Bicyclization of enynes using the Cp2TiCl2-Mg-BTC system: A practical method to bicyclic cyclopentenones

Article abstract of DOI:10.1021/jo9810718

Bicyclic titanacycles 2 generated with the Cp₂TiCl₂-Mg-P(OEt)₃ system can be trapped with bis(trichloromethyl) carbonate (BTC) to give bicyclic cyclopentenones 3 in good yields. The titanacycle 2m was isolated and well- identified. Bicyclization of enynes containing 1,2-disubstituted olefin by this method gave good results with excellent stereoselectivity.

Full text of DOI:10.1021/jo9810718

J . Org. Chem. 1998, 63, 9285-9291
9285
Bicycliza tion of En yn es Usin g th e Cp 2TiCl2-Mg-BTC System : A
P r a ctica l Meth od to Bicyclic Cyclop en ten on es
Zongbao Zhao, Yu Ding,* and Gang Zhao
Shanghai Institute of Organic Chemistry, Academia Sinica,
354 Fenglin Lu, Shanghai 200032, People’s Republic of China
Received J une 5, 1998
Bicyclic titanacycles 2 generated with the Cp2TiCl2-Mg-P(OEt)3 system can be trapped with bis-
(trichloromethyl) carbonate (BTC) to give bicyclic cyclopentenones 3 in good yields. The titanacycle
2m was isolated and well-identified. Bicyclization of enynes containing 1,2-disubstituted olefin by
this method gave good results with excellent stereoselectivity.
Sch em e 1
In recent years, cyclization reaction of alkenes with
alkynes and carbon monoxide mediated by transition-
metal complexes (Scheme 1) has been paid much atten-
tion, not only with the view of methodology research, but
also with that of organic synthesis. The most popular
version of this reaction mediated by Co2(CO)8, known as
the Pauson-Khand reaction, has become one of the most
powerful and convergent methods for the construction of
cyclopentenones,1 and several fruitful modifications have
made it more effective.2 Besides cobalt complexes, many
other complexes of transition metals,3 including Fe, W,
Cr, Mo, Ni, Ru, Rh, Ti, etc., have been used to mediate
this important transformation with various results. Up
to now, several natural products and their analogues
have been synthesized by using the Pauson-Khand
reaction as a key step.4
Sch em e 2a
a
Method A: CO, M ) Ti, Zr. Method B: R3SiCN, then HOAc
or CuSO4, M ) Ti.
search, Negishi and co-workers5 used the Cp2ZrCl2/2n-
BuLi system (Negishi reagent) to bicyclize enynes with
CO. Buchwald and co-workers,6 however, used Cp2Ti-
(PMe3)2 or Cp2Ti(CO)2 as a metallocene equivalent6c,7 to
effect this reaction.
Group IV metallocenes were also introduced to bicy-
clization of enynes to construct the bicyclic cyclopenten-
one skeleton (Scheme 2), similar to an intramolecular
Pauson-Khand reaction. In previous pioneering re-
Most of the above methods require medium- or high-
pressure CO, elevated temperature, long reaction time,
and expensive and/or unstable metal complexes. Al-
though isocyanides and trialkylsilyl cyanides have been
reported to be CO equivalents in this reaction (Scheme
2, method B), the procedure is still time-consuming and
tedious.7 In a research project on the reactions mediated
by low-valent titanocene species, we found that bis-
(trichloromethyl) carbonate (BTC), which is a stable
white crystal and has been recently used in introducing
a carbonyl group in organic synthesis (Scheme 3),8 could
be a useful substitute of CO and trialkylsilyl cyanides to
trap the titanacycles 2 (Scheme 4). The interesting
reaction provided us a simple and practical method to
* To whom correspondence should be addressed. Tel.: 86-21-
64163300. Fax: 86-21-64166128. E-mail: dingyu@pub.sioc.ac.cn.
(1) For reviews, see: (a) Schore, N. E. Org. React. 1991, 40, 1. (b)
Schore, N. E. In Comprehensive Organometallic Chemistry II; Abel,
E. W., Stone, F. G., Wilkinson, G., Eds.; Elservier Press: New York,
1995; Vol. 12, p 703. For recent examples of this reaction, see: (c)
Ahmar, M.; Locatelli, C.; Colombier, D.; Cazes, B. Tetrahedron Lett.
1997, 38, 5281. (d) J ordi, L.; Ricart, S.; Vinas, J . M.; Moreto´, J . M.
Organometallics 1997, 16, 2808.
(2) For effecting this reaction using dry-state adsorption techniques,
see: (a) Smit, W. A.; Kireev, S. L.; Nefedov, O. M.; Tarasov, V. A.
Tetrahedron Lett. 1989, 30, 4021. (b) Smit, W. A.; Gybin, A. S.;
Simonyan, S. O.; Shashkov, A. S.; Tarasov, Y. T.; Strychkov, Y. T.;
Kyz’mina, L. G.; Mikaelian, G. S.; Cable, R.; Swanson, E. D. Tetrahe-
dron Lett. 1986, 27, 1241. For effecting this reaction using various
additives, see: (c) Shambayati, S.; Crowe, W. E.; Schreiber, S. L.
Tetrahedron Lett. 1990, 31, 5289. (d) Kraft, M. E.; Scott, I. L.; Romero,
R. H.; Feibelmann, S.; Vanpelt, C. E. J . Am. Chem. Soc. 1993, 115,
7199. (e) Billington, D. C.; Helps, I. M.; Pauson, P. L.; Thomson, W.;
Willison, D. J . Organomet. Chem. 1988, 354, 233. (f) Chung, Y. K.;
Lee, B. Y.; J eong, N.; Hudecek, M.; Pauson, P. L. Organometallics 1993,
12, 220. (g) Sugihara, T.; Yamada, M.; Ban, H.; Yamaguchi, M.;
Kaneko, C. Angew. Chem., Int. Ed. Engl. 1997, 36, 2801. (h) Rajesh,
T.; Periasamy, M. Tetrahedron Lett. 1998, 39, 117.
(3) For Fe, see: (a) Pearson, A. J .; Dubbert, R. A. Organometallics
1994, 13, 1656. (b) Knolker, H. J .; Heber, J . Synlett 1993, 924. (c)
Pearson, A. J .; Yao, X. Synlett 1997, 1281. (d) Pearson, A. J .; Dubbert,
R. A. J . Chem. Soc., Chem. Commun. 1991, 202. For W, see: (e) Hoye,
T. R.; Suriano, J . A. J . Am. Chem. Soc. 1993, 115, 1154. For Cr, see:
(f) J ordi, L.; Segundo, A.; Camps, F.; Ricart, S.; Moreto, J . M.
Organometallics 1993, 12, 3795. For Mo, see: (g) J eong, N.; Lee, S. J .;
Lee, B. Y.; Chung, Y. K. Tetrahedron Lett. 1993, 34, 4027. For Ni, see:
(h) Tamao, K.; Kobayashi, K.; Ito, Y. J . Am. Chem. Soc. 1988, 110,
1286. (i) Tamao, K.; Kobayashi, K.; Ito, Y. Synlett 1992, 539. (j)
Buchwald, S. L.; Zhang, M. J . Org. Chem. 1996, 61, 4498. For Ru, Rh,
Ti, see ref 18.
(4) For examples, see: (a) J amison, T. F.; Shambayati, S.; Crowe,
W. E.; Schreiber, S. L. J . Am. Chem. Soc. 1994, 116, 5505. (b) Tormo,
J .; Moyamo, A.; Perica`s, M. A.; Rieca, A. J . Org. Chem. 1997, 62, 4851.
(c). Yoo, S. E.; Lee, S. H. J . Org. Chem. 1994, 59, 6968. (d) Alcaide, B.;
Polanco, C.; Sierra, M. A. Tetrahedron Lett. 1996, 37, 6901.
(5) (a) Negishi, E.; Holmes, S. J .; Tour, J . M.; Miller, J . A. J . Am.
Chem. Soc. 1985, 107, 2568. (b) Negishi, E.; Holmes, S. J .; Tour, J .
M.; Miller, J . A.; Cedarbaum, F. E.; Swanson, D. R.; Takahashi, T. J .
Am. Chem. Soc. 1989, 111, 3336.
(6) (a) Beck, S. C.; Grossman, R. B.; Buchwald, S. L. J . Am. Chem.
Soc. 1994, 116, 8593. (b) Grossman, R. B.; Buchwald, S. L. J . Org.
Chem. 1992, 57, 5803. (c) Hicks, F. A.; Kablaoui, N. M.; Buchwald, S.
L. J . Am. Chem. Soc. 1996, 118, 9450. (d) Nugent, W. A.; Calabrese,
J . C. J . Am. Chem. Soc. 1984, 106, 6422.
(7) Hicks, F. A.; Berk, S. C.; Buchwald, S. L. J . Org. Chem. 1996,
61, 2713.
(8) For an extensive review, see: Cotarca, L.; Delogu, P.; Nardelli,
A.; Sunjie´, V. Synthesis 1996, 553.
10.1021/jo9810718 CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/21/1998

9286 J . Org. Chem., Vol. 63, No. 25, 1998
Zhao et al.
Ta ble 1. Cyclop en ten on es fr om En yn e Eth er s
Sch em e 3
Sch em e 4
Sch em e 5a
a
Key: (i) Cp2TiCl2/Mg, THF, 0 °C, 6 h; (ii) 1.5 equiv of BTC, 0
°C, 2 h.
construct bicyclic cyclopentenone skeleton from the cor-
responding enynes with relatively stable starting mate-
rial in short reaction time.9 Here, we would like to report
our results.
a
Resu lts a n d Discu ssion s
All reactions were performed on a 2 mmol scale. For details,
b
see the Experimental Section. Isolated yields of products >95%
purity as estimated by 1H NMR analysis. c The desired product
can only be obtained in the absence of P(OEt)3 and thus gave lower
yield.
The titanacycles 2 were generated according to a recent
published procedure.10 Thus, a mixture of enyne 1a , Cp2-
TiCl2, and Mg turnings activated with 1,2-dibromoethane
was stirred at 0 °C for 6 h (procedure A) to form the key
intermediate 2a , which was relatively stable and could
be detected on TLC (silica gel, developed with petroleum
ether/ethyl acetate). If 2a was treated with 1.5 equiv of
BTC, the desired bicyclic cyclopentenone 3a was produced
as expected in 57% yield, and a byproduct 4 was formed
in 17% yield (Scheme 5). Obviously, 4 can be envisioned
as protonated product from 2a . We wondered if the
byproduct 4 came from the reaction of 2a with moisture
or not, but even the use of a strict Schlenk technique or
introduction of MS 4 Å has been proven unsuccessful to
avoid this byproduct. To improve the yield, we then tried
various ligands to stabilize the intermediate 2a . When 2
equiv of P(OEt)3 was introduced,11 the yield of 3a
increased, indeed, up to 75%. To our surprise, the
byproduct 4 could still be isolated in about 17% yield.
Other ligands, such as P(OMe)3, PPh3, and bis(trimeth-
ylsilyl)acetylene, gave poor results in this reaction,
though they have already been used to stabilize ti-
tanocene complexes elsewhere.12
powder (procedure B) without any activation. In this case,
only traces of monocyclic compounds such as 4 were
detected according to TLC monitoring. Therefore, we
believe that most of the monocyclic products may derive
from the reaction between the titanacycles 2 and the
Grignard reagent resulting from Mg turnings and 1,2-
dibromoethane, though the detailed mechanism is still
unknown. This hypothesis was further verified, since
yields of 3a up to 77% were achieved when the Mg
turnings were separated off from the resulting mixture
in the activating stage.
The results summarized in Table 1 demonstrate the
generality of this reaction. Six-membered ring system (3c
and 3d ) and quaternary center (3e and 3f) containing
products can be formed with this technique. More inter-
estingly, enyne 1h , which is an optically pure substrate,
gave only one isomer 3h . Strong interaction between 6-H
(δ 3.64) and 5-H (δ 3.17) in 3h was recorded by an NOE
analysis, which means a cis relationship of the two
protons. Thus, 3h should be the 5S,6R isomer. In this
case, the newly formed chiral center was well-controlled,
and the interesting stereocontrol will be useful in organic
When we checked the role of Mg activity, we were very
pleased to obtain satisfactory results using Aldrich Mg
(9) Part of this work has been communicated. Zhao, Z.; Ding, Y. J .
Chem. Soc., Perkin Trans. 1 1998, 171.
(10) (a) Miura, K.; Funatsu, M.; Saito, H.; Ito, H.; Hosomi, A.
Tetrahedron Lett. 1996, 37, 9059. (b) Pearson, D. E.; Cowan, D.;
Beckler, J . D. J . Org. Chem. 1959, 24, 504.
(11) (a) Horikawa, Y.; Watanabe, M.; Fujiwara, T.; Takeda, T. J .
Am. Chem. Soc. 1997, 119, 1127. (b) Takeda, T.; Shimoka, H.; Miyachi,
Y.; Fujiwara, T. Chem. Commun. 1997, 1055.
(12) (a) Rosenthal, U.; Ohff, A.; Michalik, M.; Go¨rls, H.; Burlakov,
V. V., Shur, V. B. Angew. Chem., Int. Ed. Engl. 1993, 32, 1193. (b)
Lefeber, C.; Arndt, P.; Tillack, A.; Baumann, W.; Kenpe, R.; Burlakov,
V. V.; Rosenthal, U. Organometallics 1995, 14, 3090. (c) Horikawa,
Y.; Nomura, T.; Watanabe, M.; Fujiwara, T., Takeda, T. J . Org. Chem.
1997, 62, 3678.

Practical Method to Bicyclic Cyclopentenones
J . Org. Chem., Vol. 63, No. 25, 1998 9287
Ta ble 2. Cyclop en ten on es fr om En yn es Con ta in in g
1,2-Disu bstitu ted Olefin a
Sch em e 6
Ta ble 3. Cyclop en ten on es fr om Oxygen -F r ee En yn es
a
Only one isomer was isolated in all cases; the stereochemistry
of the products was unambiguously assigned by NOE analysis.
b Isolated yield. c The starting material was also recovered in about
d
50% yield. This yield was based on the converted starting
material.
synthesis. The benzyl ether group presented in enyne 1h
is tolerable to the reaction condition.
One of the major drawbacks of bicyclization of enynes
mediated by group IV metallocene so far is its failure in
conversions of substrates containing 1,2-disubstituted
olefin.6a Very recently, Cp2Ti(CO)2 was found to be an
alternative to cyclize this kind of enynes.6c However,
there are still no transformation examples of enyne
ethers containing 1,2-disubstituted olefin with Group IV
metallocenes. Fortunately, enyne 1i could be converted
to the corresponding cyclopentenone 3i in moderate yield
with our system, and at least three other substrates were
found to give good yields (Table 2), probably because the
phenyl group presented in these substrates benefited the
reaction. It should be noted that only one stereoisomer
was isolated, and in each case the stereochemistry of the
double bond was well-related with that of the product,
i.e., the (E)-enynes producing 4,5-trans products, and vice
versa, the (Z)-enynes giving 4,5-cis products. These
outcomes showed better stereoselectivity than the related
Cp2Ti(CO)2 procedure.6c
a
b
Isolated yield. E ) CO2Et.
Sch em e 7
the reaction between titanacycles 2 and BTC proceeds
with conservation of configuration.
Bicyclic titanacyclopentenes 2 are very important
intermediates in titanocene chemistry, and their ana-
loguous titanacyclobutene complexes have been well-
characterized in the literature.13 However, to our knowl-
edge, intermediates 2 have not been separated and
identified. To see if the stereochemistry has already been
established at the stage of titanacycle formation, we have
tried to isolate and identify complexes 2. Fortunately, the
titanacycle 2m , generated from enyne 1m using the Cp2-
TiCl2-Mg system, was found to be stable in chromatog-
raphy on silica gel. An NOE analysis of 2m demonstrated
the relationship between the R-H and â-H as shown in
Scheme 6. This observation shows that the formation of
titanacycles is a highly stereospecific reaction and that
Enynes without an oxygen atom within the tether also
gave good results as demonstrated in Table 3. The ester
groups present in enynes 1t and 1u did not interfere with
the reaction, and the expected products were obtained
in good yields.
Some other substrates listed in Scheme 7 were then
chosen to study the scope of this reaction. An attempt to
convert enyne 5 containing a terminal alkyne under our
conditions was unsuccessfulsan outcome consistent with
what had been published elsewhere.6a Enyne 6 can be
converted into the corresponding titanacycle, as judged
by TLC analysis. Unfortunately, attempts to trap the
latter with BTC failed to afford the desired product. It
should be noted that similar difficulty in bicyclization of
trimethylsilyl-containing enyne has been reported by
Buchwald6a in the previous work. Enyne 7 containing a
carbonyl group within the tether between the alkyne and
(13) (a) Ogoshi, S.; Stryker, J . M. J . Am. Chem. Soc. 1998, 120, 3514.
(b) Tebbe, F. N.; Harlow, R. L. J . Am. Chem. Soc. 1980, 102, 6149.

9288 J . Org. Chem., Vol. 63, No. 25, 1998
Zhao et al.
Ta ble 4. Tr a p p in g Tita n a cycles Gen er a ted fr om Va r iou s
Meth od s Usin g BTCa ,b
Sch em e 8
a
2 equiv of P(OEt)3 was used as a ligand in all systems in order
b
to make it more comparable. 1.5 equiv of BTC was used to trap
the titanacycles generated under the conditions described. c Iso-
lated yields.
concentration and recrystallization from chloroform.
Thus, this method provided the first example of regen-
erating Cp2TiCl2 in bicyclization reactions mediated by
titanocene. With the above results in hand, we then tried
to transform this reaction into a catalytic one.18 When
0.5 equiv of Cp2TiCl2 was used to convert 1a into 3a by
general procedure B, the isolated yield of 3a , however,
reduced to 32%, and starting material 1a was recovered
(38%). Portionwise addition of BTC solution to the
reaction mixture containing 0.4 equiv of Cp2TiCl2 at 0
°C was also found to be fruitless.
In conclusion, we have found a practical and general
bicyclization method of enynes using the Cp2TiCl2-Mg-
BTC system. The features of this system include a short
reaction time, mild reaction conditions, relatively stable
starting materials, and good yields, although BTC is still
toxic. In addition, this system can be used in the
bicyclization of enynes containing a 1,2-disubstituted
olefin with highly stereoselectivity. From the viewpoint
of elementary reaction, the reaction between BTC and
titanacycles is novel and should find use elsewhere. We
will investigate the scope of this kind of reaction further.
the olefin unit was converted to a complex mixture.
Enynes 8 and 9 were also completely consumed with the
Cp2TiCl2-Mg system to afford a complex mixture.
To determine the generality of BTC in this chemistry,
we used BTC as a substitute for CO to react with
titanacycles 2 generated from enynes 1a and 1b using
other known methods. The desired product could be
obtained when either the Cp2TiCl2/2EtMgCl or Cp2TiCl2/
2n-BuLi system14 was used, giving a little poorer yield
than ours (Table 4), presumably because of uncertain
concentration of the alkylmetal reagents and other side
reactions. However, the Ti(O-iPr)4/2PrMgCl system15
failed to give any bicyclic cyclopentenone.
We then studied the mechanism of reaction between
the titanacycles and BTC. Since it is known that BTC
can generate phosgene (COCl2) in situ, we first checked
the possibility of this pathway. When COCl2 gas was
bubbled into a THF solution of titanacycle 2a generated
by general procedure A for 5 min, 3a could be isolated in
56% yield. Thus, it seems to be similar to the formation
of main-group elements containing heterocycles mediated
by zirconacene complex.16 We observed that when BTC
was introduced to the solution of titanacycles, much gas
was formed immediately. The gas was proven to be CO2
by its characteristic reaction with lime solution. Ad-
ditionally, a GC analysis verified the presence of CCl4 in
the reaction mixture. We found that the yield decreased
when BTC was loaded in less than 1 equiv. From the
above observations, it was deduced that BTC only
transferred one carbonyl group to the intermediate. Thus,
the authors suggest a direct attack between the titana-
cycles 2 and BTC, even though BTC can in situ generate
COCl2 and that COCl2 was proven to be able to trap the
titanacycle (vide ante). The reaction might proceed
through the following tentative mechanism (Scheme 8),
though it is still unclear how the postulated intermedi-
ate17 10 transformed to the final cyclopentenone 3. This
hypothesis may account for release of CO2 and the
stereoselectivity in the reaction of 1,2-disubstituted olefin
containing enynes.
Exp er im en ta l Section
1
Gen er a l Meth od s. Melting points are uncorrected. All H
NMR spectra and 13C NMR spectra are reported in δ units,
(17) (a) The exact structure like 10 is unknown; however, any other
alternatives should keep the retention of stereochemistry from titana-
cycle to final product in mind.
A simliar seven-membered ring
intermediate involving a titanium-oxygen bond has also been sug-
gested by Sato. Gao, Y.; Shirai, M.; Sato, F. Tetrahedron Lett. 1997,
38, 6849. (b) One alternative may be an intermediate like Y, which is
what we thought in the early stage of this work. However, the
stereochemistry outcome of this reaction indicates something contra-
dictory with intermediate Y, since an open chain intermediate will most
probably fail to give good stereoselectivity.
(18) A catalytic Pauson-Khand reaction is currently available with
different metal complexes. For Co, see: (a) J eong, N.; Hwang, S. H.;
Lee, Y.; Chung, Y. K. J . Am. Chem. Soc. 1994, 116, 3159. (b) Pagenkopf,
B.; Livinghouse, T. J . Am. Chem. Soc. 1996, 118, 2285. For Ru, see:
(c) Morimoto, T.; Chatani, N.; Fukumoto, Y.; Murai, S. J . Org. Chem.
1997, 62, 3762. (d) Kondo, T.; Suzuki, N.; Okada, T.; Mitsudo, T. J .
Am. Chem. Soc. 1997, 119, 6187. For Rh, see: (e) Koga, Y.; Kobayashi,
T.; Narasaka, K. Chem. Lett. 1998, 249. For Ti, see ref 6c. An
enantioselective catalytic Pauson-Khand- type reaction using ti-
tanocene dicarbonyl complex is also known. Hicks, F. A.; Buchwald,
S. L. J . Am. Chem. Soc. 1996, 118, 11688. A catalytic Pauson-Khand
reaction in super critical carbon dioxide has been developed. J eong,
N.; Hwang, S. E.; Lee, Y. W.; Lim, J . S. J . Am. Chem. Soc. 1997, 119,
10549.
According to this mechanism, Cp2TiCl2 was regener-
ated. Indeed, pure Cp2TiCl2 was recovered in 47% yield
in a typical experiment when the reaction mixture was
filtered through a short silica gel plug followed by
(14) Nugent, W. A.; RajanBabu, T. V.; Taber, D. F. Chem. Scr. 1989,
29, 439.
(15) Urabe, H.; Hata, T.; Sato, F. Tetrahedron Lett. 1995, 36, 4261.
(16) Rajanbabu, T. V.; Nugent, W. A.; Taber, D. F.; Fagan, P. J . J .
Am. Chem. Soc. 1988, 110, 7128.

Practical Method to Bicyclic Cyclopentenones
J . Org. Chem., Vol. 63, No. 25, 1998 9289
parts per million (ppm). Infrared (IR) spectra are reported in
wavenumbers (cm-1). Optical rotations were measured on a
Perkin-Elmer 241 Autopol Polarimeter. Flash column chro-
matography was performed on silica gel H (10-40 µM). All
cyclization manipulations were performed on a vacuum line
using standard Schlenk techniques with a purified argon
atmosphere. THF was distilled from sodium/benzophenone
ketyl. HMPA was redistilled before use. CH2Cl2 was distilled
from CaH2. Cp2TiCl2 was prepared according to the litera-
ture.19 Mg powder (Aldrich, 50 mesh) and P(OEt)3 (Fluka, 97%)
were used as received. Bis(trichloromethyl) carbonate (BTC)
was recrystallized from CH2Cl2 and stored in a drybox.
(2R)-1-(Ben zyloxy)-2-[(3-p h en yl-2-p r op yn )oxy]-b u t -3-
en e (1h ). This material was prepared using the general
procedure from (3R)-4-(benzyloxy)-1-but-1-en-3-ol26 and 1-phe-
nylpropargyl bromide28 in 80% yield. [R]21D: -49.3° (c 1.04,
CHCl3). IR (neat): 2238, 1490 cm-1. δH (300 MHz, CDCl3):
7.23-7.43 (m, 10H), 5.79 (m, 1H), 5.36 (m, 2H), 4.60 (m, 2H),
4.48 (d, J ) 15.7 Hz, 1H), 4.35 (d, J ) 15.7 Hz, 1H), 4.27 (m,
1H), 3.58 (m, 2H). δC (300 MHz, CDCl3): 56.7, 72.8, 73.4, 78.9,
85.5, 86.1, 119.2, 122.9, 125.9, 127.8, 128.4, 129.0, 131.8, 135.1,
138.3. MS m/z: 292 (M+, 0.95). HRMS m/z: calcd for C20H20O2
292.1463, found 292.1468.
1-[(E)-Cin n a m yloxy]bu t-2-yn e (1k ). This material was
prepared using the general procedure from but-2-yn-1-ol and
cinnamyl bromide27 in 86% yield. IR (neat): 2850, 2239, 1490
cm-1. δH (300 MHz, CDCl3): 7.33 (m, 5H), 6.65 (d, J ) 15.9
Hz, 1H), 6.31 (dt, J ) 5.9, 15.9 Hz, 1H), 4.24 (m, 2H), 4.17 (q,
J ) 2.3 Hz, 2H), 0.89 (t, J ) 2.3 Hz, 3H). MS m/z: 186 (M+,
1.02). HRMS m/z: calcd for C13H14O 186.1045, found 186.1025.
1-[(Z)-Cin n a m yloxy]oct-2-yn e (1m ). This material was
prepared using the general procedure from Z-cinnamyl28
alcohol and 1-bromooct-2-yne29 in 65% yield. IR (neat): 2933,
1748 cm-1. δH (300 MHz, CDCl3): 7.30 (m, 5H), 6.63 (d, J )
11.8 Hz, 1H), 5.87 (dt, J ) 6.3, 11.8 Hz, 1H), 4.34 (dd, J ) 1.6,
6.4 Hz, 2H), 4.17 (t, J ) 2.1 Hz, 2H), 2.19 (m, 2H), 1.49 (m,
2H), 1.33 (m, 4H), 0.90 (t, J ) 7.0 Hz, 3H). MS m/z: 242 (M+,
1.36). HRMS m/z: calcd for C17H22O 242.1671, found 242.1656.
1-[(E)-Cin n a m yloxy]oct-2-yn e (1n ). This material was
prepared using the general procedure from oct-2-yn-1-ol and
cinnamyl bromide in 92% yield. IR (neat): 2933, 2230, 1451
cm-1. δH (300 MHz, CDCl3): 7.33 (m, 5H), 6.64 (d, J ) 15.9
Hz, 1H), 6.30 (dt, J ) 6.1, 15.9 Hz, 1H), 4.23 (dd, J ) 0.8, 6.0
Hz, 2H), 4.19 (t, J ) 2.1 Hz, 2H), 2.24 (m, 2H), 1.54 (m, 2H),
1.37 (m, 4H), 0.92 (t, J ) 7.0 Hz, 3H). MS m/z: 242 (M+, 0.28).
HRMS m/z: calcd for C17H21O [M - 1]+ 241.1593, found
241.1594.
All of the starting enynes and the bicyclization products are
colorless oils unless demonstrated otherwise.
The following starting materials were known and thus
prepared accordingly: 3-(allyloxy)-1-phenyl-1-propyne6a (1a ),
3-[(2-methyl-2-propenyl)oxy]-1-phenyl-1-propyne6a (1b), 3-[(3-
butenyl)oxy]-1-phenyl-1-propyne6a (1c), 3-[2(E)-butenyl)oxy]-
1-phenyl-1-propyne20 (1i), 1-phenyl-6-hepten-1-yne6a (1p ), di-
ethyl 7-octen-2-yne-5,5-dicarboxylate6a (1t), and diethyl 1-phenyl-
6-hepten-1-yne-5,5-dicarboxylate13 (1u ). Other starting materials
are described below.
Gen er al P r ocedu r e21 for P r epar ation of Star tin g En yn e
Eth er s. To a suspension of NaH (80%, 1.32 g, 44 mmol) in 20
mL of dry THF was added dropwise the alcohol (40 mmol) in
10 mL of dry THF. After the mixture was stirred for 20 min
at room temperature, the halide (45 mmol) was added por-
tionwise, and the mixture was stirred at ambient temperature
for another 1-3 h. The mixture was poured into water,
extracted with ether, washed with brine, dried over anhydrous
MgSO4, evaporated, and purified by flash chromatography on
silica gel (30:1 petroleum ether/ethyl acetate) to give the
product.
4-(Allyloxy)-1-p h en yl-1-bu tyn e (1d ). This material was
prepared using the general procedure from 4-phenyl-3-propyn-
1-ol22 and allyl bromide in 96% yield. IR (neat): 2235, 1491
cm-1. δH (300 MHz, CDCl3): 7.40 (m, 2H), 7.28 (m, 3H), 5.94
(m, 1H), 5.27 (m, 2H), 4.06 (d, J ) 5.5 Hz, 2H), 3.66 (t, J ) 7.1
Hz, 2H), 2.71 (t, J ) 7.1 Hz, 2H). MS m/z: 186 (M+, 4.73).
HRMS m/z: calcd for C13H14O 186.1045, found: 186.1052.
3-Meth yl-3-(a llyloxy)-1-p h en yl-1-bu tyn e (1e). This ma-
terial was prepared using the general procedure from 2-meth-
yl-4-phenyl-3-butyn-1-ol23 and allyl bromide in 36% yield. IR
(neat): 2985, 1490 cm-1. δH (300 MHz, CDCl3): 7.44 (m, 2H),
7.32 (m, 3H), 6.01 (m, 1H), 5.35 (m, 1H), 5.19 (dd, J ) 1.1,
10.3 Hz, 1H), 4.21 (d, J ) 5.6 Hz, 2H), 1.60 (s, 6H). MS m/z:
199 (M+ - 1, 0.53). HRMS m/z: calcd for C14H15O [M - 1]+
199.1123, found 199.1102.
1-(Allyloxy)-1-(2-p h en yleth yn yl)cyclop en ta n e (1f). This
material was prepared using the general procedure from 1-(2-
phenylethynyl)-cyclopentanol24 and allyl bromide in 42% yield.
IR (neat): 2873, 1599, 1490 cm-1. δH (300 MHz, CDCl3): 7.43
(m, 2H), 7.30 (m, 3H), 5.64-6.01 (m, 1H), 5.01-5.36 (m, 2H),
4.16 (m, 2H), 2.09 (m, 4H), 1.70 (m, 4H). MS m/z: 226 (M+,
1.60). HRMS m/z: calcd for C16H18O 226.1357, found 226.1359.
1-(Allyloxy)-2-octyn e (1g). This material was prepared
using the general procedure from oct-2-yn-1-ol25 and allyl
bromide in 78% yield. IR (neat): 2958, 1355 cm-1. δH (300
MHz, CDCl3): 5.88 (m, 1H), 5.27 (dd, J ) 1.5, 17.3 Hz, 1H),
5.17 (dd, J ) 0.8, 10.8 Hz, 1H), 4.10 (t, J ) 2.1 Hz, 2H), 4.02
(d, J ) 5.7 Hz, 2H), 2.18 (m, 2H), 1.48 (m, 2H), 1.30 (m, 4H),
0.87 (t, J ) 7.0 Hz, 3H). MS m/z: 166 (M+, 0.53). HRMS m/z:
calcd for C11H17O [M - 1]+ 165.1279, found 165.1283.
Gen er a l P r oced u r e30 for P r ep a r a t ion of St a r t in g
En yn es. To a solution of the alkyne (11 mmol) in 15 mL of
dry THF and 10 mL of HMPA was added dropwise n-BuLi
(13 mmol) at -78 °C. The mixture was allowed to reach 0 °C,
stirred for 20 min, and then cooled to -30 °C, and the
corresponding iodide (12 mmol) was added. After being stirred
for an additional 3 h at ambient temperature, the mixture was
poured into water, extracted with ether, washed with brine,
dried over MgSO4, evaporated, and chromatographed on silica
gel (petroleum ether) to give the product.
5,5-Dim eth yl-1-p h en yl-6-h ep ten -1-yn e (1q). This mate-
rial was prepared using the general procedure from pheny-
lacetylene and 5-iodo-3,3-dimethyl-1-pentene31 in 70% yield.
IR (neat): 2963, 1491 cm-1. δH (300 MHz, CDCl3): 7.40 (m,
2H), 7.29 (m, 3H), 5.79 (dd, J ) 10.8, 17.3 Hz, 1H), 4.97 (m,
2H), 2.33 (m, 2H), 1.68 (m, 2H), 1.05 (s, 6H). MS m/z: 198
(M+, 4.48). HRMS m/z: calcd for C15H18 198.1409, found
198.1417.
9,9-Dim eth yl-10-u n d ecen -5-yn e (1s). This material was
prepared using the general procedure from 1-hexyne and
5-iodo-3,3-dimethyl-1-pentene in 74% yield. IR (neat): 2933,
1641 cm-1. δH (300 MHz): 5.72 (dd, J ) 10.9, 17.5 Hz, 1H),
4.91 (m, 2H), 2.13 (m, 2H), 2.04 (m, 2H), 1.53 (m, 2H), 1.41
(m, 4H), 0.98 (s, 6H), 0.90 (t, J ) 7.0 Hz, 3H). MS m/z: 178
(M+, 0.09). HRMS m/z: calcd for C12H19 [M - CH3]+ 163.1486,
found 163.1485.
Gen er a l P r oced u r e for th e Con ver sion of En yn es to
Bicyclic Cyclop en ten on es. Typ ica l P r oced u r e A. Under
an argon atmosphere, to a solution of 1,2-dibromoethane (50
(19) Siegert, F. W.; Deliefde Merjies, N. J . J . Organomet. Chem.
1970, 23, 177.
(20) Zhang, M.; Buchwald, S. L. J . Org. Chem. 1996, 61, 4498.
(21) Brown, C. A.; Barton, D.; Sivaram, S. Synthesis 1974, 434.
(22) Denis, J . N.; Greene, A. E.; Serra, A. A.; Luche, M. J . J . Org.
Chem. 1986, 51, 46.
(26) Schnurrenberger, P.; Hungerbu¨hler, E.; Seebach, D. Liebigs
Ann. Chem. 1987, 733.
(27) Lin, C.-H.; Aristoff, P. A.; J ohnson, P. D.; McGrath, J . P.; Timko,
J . M.; Robert, A. J . Org. Chem. 1987, 52, 5594.
(28) McCombie, S. W.; Nagabhushan, T. L. Tetrahedron Lett. 1987,
28, 5395.
(23) Yu, W. Y.; Alper, H. J . Org. Chem. 1997, 62, 5684.
(24) Mayr, H.; Halberstadt-Kausch, I. K. Chem. Ber. 1982, 115, 3497.
(25) (a) Kanakam, C. C.; Mani, N. S.; Ramanathan, H.; Subba Rao,
G. S. R. J . Chem. Soc., Perkin Trans. 1 1989, 1907. (b) Sakai, T.;
Hamamoto, H.; Mori, K. Agric. Biol. Chem. 1986, 50, 1621.
(29) Crombie, L.; Morgan, D. O.; Smith, E. H. J . Chem. Soc., Perkin
Trans. 1 1991, 567.
(30) Beckmann, W.; Doerjer, G.; Logemann, E.; Merkel, C.; Schill,
G.; Zu¨rcher, C. Synthesis 1975, 423.
(31) Marshall, J . A.; Cleary, D. G. J . Org. Chem. 1986, 51, 858.

9290 J . Org. Chem., Vol. 63, No. 25, 1998
Zhao et al.
µL) in dry THF (0.8 mL) was added well-pestled Mg turnings
(5 mmol). After being stirred for 15 min, the solvent was
removed at reduced pressure, and dry THF (20 mL), Cp2TiCl2
(2.2 mmol), the enyne (2 mmol), and P(OEt)3 (4 mmol) were
added successively. A solution of BTC (2.5 mmol) in dry THF
(5 mL) was added dropwise to the mixture after being stirred
at 0 °C for 6 h. (Caution: BTC can slowly generate dangerous
phosgene gas.) The mixture was allowed to reach room
temperature, stirred for an additional 1-2 h, and then diluted
with ether (50 mL), washed with water, dried over MgSO4,
concentrated in vacuo, and chromatographed on silica gel
(petroleum ether/ethyl acetate) to afford the product.
Gen er a l P r oced u r e B. Under an argon atmosphere, to a
mixture of Cp2TiCl2 (2.2 mmol), the enyne (2 mmol), and
P(OEt)3 (4 mmol) in dry THF (20 mL) was added Mg powder
(2.5 mmol). The mixture was stirred at 0 °C for 6 h. Other
operations were the same as procedure A.
The analytical data for the following compounds were
identical with those presented in the literature: 2-Phenyl-7-
oxabicyclo[3.3.0]oct-1-en-3-one6a (3a ), 3-benzylidene-4-meth-
yltetrahydrofuran10a (4), 2-phenyl-5-methyl-7-oxabicyclo[3.3.0]-
oct-1-en-3-one6a (3b). 2-phenylbicyclo[3.3.0]oct-1-en-3-one6a (3p),
and diethyl 2-methyl-3-oxobicyclo[3.3.0]oct-1-ene-7,7-di-
carboxylate6a (3t).
(()-2-P h en yl-8-oxabicyclo[3.4.0]n on -1-en -3-on e (3c). This
compound was prepared using the general procedure A from
1c in 30% yield. IR (neat): 1702 cm-1. δH (300 MHz, CDCl3):
7.20-7.41 (m, 5H), 4.84 (d, J ) 13.7 Hz, 1H), 4.28 (d, J ) 13.7
Hz, 1H), 4.08 (m, 1H), 3.68 (dt, J ) 1.8, 12.0 Hz, 1H), 2.98 (m,
1H), 2.80 (dd, J ) 6.5, 18.7 Hz, 1H), 2.24 (dd, J ) 3.2, 18.7
Hz, 1H), 2.16 (m, 1H), 1.62-1.76(m, 1H). 13C NMR (300 MHz,
CDCl3): 205.7, 169.0, 137.9, 130.1, 129.0, 128.3, 128.2, 67.1,
65.9, 41.6, 37.1, 34.8. MS m/z: 214 (M+, 70.42). HRMS m/z:
calcd for C14H14O2 214.0993, found 214.1012.
(()-2-P h en yl-7-oxabicyclo[3.3.0]oct-1-en -3-on e (3d). This
compound was prepared in the absence of P(OEt)3 using
general procedure A from 1d in 39% yield or procedure B, in
63% yield. IR (neat): 1700 cm-1. δH (300 MHz, CDCl3): 7.26-
7.43 (m, 5H), 4.35 (m, 1H), 4.20 (m, 1H), 3.39 (dt, J ) 2.6,
11.6 Hz, 1H), 3.08-3.20 (m, 2H), 2.92 (d, J ) 13.9 Hz, 1H),
2.59-2.77 (m, 2H), 2.05 (d, J ) 18.8 Hz, 1H). 13C NMR (300
MHz, CDCl3): 205.2, 172.7, 137.7, 130.6, 129.0, 128.4, 127.9,
126.4, 73.9, 67.8, 39.8, 36.9, 30.6. MS m/z: 214 (M+, 100).
HRMS m/z: calcd for C14H14O2 214.0993, found 214.1008.
(()-2-P h en yl-8,8-d im eth yl-7-oxa bicyclo[3.3.0]oct-1-en -
3-on e (3e). This compound was prepared using general
procedure B from 1e in 54% yield. Mp: 98-99 °C. IR (neat):
1713 cm-1. δH (300 MHz, CDCl3): 7.31 (m, 3H), 7.21 (m, 2H),
4.23 (t, J ) 7.5 Hz, 1H), 3.42 (m, 1H), 3.30 (dd, J ) 7.8, 11.2.Hz,
1H), 2.71 (dd, J ) 6.4, 17.9 Hz, 1H), 2.23 (dd, J ) 3.5, 17.9
Hz, 1H), 1.58 (s, 3H), 1.06 (s, 3H). 13C NMR (300 MHz,
CDCl3): 207.4, 184.0, 136.1, 130.8, 129.0, 128.3, 78.7, 69.9,
43.9, 39.2, 29.2, 24.1. MS m/z: 228 (M+, 19.32). HRMS m/z:
calcd for C15H16O2 228.1550, found 228.1550.
(-)-(5S ,5R,6â)-2-P h e n yl-6-(b e n zyloxym e t h yl)-7-oxa -
bicyclo[3.3.0]oct-1-en -3-on e (3h ). This compound was pre-
pared using general procedure A from 1h in 45% yield or
procedure B in 64% yield. [R]20D: -63.3° (c 1.25, CHCl3). IR
(neat): 1709 cm-1. δH (300 MHz CDCl3): 7.51 (m, 2H), 7.32-
7.44 (m, 8H), 5.04 (dd, J ) 1.4, 16.2 Hz, 1H), 4.67 (dt, J ) 1.3,
16.2 Hz, 1H), 4.64 (s, 2H), 3.76 (m, 2H), 3.64 (dt, J ) 4.5, 10.3
Hz, 1H), 3.17 (m, 1H), 2.79 (ddd, J ) 0.4, 6.5, 17.8 Hz, 1H),
2.35 (dd, J ) 3.5, 17.8 Hz, 1H). 13C NMR (300 MHz CDCl3):
206.7, 177.2, 137.9, 135.0, 130.5, 128.7, 128.5, 128.3, 128.1,
127.9, 127.7, 81.7, 73.7, 70.7, 67.0, 45.3, 40.2. MS m/z: 321
(M+ + 1, 59.86). HRMS m/z: calcd for C21H20O3 320.1413,
found 320.1418.
(()-(4R,5R)-4-Meth yl-2-p h en yl-7-oxa bicyclo[3.3.0]oct-1-
en -3-on e (3i). This compound was prepared using the general
procedure B from 1i in 63% yield. IR (neat): 1709 cm-1. δH
(300 MHz, CDCl3): 7.53 (m, 2H), 7.35 (m, 3H), 4.93 (dd, J )
1.6, 16.6 Hz, 1H), 4.61 (dd, J ) 0.5, 16.4 Hz, 1H), 4.42 (t, J )
8.0 Hz, 1H), 3.29 (dd, J ) 8.0, 11.1 Hz, 1H), 2.98 (m, 1H), 2.35
(dq, J ) 4.0, 7.2 Hz, 1H), 1.35 (d, J ) 7.2 Hz, 3H). 13C NMR
(300 MHz CDCl3): 208.8, 174.7, 133.8, 130.9, 128.7, 128.6,
128.0, 71.2, 66.5, 52.1, 47.5, 13.8. MS m/z: 214 (M+, 85.48).
HRMS m/z: calcd for C14H14O2 214.0994, found 214.0991.
(()-(4R,5R)-2-Meth yl-4-p h en yl-7-oxa bicyclo[3.3.0]oct-1-
en -3-on e (3k ). This compound was prepared using the general
procedure A from 1k in 32% yield. IR (neat): 1718 cm-1. δH
(400 MHz, CDCl3): 7.16-7.35 (m, 5H), 4.64 (d, J ) 15.7 Hz,
1H), 4.54 (d, J ) 15.7 Hz, 1H), 4.37 (t, J ) 5.8 Hz, 1H), 3.32-
3.40 (m, 2H), 3.29 (d, J ) 3.4 Hz, 1H), 1.83 (s, 3H). 13C NMR
(400 MHz CDCl3): 208.2, 174.0, 137.8, 131.4, 128.8, 128.3,
127.2, 71.7, 64.9, 57.0, 52.3, 9.4. MS m/z: 214 (M+, 52.88).
HRMS m/z: calcd for C14H14O2 214.0994, found 214.0990.
(()-(4R,5â)-2-P en tyl-4-p h en yl-7-oxa bicyclo[3.3.0]oct-1-
en -3-on e (3m ). This compound was prepared using the
general procedure B from 1m in 74% yield. IR (neat): 1714
cm-1. δH (300 MHz, CDCl3): 7.24 (m, 3H), 6.95 (m, 2H), 4.64
(d, J ) 15.8 Hz, 1H), 4.54 (dd, J ) 0.8, 15.8 Hz, 1H), 4.00 (d,
J ) 7.2 Hz, 1H), 3.86 (t, J ) 8.2 Hz, 1H), 3.53 (m, 1H), 2.84
(dd, J ) 8.3, 11.3 Hz, 1H), 2.33 (m, 2H), 1.54 (m, 2H), 1.34 (m,
4H), 0.91 (t, J ) 6.8 Hz, 3H). 13C NMR (300 MHz, CDCl3):
209.4, 176.1, 137.0, 128.7, 128.2, 127.1, 68.2, 65.5, 54.1, 48.9,
31.8, 27.4, 24.3, 22.4, 14.0. MS m/z: 270 (M+, 100). HRMS
m/z: calcd for C18H22O2 270.1620, found 270.1619.
(()-(4R,5R)-2-P en tyl-4-p h en yl-7-oxa bicyclo[3.3.0]oct-1-
en -3-on e (3n ). This compound was prepared using the general
procedure B from 1n in 61% yield. IR (neat): 1717 cm-1. δH
(300 MHz, CDCl3): 7.17-7.38 (m, 5H), 4.68 (d, J ) 15.7 Hz,
1H), 4.58 (d, J ) 15.7 Hz, 1H), 4.38 (m, 1H), 3.37 (m, 3H),
2.31 (m, 1H), 2.22 (m, 1H), 1.51 (m, 2H), 1.32 (m, 4H), 0.89 (t,
J ) 6.8 Hz, 3H). 13C NMR (400 MHz, CDCl3): 208.0, 173.5,
137.9, 135.9, 128.9, 128.6, 128.5, 128.3, 127.3, 71.8, 65.2, 57.2,
52.5, 31.8, 27.5, 24.6, 22.5, 14.0. MS m/z: 270 (M+, 100). HRMS
m/z: calcd for C18H22O2 270.1620, found 270.1649.
(()-6,6-Dim e t h yl-2-p h e n ylb icyclo[3.3.0]oct -1-e n -3-
on e (3q). This compound was prepared using the general
procedure A from 1q in 70% yield. IR (neat): 1701 cm-1. δH
(300 MHz CDCl3): 7.62 (m, 2H), 7.40 (m, 2H), 7.29 (m, 1H),
2.94 (dd, J ) 10.4, 19.5 Hz, 1H), 2.81 (m, 1H), 2.67 (m, 1H),
2.55 (dd, J ) 6.5, 18.0 Hz, 1H), 2.25 (dd, J ) 3.2, 18.1 Hz,
1H), 1.95 (m, 1H), 1.81 (m, 1H), 1.19 (s, 3H), 0.67 (s, 3H). 13C
NMR (300 MHz CDCl3): 208.7, 184.9, 134.9, 131.8, 128.3,
128.2, 127.7, 54.7, 41.4, 38.6, 37.4, 27.7, 26.9, 20.2. MS m/z:
226 (M+, 100). HRMS m/z: calcd for C16H18O 226.1358, found
226.1354.
(()-2-Bu tyl-6,6-dim eth ylbicyclo[3.3.0]oct-1-en -3-on e (3s).
This compound was prepared using the general procedure B
from 1s in 58% yield. IR (neat): 1706 cm-1. δH (300 MHz
CDCl3): 2.59 (m, 1H), 2.49 (m, 2H), 2.31 (dd, J ) 6.3, 18.1 Hz,
1H), 2.11 (m, 2H), 1.98 (dd, J ) 3.0, 18.1 Hz, 1H), 1.78 (m,
2H), 1.36 (m, 2H), 1.23 (dd, J ) 7.2, 15.1 Hz, 2H), 1.10 (s, 3H),
0.84 (t, J ) 7.2 Hz, 3H), 0.59 (s, 3H). 13C NMR (300 MHz
CDCl3): 210.9, 183.4, 136.9, 54.5, 41.4, 38.7, 36.4, 30.1, 27.8,
24.7, 23.4, 22.7, 20.0, 13.9. MS m/z: 206 (M+, 80.72). HRMS
m/z: calcd for C14H22O 206.1670, found 206.1676.
(()-6-P h en yl-3a,4-dih ydr ospir o(1H-cyclopen ta[c]fu r an -
1,1′-cyclop en ta n )-5(3H)-on e (3f). This compound was pre-
pared using the general procedure A from 1f in 43% yield or
procedure B in 78% yield. Mp: 93-94 °C. IR (KBr): 1701 cm-1
.
δH (300 MHz, CDCl3): 7.38 (m, 3H), 7.27 (m, 2H), 4.30 (t, J )
7.7 Hz, 1H), 3.48 (m, 1H), 3.29 (dd, J ) 7.9, 11.2 Hz, 1H), 2.78
(dd, J ) 6.4, 17.8 Hz, 1H), 2.31 (dd, J ) 3.7, 17.8 Hz, 1H),
2.21 (m, 2H), 1.88 (m, 1H), 1.69 (m, 2H) 1.55 (m, 3H). 13C NMR
(300 MHz, CDCl3): 207.5, 183.7, 135.8, 132.0, 131.0, 129.3,
128.4, 89.0, 69.9, 45.1, 41.4, 39.4, 36.2, 25.2. MS m/z: 254 (M+,
100). HRMS m/z: calcd for C17H18O2 254.1306, found 254.1303.
(()-2-n -P en tyl-7-oxa bicyclo[3.3.0]oct-1-en -3-on e (3g).
This compound was prepared using the general procedure A
from 1g in 41% yield or procedure B in 77% yield. IR (neat):
1712 cm-1. δH (300 MHz CDCl3): 4.61 (d, J ) 15.5 Hz, 1H),
4.51 (d, J ) 15.6 Hz, 1H), 4.31 (m, 1H), 3.18 (m, 2H), 2.66 (dd,
J ) 5.6, 17.6 Hz, 1H), 2.07-2.30 (m, 3H), 1.21-1.49 (m, 6H),
0.88 (t, J ) 7 Hz, 3H). 13C NMR (300 MHz CDCl3): 209.1,
176.0, 137.0, 72.2, 64.8, 43.3, 39.1, 31.5, 27.3, 24.1, 22.2, 13.9.
MS m/z: 195 (M+ + 1, 100). HRMS m/z: calcd for C12H18O2
194.1306, found 194.1291

Practical Method to Bicyclic Cyclopentenones
J . Org. Chem., Vol. 63, No. 25, 1998 9291
(()-Dieth yl 2-p h en yl-3-oxobicyclo[3.3.0]oct-1-en e-7,7-
d ica r boxyla te (3u ). This compound was prepared using the
general procedure A from 1u in 46% yield or Procedure B in
65% yield. IR (neat): 1732, 1707 cm-1. δH (300 MHz): 7.24-
7.57 (m, 2H), 7.38 (m, 3H), 4.28 (q, J ) 7.1 Hz, 2H), 4.17 (dq,
J ) 2.5, 7.1 Hz, 2H), 3.64 (d, J ) 19.2 Hz, 1H), 3.29 (d, J )
19.2 Hz, 1H), 3.12 (m, 1H), 2.82 (m, 2H), 2.31 (dd, J ) 3.3,
17.8 Hz, 1H), 1.76 (t, J ) 12.6 Hz, 1H), 1.31 (t, J ) 7.1 Hz,
3H), 1.22 (t, J ) 7.1 Hz, 3H). 13C NMR (300 MHz, CDCl3):
207.1, 179.0, 171.6, 170.7, 135.6, 131.0, 128.5, 128.2, 62.2, 62.0,
61.4, 42.9, 42.7, 38.8, 36.0, 14.1, 14.0. m/z (%): 342 (M+, 31.77),
268 (100). HRMS m/ z: calcd for C20H22O5 342.1467, found
342.1467.
Bicyclic Tita n a cycle (2m ). Under an argon atmosphere,
to a mixture of Cp2TiCl2 (2.2 mmol), enyne 1m (2 mmol), and
P(OEt)3 (4 mmol) in dry THF (20 mL) was added Mg powder
(2.5 mmol). The mixture was stirred at 0 °C for 6 h and then
passed through a short silica gel plug eluting with dry CH2-
Cl2. The solvents were removed under reduced pressure, and
the black residue was chromatographed on silica gel (15:1
petroleum/CH2Cl2) to give 560 mg (66%) of a dark-purple
viscous material. An analytical sample was obtained by further
purification by flash chromatography on silica gel. IR (neat):
3024, 2957, 2927, 2856, 1595, 1489, 1446, 1048, 1019, 918, 813,
752, 697 cm-1. δH (300 MHz, CDCl3): 7.14 (m, 2H), 6.83 (m,
3H), 6.23 (s, 5H), 5.81 (s, 5H), 4.29 (d, J ) 12.6 Hz, 1H), 4.19
(t, J ) 7.1 Hz, 1H), 3.93 (d, J ) 12.6 Hz, 1H), 3.73 (d, J ) 10.2
Hz, 1H), 2.86 (m, 1H), 2.73 (dd, J ) 7.7, 10.2 Hz, 1H), 2.15
(m, 1H), 2.05 (m, 1H), 1.0-1.35 (m, 6H), 0.90 (t, J ) 7.2 Hz,
3H). 13C NMR (300 MHz, CDCl3): 194.4, 152.3, 128.5, 128.1,
126.5, 123.5, 121.2, 119.8, 113.9, 113.4, 78.1, 70.5, 63.8, 40.6,
38.7, 32.6, 29.6, 22.6, 14.1. MS (FAB): 420 (M+). Anal. Calcd
for C27H32OTi: C, 77.14, H, 7.66. Found: C, 76.90, H, 7.92.
Ack n ow led gm en t. We thank the National Natural
Science Foundation for support of this research.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
new compounds 1d -g,k ,m ,n ,q,s, 2m , and 3c-i,k ,m ,n ,q,s,u
(23 pages). This material is contained in libraries on micro-
fiche, immediately follows this article in the microfilm version
of the journal, and can be ordered from the ACS; see any
current masthead page for ordering information.
J O9810718