Synthesis of 2-alkylidenecyclopentanones via palladium-catalyzed carbopalladation/ring expansion of 1-(1-alkynyl)cyclobutanols

Article abstract of DOI:10.1021/jo010577e

The palladium-catalyzed cross-coupling of aryl halides or vinylic halides or triflates and 1-(1-alkynyl)cyclobutanols affords good yields of stereoisomerically pure 2-arylidene- or 2-(2-al-kenylidene)cyclopentanones, respectively. The process involves (1)

Full text of DOI:10.1021/jo010577e

J . Org. Chem. 2002, 67, 2027-2033
2027
Syn th esis of 2-Alk ylid en ecyclop en ta n on es via
P a lla d iu m -Ca ta lyzed Ca r bop a lla d a tion /Rin g Exp a n sion of
1-(1-Alk yn yl)cyclobu ta n ols†
Richard C. Larock* and Ch. Kishan Reddy
Department of Chemistry, Iowa State University, Ames, Iowa 50011
larock@iastate.edu
Received J une 11, 2001
The palladium-catalyzed cross-coupling of aryl halides or vinylic halides or triflates and 1-(1-
alkynyl)cyclobutanols affords good yields of stereoisomerically pure 2-arylidene- or 2-(2-al-
kenylidene)cyclopentanones, respectively. The process involves (1) oxidative addition of the organic
halide or triflate to Pd(0), (2) regioselective, intermolecular carbopalladation of the carbon-carbon
triple bond of the 1-(1-alkynyl)cyclobutanol to produce a vinylic palladium intermediate, (3)
regioselective ring expansion to a palladacycle, and (4) reductive elimination of the 2-alkylidenecy-
clopentanone with simultaneous regeneration of the Pd(0) catalyst. Generally, the best results are
obtained by employing 10 mol % of Pd(OAc)2, 20 mol % of PPh3, 2 equiv of the aryl or vinylic iodide
or vinylic triflate, 2 equiv of diisopropylethylamine, and n-Bu4NCl in DMF as the solvent.
In tr od u ction
ence of phenols to produce 2-(1-aryloxyvinyl)cyclopen-
tanones.10 Finally, 1-allenylcyclobutanols react with aryl
or vinylic halides in the presence of a palladium catalyst
by a process involving carbopalladation of the allene and
subsequent ring expansion of the resulting π-allylpalla-
dium intermediate to generate unsaturated cyclopen-
tanones (eq 1).11
The synthesis of 2-alkylidenecyclopentanones has re-
ceived considerable attention in the literature due to the
fact that some of the natural products containing or
derived from such alkylidenecyclopentanones show sig-
nificant biological activity.1 A number of reactions of
palladium reagents and 3- or 4-membered ring alkenes
and alcohols have been reported to produce ketones,
particularly cycloalkanones. For example, cyclopropanols
react with Pd(II) salts to produce 2-alkenones.2 Silyloxy-
cyclopropanes react with aryl triflates in the presence of
a palladium catalyst to afford 3-arylalkanones.3 Meth-
ylenecyclobutanes undergo palladium(II)-catalyzed ring
expansion to cyclopentanones.4 The reaction of cyclobu-
tanols and catalytic amounts of Pd(OAc)2 generates
3-alkenones.5 The analogous palladium(0)-catalyzed reac-
tion of cyclobutanols and aryl halides affords 4-arylal-
kanones.6 Recently, 1-vinylcyclobutanols or the corre-
sponding silyl ethers have been shown to react with
palladium(II) salts to produce ring-expanded palladiocy-
clopentanones, which undergo either hydride elimination
to unsaturated cyclopentanones7 or further cyclization to
produce unsaturated bicyclic ketones.8 2-(1-Alkynyl)-2-
hydroxycyclobutanones undergo palladium(II)-catalyzed
ring expansion to 2-alkylidene-1,3-cyclopentanediones.9
1-(3-Methoxycarbonyloxy-1-propynyl)cyclobutanols un-
dergo palladium(0)-catalyzed ring expansion in the pres-
Despite the fact that we have carried out a large
number of carbopalladation reactions on 1-(1-alkynyl)-
cycloalkanols bearing 5- or 6-membered rings without
any involvement of the carbocyclic ring, this latter
process involving allenylcyclobutanols encouraged us to
examine the possibility that 1-(1-alkynyl)cyclobutanols
might undergo an analogous carbopalladation/ring-
expansion process to afford 2-alkylidenecyclopentanones.
We now wish to report just such a process.12
(7) (a) Clark, G. R.; Thiensathit, S. Tetrahedron Lett. 1985, 26, 2503.
(b) Demuth, M.; Pandey, B.; Wietfeld, B.; Said, H.; Viader, J . Helv.
Chim. Acta 1988, 71, 1392. (c) de Almeida Barbosa, L.-C.; Mann, J . J .
Chem. Soc., Perkin Trans. 1 1990, 177. (d) Nemoto, H.; Nagamochi,
M.; Fukumoto, K. J . Chem. Soc., Perkin Trans. 1 1993, 2329. (e)
Nemoto, H.; Nagamochi, M.; Ishibashi, H.; Fukumoto, K. J . Org. Chem.
1994, 59, 74. (f) Nemoto, H.; Miyata, J .; Fukumoto, K. Tetrahedron
1996, 52, 10363. (g) Nemoto, H.; Miyata, J .; Ihara, M. Tetrahedron
Lett. 1999, 40, 1933.
(8) (a) Nemoto, H.; Shiraki, M.; Fukumoto, K. Synlett 1994, 599.
(b) Nemoto, H.; Miyata, J .; Yoshida, M.; Raku, N.; Fukumoto, K. J .
Org. Chem. 1997, 62, 7850. (c) Nemoto, H.; Yoshida, M.; Fukumoto,
K.; Ihara, M. Tetrahedron Lett. 1999, 40, 907.
† This paper is dedicated to Professor Herbert C. Brown, a pioneer
in organometallic chemistry directed toward organic synthesis, on the
occasion of his 90th birthday.
(1) See: Liebeskind, L. S.; Chidambaram, R.; Mitchell, D. Pure Appl.
Chem. 1988, 60, 27 and references therein.
(2) (a) Park, S.-B.; Cha, J . K. Org. Lett. 2000, 2, 147. (b) Okumoto,
H.; J innai, T.; Shimizu, H.; Harada, Y.; Mishima, H.; Suzuki, A. Synlett
2000, 629.
(3) Aoki, S.; Fujimura, T.; Nakamura, E.; Kuwajima, I. J . Am. Chem.
Soc. 1988, 110, 3296.
(9) (a) Liebeskind, L. S.; Mitchell, D.; Foster, B. S. J . Am. Chem.
Soc. 1987, 109, 7908. (b) Liebeskind, L. S.; Chidambaram, R.; Mitchell,
D.; Foster, B. S. Pure Appl. Chem. 1988, 60, 2734. (c) Mitchell, D.;
Liebeskind, L. S. J . Am. Chem. Soc. 1990, 112, 291.
(4) Boontanonda, P.; Grigg, R. J . Chem. Soc., Chem. Commun. 1977,
583.
(5) Nishimura, T.; Ohe, K.; Uemura, S. J . Am. Chem. Soc. 1999,
121, 2645.
(10) Yoshida, M.; Nemoto, H.; Ihara, M. Tetrahedron Lett. 1999, 40,
8583.
(11) (a) Nemoto, H.; Yoshida, M.; Fukumoto, K. J . Org. Chem. 1997,
62, 6450. (b) Yoshida, M.; Sugimoto, K.; Ihara, M. Tetrahedron Lett.
2000, 41, 5089.
(6) Nishimura, T.; Uemura, S. J . Am. Chem. Soc. 1999, 121, 11010.
10.1021/jo010577e CCC: $22.00 © 2002 American Chemical Society
Published on Web 02/26/2002

2028 J . Org. Chem., Vol. 67, No. 7, 2002
Larock et al.
Ta ble 1. P a lla d iu m -Ca ta lyzed Ca r bop a lla d a tion /Rin g
Exp a n sion of 1-(P h en yleth yn yl)cyclobu ta n ol (1) a n d
Iod oben zen e (Eq 2)a
the yield of this process, we have looked at the effect
of several different palladium catalysts [Pd(PPh3)4,
Pd(OAc)2, and Pd(dba)2], various inorganic and organic
bases, two different chloride sources [LiCl and n-Bu4NCl
(TBAC)], and the ligand PPh3. The results are sum-
marized in Table 1. This investigation led to the following
standard reaction procedure: 10 mol % of Pd(OAc)2, 20
mol % of PPh3, 2 equiv of aryl or vinylic iodide or triflate,
2 equiv of diisopropylethylamine as the base, and 2 equiv
of n-Bu4NCl in DMF as the solvent at 80 °C. This
procedure afforded a 70% yield of cyclopentanone 2 after
12 h reaction time (Table 1, entry 21). Only much later
after encountering difficulties with some synthetic ex-
amples did we go back and examine additional variables.
It was then observed that a slightly higher yield of
cyclopentanone 2 could be obtained by using 10 mol % of
Pd(PPh3)4 and 2 equiv of Na2CO3 and n-Bu4NCl (Table
1, entry 27), but this procedure did not provide as high
yields on a number of other starting materials as our
original procedure above and often afforded products
arising by phenyl transfer from the PPh3 and has thus
not been widely employed.
With our standard procedure in hand, we next set out
to explore the scope and limitations of this novel route
to 2-alkylidenecyclopentanones by examining a wide
variety of 1-(1-alkynyl)cyclobutanols and aryl or vinylic
iodides or triflates as shown in Table 2. The reaction of
1-(phenylethynyl)cyclobutanol (1) and electron-rich meth-
oxy-containing aromatic iodides provided the correspond-
ing 2-arylidenecyclopentanones as single stereoisomers
in good yields (Table 2, entries 2 and 3). However, the
reaction of 1-(phenylethynyl)cyclobutanol (1) and 4-io-
doanisole under our standard conditions also produced
a side product 2-(diphenylmethylene)cyclopentanone (2)
in 11% yield (Table 2, entry 3). The phenyl group must
be coming from the ligand PPh3 added to this reaction.
This type of aryl exchange between arylpalladium inter-
mediates and triarylphosphines is well documented.14
Steric hindrance appears to be no problem here, since
the more hindered ortho-substituted system actually gave
a higher yield. Even o-iodoaniline reacted well, although
it usually undergoes oxidative addition only slowly and
requires an elevated temperature (Table 2, entry 4).
Under the usual reaction conditions, the cyclopentanone
5 could be isolated in good yield, but this product proved
unstable. When the reaction was run at 150 °C for 12 h,
the product was the interesting tricyclic pyridine deriva-
tive 6, apparently formed by olefin inversion in the
initially formed cyclopentanone and intramolecular con-
densation of the amino group and the ketone (Table 2,
entry 5). A high yield was also obtained from the electron-
poor o-iodonitrobenzene (Table 2, entry 6). Under our
standard reaction conditions for aryl halides, phenyl
triflate failed to produce any of the expected cyclopen-
tanone product, although the starting alkyne was ob-
served to disappear during the reaction.
Pd
PPh3
(%) base (equiv)
chloride source % isolated
entry catalyst
(equiv)
yield of 2
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
Pd(PPh3)4
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)4
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
K2CO3 (2)
K2CO3 (2)
58
47
45
46
40
65
58
0b
20
20
20
20
20
20
10
20
20
20
20
20
20
20
20
20
20
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
Na2CO3 (2)
NaHCO3 (2)
KOAc (2)
KHCO3 (2)
Na2CO3 (1)
Na2CO3 (2)
Na2CO3 (2)
Na2CO3 (2)
Na2CO3 (2)
Et3N (4)
LiCl (2)
TBAC (2)
LiCl (2)
TBAC (2)
TBAC (2)
TBAC (2)
TBAC (2)
TBAC (2)
TBAC (2)
TBAC (2)
TBAC (1)
TBAC (2)
TBAC (2)
TBAC (2)
TBAC (2)
TBAC (2)
TBAC (2)
TBAC (2)
TBAC (2)
TBAC (1)
TBAC (1)
TBAC (2)
TBAC (2)
TBAC (3)
TBAC (2)
TBAC (2)
TBAC (1)
53c
68
66
46
45
61
61
46d
62e
57f
69
10
70
66
58
62
64
54g
75h
58h
0h
Et3N (4)
20
20
20
20
20
10
i-Pr2NEt (2)
i-Pr2NEt (1)
i-Pr2NEt (4)
i-Pr2NEt (2)
i-Pr2NEt (1)
i-Pr2NEt (2)
Na2CO3 (2)
Na2CO3 (2)
i-Pr2NEt (2)
Na2CO3 (1)
Na2CO3 (2)
0h
0h
a
Unless otherwise stated, all reactions were carried out under
an argon atmosphere using 1 equiv of 1 (0.5 mmol), 2 equiv of 2
(1.0 mmol), 10 mol % of the Pd catalyst (0.05 mmol), 20 mol % of
PPh3 (0.1 mmol), 2 equiv of n-Bu4NCl (TBAC, 1.0 mmol), 2 equiv
b
of base (1.0 mmol), and DMF (5 mL) at 80 °C for 12 h. The
reaction was carried out at 70 °C. c The reaction was carried out
using 5 mol % of Pd(OAc)2 and 10 mol % of PPh3 at 80 °C for 12
d
h. The reaction was carried out using 1.2 equiv of 2. e The
reaction was carried out using 10 mL of DMF. f The reaction was
g
carried out using 20 mol % of (o-CH3C6H4)3P. The reaction was
h
carried out using 5 mol % of Pd(OAc)2 and 10 mol % PPh3. The
reaction was carried out at 80 °C for 24 h.
Resu lts a n d Discu ssion
1-(1-Alkynyl)cyclobutanols are easily prepared by metal
acetylide addition to the appropriate cyclobutanones,
which are in turn readily available by ketene cycloaddi-
tion to olefins.13 With a wide variety of 1-(1-alkynyl)-
cyclobutanols readily available, we focused our initial
studies on the reaction of 1-(phenylethynyl)cyclobutanol
(1) and iodobenzene as our model system (eq 2).
We were also curious as to whether this process could
be applied to vinylic halides. The reaction of 1-(phenyl-
ethynyl)cyclobutanol (1) and (E)-1-iodo-1-hexene (2 equiv)
under our standard conditions afforded a single isomeric
product 8 in 40% yield (Table 2, entry 7). The product
was characterized by 1D and 2D NMR HMQC, COSY,
and NOESY spectroscopy. The 2D NOESY spectrum of
2-[(2E)-1-phenylhept-2-enylidene]cyclopentanone (8) clearly
The reaction of alkynol 1 with 2 equiv of iodobenzene
in the presence of 10 mol % of Pd(PPh3)4 and 2 equiv of
K2CO3 as a base in DMF as the solvent at 80 °C resulted
in the formation of arylidenecyclopentanone 2 in 58%
yield after 12 h (Table 1, entry 1). In an effort to optimize
(12) For a previous communication, see: Larock, R. C.; Reddy, C.
K. Org. Lett. 2000, 2, 3325.
(13) (a) Grieco, P. A. J . Org. Chem. 1972, 37, 2363. (b) Krepski, L.
R.; Hassner, A. J . Org. Chem. 1978, 43, 2879.
(14) Kong, K.-C.; Cheng, C.-H. J . Am. Chem. Soc. 1991, 113, 6313.

Synthesis of 2-Alkylidenecyclopentanones
J . Org. Chem., Vol. 67, No. 7, 2002 2029
Ta ble 2. P a lla d iu m -Ca ta lyzed Ca r bop a lla d a tion /Rin g Exp a n sion of 1-(1-Alk yn yl)cyclobu ta n olsa
a
Unless otherwise stated, all reactions were carried out under an argon atmosphere using 1 equiv of cyclobutanol (0.5 mmol), 2 equiv
of organic halide or triflate (1.0 mmol), 10 mol % Pd(OAc)2 (0.05 mmol), 20 mol % of PPh3 (0.1 mmol), 2 equiv of n-Bu4NCl (TBAC, 1.0
b
mmol), 2 equiv of i-Pr2NEt (1.0 mmol), and DMF (5 mL) at 80 °C for 12 h. An 11% yield of 2-(diphenylmethylene)cyclopentanone (2) was
d
also observed. c The reaction was carried out at 150 °C for 12 h. These reactions were carried out for 6 h at 80 °C. e A 10% yield of
bicyclononanone 26 was also observed.
shows a cross-peak between the protons of the cyclopen-
tanone allylic methylene and the vinylic proton and no
interaction between the protons of the phenyl group and
the cyclopentanone allylic methylene protons. This is only

2030 J . Org. Chem., Vol. 67, No. 7, 2002
Larock et al.
Sch em e 1
consistent with the carbonyl group and the new vinylic
moiety being trans to each other.
In view of our failure to obtain any cyclopentanone
product from phenyl triflate, it was rather surprising that
we obtained a decent yield of the anticipated cyclopen-
tanone 9a when cyclohex-1-enyl triflate was employed
as a starting material (Table 2, entry 8). This product
was accompanied by substantial amounts of the stereo-
isomeric dienone 9b. Unfortunately, neither of these
compounds was stable enough for full characterization.
It appears that the increased steric bulk of the cyclohex-
enyl group leads to the low stereoselectivity of this
reaction and probably to the instability of the products.
4-Phenylcyclohex-1-enyl triflate afforded a good yield of
essentially equal amounts of two stereoisomeric dienones
10a and 10b, which also proved to be relatively unstable
(Table 2, entry 9). The stereochemistry of the products
in entries 8 and 9 of Table 2 is based on the assumption
that the vinylic proton trans to the carbonyl should
1
appear further downfield in the H NMR spectrum than
the corresponding cis proton.
cyclobutanol has undergone exclusive migration. The
reaction of bicyclobutanol 25 and 4-iodoanisole under our
standard conditions gave a single stereo- and regioisomer
27 (Table 2, entry 22). Once again, the more highly
substituted carbon of the cyclobutanol has undergone
migration. In this reaction, we once again observed
another minor product, 7-diphenylmethylene-1-methylbi-
cyclo[4.3.0]nonan-8-one (26), in 10% yield. The new
phenyl group in the product again apparently comes from
the PPh3 ligand.
The reaction of 1-(prop-1-ynyl)cyclobutanol (11) and
iodobenzene under our standard conditions again gave
a single isomeric product 12 (Table 2, entry 10). The
product was characterized by 1D and 2D NMR HMQC,
COSY, and NOESY spectroscopy. The 2D NOESY spec-
trum of 2-(1-phenylethylidene)cyclopentanone (12) (entry
10) clearly shows a cross-peak between the protons of the
phenyl group and the allylic methylene protons of the
cyclopentanone and no interaction between the methyl
protons and the allylic methylene protons of the cyclo-
pentanone. This is consistent with the structure 12 with
the phenyl group trans to the carbonyl. Further examples
of the reaction of 1-(prop-1-ynyl)cyclobutanol (11) and
various aryl iodides or one vinylic iodide produced
analogous ring expanded products in slightly lower yields
than those obtained with 1-(phenylethynyl)cyclobutanol
(1) (Table 2, entries 11-14). In all cases, a single
stereoisomeric product was obtained. Good results were
also obtained when reactions between 3-phenyl-1-(phen-
ylethynyl)cyclobutanol (17) and several aryl iodides were
carried out (Table 2, entries 15-17).
To gain better mechanistic insight into this interesting
process, we next carried out a reaction between 6-(phenyl-
ethynyl)bicyclo[3.2.0]hept-2-en-6-ol (21), an unsymmetri-
cal cyclobutanol, and iodobenzene under our standard
reaction conditions. This reaction gave a single regioiso-
meric product 22 in good yield (Table 2, entry 18). The
product was characterized by 1D and 2D NMR HMQC,
COSY, and NOESY spectroscopy. The 2D NOESY spec-
trum of the product 2-(diphenylmethylene)bicyclo[3.3.0]-
oct-6-en-3-one (22) clearly shows a cross-peak between
the protons of the phenyl group and the bicyclic bridge-
head proton. This result is consistent with a mechanism
in which an electron-deficient intermediate is being
generated and the more substituted, electron-rich carbon
of the cyclobutanol undergoes subsequent migration.
Single stereoisomeric products were also obtained in
decent yields from the reactions of o-iodoanisole (Table
2, entry 19) and ethyl p-iodobenzoate (Table 2, entry 20)
and cyclobutanol 21.
Based on the above results and previous work,10,11 we
believe that this novel ring-expansion process proceeds
as shown in Scheme 1 by a sequence involving (1)
reduction of Pd(OAc)2 to the actual Pd(0) catalyst, (2)
oxidative addition of the aryl or vinylic iodide or triflate
to Pd(0), (3) vinylic or arylpalladium coordination to the
carbon-carbon triple bond of the alkynylcyclobutanol and
subsequent regio- and stereoselective insertion of the
alkynylcyclobutanol to form a vinylpalladium intermedi-
ate, (4) release of the cyclobutane ring strain by migration
of the more highly substituted, electron-rich carbon of
the cyclobutanol to palladium to produce a palladacyclo-
hexanone, and (5) reductive elimination to afford a single
stereoisomeric 2-alkylidenecyclopentanone with simul-
taneous regeneration of the Pd(0) catalyst. Ring expan-
sion to a palladacycle nicely explains the fact that the
aryl or vinylic group arising from the iodide or triflate
always ends up trans to the carbonyl carbon. Were the
cyclobutanol carbon to migrate so as to effect a direct
backside displacement of the vinylic palladium, one
would expect the opposite stereochemistry in the final
product.
In conclusion, a variety of highly substituted 2-alkyl-
idenecyclopentanones have been prepared by the reaction
of aryl or vinylic iodides or triflates and 1-(1-alkynyl)-
cyclobutanols in the presence of a palladium catalyst.
These products are formed regio- and stereoselectively
in moderate yields. The process appears to involve a novel
ring expansion to a palladacyclohexanone and subse-
quent reductive elimination. It would be very hard to
prepare such products by any other present methodology.
Several reactions have also been successfully carried
out with 1-methyl-7-(phenylethynyl)bicyclo[4.2.0]octan-
7-ol (25) (Table 2, entries 21-23). The reaction of
iodobenzene gave a good yield of the bicyclononanone 26
in which the more substituted neighboring carbon of the
Exp er im en ta l Section
Gen er a l Meth od s. 1H and 13C NMR spectra were recorded
at 300 or 400 and 75.5 or 100 MHz, respectively. Thin-layer

Synthesis of 2-Alkylidenecyclopentanones
J . Org. Chem., Vol. 67, No. 7, 2002 2031
1
chromatography (TLC) was performed using commercially
prepared 60-mesh silica gel plates (Whatman K6F), and
visualization was effected with short wavelength UV light (254
nm) and basic KMnO4 solution [3 g of KMnO4 + 20 g of K2CO3
+ 5 mL of NaOH (5%) + 300 mL of H2O]. All melting points
are uncorrected. High-resolution mass spectra were recorded
on a Kratos MS50TC double-focusing magnetic sector mass
spectrometer using EI at 70 eV. Elemental analyses were
performed at Iowa State University on a Perkin-Elmer 2400
CHNS/O Series II analyzer. Reaction products were purified
by flash column chromatography with 40-63 µm SiO2 (Merck).
Rea gen ts. All reagents were used directly as obtained
commercially unless otherwise noted. Anhydrous forms of
Na2CO3, K2CO3, NaOAc, NaHCO3, LiCl, DMF, THF, diethyl
ether, and hexanes were purchased from Fisher Scientific. All
palladium salts and PPh3 were donated by Kawaken Fine
Chemicals Co., Ltd. Cyclobutanone, phenylacetylene, dicyclo-
pentadiene, 1-methylcyclohexene, styrene, zinc dust, 1-propy-
nylmagnesium bromide, Et3N, and i-Pr2NEt were purchased
from Aldrich Chemical Co., Inc. n-Bu4NCl was purchased from
Lancaster Synthesis, Inc.
compound as a yellow solid: mp 110 °C; H NMR (CDCl3) δ
1.89-1.99 (m, 2H), 2.37 (t, J ) 7.8 Hz, 2H), 2.87 (t, J ) 6.9
Hz, 2H), 3.82 (s, 3H), 6.85-6.88 (m, 2H), 7.11-7.17 (m, 4H),
7.32-7.35 (m, 3H); 13C NMR (CDCl3) δ 20.6, 33.2, 39.7, 55.2,
113.2, 127.6, 127.7, 129.4, 131.4, 133.2, 134.0, 140.5, 148.0,
159.7, 206.4; IR (CHCl3, cm-1) 1712; HRMS calcd for C19H17O2
277.1229, found 277.1232.
(E)-2-[(4-Meth oxyp h en yl)p h en ylm eth ylen e]cyclop en -
ta n on e (4). The reaction mixture was chromatographed using
60:40 hexanes/ether to afford 84 mg (60%) of the indicated
1
compound as a yellow solid: mp 110 °C; H NMR (CDCl3) δ
1.85-1.95 (m, 2H), 2.40 (t, J ) 7.8 Hz, 2H), 2.54 (t, J ) 7.2
Hz, 2H), 3.74 (s, 3H), 6.91-6.96 (m, 2H), 7.04-7.07 (m, 1H),
7.21-7.33 (m, 6H); 13C NMR (CDCl3) δ 19.6, 31.8, 40.3, 55.4,
111.3, 120.4, 127.3, 127.5, 128.9, 129.2, 129.8, 131.2, 135.0,
139.6, 145.2, 156.0, 205.9; IR (CHCl3, cm-1) 1712; MS m/z (rel
intensity) 278 (50, M+), 247 (100). Anal. Calcd for C19H18O2:
C, 81.99; H, 6.52. Found: C, 81.47; H, 6.75.
(E )-[(2-Am in o p h e n y l)p h e n y lm e t h y le n e ]c y c lo p e n -
ta n on e (5). The reaction mixture was chromatographed using
60:40 hexanes/ether to afford 76 mg (75%) of the indicated
compound as a yellow solid: 1H NMR (CDCl3) δ 1.88-1.98 (m,
2H), 2.43 (t, J ) 7.8 Hz, 2H), 2.64 (t, J ) 6.9 Hz, 2H), 3.68 (br
s, 2H), 6.70 (dd, J ) 1.2, 8.1 Hz, 1H), 6.74 (dt, J ) 1.2, 7.2 Hz,
1H), 6.96 (dd, J ) 1.5, 7.5 Hz, 1H), 7.13 (ddd, J ) 1.8, 7.5, 8.1
Hz, 1H), 7.26-7.32 (m, 5H); 13C NMR (CDCl3) δ 19.7, 32.2,
40.3, 115.9, 117.9, 127.4, 127.7, 128.3, 129.1, 129.3, 129.6,
135.4, 138.3, 143.3, 145.8, 206.1. This compound was too
unstable to get further characterization.
Rep r esen ta tive Syn th esis of a 1-(1-Alk yn yl)cyclobu -
ta n ol: 1-(P h en yleth yn yl)cyclobu ta n ol (1). A three-neck
flask with thermometer inlet was charged with diisopropyl-
amine (1.212 g, 12 mmol) in THF (5 mL). The flask was cooled
to -78 °C, and n-BuLi (12 mmol) in hexanes (2.10 mol L-1
)
was added dropwise under an argon atmosphere. The reaction
mixture was allowed to warm to room temperature for 20 min
and then cooled to -78 °C, and phenylacetylene (1.224 g, 12
mmol) in THF (2 mL) was added. The flask was allowed to
warm to 0 °C for 20 min and then stirred for 1 h. The flask
was again cooled to -78 °C, and cyclobutanone (0.700 g, 10
mmol) in THF (4 mL) was added. The flask was allowed to
warm to room temperature for 30 min, further stirred for 2 h,
quenched with water, and extracted with ether (3 × 25 mL),
and the combined extracts were washed with saturated
aqueous NH4Cl, water, and brine, dried (Na2SO4), and filtered.
The solvent was removed under reduced pressure, and the
resulting oil was purified by flash column chromatography
using 60:40 hexanes/diethyl ether to afford 1.566 g (91%) of
9-P h en yl-1,2,3-tr ih yd r op en ta [1,2-b]qu in olin e (6). The
reaction mixture was chromatographed using 60:40 hexanes/
ether to afford 71 mg (58%) of the indicated compound as a
1
yellow solid: mp 128-130 °C; H NMR (CDCl3) δ 2.13-2.20
(m, 2H), 2.89 (t, J ) 7.3 Hz, 2H), 3.23 (t, J ) 7.6 Hz, 2H),
7.33-7.39 (m, 3H), 7.45-7.54 (m, 3H), 7.59-7.64 (m, 2H),
8.05-8.09 (m, 1H); 13C NMR (CDCl3) δ 23.5, 30.3, 35.2, 125.5,
125.6, 126.2, 127.9, 128.2, 128.5, 128.8, 129.3, 133.6, 136.7,
142.7, 147.9, 167.4; IR (CHCl3, cm-1) 3027, 2976; MS m/z (rel
intensity) 246 (20, M + 1), 245 (100). Anal. Calcd for C18H15N:
C, 88.13; H, 6.16; N, 5.71. Found: C, 87.90; H, 6.23; N, 5.55.
(E )-2-[(2-Nit r op h e n yl)p h e n ylm e t h yle n e ]cyclop e n -
ta n on e (7). The reaction mixture was chromatographed using
60:40 hexanes/ether to afford 103 mg (70%) of the indicated
compound as a yellow viscous oil: 1H NMR (CDCl3) δ 1.88-
1.97 (m, 2H), 2.38-2.51 (m, 4H), 7.24-7.29 (m, 5H), 7.39 (dd,
J ) 1.5, 7.5 Hz, 1H), 7.49 (dt, J ) 1.5, 7.5 Hz, 1H), 7.66 (dt, J
) 1.2, 7.5 Hz, 1H), 8.00 (dd, J ) 1.5, 8.4 Hz, 1H); 13C NMR
(CDCl3) δ 19.5, 31.8, 40.1, 124.8, 127.5, 128.4, 128.8, 129.5,
130.7, 133.4, 134.6, 136.5, 136.9, 144.4, 147.5, 205.0; IR
(CHCl3, cm-1) 1716, 1524, 1348; HRMS calcd for C18H14NO3
292.0974, found 292.0968.
1
the desired compound as a white solid: mp 42 °C; H NMR
(CDCl3) δ 1.82-1.93 (m, 2H), 2.10 (br s, 1H), 2.23-2.40 (m,
2H), 2.50-2.58 (m, 2H), 7.26-7.34 (m, 3H), 7.42-7.46 (m, 2H);
13C NMR (CDCl3) δ 12.3, 38.6, 68.2, 83.4, 92.6, 122.7, 128.2,
131.7 (one carbon missing as a result of overlap). The synthe-
ses of cyclobutanols 11, 17, 21, and 25 are reported in the
Supporting Information.
Gen er a l P r oced u r e for th e P a lla d iu m -Ca ta lyzed Ca r -
bop a lla d a tion /Rin g Exp a n sion of 1-(1-Alk yn yl)cyclobu -
ta n ols by Or ga n ic Ha lid es. DMF (5 mL), Pd(OAc)2 (11 mg,
0.05 mmol), PPh3 (26 mg, 0.1 mmol), the organic iodide or
triflate (1.0 mmol), i-Pr2NEt (130 mg, 1.0 mmol), n-Bu4NCl
(277 mg, 1.0 mmol), and the 1-(1-alkynyl)cyclobutanol (0.5
mmol) were placed in a 4 dram vial. The vial was flushed with
Ar and heated in an oil bath at 80 °C for the indicated period
of time. The reaction was monitored by TLC to establish
completion. The reaction mixture was cooled, diluted with 30
mL of ether, washed with 40 mL of saturated NaCl, dried (Na2-
SO4), and filtered. The solvent was evaporated under reduced
pressure, and the product was isolated by chromatography on
a silica gel column.
Com p ou n d s P r ep a r ed . 2-(Dip h en ylm eth ylen e)cyclo-
p en ta n on e (2). The reaction mixture was chromatographed
using 60:40 hexanes/ether to afford 87 mg (70%) of the
indicated compound as a yellow solid: mp 105 °C; 1H NMR
(CDCl3) δ 1.93 (m, 2H), 2.38 (t, J ) 7.8 Hz, 2H), 2.82 (t, J )
7.0 Hz, 2H), 7.10-7.14 (m, 2H), 7.17-7.20 (m, 2H), 7.30-7.35
(m, 6H); 13C NMR (CDCl3) δ 20.5, 32.9, 39.8, 127.8, 127.9,
128.3, 129.4, 129.6, 134.3, 140.1, 141.8, 148.2, 206.5 (one
carbon missing as a result of overlap); IR (CHCl3, cm-1) 1706;
MS m/z (rel intensity) 248 (50, M+), 247 (100), 191 (30). Anal.
Calcd for C18H16O: C, 87.06; H, 6.49. Found: C, 86.90; H, 6.80.
(E)-2-[(2-Meth oxyp h en yl)p h en ylm eth ylen e]cyclop en -
ta n on e (3). The reaction mixture was chromatographed using
60:40 hexanes/ether to afford 103 mg (74%) of the indicated
(E )-2-[(2E )-1-P h e n ylh e p t -2-e n ylid e n e ]cyclop e n t a n -
on e (8). The reaction mixture was chromatographed using 70:
30 hexanes/ether to afford 50 mg (40%) of the indicated
compound as a yellow oil: 1H NMR (CDCl3) δ 0.88 (t, J ) 6.9
Hz, 3H), 1.27-1.37 (m, 4H), 1.95-2.03 (m, 2H), 2.17 (q, J )
6.6 Hz, 2H), 2.29 (t, J ) 7.8 Hz, 2H), 2.88 (t, J ) 7.2 Hz, 2H),
5.55-5.65 (m, 1H), 6.47 (d, J ) 15.3 Hz, 1H), 7.02-7.05 (m,
2H), 7.31-7.39 (m, 3H); 13C NMR (CDCl3) δ 13.8, 19.4, 22.2,
29.2, 30.9, 33.3, 40.2, 126.9, 127.6, 128.6, 130.8, 131.1, 138.0,
144.9, 206.0; IR (CHCl3, cm-1) 1708; HRMS calcd for C18H22
254.1671, found 254.1670.
O
(E )-[(Cycloh e x-1-e n yl)p h e n ylm e t h yle n e ]cyclop e n -
ta n on e (9a ). The reaction mixture was chromatographed
using 60:40 hexanes/ether to afford 43 mg (34%) of the
indicated compound as a yellow viscous oil: 1H NMR (CDCl3)
δ 1.57-1.61 (m, 4H), 1.84-1.97 (m, 4H), 2.16-2.18 (m, 2H),
2.30 (t, J ) 7.8 Hz, 2H), 2.79 (t, J ) 6.9 Hz, 2H), 5.78-5.81
(m, 1H), 7.11-7.15 (m, 2H), 7.27-7.34 (m, 3H); 13C NMR
(CDCl3) δ 20.5, 21.9, 22.7, 25.5, 27.4, 32.4, 40.0, 127.5, 127.7,
128.5, 129.3, 131.7, 138.9, 139.2, 151.3, 206.7. This compound
was too unstable for further characterization.
(Z)-[(Cycloh e x-1-e n yl)p h e n ylm e t h yle n e ]cyclop e n -
ta n on e (9b). The reaction mixture was chromatographed
using 60:40 hexanes/ether to afford 29 mg (23%) of the

2032 J . Org. Chem., Vol. 67, No. 7, 2002
Larock et al.
indicated compound as a yellow viscous oil: 1H NMR (CDCl3)
δ 1.63-1.70 (m, 4H), 1.81-1.89 (m, 2H), 1.98-2.00 (m, 2H),
2.10-2.13 (m, 2H), 2.35 (t, J ) 7.5 Hz, 2H), 2.65 (t, J ) 6.9
Hz, 2H), 5.46-5.50 (m, 1H), 7.29-7.37 (m, 5H). This compound
was too unstable for further characterization.
(E)-[P h en yl(4-p h en ylcycloh ex-1-en yl)m et h ylen e]cy-
clop en ta n on e (10a ). The reaction mixture was chromato-
graphed using 60:40 hexanes/ether to afford 60 mg (36%) of
the indicated compound as a yellow viscous oil: 1H NMR
(CDCl3) δ 1.75-1.85 (m, 1H), 1.93-2.11 (m, 5H), 2.33-2.43
(m, 3H), 2.50-2.56 (m, 1H), 2.79-2.90 (m, 3H), 5.95 (s, 1H),
7.19-7.41 (m, 10H); 13C NMR (CDCl3) δ 20.4, 27.9, 29.8, 32.3,
33.5, 39.5, 39.9, 126.1, 126.7, 127.5, 127.7, 128.3, 128.4, 128.6,
131.9, 138.7, 139.0, 146.4, 150.6, 206.5. This compound was
too unstable for further characterization.
(Z)-[P h en yl(4-p h en ylcycloh ex-1-en yl)m et h ylen e]cy-
clop en ta n on e (10b). The reaction mixture was chromato-
graphed using 60:40 hexanes/ether to afford 57.4 mg (35%) of
the indicated compound as a yellow viscous oil: 1H NMR
(CDCl3) δ 1.83-2.13 (m, 5H), 2.25-2.48 (m, 5H), 2.71 (t, J )
6.9 Hz, 2H), 2.90-3.00 (m, 1H), 5.61-5.62 (m, 1H), 7.19-7.41
(m, 10H); 13C NMR (CDCl3) δ 20.7, 29.1, 30.0, 32.2, 33.8, 39.5,
39.7, 125.7, 125.9, 126.9, 128.0, 128.3, 128.7, 133.3, 138.1,
140.4, 145.0, 147.2, 150.7, 207.2. This compound was too
unstable for further characterization.
(E)-2-(1-P h en yleth ylid en e)cyclop en ta n on e (12). The re-
action mixture was chromatographed using 60:40 hexanes/
ether to afford 56 mg (60%) of the indicated compound as a
yellow oil: 1H NMR (CDCl3) δ 1.74-1.83 (m, 2H), 2.37 (t, J )
7.5 Hz, 2H), 2.52-2.60 (m, 5H), 7.22-7.39 (m, 5H); 13C NMR
(CDCl3) δ 19.8, 20.3, 31.7, 40.5, 127.2, 127.8, 128.1, 132.6,
143.5, 147.4, 208.8; IR (CHCl3, cm-1) 1703; HRMS calcd for
as a yellow solid: mp 119-120 °C; 1H NMR (CDCl3) δ 2.68
(dd, J ) 10.8, 18.0 Hz, 1H), 2.89 (ddd, J ) 1.8, 7.5, 18.0 Hz,
1H), 3.05 (dd, J ) 10.2, 16.0 Hz, 1H), 3.25 (ddd, J ) 1.5, 6.9,
16.0 Hz, 1H), 3.42-3.54 (m, 1H), 7.23-7.43 (m, 15H); 13C NMR
(CDCl3) δ 39.5, 41.1, 46.9, 126.6, 126.7, 127.8, 127.9, 128.0,
128.5, 128.6, 129.4, 129.5, 133.9, 139.9, 141.5, 143.1, 148.8,
204.5; IR (CHCl3, cm-1) 1709; HRMS calcd for C24H20
324.1514, found 324.1511.
O
(E)-4-P h en yl-2-[ph en yl[4-(tr iflu or om eth yl)ph en yl]m eth -
ylen e]cyclop en ta n on e (19). The reaction mixture was chro-
matographed using 80:20 hexanes/ether to afford 106 mg (54%)
of the indicated compound as a yellow oil: 1H NMR (CDCl3) δ
2.68 (dd, J ) 10.8, 18.3 Hz, 1H), 2.85-3.02 (m, 2H), 3.17 (ddd,
J ) 1.8, 6.9, 16.2 Hz, 1H), 3.42-3.54 (m, 1H), 7.19-7.42 (m,
12H), 7.61-7.64 (m, 2H); 13C NMR (CDCl3) δ 39.4, 40.9, 46.9,
122.1, 125.0, 125.1, 125.1, 125.2, 125.7, 126.7, 126.8, 128.0,
128.3, 128.7, 129.3, 129.7, 130.0, 130.4, 135.1, 139.1, 142.8,
145.1, 147.1, 204.3; IR (CHCl3, cm-1) 1710; HRMS calcd for
C
25H19F3O 392.1388, found 392.1383.
(E)-Eth yl 4-[(2-Oxo-4-p h en ylcyclop en tylid en e)p h en yl-
m eth yl]ben zoa te (20). The reaction mixture was chromato-
graphed using 80:20 hexanes/ether to afford 126 mg (64%) of
the indicated compound as a yellow oil: 1H NMR (CDCl3) δ
1.40 (t, J ) 7.0 Hz, 3H), 2.65 (dd, J ) 10.8, 18.0 Hz, 1H), 2.83-
3.02 (m, 2H), 3.19 (dd, J ) 6.9, 15.9 Hz, 1H), 3.40-3.52 (m,
1H), 4.41 (q, J ) 7.0 Hz, 2H), 7.17-7.39 (m, 12H), 8.05 (d, J
) 8.4 Hz, 2H); 13C NMR (CDCl3) δ 14.2, 39.2, 40.9, 46.8, 61.0,
126.6, 126.7, 127.9, 128.2, 128.6, 129.2, 129.3, 129.4, 130.2,
134.8, 139.1, 142.8, 145.9, 147.6, 165.9, 204.3 (two carbons
missing as a result of overlap); IR (CHCl3, cm-1) 1710; HRMS
calcd for C27H24O3 396.1726, found 396.1720.
2-(Diph en ylm eth ylen e)bicyclo[3.3.0]oct-6-en -3-on e (22).
The reaction mixture was chromatographed using 60:40 hex-
anes/ether to afford 70 mg (50%) of the indicated compound
as a yellow oil: 1H NMR (CDCl3) δ 2.20-2.33 (m, 2H), 2.47-
2.57 (m, 1H), 2.70 (dd, J ) 9.9, 18.6 Hz, 1H), 3.30-3.37 (m,
1H), 3.79-3.87 (m, 1H), 5.66-5.73 (m, 2H), 7.12-7.36 (m,
10H); 13C NMR (CDCl3) δ 41.4, 42.4, 44.0, 44.4, 127.7, 127.8,
128.0, 128.2, 128.9, 129.2, 130.8, 133.9, 139.4, 140.6, 141.9,
C
13H14O 186.1045, found 186.1039.
(E)-2-[(2-Met h oxyp h en yl)et h ylid en e]cyclop en t a n on e
(13). The reaction mixture was chromatographed using 60:40
hexanes/ether to afford 63 mg (63%) of the indicated compound
as a yellow oil: 1H NMR (CDCl3) δ 1.73-1.83 (m, 2H), 2.34-
2.45 (m, 7H), 3.79 (s, 3H), 6.89-7.04 (m, 3H), 7.24-7.29 (m,
1H); 13C NMR (CDCl3) δ 19.8, 19.9, 30.8, 40.7, 55.4, 111.0,
120.5, 128.1, 128.8, 132.4, 133.3, 145.8, 155.4, 208.7; IR
(CHCl3, cm-1) 1701; HRMS calcd for C14H16O2 216.1150, found
216.1145.
150.1, 206.7; IR (CHCl3, cm-1) 1706; HRMS calcd for C21H18
286.1358, found 286.1352.
O
(E)-2-[(2-Met h oxyp h en yl)p h en ylm et h ylen e]b icyclo-
[3.3.0]oct-6-en -3-on e (23). The reaction mixture was chro-
matographed using 60:40 hexanes/ether to afford 82 mg (52%)
of the indicated compound as a yellow oil: 1H NMR (CDCl3) δ
2.23-2.31 (m, 3H), 2.69 (dd, J ) 9.9, 18.9 Hz, 1H), 3.25-3.33
(m, 1H), 3.51-3.59 (m, 1H), 3.72 (s, 3H), 5.62-5.69 (m, 2H),
6.89-6.98 (m, 2H), 7.22-7.31 (m, 7H); 13C NMR (CDCl3) δ
42.4, 44.1, 45.0, 55.4, 111.4, 120.5, 127.3, 127.5, 128.7, 129.1,
130.7, 133.9, 140.0, 206.4 (six carbons missing as a result of
overlap); IR (CHCl3, cm-1) 1706; HRMS calcd for C22H20O2
316.1463, found 316.1457.
(E)-E t h yl 4-[(3-Oxob icyclo[3.3.0]oct -6-en -2-ylid en e)-
p h en ylm eth yl]ben zoa te (24). The reaction mixture was
chromatographed using 60:40 hexanes/ether to afford 75 mg
(42%) of the indicated compound as a yellow oil: 1H NMR
(CDCl3) δ 1.39 (t, J ) 7.2 Hz, 3H), 2.15-2.32 (m, 2H), 2.43-
2.53 (m, 1H), 2.69 (dd, J ) 9.9, 18.9 Hz, 1H), 3.32-3.36 (m,
1H), 3.73-3.80 (m, 1H), 4.39 (q, J ) 7.2 Hz, 2H), 5.63-5.71
(m, 2H), 7.08-7.11 (m, 2H), 7.25-7.31 (m, 5H), 8.01-8.04 (m,
2H); 13C NMR (CDCl3) δ 14.3, 41.4, 42.5, 43.9, 44.4, 61.1, 127.9,
128.1, 128.9, 129.2, 129.5, 130.0, 130.7, 134.0, 139.9, 140.3,
146.5, 148.9, 166.1, 206.5 (one carbon missing as a result of
overlap); IR (CHCl3, cm-1) 1709; HRMS calcd for C24H22O3
358.1569, found 358.1562.
(E)-Eth yl 4-[1-(2-oxocyclop en tylid en e)eth yl]ben zoa te
(14). The reaction mixture was chromatographed using 60:40
hexanes/ether to afford 42 mg (33%) of the indicated compound
as a yellow oil: 1H NMR (CDCl3) δ 1.39 (t, J ) 7.0 Hz, 3H),
1.76-1.85 (m, 2H), 2.39 (t, J ) 7.8 Hz, 2H), 2.51-2.56 (m, 5H),
4.39 (q, J ) 7.2 Hz, 2H), 7.28-7.32 (m, 2H), 8.02-8.06 (m,
2H); 13C NMR (CDCl3) δ 14.4, 19.7, 20.3, 31.5, 40.5, 61.1, 127.2,
129.6, 129.8, 133.3, 146.2, 148.0, 166.2, 208.7 (one carbon
missing as a result of overlap); IR (CHCl3, cm-1) 1717, 1606;
HRMS calcd for C16H18O3 258.1256, found 258.1252.
(E)-2-[1-(2-Nitr oph en yl)eth yliden e]cyclopen tan on e (15).
The reaction mixture was chromatographed using 60:40 hex-
anes/ether to afford 54 mg (47%) of the indicated compound
as a yellow oil: 1H NMR (CDCl3) δ 1.73-1.83 (m, 2H), 2.20-
2.24 (m, 2H), 2.36 (t, J ) 7.8 Hz, 2H), 2.46 (s, 3H), 7.22 (dd, J
) 1.5, 7.8 Hz, 1H), 7.48 (dt, J ) 1.5, 7.5 Hz, 1H), 7.65 (dt, J )
1.2, 7.5 Hz, 1H), 8.07 (dd, J ) 0.9, 8.4 Hz, 1H); 13C NMR
(CDCl3) δ 19.6, 19.8, 30.4, 40.5, 124.7, 128.4, 129.1, 132.4,
133.9, 138.9, 144.7, 146.4, 207.8; IR (CHCl3, cm-1) 1709, 1633,
1606, 1526, 1347; HRMS calcd for C13H13NO3 231.0895, found
231.0892.
(E )-2-[(2E )-1-Me t h ylh e p t -2-e n ylid e n e ]cyclop e n t a n -
on e (16). The reaction mixture was chromatographed using
60:40 hexanes/ether to afford 34 mg (35%) of the indicated
compound as a yellow oil: 1H NMR (CDCl3) δ 0.91 (t, J ) 6.6
Hz, 3H), 1.29-1.45 (m, 4H), 1.85-1.92 (m, 2H), 2.18-2.36 (m,
7H), 2.72 (t, J ) 6.3 Hz, 2H), 6.21-6.25 (m, 2H); 13C NMR
(CDCl3) δ 13.1, 13.9, 19.4, 22.3, 29.3, 31.3, 33.4, 40.8, 131.0,
131.1, 139.9, 142.7, 208.9; IR (CHCl3, cm-1) 1692, 1585; HRMS
calcd for C13H20O 192.1514, found 192.1513.
7-Dip h en ylm eth ylen e-1-m eth ylbicyclo[4.3.0]n on a n -8-
on e (26). The reaction mixture was chromatographed using
60:40 hexanes/ether to afford 94 mg (60%) of the indicated
compound as a yellow solid: mp 157-158 °C; 1H NMR (CDCl3)
δ 1.07-1.47 (m, 7H), 1.59-1.72 (m, 4H), 1.93 (dd, J ) 1.5,
18.0 Hz, 1H), 2.50 (dd, J ) 5.7, 10.8 Hz, 1H), 2.68 (d, J ) 18.0
Hz, 1H), 7.16-7.36 (m, 10H); 13C NMR (CDCl3) δ 21.7, 24.5,
29.2, 30.2, 34.8, 35.3, 47.2, 49.1, 127.6, 127.7, 128.1, 128.4,
128.9, 140.3, 140.7, 141.9, 148.3, 206.4 (one carbon missing
2-Dip h en ylm et h ylen e-4-p h en ylcyclop en t a n on e (18).
The reaction mixture was chromatographed using 80:20 hex-
anes/ether to afford 115 mg (71%) of the indicated compound

Synthesis of 2-Alkylidenecyclopentanones
J . Org. Chem., Vol. 67, No. 7, 2002 2033
as a result of overlap); IR (CHCl3, cm-1) 1710; HRMS calcd
for C23H23O (M - 1) 315.1749, found 315.1755.
(d, J ) 15.3 Hz, 1H), 7.01-7.04 (m, 2H), 7.32-7.35 (m, 3H);
13C NMR (CDCl3) δ 13.8, 22.0, 22.3, 25.0, 29.7, 31.0, 31.1, 33.3,
35.0, 35.2, 47.1, 47.9, 126.8, 127.7, 128.6, 130.3, 138.0, 138.3,
144.4, 144.8, 205.9; IR (CHCl3, cm-1) 1700, 1621, 1583; HRMS
calcd for C23H30O 322.2297, found 322.2296.
(E)-1-Meth yl-7-[(4-m eth oxyp h en yl)p h en ylm eth ylen e]-
bicyclo[4.3.0]n on a n -8-on e (27). The reaction mixture was
chromatographed using 70:30 hexanes/ether to afford 74 mg
(44%) of the indicated compound as a yellow oil: 1H NMR
(CDCl3) δ 1.10-1.45 (m, 7H), 1.57-1.75 (m, 4H), 1.90 (dd, J
) 1.5, 17.7 Hz, 1H), 2.52-2.63 (m, 2H), 3.82 (s, 3H), 6.85-
6.88 (m, 2H), 7.10-7.14 (m, 4H), 7.28-7.30 (m, 3H); 13C NMR
(CDCl3) δ 21.8, 24.5, 29.2, 30.1, 34.9, 35.5, 47.3, 49.3, 55.1,
113.5, 127.6, 127.7, 129.1, 130.1, 134.3, 140.2, 140.9, 148.1,
159.3, 206.6 (two carbons missing as a result of overlap); IR
(CHCl3, cm-1) 1708, 1604; HRMS calcd for C24H26O2 346.1933,
found 346.1929.
Ack n ow led gm en t. We gratefully acknowledge the
donors of the Petroleum Research Fund, administered
by the American Chemical Society, for partial support
of this research; Kawaken Fine Chemicals Co., Ltd. for
donation of the palladium acetate; and Merck and Co.,
Inc., for an Academic Development Award in Chemistry.
(E)-1-Meth yl-7-[(2E)-1-p h en ylh ep t-2-en ylid en e]bicyclo-
[4.3.0]n on a n -8-on e (28). The reaction mixture was chromato-
graphed using 70:30 hexanes/ether to afford 68 mg (43%) of
the indicated compound as a yellow oil: 1H NMR (CDCl3) δ
0.88 (t, J ) 6.9 Hz, 3H), 1.06 (s, 3H), 1.23-1.39 (m, 8H), 1.66-
1.76 (m, 4H), 1.94-1.99 (m, 1H), 2.12-2.19 (m, 2H), 2.59 (d,
J ) 17.4 Hz, 1H), 2.68-2.73 (m, 1H), 5.51-5.61 (m, 1H), 6.48
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for all ketone products in Table 2 and preparative
procedures and characterization for 1-(1-alkynyl)cyclobutanols
11, 17, 21, and 25. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O010577E