesium20 have been well
xylene after 6.5 h at 80 °C (entry 13). However, bicyclic
product 36 was formed in 62% yield together with a 16%
yield of monocycle 37 after heating in DMF for 23.5 h
(entry 14). The 1H NMR data of the obtained product
36 are as follows: 5.23 (s, 2 H), 5.04 (s, 2 H), 3.70 (s, 12
H), 2.82 (s, 4 H), 2.63 (s, 4 H) ppm. The simplicity of
the 1H NMR data led us to doubt the structure of
this cyclized product, since steric interactions are likely
to distort the six sp2-carbon atoms out-of-plane. This
would, in principle, make the cyclic protons chemical
environmentally unequal, thus complicating the splitting
patterns. Ultimately, we determined the structure of
the cyclization product as 36 unambiguously by X-ray
analysis, and the six sp2-carbon atoms are truly not
coplanar as judged from the ORTEP presentation (Figure
1 in the Supporting Information). The best results were
obtained with 10 mol % Pd(PPh3)4, K2CO3 (10 equiv), and
n-Bu4NCl (2 equiv)16 in xylene at 80-85 °C for 24 h
(condition A) affording fused 6,6-bicyclic product 36 in
68% yield (entry 15).
(16) For the efficiency of tetraalkylammonium salts in Heck type
reactions, see: (a) J effery, T. J . Chem. Soc., Chem. Commun. 1984,
1287-1289. (b) J effery, T. Tetrahedron Lett. 1985, 26, 2667-2670. (c)
J effery, T. Synthesis 1987, 70-71. (d) J effery, T. Tetrahedron 1996,
52, 10113-10130.
(17) For the formation of alkylidenecarbenes, see: (a) Stang, P. J .
Chem. Rev. 1978, 78, 383-405. (b) Stang, P. J . Acc. Chem. Res. 1982,
15, 348-354.
(18) (a) Beny, J .-P.; Dhawan, S. N.; Kagan, J .; Sundlass, S. J . Org.
Chem. 1982, 47, 2201-2204. (b) Padwa, A.; Wong, G. S. K. J . Org.
Chem. 1986, 51, 3125-3133. (c) Kozikowski, A. P.; Okita, M.; Koba-
yashi, M.; Floss, H. G. J . Org. Chem. 1988, 53, 863-869. (d) Harada,
T.; Hara, D.; Hattori, K.; Oku, A. Tetrahedron Lett. 1988, 29, 3821-
3824. (e) Piers, E.; Chong, J . M.; Morton, H. E. Tetrahedron 1989, 45,
363-380. (f) Nicolauo, K. C.; Marron, B. E.; Veale, C. A.; Webber, S.
E.; Serhan, C. N. J . Org. Chem. 1989, 54, 5527-5535. (g) McIntosh,
M. C.; Weinreb, S. M. J . Org. Chem. 1993, 58, 4823-4832. (h) Braun,
M. Angew. Chem., Int. Ed. Engl. 1998, 37, 430-451.
(19) (a) Baird, M. S.; Baxter, A. G. W.; Hoorfar, A.; J efferies, I. J .
Chem. Soc., Perkin Trans I 1991, 2575-2581. (b) Hartzler, H. D. J .
Am. Chem. Soc. 1964, 86, 526-527.
(20) Wakabayashi, N. J . Org. Chem. 1967, 32, 489-490.

8536 J . Org. Chem., Vol. 65, No. 25, 2000
Ma et al.
Sch em e 10
Sch em e 11
documented. Recently, an elegant generation of alkyli-
dene carbenes from 1,1-dibromo-1-alkenes by the reaction
with SmI2 was reported by Tani et al.21 Mori and
co-workers found alkylidene carbenes could be produced
by R-elimination wthin a 1,1-dibromoalkene precursors
using stannyl anion generated from Me3SiSnBu3 and
TASF.22 The generated alkylidene carbene can undergo
either an intramolecular 1,2-shift reaction or 1,5-C-H
insertion reaction depending on the substituent at the
R-position (Scheme 10).
Thus, the following experiments under these standard
reaction conditions were designed to further study the
possibility of alkylidene carbene gereration through an
R-dehalopalladation reaction:
(1) We studied the oxidative addition reaction of
2,2-diphenyl-1,1-dibromoethene23,24 with a stoichiometric
amount of Pd(PPh3)4. In the event, the R-elimination reac-
tion will presumably afford 1,2-diphenylacetylene25 via
the phenyl-migration reaction of the putative (diphenyl-
methylidene)carbene intermediate. We did observe the
formation of the rearrangement product via Raman and
GC-MS spectra by comparison with the authentic
sample,26 indicating that R-debromopalladation is feasible
in this case. At the same time, 1,1-diphenylethene was
also formed (Scheme 11). 1,1-Dibromo-2-phenylpropene
reacted with a stoichiometric amount of Pd(PPh3)4 to
afford R-methylstyrene and 1-phenylpropyne similarly.
To the best of our knowledge, these results are the first
entries of R-dehalopalladation reactions.5-9
(2) However, for the bicyclization reaction of 10 under
condition A, after careful examination of the crude
reaction mixture, 1,2-alkyl migration product 43,27 the
intramolecular 1,5-C-H insertion28 product 44, the cor-
responding intermolecular C-H insertion products of
carbene intermediate 41 with xylene,29 i.e., 45 and 46,
and possible cyclopropanation products were not formed
(Scheme 12).
(3) As it was reported that carbene intermediates could
react with diphenylmethane,29 we studied the cyclization
of 10 in the presence of diphenylmethane under condition
A. In this case, the bicyclization products 36 and 40
(decarboxylation product of 36) were isolated in 62% and
9% yields, respectively (Scheme 13). The formation of
C-H bond insertion product 42 of the possible carbene
intermediate 41 with diphenylmethane was not detected.
(4) It is also noteworthy that the reaction of the 1,1-
dibromo-1-alkene with one methyl and one terminal Cd
C bond connected, i.e., 35, under condition A afforded two
monocyclic products 48 and 49 (the decarboxylation
product of 48) containing the original C-Br bond cis to
the methyl group in 32% and 32% yields, respectively.
(27) For 1,2-shift reaction of alkylidenecarbenes, see: (a) Bothner-
by, A. A. J . Am. Chem. Soc. 1955, 77, 3293-3296. (b) Wolinsky, J . J .
Org. Chem. 1961, 26, 704-711. (c) Erickson, K. L.; Wolinsky, J . J . Am.
Chem. Soc. 1965, 87, 1142-1143. (d) Newman, M. S.; Gromelski, S. J .
J . Org. Chem. 1972, 37, 3220-3224. (e) Kobrich, G.; Merkel, D.; Thiem,
K.-W. Chem. Ber. 1972, 105, 1683-1693. (f) Wolinsky, J .; Clark, G.
W.; Thorstenson, P. C. J . Org. Chem. 1976, 41, 745-750. (g) Kowalski,
C. J .; Fields, K. W. J . Am. Chem. Soc. 1982, 104, 321-323. (h) Gilbert,
J . C.; Weerasooriya, U. J . Org. Chem. 1982, 47, 1837-1845. (i)
McDouall, J . J . W.; Schlegel, H. B.; Francisco, J . S. J . Am. Chem. Soc.
1989, 111, 4622-4627. (j) Walsh, R.; Untiedt, S.; Stohlmeier, M.;
Meijere, A. Chem. Ber. 1989, 122, 637-642. (k) Ochiai, M.; Ito, T.;
Takaoka, Y.; Masaki, Y.; Kunishma, M.; Tani, S.; Nagao, Y. J . Chem.
Soc., Chem. Commun. 1990, 118-119. (l) Fischer, D. R.; Williamson,
B. L.; Stang, P. J . Synlett 1992, 535-536. (m) Ohira, S.; Moritani, M.;
Ida, T.; Yamato, M. J . Chem. Soc., Chem. Commun. 1993, 1299-1300.
(n) Likhotvorik, I. R.; Brown, D. W.; J ones, J r., M. J . Am. Chem. Soc.
1994, 116, 6175-6178.
(28) For intramolecular 1,5-C-H insertion of alkylidenecarbene,
see: (a) Walsh, R. A.; Bottini, A. T. J . Org. Chem. 1970, 35, 1086-
1092. (b) Fischer, R. H.; Baumann, M.; Kobrich, G. Tetrahedron Lett.
1974, 1207-1208. (c) Karpf, M.; Dreiding, A. S. Helv. Chim. Acta 1979,
62, 852-865. (d) Gilbert, J . C.; Giamalva, D. H.; Weerasoonriya, U. J .
Org. Chem. 1983, 48, 5251-5256. (e) Gilbert, J . C.; Blackburn, B. K.
Tetrahedron Lett. 1984, 25, 4067-4070. (f) Gilbert, J . C.; Giamalva,
D. H.; Baze, M. E. J . Org. Chem. 1985, 50, 2557-2563. (g) Gilbert, J .
C.; Blackburn, B. K. J . Org. Chem. 1986, 51, 4087-4089. (h) Ohira,
S.; Okai, K.; Moritani, T. J . Chem. Soc., Chem. Commun. 1992, 721-
722. (i) Kim, S.; Cho, C. M. Tetrahedron Lett. 1994, 35, 8405-8408. (j)
Williamson, B. L.; Tykwinski, R. R.; Stang, P. J . J . Am. Chem. Soc.
1994, 116, 93-98. (k) Tykwinski, R. R.; Stang, P. J .; Persky, N. E.
Tetrahedron Lett. 1994, 35, 23-26. (l) Schildknegt, K.; Bohnstedt, A.
C.; Feldman, K. S.; Sambandam, A. J . Am. Chem. Soc. 1995, 117,
7544-7545. (m) Ohira, S.; Sawamoto, T.; Yamato, M. Tetrahedron Lett.
1995, 36, 1537-1538. (n) Taber, D. F.; Meagley, R. P.; Doren, D. J . J .
Org. Chem. 1996, 61, 5723-5728.
(21) (a) Kunishima, M.; Hioki, K.; Ohara, T.; Tani, S. J . Chem. Soc.,
Chem. Commun. 1992, 219-220. (b) Kunishima, M.; Hioki, K.; Tani,
S.; Kato, A. Tetrahedron Lett. 1994, 35, 7253-7254.
(22) Sato, H.; Isono, N.; Miyoshi, I.; Mori, M. Tetrahedron 1996, 52,
8143-8158.
(23) Ko¨brich, G. Angew. Chem., Int. Ed. Engl. 1965, 4, 49-68.
(24) (a) Posner, G. H.; Loomis, G. L.; Sawaya, H. S. Tetrahedron
Lett. 1975, 1373-1376. (b) Speziale, A. J .; Ratts, K. W. J . Am. Chem.
Soc. 1962, 84, 854-859.
(25) For 1,2-migration of R-aryl groups of alkylidene carbenes, see:
(a) Stang, P. J .; Mangum, M. G.; Fox, D. P.; Haak, P. J . Am. Chem.
Soc. 1974, 96, 4562-4569. (b) Stang, P. J .; Fox, D. P.; Collins, C. J .;
Watson, C. R., J r. J . Org. Chem. 1978, 43, 364-365. (c) Gilbert, J . C.;
Weerasooriya, U. J . Org. Chem. 1982, 47, 1837-1845.
(26) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 4467-4470.
(29) Doyle, M. P.; Taunton, J .; Oon, S. M.; Liu, M. T. H.; Soundara-
rajan, N.; Platz, M. S. J ackson, J . E. Tetrahedron Lett. 1988, 29, 5863-
5866.

Efficient Entry to Fused Bicycles
J . Org. Chem., Vol. 65, No. 25, 2000 8537
Sch em e 12
Sch em e 13
marized in Table 2. From Table 2, it is obvious that a
series of bicycles, i.e., fused 5,6- (entry 12, Table 2), 6,6-
(entries1-6 and 8-11, Table 2), 6,7- (entries 14 and 15,
Table 2), and 7,7-bicyclic compounds (entry 16, Table 2),
can be efficiently prepared.
To explore the influence of steric effects on the reactiv-
ity of CdC double bonds, the bicyclic carbopalladation
reactions of four additional precursors in which the
double bonds were substituted with one or two phenyl
groups were studied. Products 54 and 55 could be
synthesized in xylene under condition B in 37% and 46%
yields, respectively (entries 3 and 4, Table 2). From
precursor 12, in which the two CdC bonds were both
substituted with phenyl groups, the bicyclic product 56
can also be prepared in reasonable yield accompanied by
the formation of the monocyclic reduction product 57
(entry 5, Table 2). The formation of 57 may be due to
the high steric hindrance of the phenyl group. Thus, the
phenyl-substituted CdC bond was apparently did not
insert into the C-Pd bond of intermediate 58. Instead,
the second C-Pd bond was reduced to afford 57 (Figure
1).30
When the reaction was performed in refluxing CH3CN
for 13 h under the catalysis of Pd(PPh3)4 using Et3N as
the base, 48 could be isolated in 61% yield. It is obvious
that the reaction proceeds via a simple cyclic carbo-
palladation process instead of an R-debromopalladation-
1,2-alkyl shift to form alkyne 5027 or an 1,5-C-H bond
insertion to produce 51 (Scheme 13).28 Here, the carbon-
bromine bond trans to the methyl group in 35 appears
to be regiospecifically activated, perhaps as a conse-
quence of coordination between the palladium atom and
the CdC bond.
In summary, 1-bromo-1-alkenylpalladium bromides,
formed by the oxidative addition reaction of 10 and 35,
underwent a faster cyclic carbopalladation reaction rather
than an R-debromopalladation reaction.
Th e Scop e of Bicyclic Ca r bop a lla d a tion Rea c-
tion s. Having established the standard reaction condi-
tions for bicyclic carbopalladation reaction of 10, we tried
to investigate the scope and cyclization patterns of this
bicyclization reaction. Some typical examples are sum-
For precursor 17, the bicyclic product 59 can be
prepared only in 19% yield under condition C at 85 °C
for 23.5 h, together with the monocyclic product 60 (20%
yield) and the corresponding monocyclic reduction prod-
uct 61 (12% yield) (entry 6, Table 2). For 13, in which
the two CdC bonds were substituted with methoxycar-
bonyl groups, only monocyclic product 62 was isolated
in 94% yield under catalysis by Pd2(dba)3-CHCl3. No
bicyclic product was formed in any detectable yield (entry
7, Table 2).
1
When 16 was submitted to condition B, the H NMR
signals for the vinyl protons of the bicyclic product 63
were observed as follows: 5.36 (s, 1H), 5.31 (s, 1H), 5.20
(s, 1H), 5.15 (s, 1H) ppm. It is obvious that a 1:1 ratio of
(30) (a) Abelman, M. M.; Oh, T.; Overman, L. E. J . Org. Chem.
1987, 52, 4130-4133. (b) Zask, A.; Helquist, P. J . Org. Chem. 1978,
43, 1619-1620. (c) Ma, S.; Negishi, E. J . Am. Chem. Soc. 1995, 117,
6345-6357.

8538 J . Org. Chem., Vol. 65, No. 25, 2000
Ma et al.
Ta ble 2. Syn th esis of Bicycles via Bica r bop a lla d a tion
Sch em e 14
the same condition. Its 1H NMR spectrum showed the
signal of the vinylic protons at 5.36 (s, 1H) and 5.20 (s,
1H) ppm, respectively, which led us to assign the other
1
set of signal in the H NMR spectrum of 63 to the meso
diastereomer (entry 9, Table 2). Similarly, from 23 and
the corresponding optically pure precursor (S)-23, bicyclic
product 64 and (S)-64, respectively, could be prepared
successfully. Thus, bicyclic products with different stereo-
chemistry in different rings can also be synthesized in
one step (entries 10 and 11, Table 2).
Under condition C, 28 could give 5,6-bicyclic product
65 in 33% yield together with monocyclic products 66 and
67 in 8% and 3% yields, respectively (entry 12, Table 1
and Figure 1). In this reaction, the ratio of 65/66/67 did
not change with prolonged reaction time. The attempt
to prepare fused 5, 7-bicycles failed. From 26, the reaction
only gave monocyclic product 68 under condition A (entry
13, Table 2).
Apart from the results given above, we tried and failed
to construct fused 6, 14- and 6, 21-bicyclic products from
31 and 33. Under the usual reaction conditions, 31 and
33 gave monocyclic products 72 and 73, respectively
(Scheme 14).
Oxid a t ive Ad d it ion R ea ct ion of 1,1-Dich lor o-
1-a lk en e. To test the possibility of bicyclic carbo-
palladation of 1,1-dichloro-1-alkenes, 14 was submitted
to condition A. After reacting for 13 h at 80 °C, the
starting material was almost quantitatively recovered.
On the other hand, when a 1:1 mixture of 10 and 14 was
reacted under the same conditions, the bicyclic product
36 could be isolated in 64% yield together with quantita-
tive recovery of starting material 14. Obviously, the
bicyclic carbopalladation of 1,1-dichloro-1-alkenes did not
proceed due to the low reactivity of carbon-chlorine
bonds toward palladium in the oxidative addition reac-
tion (Scheme 15).32
Mech a n ism . For the propose of mechanistic study,
the cyclization of the monocyclic product 37, which
was prepared from monocyclization of 10 under the
catalysis of Pd(PPh3)4 (75% yield, entry 12, Table 1),
was attempted under condition A for 16 h and the bi-
cyclic product 36 was formed in 92% 1H NMR yield
(Scheme 16).
Furthermore, when compound 10 was submitted to
condition A for 0.5 h, the monocyclic product 37 could be
isolated in 79% yield. At this point, the bicyclic product
36 was not formed. Thus, a stepwise cyclization catalytic
the diastereomers of 63 were formed (entry 8, Table 2).
(S,S)-16 was synthesized and afforded the optically pure
product (S,S)-63, with the retention of the absolute
configuration of the chiral center,31 in 55% yield under
(31) HPLC (Column: Chiralcel OD (Daicel); Eluent: n-hexane/2-
propanol ) 100:4) showed a simple peak for these optically active
compounds.
(32) Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R. In Purification
of Laboratory Chemicals, 2nd ed.; Pergamon: Oxford, 1980.

Efficient Entry to Fused Bicycles
J . Org. Chem., Vol. 65, No. 25, 2000 8539
were determined by using methylene bromide as the internal
reference. GC yields were determined on Perkin-Elmer auto-
system XL using EC-5 (Column: Alltech, 30 m × 0.32 mm,
film thickness: 0.25 µm). Unless otherwise stated, all reactions
were run under a nitrogen atmosphere. All commercially
available reagents were used without further purification
unless otherwise stated. All solvents used were of reagent
grade and were further dried.33 Reactions were monitored by
Sch em e 15
36
TLC. Pd(PPh3)4,34 Pd(OAc)2,35 and Pd2(dba)3-CHCl3 were
prepared as reported.
Sta r tin g Ma ter ia ls. (1) P r ep a r a tion of Dim eth yl 2-(2′-
P r open yl)m alon ate (3).37 Repr esen tative P r ocedu r e (P r o-
ced u r e A). To a suspension of NaH (11.00 g, 60% in paraffin
oil, 0.28 mol) in THF (200 mL) was added dimethyl malonate
(33.00 g, 0.25 mol) slowly through a dropping funnel. After
the addition, the mixture was stirred for additional 15 min at
room temperature. Then, allyl bromide (30.25 g, 0.25 mol) was
added dropwise at room temperature. After 2 h, the reaction
mixture was quenched with water, extracted with ether, and
washed with brine. The combined organic extracts were dried
over MgSO4 and evaporated. The crude product was further
purified by flash column chromatography on silica gel (petro-
leum ether/ethyl acetate ) 15:1) to give 3 (37.10 g, 86%) as a
colorless liquid: 1H NMR δ 5.9-5.6 (m, 1H), 5.25-4.95 (m,
2H), 3.75 (s, 6H), 3.48 (t, J ) 7.6 Hz, 1H), 2.66 (t, J ) 6.79 Hz,
Sch em e 16
2H); IR (neat) 2954, 1734, 1638, 1438 cm-1
.
(2) 6-(1′,1′-Dibr om om eth ylen e)-4,8-d ioxa -1,10-u n d eca -
d ien e (15) (P r oced u r e B). To a suspension of NaH (200 mg,
60% in paraffin oil, 5.00 mmol, 20 min) in THF (5 mL) was
added allyl alcohol (300 mg, 5.17 mmol) slowly through a
dropping funnel. After the addition, the mixture was stirred
for an additional 20 min at room temperature. Then 2a
(700 mg, 1.88 mmol) in THF (5 mL) was added dropwise at
room temperature. After the mixture was stirred at room
temperature for 5 h, the reaction was quenched with water,
extracted with ether, and washed with brine. The combined
organic extracts were dried over MgSO4 and evaporated. The
crude product was further purified by flash column chroma-
tography (petroleum ether/ethyl acetate ) 100:1) to give 15
(400 mg, 65%) as a colorless liquid: 1H NMR δ 5.95-5.70(m,
2H), 5.35-5.0 (m, 4H), 4.15 (s, 4H), 3.93 (m, 4H); MS (70 eV,
79
EI) m/z 327 (3.29) [M+(2 × 81Br)-H], 325 (3.23) [M+(81Br,
-
Br)-H], 323 (1.05) [M+(2 × 79Br)-H], 149 (100.00) [M+ - 2 ×
Br(1 × 81Br, 1 × 79Br)-CH2]; IR (neat) 2924, 1448, 1422, 1162
cm-1. Anal. Calcd for C10H14Br2O2: C, 36.84; H, 4.33. Found:
C, 37.05; H, 4.31.
cycle is proposed for this reaction as summarized in
Scheme 17.
Con clu sion
(3) Syn t h esis of 6-(1′,1′-Dib r om om et h ylen e)-3,9-d i-
m eth yl-4,8-d ioxa -1,10-u n d eca d ien e (16). Rep r esen ta tive
P r oced u r e (P r oced u r e C). To the suspension of NaH (0.93
g, 55% in paraffin oil, 21.31 mmol) in THF (15 mL) was added
3-buten-2-ol (1.40 g, 19.44 mmol) dropwise. After the addition,
the mixture was stirred at room temperature for 1.5 h, HMPA
(3 mL) was added, and the mixture was cooled to -78 °C with
a dry ice-acetone bath. After 5 min, 2a (2.86 g, 7.69 mmol) in
THF (1.0 mL) was introduced at -78 °C, and then the
temperature was raised to room temperature slowly and
stirred for additional 5 h. The reaction was quenched with
water, extracted with ether, and washed with brine. The
combined organic extracts were dried over MgSO4 and evapo-
rated. The crude product was further purified by flash column
chromatography (petroleum ether/ethyl acetate ) 100:1) to
afford 16 (1.72 g, 63%) as a colorless liquid: 1H NMR δ 5.90-
5.55 (m, 2H), 5.40-4.90 (m, 4H), 4.4-3.95 (m, 4H), 3.95-3.65
(m, 2H), 1.24 (d, J ) 6.44 Hz, 6H); MS (70 eV, EI) m/z (%) 357
(47.42) [M+H (2 × 81Br)], 355 (100.00) [M+H (81Br, 79Br)], 353
(53.77) [M+H (2 × 79Br)]; IR (neat) 2974, 1614, 1444, 1372,
(1) The oxidative addition reaction of 1,1-dihalo-1-
alkenes is a coordination-directed highly regioselective
reaction;
(2) Αn R-dehalopalladation reaction was observed
for the first time in the reaction of 1,1-dibromo-2,2-
diphenylethene or 1,1-dibromo-2-phenylpropene with a
stoichiometric amount of Pd(PPh3)4. However, the R-
dehalopalladation reaction was not observed in any pre-
cursors for bicyclization under the reaction conditions
tested, probably due to the fast intramolecular carbo-
palladation reaction of the CdC bonds;
(3) A new and highly convenient bicyclic carbopalla-
dation reaction was developed. By this protocol, a serial
of bicycles, i.e., fused 5,6-, 6,6-, 6,7-, and 7,7-bicyclic
compounds, can be efficiently prepared. This reaction
should open up new and efficient opportunities for the
construction of bicyclic products.
(4) Under different reaction conditions, the mono-
cyclization and bicyclization can be controlled;
(5) The bicyclic carbopalladation reaction proceeded in
a stepwise manner.
(33) Still, J . K. In Chemistry of the Metal-Carbon Bond; Hartley,
F., Ed.; J ohn Wiley & Sons: New York, 1987; Vol. 1.
(34) Coulson, D. R. Inorg. Synth. 1972, 13, 121-124.
(35) Stephenson, T. A.; Morehouse, S. M.; Powell, A. R.; Heffer, J .
P.; Wilkinson, G. J . Chem. Soc. 1965, 3632-3640.
(36) Ukai, T.; Kawazura, H.; Ishii, Y.; Bonnet, J . J .; Ibers, J . A. J .
Organomet. Chem. 1974, 65, 253-266.
Exp er im en ta l Section
1
Gen er a l Tech n iqu es. The H NMR spectra were recorded
(37) Oppolzer, W.; Gaudin, J .-M.; Birkinshaw, T. N. Tetrahedron
Lett. 1988, 29, 4705-4708.
using CDCl3 as the solvent and internal standard. NMR yields

8540 J . Org. Chem., Vol. 65, No. 25, 2000
Ma et al.
Sch em e 17
1152, 1086 cm-1; HRMS calcd for C12H1979Br2O2 (M+H) 352.9752,
found 352.9765.
of the solvent, the residue was purified by flash column
chromatography (petroleum ether/ethyl acetate ) 10:1) to
afford compounds 48 (40 mg, 32%) and 49 (32 mg, 32%). 48:
(4) 7-(1′,1′-Dibr om om eth ylen e)-5,5-bis(m eth oxyca r bo-
n yl)-1,10-u n d eca d ien e (26). Rep r esen ta tive P r oced u r e
(P r oced u r e D). A solution of 25 (0.50 g, 1.05 mmol) in THF
(2 mL) was treated with allylzinc chloride, which was prepared
from zinc-copper couple (3.00 g) and allyl chloride (2 mL) in
DMSO (10 mL).14 After being stirred at room temperature for
19 h, the reaction was quenched with water, neutralized with
HCl (2 N, 3 mL), extracted with ether (3 × 10 mL), and washed
with brine. The combined organic extracts were dried over
MgSO4 and evaporated. The crude product was further purified
by flash column chromatography (petroleum ether/ethyl ac-
etate ) 20:1) to give 26 (0.34 g, 74%) as a colorless liquid
together with the recovered 25 (0.10 g). 26: 1H NMR δ 5.9-
5.6 (m, 2H), 5.15-4.80 (m, 4H), 3.72 (s, 6H), 3.05 (s, 2H), 2.4-
2.1 (m, 4H), 2.1-1.9 (m, 4H); MS (70 eV, EI) m/z 441 (0.88)
[M+H (2 × 81Br)], 439 (1.57) [M+H (81Br, 79Br)], 437 (0.90) [M+H
(2 × 79Br)], 185 (100.00) [CH2dCHCH2CH2C(COOCH3)2+]; IR
(neat) 2950, 1730, 1636, 1438, 1276 cm-1; HRMS calcd for
1
liquid; H NMR δ 5.33 (s, 1H), 4.95 (s, 1H), 3.64 (s, 6H), 2.90
(s, 2H), 2.70 (s, 2H), 1.93 (s, 3H); MS (70 eV, EI) m/z 305 (4.24)
[M+H(81Br)], 303 (4.77) [M+H(79Br)], 245 (100.00) [M+(81Br) -
COOMe], 243 (96.87) [M+(79Br) - COOMe]; IR (neat) 2952,
1734, 1626, 1438, 1378 cm-1; HRMS calcd for C12H1579BrO4
(M+) 302.0153, found 302.0182.
1-Br om o-2-m eth yl-4-m eth oxyca r bon yl-6-m eth ylen ecy-
1
cloh exen e (49): liquid; H NMR δ 5.38 (s, 1H), 4.98 (s, 1H),
3.70 (s, 3H), 2.95-2.35 (m, 5H), 2.0 (s, 3H); MS (70 eV, EI)
m/z 246 (23.07) [M+(81Br)], 244 (23.56) [M+(79Br)], 106 (100.00)
[M+ - Br - COOMe]; IR (neat) 2950, 1730, 1626, 1438, 1376,
1272 cm-1; HRMS calcd for C10H1379BrO2 (M+) 244.0099, found
244.0094.
(b )
1-Br om o-2-m et h yl-4,4-b is(m et h oxyca r b on yl)-6-
m et h ylen ecycloh exen e (48). A mixture of compound 35
(250 mg, 0.65 mmol), Et3N (0.25 mL), and Pd(PPh3)4 (45 mg,
6 mol %) in CH3CN (4 mL) was refluxed for 13 h to afford 48
(120 mg, 61%).
C
16H2279Br2O4 (M+) 435.9885, found 435.9899.
See the Supporting Information for all the experimental
(c) 1-Br om o-2-(2′,2′-bis(m eth oxyca r bon yl)-4′-p en ten yl)-
4,4-bis(m eth oxyca r bon yl)-6-m eth ylen ecycloh exen e (37).
A solution of 10 (500 mg, 0.90 mmol), Et3N (0.50 mL, 3.60
mmol), and Pd(PPh3)4 (105 mg, 10 mol %) in CH3CN (6 mL)
was stirred at 56 °C for 23 h to afford 37 (320 mg, 75%) as a
yellowish liquid: 1H NMR δ 5.95-5.70 (m, 1H), 5.52 (s, 1H),
5.18-4.95 (m, 3H), 3.72 (s, 12H), 3.20 (s, 2H), 2.95 (s, 2H),
2.70 (s, 2H), 2.67 (d, J ) 7.61 Hz, 2H); MS (70 eV, EI) m/z 474
(2.03) [M+(81Br)], 472 (2.03) [M+(79Br)], 59 (100.00) [+COOCH3];
IR (neat) 2934, 1732, 1438, 1260-1230 cm-1; HRMS calcd for
details and spectra data of other starting materials.
Ca r bop a lla d a tion Rea ction of 2,2-Dibr om o-1-p h en yl-
styr en e w ith a Stoich iom etr ic Am ou n t of P d (P P h 3)4. To
a degassed solution of 2,2-dibromo-1-phenylstyrene (40 mg,
0.12 mmol), K2CO3 (82 mg, 0.59 mmol), and n-Bu4NCl (33 mg,
0.12 mmol) in xylene (2 mL) was added Pd(PPh3)4 (137 mg,
0.12 mmol) under N2. The reaction mixture was stirred at 80-
85 °C for 3 h. The residue was filtered to remove the catalyst
and the inorganic salts. The filtrate was submitted directly to
GC and GC-MS analysis. 1,2-Diphenylacetylene and 1,1-
diphenylethene were formed in 18% and 15% yield, respec-
tively, as determined by GC analysis with authentic samples.
The starting material was recovered in 6% GC yield.
A similar procedure was performed for the mixture of
1,1-dibromo-2-phenylpropene (87 mg, 0.32 mmol), Pd(PPh3)4
(366 mg, 0.32 mmol), K2CO3 (219 mg, 1.59 mmol), and n-Bu4-
NCl (88 mg, 0.32 mmol) in xylene (3 mL) at 80-85 °C for
2.5 h to give R-methylstyrene (15%) and 1-phenylpropyne
(35%) together with recovered starting material (16%) by GC
analysis.
Mon ocycliza t ion R ea ct ion u n d er t h e Ca t a lysis of
P d (P P h 3)4. (a ) Syn t h esis of 1-Br om o-2-m et h yl-4,4-b is-
(m eth oxyca r bon yl)-6-m eth ylen ecycloh exen e (48). Rep -
r esen ta tive P r oced u r e (Con d ition A). To a degassed solu-
tion of compound 35 (160 mg, 0.42 mmol), K2CO3 (575 mg, 4.17
mmol), and n-Bu4NCl (231 mg, 0.83 mmol) in xylene (4 mL)
was added Pd(PPh3)4 (48 mg, 10 mol %) under N2. The reaction
mixture was stirred at 80-85 °C for 11 h as monitored by TLC
(eluent: petroleum ether/ethyl acetate ) 10:1). The residue
was passed through a short column of silica gel (eluent: ether)
to remove the catalyst and inorganic salts. After evaporation
C
20H2579BrO8 (M+) 472.0733, found 472.0727.
Bicycliza tion Rea ction u n d er th e Ca ta lysis of P a l-
la d iu m (0). (a ) Syn t h esis of 2,10-Dim et h ylen e-4,4,8,8-
tetr akis(m eth oxycar bon yl)bicyclo[4.4.0]dec-1(6)-en e (36).
Con d ition A. A degassed solution of compound 10 (52 mg,
0.09 mmol), Pd(PPh3)4 (11 mg, 10 mol %), K2CO3 (130 mg, 0.94
mmol), and n-Bu4NCl (52 mg, 0.19 mmol) in xylene (2 mL)
was stirred at 80-85 °C for 24 h to afford compound 36 (25
mg, 68%) as a white solid: mp 58-9 °C (ethyl acetate); 1H
NMR δ 5.23 (s, 2H), 5.04 (s, 2H), 3.70 (s, 12H), 2.82 (s, 4H),
2.63 (s, 4H); MS (70 eV, EI) m/z 392 (0.7) [M+], 43 (100.00)
[C3H7+]; IR (KBr) 2958, 1730, 1428 cm-1. Anal. Calcd for
C
20H24O8: C, 61.22; H, 6.16. Found: C, 61.03; H, 6.04.
(b) Syn th esis of 2,10-Dim eth ylen e-4,8-d ioxa bicyclo-
[4.4.0]d ec-1(6)-en e (52). Con d ition A. A degassed solution
of compound 15 (75 mg, 0.23 mmol), Pd(PPh3)4 (27 mg, 0.02
mmol), K2CO3 (317 mg, 2.30 mmol), and n-Bu4NCl (128 mg,
0.46 mmol) in xylene (5 mL) was stirred at 85 °C for 15.5 h to
afford 52 (31 mg, 83%) as a white solid: mp 80 °C (acetone);
1H NMR δ 5.40 (s, 2H), 5.12 (s, 2H), 4.21 (s, 4H), 4.15 (s, 4H);
MS (70 eV, EI) m/z 164 (60.45) [M+], 133 (100.00) [M+ - CH2O

Efficient Entry to Fused Bicycles
J . Org. Chem., Vol. 65, No. 25, 2000 8541
- H]; IR (KBr) 2922, 1438, 1164, 1094, 1056 cm-1. Anal. Calcd
for C10H12O2: C, 73.15; H, 7.37. Found: C, 73.49; H, 7.81.
(c) Syn t h esis of 2,10-Bis(m et h ylen e)-4-oxa -8,8-b is-
(m eth oxyca r bon yl)bicyclo[4.4.0] d ec-1(6)-en e (53). Con -
d ition A. A degassed solution of compound 21 (65 mg, 0.148
mmol), Pd2(dba)3-CHCl3 (8 mg, 0.08 mmol), K2CO3 (103 mg,
0.75 mmol), and dppe (12 mg, 0.03 mmol) in DMF (2 mL) was
stirred at 100 °C for 11 h. Flash chromatography (petroleum
ether/ethyl acetate ) 15:1) provided compound 53 (26 mg, 63%)
J ) 15.9, 6.03 Hz, 1H), 4.63 (s, 2H), 4.44 (s, 2H), 4.40 (s, 2H),
4.18 (dd, J ) 6.0, 1.42 Hz, 2H); IR (neat) 2924, 2850, 1672,
1624, 1492, 1448, 1358, 1080 cm-1; MS (70 eV, EI) m/z
398 (0.9) [M+(81Br)], 396 (0.95) [M+(79Br)], 117 (100.00)
[PhC3H4+]; HRMS calcd for C22H2179BrO2 (M+) 396.0725, found
396.0753.
3-(E)-Ben zylid en e-5-oxa -1-(2′-oxa -5′-p h en yl-4′(E)-p en -
ten yl)cycloh exen e (61): mp 50-51 °C (hexane); 1H NMR
(400 MHz, CDCl3) δ 7.50-7.10 (m, 10H), 6.54 (d, J ) 16.0 Hz,
1H), 6.25-6.05 (m, 3H), 4.57 (d, J ) 1.56 Hz, 2H), 4.21 (s,
2H), 4.09 (dd, J ) 6.1, 1.4 Hz, 2H), 4.02 (s, 2H); IR (KBr) 2922,
2842, 1670, 1596, 1492, 1446, 1078 cm-1; MS (70 eV, EI) m/z
318 (1.66) [M+], 105 (100.00) [PhC2H4+]; HRMS calcd for
C22H22O2 (M+) 318.1620, found 318.1596.
1
as a white solid: mp 85-6 °C (acetone-hexane); H NMR δ
5.33 (s, 1H), 5.30 (s, 1H), 5.10 (s, 1H), 5.08 (s, 1H), 4.18 (s,
2H), 4.17 (s, 2H), 3.71 (s, 6H), 2.85 (s, 2H), 2.52 (s, 2H); IR
(KBr) 2920, 1731, 1643, 1439, 1083 cm-1; MS (70 eV, EI) m/z
278 (45.92) [M+], 131 (100.00) [M+H - 2 × COOMe - CH2O].
Anal. Calcd for C15H18O5: C, 64.74; H, 6.52. Found: C, 64.51;
H, 6.36.
(d ) Syn t h esis of 2-(E)-Ben zylid en e-10-m et h ylen e-
4-oxa -8,8-b is(m et h oxyca r b on yl)b icyclo[4.4.0]d ec-1(6)-
en e (54). Con d ition A. A degassed solution of compound 24
(200 mg, 0.39 mmol), Pd(PPh3)4 (45 mg, 0.04 mmol), K2CO3
(268 mg, 1.94 mmol), and n-Bu4NCl (108 mg, 0.39 mmol)
in xylene (2.5 mL) was stirred at 85 °C for 24 h to afford
54 (50 mg, 37%) as a solid: mp 132 °C (CHCl3); 1H NMR δ
7.45-7.02 (m, 5H), 6.95(s, 1H), 5.36 (s, 1H), 5.16 (s, 1H), 4.50
(s, 2H), 4.19 (s, 2H), 3.73 (s, 6H), 2.91 (s, 2H), 2.57 (s, 2H);
IR (KBr) 2926, 1730, 1634, 1540, 1434, 1068 cm-1; MS
(70 eV, EI) m/z 354 (10.23) [M+], 91 (100.00) [PhCH2+]. Anal.
Calcd for C21H22O5: C, 71.17; H, 6.26. Found: C, 71.13; H,
6.22.
(h ) Syn th esis of 1-Br om o-2-(2′,2′,5′-tr is(m eth oxyca r -
bon yl)-4′(E)-p en ten yl)-4,4-bis(m eth oxyca r bon yl)-6-((E)-
m eth oxyca r bon ylm eth ylen e)cycloh exen e (62). Con d i-
tion A. A degassed solution of compound 13 (70 mg, 0.10
mmol), Pd2(dba)3-CHCl3 (6 mg, 0.06 mmol), Ag2CO3 (86 mg,
0.31 mmol), and PPh3 (12 mg, 0.05 mmol) in xylene (2 mL)
was stirred at 90 °C for 14 h to afford 62 (58 mg, 94%) as a
1
white solid: mp 90-1 °C (ethyl acetate); H NMR δ 6.89 (dt,
J ) 15.27, 7.71 Hz, 1H), 6.44 (s, 1H), 5.88 (d, J ) 15.5 Hz,
1H), 3.76 (s, 3H), 3.75(s, 6H), 3.73(s, 3H), 3.72 (s, 6H), 3.57 (s,
2H), 3.28(s, 2H), 2.83 (s, 2H), 2.82 (d, J ) 6.43 Hz, 2H); IR
(KBr) 2952, 1732, 1610, 1436, 1366 cm-1; MS (70 eV, EI) m/z
591 (6.49) [M+H(81Br)], 589 (6.29) [M+H(79Br)], 59 (100.00)
[COOCH3+]; HRMS calcd for C24H3079BrO12 (M+H) 589.0921,
found 589.0974.
(e) Syn th esis of 2-Meth ylen e-10-(E)-ben zyliden e-4,4,8,8-
tetr akis(m eth oxy-car bon yl)bicyclo[4.4.0]dec-1(6)-en e (55).
Con d ition A. A degassed solution of compound 30 (58 mg,
0.09 mmol), Pd(PPh3)4 (10 mg, 0.01 mmol), K2CO3 (64 mg, 0.46
mmol), and n-Bu4NCl (26 mg, 0.09 mmol) in xylene (1.5 mL)
was stirred at 90 °C for 22 h to afford 55 (20 mg, 46%) as a
liquid: 1H NMR δ 7.4-7.1 (m, 5H), 6.83 (s, 1H), 5.29 (s, 1H),
5.09 (s, 1H), 3.69 (s, 6H), 3.52 (s, 6H), 3.12 (s, 2H), 2.88 (s,
2H), 2.67 (s, 2H), 2.63 (s, 2H); MS (70 eV, EI) m/z 468 (100.00)
[M+]; IR (neat) 2952, 1732, 1436 cm-1; HRMS calcd for
(i) Syn t h esis of 2,10-Dim et h ylen e-3,9-d im et h yl-4,8-
d ioxa bicyclo[4.4.0]d ec-1(6)-en e (63). Con d ition A. A de-
gassed solution of compound 16 (100 mg, 0.28 mmol), Pd-
(PPh3)4 (16 mg, 5 mol %), K2CO3 (196 mg, 1.42 mmol), and
n-Bu4NCl (78 mg, 0.28 mmol) in xylene (1.5 mL) was stirred
at 85 °C for 20 h. Flash chromatography (petroleum ether/
ethyl acetate ) 40:1) afforded 63 (30 mg, 55%) as a white solid,
mp 50-2 °C (acetone-hexane). meso-63: 1H NMR δ 5.31 (s,
2H), 5.15 (s, 2H), 4.19 (dd, J ) 45.93, 18.32 Hz, 4H), 4.14 (q,
J ) 6.02 Hz, 2H), 1.38 (d, J ) 6.40 Hz, 6H); (R*, R*)-63: 1H
NMR δ 5.36 (s, 2H), 5.20 (s, 2H), 4.19 (dd, J ) 45.93, 18.32
Hz, 4H), 4.14 (q, J ) 6.02 Hz, 2H), 1.41 (d, J ) 6.35 Hz, 6H);
C
26H28O8 (M+) 468.1784, found 468.1783.
(f) Syn t h esis of 2,10-Bis((E)-b en zylid en e)-4,4,8,8-
tetr akis(m eth oxycar bon yl)bicyclo[4.4.0]dec-1(6)-en e (56).
Con d ition s A. A degassed solution of compound 12 (71 mg,
0.11 mmol), Pd(PPh3)4 (11 mg, 0.01 mmol), K2CO3 (69 mg, 0.50
mmol), and n-Bu4NCl (28 mg, 0.10 mmol) in xylene (2 mL)
was stirred at 85 °C for 22.5 h to afford 56 (21 mg, 39%) and
57 (5 mg, 9%). 56: mp 168-170 °C (ethyl acetate-hexane);
1H NMR δ 7.35-7.00 (m, 10H), 6.82 (s, 2H), 3.47 (s, 12H),
3.13 (s, 4H), 2.61 (s, 4H); IR (KBr) 2952, 1732, 1438 cm-1; MS
(70 eV, EI) m/z 544 (0.23) [M+], 45 (100.00) [COOH+]. Anal.
Calcd for C32H32O8: C, 70.58; H, 5.92. Found: C, 70.62; H,
5.97.
3-(E)-Ben zylid ien e-5,5-b is(m et h oxyca r b on yl)-1-(2′,2′-
b is(m et h oxyca r b on yl)-5′-p h en yl-4′(E)-p en t en yl)cyclo-
h exen e (57): liquid; 1H NMR δ 7.45-7.1 (m, 10H), 6.41 (d, J
) 15.8 Hz, 1H), 6.28 (s, 1H), 6.07 (dt, J ) 15.64, 7.36 Hz, 1H),
5.68 (s, 1H), 3.71 (s, 4H), 3.69 (s, 12H), 3.02 (s, 2H), 2.74 (d,
J ) 7.45 Hz, 2H); IR (neat) 2952, 1728, 1438, 1264-1098
cm-1; MS (70 eV, EI) m/z 531 (0.23) [M+ - CH3], 45 (100)
[+COOH]; HRMS calcd for C32H34O8 (M+) 546.2254, found
546.2226.
(g) Syn t h esis of 2,10-Bis((E)-b en zylid en e)-4,8-d ioxa -
bicyclo[4.4.0]d ec-1(6)-en e (59). Con d ition s A. A degassed
solution of compound 17 (250 mg, 0.52 mmol), Pd(PPh3)4 (30
mg, 0.03 mmol), K2CO3 (362 mg, 2.62 mmol), and n-Bu4NCl
(145 mg, 0.52 mmol) in xylene (3 mL) was stirred at 85 °C for
23.5 h to afford 59 (31 mg, 19%), 60 (40 mg, 20%), and 61 (20
mg, 12%). 59: mp 110-112 °C (hexane); 1H NMR δ 7.45-7.05
(m, 10H), 7.00 (s, 2H), 4.52 (s, 4H), 4.13 (s, 4H); IR (KBr) 2920,
1446, 1378, 1118 cm-1; MS (70 eV, EI) m/z 316 (28.69) [M+],
91(100.00) [PhCH2+]; HRMS calcd for C22H20O2 (M+) 316.1463,
found 316.1455.
MS (70 eV, EI) m/z 192 (21.37) [M+], 147 (100.00) [M+
-
OC2H5]; IR (KBr) 2976, 1446, 1408, 1062 cm-1; HRMS calcd
for C12H16O2 (M+) 192.1150, found 192.1154.
(j) Syn th esis of 2,10-Dim eth ylen e-3(S),9(S)-d im eth yl-
4,8-d ioxa bicyclo[4.4.0]d ec-1(6)-en e ((S,S)-63). Con d ition
A. A degassed solution of compound (S,S)-16 (50 mg, 0.14
mmol), Pd(PPh3)4 (8 mg, 5 mol %), K2CO3 (98 mg, 0.71 mmol),
and n-Bu4NCl (40 mg, 0.14 mmol) in xylene (1.5 mL) was
stirred at 85 °C for 21 h. Flash chromatography (petroleum
ether/ethyl acetate ) 40:1) afforded (S,S)-63 (15 mg, 55%)
1
as a white solid: mp 50-2 °C (acetone-hexane); H NMR δ
5.36 (s, 2H), 5.20 (s, 2H), 4.18 (dd, J ) 45.56, 17.7 Hz, 4H),
4.15 (q J ) 6.02 Hz, 2H), 1.41 (d, J ) 6.29 Hz, 6H); IR
(KBr) 2976, 1446, 1408, 1062 cm-1; [R]20 ) +83.0° (c 0.2,
D
chloroform).
(k ) Syn th esis of 2,10-Dim eth ylen e-3-m eth yl-4-oxa -8,8-
bis(m eth oxycar bon yl)bicyclo[4.4.0]dec-1(6)-en e (64). Con -
d ition A. A degassed solution of compound 23 (150 mg, 0.33
mmol), Pd(PPh3)4 (19 mg, 5 mol %), K2CO3 (229 mg, 1.66
mmol), and n-Bu4NBr (107 mg, 0.33 mmol) in xylene (2 mL)
was stirred at 85 °C. After the mixture was stirred for 18 h,
another portion of Pd(PPh3)4 (19 mg, 5 mol %) was added under
N2, and then the mixture was stirred for an additional 8 h at
85 °C. Flash chromatography afford 64 (66 mg, 67%) as a white
1
solid: mp 50-1 °C (acetone); H NMR δ 5.30 (s, 1H), 5.28 (s,
1H), 5.15 (s, 1H), 5.09 (s, 1H), 4.45-4.0 (m, 3H), 3.71 (s, 3H),
3.70 (s, 3H), 2.86 (dd, J ) 22.30, 13.22 Hz, 2H), 2.50 (dd, J )
42.24, 17.89 Hz, 2H), 1.36 (d, J ) 6.4 Hz, 3H); MS (70 eV, EI)
m/z 292 (22.61) [M+], 43 (100.00) [C3H7+]; IR (KBr) 2954, 1732,
1436, 1082 cm-1. Anal. Calcd for C16H20O5: C, 65.74; H, 6.90.
Found: C, 65.50; H 7.02.
1-Br om o-2-(2′-oxa -5′-p h en yl-4′(E)-p en ten yl)-4-oxa -6(E)-
ben zylid en ecycloh exen e (60): liquid; 1H NMR δ 7.6-7.1
(m, 10H), 7.02 (s, 1H), 6.65 (d, J ) 15.98 Hz, 1H), 6.29 (dt,
(l) Syn th esis of 2,10-Dim eth ylen e-3(S)-m eth yl-4-oxa -
8,8-bis(m eth oxyca r bon yl)bicyclo[4.4.0]d ec-1(6)-en e ((S)-
64). Con d ition A. A degassed solution of compound (S)-23

8542 J . Org. Chem., Vol. 65, No. 25, 2000
Ma et al.
(30 mg, 0.07 mmol), Pd(PPh3)4 (4 mg, 5 mmol %), K2CO3 (46
mg, 0.33 mmol), and n-Bu4NBr (22 mg, 0.07 mmol) in xylene
(1 mL) was stirred at 85 °C. After the mixture was stirred for
11.5 h, another portion of Pd(PPh3)4 (4 mg, 5 mol %) was added
under N2, and then the mixture was stirred for an additional
3 h at 85 °C. Flash chromatography afforded (S)-64 (13 mg,
67%) as a colorless liquid: 1H NMR data are the same as those
(KBr) 2932, 1738, 1436 cm-1; HRMS calcd for C21H26O8 (M+)
406.1628, found 406.1628.
(q ) Syn t h esis of 2,12-Bis(m et h ylen e)-5,5,9,9-t et r a -
k is(m eth oxyca r bon yl)bicyclo[5.5.0]d od ec-1(7)-en e (71).
Con d ition A. A degassed solution of compound 11 (100 mg,
0.17 mmol), Pd(PPh3)4 (20 mg, 10 mol %), Ag2CO3 (115 mg,
0.42 mmol), and n-Bu4NCl (95 mg, 0.34 mmol) in xylene (4.5
mL) was stirred at 80 °C for 5 h. After purification (petroleum
ether/dichloromathane ) 1.5:1), the reaction afforded 71 (27
mg, 38%) as a liquid: 1H NMR δ 5.05 (s, 2H), 4.79 (s, 2H),
3.72 (s, 12H), 2.83 (s, 4H), 2.50-2.35 (m, 4H), 2.25-2.10
(m, 4H); MS (70 eV, EI) m/z 420 (5.95) [M+], 241 (100.00)
[M+H - 2 × COOCH3 - 2 × OCH3]; IR (neat) 2954, 1728,
1496 cm-1; HRMS calcd for C22H28O8 (M+) 420.1784, found
420.1778.
for 64; [R]20 ) +23.2° (c 0.466, chloroform).
D
(m ) Syn th esis of 2,9-Bis(m eth ylen e)-4,4-bis(m eth oxy-
ca r bon yl)bicyclo[4.3.0]n on -1(5)-en e (65). Con d ition s A.
A degassed solution of compound 28 (400 mg, 0.94 mmol), Pd-
(PPh3)4 (54 mg, 5 mol %), K2CO3 (654 mg, 4.74 mmol), and
n-Bu4NCl (262 mg, 0.95 mmol) in xylene (2 mL) was stirred
at 85 °C for 13.5 h to afford 65 (80 mg, 33%), 66 (24 mg, 8%),
1
and 67 (10 mg, 3%). 65: liquid; H NMR δ 5.35 (s, 1H), 5.09
(r ) Syn t h esis of 2-Br om o-1-(2′,2′,9′,9′-t et r a k is(m et h -
oxyca r b on yl)-19′-eicosen yl)-5,5-b is(m et h oxyca r b on yl)-
3-m et h ylen ecycloh exen e (72). Con d it ion A. A degassed
solution of compound 31 (132 mg, 0.15 mmol), Pd(PPh3)4
(9 mg, 5 mol %), K2CO3 (104 mg, 0.75 mmol), and n-Bu4NCl
(42 mg, 0.15 mmol) in xylene (1.5 mL) was stirred at 85 oC
for 12 h. After purification (petroleum ether/ethyl acetate )
6:1), the reaction afforded 72 (73 mg, 61%) as a liquid: 1H
NMR (400 MHz, CDCl3) δ 5.9-5.65 (m, 1H), 5.45 (s, 1H),
5.05 (s, 1H), 5.05-4.75 (m, 2H), 3.64 (s, 6H), 3.63 (s, 6H),
3.62 (s, 6H), 3.11 (s, 2H), 2.88 (s, 2H), 2.60 (s, 2H), 2.05-1.85
(m, 2H), 1.85-1.60 (m, 6H), 1.40-1.15 (m, 18H), 1.15-0.85
(m, 4H); MS (70 eV, EI) m/z 719 (74.27) [M+ - Br], 145
(100.00) [+CH3C(COOMe)2]; IR (neat) 2926, 1730, 1436
cm-1; HRMS calcd for C39H5979BrO12 (M+) 798.3190, found
798.3179.
(s) Syn th esis of 2-Br om o-1-(2′,2′-bis(m eth oxyca r bo-
n yl)-12′-tr id ecen yl)-5,5-bis(m eth oxyca r bon yl)-3-m eth yl-
en ecycloh exen e (73). Con d ition A. A degassed solution of
compound 33 (200 mg, 0.30 mmol), Pd(PPh3)4 (17 mg, 5 mol
%), K2CO3 (208 mg, 1.51 mmol), and n-Bu4NCl (83 mg, 0.30
mmol) in xylene (2 mL) was stirred at 85 °C for 12 h to afford
73 (0.10 g, 57%) as a liquid: 1H NMR δ 5.91-5.69 (m, 1H),
5.51 (s, 1H), 5.12 (s, 1H), 5.05-4.80 (m, 2H), 3.70 (s, 6H), 3.69
(s, 6H), 3.19 (s, 2H), 2.94 (s, 2H), 2.66 (s, 2H), 2.10-1.94 (m,
2H), 1.94-1.70 (m, 2H), 1.50-0.95 (m, 14H); MS (70 eV, EI)
m/z 586 (0.3) [M+ (81Br)], 584 (0.3) [M+ (79Br)], 445 (100.00)
[M+ - Br - COOCH3 - H]; IR (neat) 2924, 2854, 1732, 1436
cm-1; HRMS calcd for C28H4179BrO8 (M+) 584.1985, found
584.1998.
Bicycliza t ion of Com p ou n d 10 in t h e P r esen ce of
Dip h en ylm eth a n e. Con d ition A. A degassed solution of
compound 10 (60 mg, 0.11 mmol), Pd(PPh3)4 (13 mg, 10 mol
%), K2CO3 (150 mg, 1.09 mmol), n-Bu4NCl (60 mg, 0.22 mmol),
and diphenylmethane (18 mg, 0.11 mmol) in xylene (2 mL)
was stirred at 83 °C for 16 h to afford compounds 36 (26 mg,
62%) and 40 (3 mg, 9%). Diphenylmethane was recovered in
90% NMR yield.
2,10-Dim eth ylen e-4,4,8-tr is(m eth oxyca r bon yl)bicyclo-
[4.4.0]d ec-1(6)-en e (40): liquid; 1H NMR δ 5.26 (s, 1H), 5.20
(s, 1H), 5.06 (s, 1H), 5.04 (s, 1H), 3.72 (s, 3H), 3.69 (s, 6H),
3.05-2.10 (m, 9H); MS (70 eV, EI) m/z 334 (0.95) [M+], 155
(100.00) [M+H - 2 × COOCH3 - 2 × OCH3]; IR (neat) 2920,
1732, 1436 cm-1; HRMS calcd for C18H22O6 (M+) 334.1417,
found 334.1407.
(s, 1H), 5.03 (s, 1H), 4.86 (s, 1H), 3.70 (s, 6H), 2.85 (s, 2H),
2.77 (s, 2H), 2.70-2.50 (m, 2H), 2.50-2.30 (m, 2H); MS (70
eV, EI) m/z 262 (19.91) [M+], 203 (100.00) [M+ - COOCH3];
IR (neat) 2952, 1732, 1638, 1436 cm-1; HRMS calcd for
C
15H18O4 (M+) 262.1205, found 262.1219.
2-Br om o-1-(2′,2′-bis(m eth oxyca r bon yl)-4′-p en ten yl)-3-
m eth ylen ecyclop en ten e (66): liquid; 1H NMR δ 5.90-5.65
(m, 1H), 5.18-4.95 (m, 3H), 4.85 (s, 1H), 3.70 (s, 6H), 3.03 (s,
2H), 2.62 (s, 2H), 2.60 (s, 2H), 2.45-2.25 (m, 2H); MS (70 eV,
EI) m/z 343 (1.43) [M+(81Br) - H], 341 (1.51) [M+(79Br) - H],
203 (100.00) [M+ - Br - COOCH3 - H]; IR (neat) 2950, 1732,
1630, 1438 cm-1; HRMS calcd for C15H1979BrO4 (M+) 342.0467,
found 342.0461.
2-Br om o-1-(3′-b u t en yl)-5,5-b is(m et h oxyca r b on yl)-3-
1
m eth ylen ecycloh exen e (67): liquid; H NMR δ 5.95-5.70
(m, 1H), 5.44 (s, 1H), 5.65-4.90 (m, 3H), 3.70 (s, 6H), 2.98 (s,
2H), 2.79 (s, 2H), 2.55-2.32 (m, 2H), 2.32-2.10 (m, 2H); MS
(70 eV, EI) m/z 343 (1.83) [M+(81Br) - H], 341 (1.97) [M+(79Br)
- H], 243 (100.00) [M+(81Br) - COOMe - C3H6], 241 (92.72)
[M+(81Br) - COOMe - C3H6]; IR (neat) 2950, 1734, 1614, 1438,
1256 cm-1; HRMS for C15H1979BrO4 (M+) calcd 342.0467, found
342.0490.
(n ) Syn t h esis of 2-Br om o-1-(2′,2′-b is(m et h oxyca r -
bon yl)-5′-h exen yl)-3-m eth ylen ecyclop en ten e (68). Con -
d it ion A. A degassed solution of compound 26 (54 mg,
0.12 mmol), Pd(PPh3)4 (14 mg, 10 mol %), K2CO3 (170 mg,
1.23 mmol), and n-Bu4NCl (68 mg, 2.45 mmol) in xylene
(1 mL) was stirred at 85 °C for 23 h to afford 68 (26 mg, 60%)
as a liquid: 1H NMR δ 5.95-5.5 (m, 1H), 5.2-4.90 (m, 3H),
4.85 (s, 1H), 3.72 (s, 6H), 3.05 (s, 2H), 2.75-2.45 (m, 2H),
2.4-2.15 (m, 2H), 2.15-1.75 (m, 4H); IR (neat) 2950, 1730,
1632, 1436, 1276 cm-1; MS (70 eV, EI) m/z 358 (9.22)
[M+(81Br)], 356 (9.48) [M+(79Br)], 217 (100.00) [M+ - Br -
COOCH3 - H]; HRMS calcd for C16H2179BrO4 (M+) 356.0623,
found 356.0596.
(o) Syn t h esis of 2,11-Bis(m et h ylen e)-9-oxa -5,5-b is-
(m eth oxycar bon yl)bicyclo[5.4.0]u n dec-1(7)-en e (69). Con -
d ition A. A degassed solution of compound 22 (52 mg, 0.12
mmol), Pd(PPh3)4 (14 mg, 10 mol %), K2CO3 (160 mg, 1.16
mmol), and n-Bu4NCl (64 mg, 0.23 mmol) in xylene (3 mL)
was stirred at 83 °C for 15 h. Flash chromatography (petro-
leum ether/dichloromathane ) 1.5:1) afforded 69 (19 mg, 57%)
as a liquid: 1H NMR δ 5.31 (s, 1H), 5.07 (s, 1H), 4.85 (s, 1H),
4.79 (s, 1H), 4.21 (s, 4H), 3.72 (s, 6H), 2.55 (s, 2H), 2.45-2.15
(m, 4H); MS (70 eV, EI) m/z 292 (100.00) [M+]; IR (neat) 2952,
1728, 1448, 1106 cm-1; HRMS calcd for C16H20O5 (M+) 292.1311,
found 292.1311.
Ca r bop a lla d a tion Rea ction of a Mixtu r e of 10 a n d 14
u n d er Ca ta lysis of P d (P P h 3)4. Con d ition A. A degassed
solution of compounds 10 (50 mg, 0.09 mmol) and 14 (50 mg,
0.11 mmol), Pd(PPh3)4 (25 mg, 10 mol %), K2CO3 (273 mg, 1.98
mmol), and n-Bu4NCl (110 mg, 0.40 mmol) in xylene (4 mL)
was stirred at 80 °C for 13 h. After evaporation of the solvent,
methylene bromide (35 µL) was added as the internal refer-
ence. 37 was afforded in 64% NMR yield, and 14 was recovered
in 98% NMR yield.
Mon ocycliza tion Rea ction of 10 u n d er th e Ca ta lysis
of P d (P P h 3)4. Con d ition A. A degassed solution of compound
10 (300 mg, 0.54 mmol), Pd(PPh3)4 (62 mg, 10 mol %), K2CO3
(747 mg, 5.41 mmol), and n-Bu4NCl (300 mg, 1.08 mmol) in
xylene (5 mL) was stirred at 80-85 °C for 0.5 h to afford 37
(0.201 g, 79%) and recovered 10 (4 mg).
(p ) Syn th esis of 2,11-Bis(m eth ylen e)-5,5,9,9-tetr a k is-
(m eth oxycar bon yl)bicyclo[5.4.0]u n dec-1(7)-en e (70). Con -
d ition A. A degassed solution of compound 29 (80 mg, 0.14
mmol), Pd(PPh3)4 (16 mg, 10 mol %), K2CO3 (190 mg, 1.38
mmol), and n-Bu4NCl (85 mg, 0.31 mmol) in xylene (4 mL)
was stirred at 85 °C for 11 h. After purification (petroleum
ether/dichloromathane ) 1.5:1), the reaction afforded 70 (32
1
mg, 56%) as a solid: mp 90-2 °C (ethyl acetate); H NMR δ
5.24 (s, 1H), 5.07 (s, 1H), 4.87 (s, 1H), 4.74 (s, 1H), 3.73 (s,
6H), 3.69 (s, 6H), 2.82 (s, 2H), 2.75 (s, 2H), 2.72 (s, 2H), 2.40-
2.22 (m, 2H), 2.20-2.15 (m, 2H); MS (70 eV, EI) m/z 406 (2.15)
[M+], 227 (100.00) [M+H - 2 × COOCH3 - 2 × OCH3]; IR

Efficient Entry to Fused Bicycles
J . Org. Chem., Vol. 65, No. 25, 2000 8543
Bicycliza tion Rea ction of 42 u n d er Ca ta lysis of P d -
(P P h 3)4. Con d ition A. A degassed solution of compound 37
(40 mg, 0.09 mmol), Pd(PPh3)4 (10 mg, 10 mol %), K2CO3 (117
mg, 0.85 mmol), and n-Bu4NCl (47 mg, 0.17 mmol) in xylene
(2 mL) was stirred at 85 °C for 16 h. After evaporation of the
solvent, methylene bromide was added as the internal refer-
ence. 36 was afforded in 92% NMR yield.
Qiu Shi Foundation of Science and Technology (1999-
2002) and the Special Starting Grant for Outstanding
Young Chemists issued by the National Natural Science
Foundation of China (29525202).
Su p p or tin g In for m a tion Ava ila ble: The Experimental
details of starting materials not listed in the text, the ORTEP
presentation of compound 36, and a set of 1H NMR spectra of
all the new products. This material is available free of charge
via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. Financial support from the Chi-
nese Academy of Sciences and Shanghai Municipal
Committee of Science and Technology is greatly ap-
preciated. S.M. is the recipient of a 1999 Qiu Shi Award
for Young Scientific Workers issued by the Hong Kong
J O005542D