Synthesis of β,γ-unsaturated ketones from acid chlorides through carbon-pentamethylcyclopentadienyl bond formation and cleavage

Article abstract of DOI:10.1246/bcsj.80.2400

Reaction of acid chlorides with lithium pentamethylcyclopentadienide afforded the corresponding pentamethyl-cyclopentadienyl ketones in high yield. These ketones were treated with an allylaluminum reagent to form the corresponding 3-butenyl alcohols. Removal of pentamethylcyclopentadiene upon heating or treatment with a catalytic amount of trichloroacetic acid yielded the corresponding β,γ-unsaturated ketones in good yields.

Full text of DOI:10.1246/bcsj.80.2400

2400 Bull. Chem. Soc. Jpn. Vol. 80, No. 12, 2400–2405 (2007)
ꢀ 2007 The Chemical Society of Japan
Synthesis of ꢀ,ꢁ-Unsaturated Ketones from Acid Chlorides through
Carbon–Pentamethylcyclopentadienyl Bond Formation and Cleavage
ꢀ
ꢀ
Minoru Uemura, Masayuki Iwasaki, Eiji Morita, Hideki Yorimitsu, and Koichiro Oshima
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510
Received June 19, 2007; E-mail: yori@orgrxn.mbox.media.kyoto-u.ac.jp
Reaction of acid chlorides with lithium pentamethylcyclopentadienide afforded the corresponding pentamethyl-
cyclopentadienyl ketones in high yield. These ketones were treated with an allylaluminum reagent to form the corre-
sponding 3-butenyl alcohols. Removal of pentamethylcyclopentadiene upon heating or treatment with a catalytic amount
of trichloroacetic acid yielded the corresponding ꢀ,ꢁ-unsaturated ketones in good yields.
We have been exploring applications of pentamethylcyclo-
ꢀ
od to synthesize ꢀ,ꢁ-unsaturated ketones from acid chlorides
in three steps as shown in Scheme 2, wherein R–M is an allyl-
metal reagent.
pentadiene (Me5C5H, Cp H) as a reagent in organic synthesis
ꢀ
and developing new reactions.1 We have reported that Cp Li
reacted with aromatic aldehydes 1 to provide the correspond-
Results and Discussion
ing secondary alcohols 2 in excellent yields. The secondary
ꢀ
ꢀ
alcohols easily returned to the parent aldehydes and Cp H
under thermal or acidic conditions (Scheme 1).1a,1c
Treatment of Cp Li (1.1 molar amount) with benzoyl chlo-
ride (3a) in THF at 0 ꢁC for 30 min afforded pentamethylcyclo-
pentadienyl phenyl ketone (4a) in excellent yield (Table 1,
Entry 1). A variety of aromatic acid chlorides 3 were subjected
Thus, we expected that alcohol 5, which is prepared from
acid chloride 3 via 4, would smoothly transform to ketone 6
ꢀ
ꢀ
by removal of Cp H (Scheme 2). Using this approach, we
to the nucleophilic addition reaction of Cp Li to afford aryl
planned to synthesize ꢀ,ꢁ-unsaturated ketones.2 Synthesis of
ꢀ,ꢁ-unsaturated ketones is often complicated, since ꢀ,ꢁ-un-
saturated ketones easily isomerize to ꢂ,ꢀ-unsaturated ketones
under acidic or basic conditions. Here, we report1e a new meth-
pentamethylcyclopentadienyl ketones 4. Acid chlorides 3 bear-
ing an electron-withdrawing group (Entry 2) or an electron-
donating group (Entry 3) afforded 4 in high yields. Bromine
(Entry 4) and chlorine (Entry 5) on the aromatic ring did not
OH
OH
O
∆ or cat. CCl3COOH
Cp*Li
O
O
O
Cp*Li
R–M
–Cp*H
1
Ar
H
–Cp*H
Ar
R
Ar
H
Ar
Cl
Ar
Cp*
Ar
R
Cp*
Cp*
1
2
4
5
3
6
Scheme 1.
Scheme 2.
Table 1. Synthesis of Allyl Aryl Ketones
AlMe2
Cp*Li
OH
O
(1.1 mol. amt.)
(1.5 mol. amt.)
3
4
Ar
toluene, reflux
Time
THF, 0 °C
THF, –20 °C
Ar
Cp*
7
30 min
1 h
8
Entry
Ar
Yield (4)/%
Time/min
Yield (8)/%a),b)
1
2
3
4
5
6
7
8
9
Ph (a)
96
92
85
93
98
96
78
91
91
60
75
60
75
90
—
—
30
45
70
68
90
80
66
—
—
65
8c)
4-CF3C6H4 (b)
4-MeOC6H4 (c)
4-BrC6H4 (d)
3-ClC6H4 (e)
2-MeC6H4 (f)
2-IC6H4 (g)
2-Thienyl (h)
2-Furyl (i)
a) Isolated yield based on 4. b) Trace amounts (<0–7%) of ꢂ,ꢀ-unsaturat-
ed ketones were detected. c) NMR yield.
Published on the web December 13, 2007; doi:10.1246/bcsj.80.2400

M. Uemura et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 12 (2007) 2401
MgCl
OMgCl
OH
AlMe2
(1.5 mol. amt.)
(1.2 mol. amt.)
4a
1.0 mmol
3a
0.5 mmol
Ph
Ph
THF, –20 °C
THF, –20 °C
Cp*
1 h
10
9 0.24 mmol
MgCl
–Cp*MgCl
Scheme 3.
9
8a
0.56 mmol
Scheme 4.
AlMe2
(1.5 mol. amt.)
OH
O
4a
toluene, reflux
30 min
THF, –20 °C, 1 h Ph
Ph
Cp*
11
12 quant.
Scheme 5.
interfere with the reaction. Reaction of ortho-substituted 3 also
proceeded smoothly (Entries 6 and 7). Heteroaromatic acid
chlorides, such as thiophene- (Entry 8) and furancarbonyl
chloride (Entry 9), could be used in this reaction.
O
O
Cp*Li (1.1 mol. amt.)
THF, 0 °C, 30 min
R
Cp*
R
Cl
13
14a: R = n–C7H15 92%
14b: R = c–C6H11 84%
Ketone 4a was treated with 1.5 molar amount of an allyl-
aluminum reagent, which was prepared from allylmagnesium
bromide and dimethylaluminum chloride, at ꢂ20 ꢁC for 1 h
to afford the homoallyl alcohol 7a in 98% yield.3 In contrast,
the reaction of benzoyl chloride (3a), instead of 4a, with the
allylaluminum reagent gave diallylated alcohol 9 (Scheme 3).
In addition, when 4a was treated with allylmagnesium chlo-
ride, instead of the allylaluminum reagent, 9 was obtained
exclusively (Scheme 4). Nucleophilic addition of allylmagne-
sium chloride to ketone 8a, which was generated by in situ
Scheme 6.
4a and a methallylaluminum reagent in quantitative yield
(Scheme 5). Unfortunately, nucleophilic addition reactions of
2-butenyl- and 2-methyl-2-butenylaluminum reagents with
4a resulted in recovery of 4a even at 0 ꢁC.
Preparation of aliphatic pentamethylcyclopentadienyl ke-
tone 14 was performed in a similar fashion (Scheme 6). Al-
though allylation and methallylation of heptyl ketone 14a
proceeded smoothly to provide alcohols 15 (Scheme 7), cyclo-
hexyl ketone 14b resisted the allylation. In contrast to aromatic
alcohols 7, alcohols 15 were stable at reflux in toluene
(110 ꢁC). However, 15 were unstable under acidic conditions
and were transformed into the ꢀ,ꢁ-unsaturated ketones effec-
tively. Treatment of 15 with 0.10 molar amount of trichloro-
acetic acid in dichloromethane at room temperature for 1 h
provided the corresponding ketones 16 in moderate to good
yields (Scheme 7).
ꢀ
elimination of Cp MgCl from alkoxide 10, should give 9.
ꢀ
At room temperature, Cp H was liberated from 7a very
slowly to give allyl phenyl ketone (8a). Then, we found that
heating crude 7a in toluene at reflux for 1 h provided 8a in
good yield (Table 1, Entry 1). The reaction of ketones 4
having trifluoromethyl (Entry 2), methoxy (Entry 3), bromo
(Entry 4), or chloro moieties (Entry 5) also afforded 8 in mod-
erate to good yields. Unfortunately, ortho-substituted 4f and 4g
(Entries 6 and 7) did not undergo the nucleophilic addition re-
action with the allylaluminum reagent even at 0 ꢁC. Allylation
of 4f and 4g took place at room temperature. However, similar
diallylation as shown in Scheme 3 occurred. Although the
reaction of 2-furyl pentamethylcyclopentadienyl ketone (4i)
with the allylaluminum reagent afforded 7i in high yield,
heating 7i provided a complex mixture (Entry 9).
ꢀ
The proposed reaction mechanisms of the removal of Cp H
are shown in Schemes 8 and 9.1a,1c A retro-carbonyl-ene
mechanism could be used to rationalize the fragmentation re-
action under thermal conditions (Scheme 8). Protonation at
ꢀ
the Cp group could facilitate carbon–carbon bond cleavage
under acidic conditions (Scheme 9).
A typical Suzuki–Miyaura cross-coupling reaction needs a
2-Methyl-2-propenyl (here after named methallyl) phenyl
ketone (12) was also synthesized in a similar manner from
R
OH
R
AlMe2
(1.5 mol. amt.)
THF, –20 °C, 1 h
CCl3COOH
(0.10 mol. amt.)
O
R
n–C7H15
14a
Cp*
CH2Cl2, rt, 1 h
n–C7H15
15
16a: R = H 80%
16b: R = Me 50%
Scheme 7.

2402 Bull. Chem. Soc. Jpn. Vol. 80, No. 12 (2007)
Synthesis of ꢀ,ꢁ-Unsaturated Ketones
O
O
ArB(OH)2
Pd, Base
∆
Ar
Ar
H
+
Br
Ar
O
8d
17
O
8
H
Scheme 10.
PhB(OH)2 (1.2 mol. amt.)
Pd(OAc)2 (0.05 mol. amt.)
PPh3 (0.15 mol. amt.)
Scheme 8.
O
O
Na2CO3 (1.2 mol. amt.)
Cp*
Cp*
i–PrOH–H2O (2:1)
reflux, 3 h
Br
Ph
O
n–C7H15
4d
18a 98%
H
n–C7H15
AlMe2
(1.5 mol. amt.)
+
OH
OH
H
THF, –20 °C, 1 h toluene, reflux
1 h
Ph
19a 94%
Scheme 9.
Scheme 11.
O
Pd(OAc)2 (0.05 mol. amt.)
PPh3 (0.15 mol. amt.)
CsF (2.4 mol. amt.)
Cp*
4d
+
DME, reflux, 13 h
B(OH)2
MeO
MeO
O
18b 94%
O
(1.2 mol. amt.)
AlMe2
O
(1.5 mol. amt.)
THF, –20 °C, 1 h
toluene, reflux
30 min
MeO
O
19b 49%
Scheme 12.
strong base and high temperature.4 If 8d was used as a sub-
strate of Suzuki–Miyaura cross-coupling reaction, an ꢂ,ꢀ-un-
saturated coupling product would be obtained (Scheme 10).
Thus, we examined an alternative method to prepare ꢀ,ꢁ-
unsaturated coupling product 19. Aryl halides that have a pen-
tamethylcyclopentadienylcarbonyl part were used in the cross-
coupling reaction, and then the coupling products were trans-
formed to ꢀ,ꢁ-unsaturated ketones upon treatment with an
allylaluminum reagent, followed by heating. Treatment of 4d
and 4e with arylboronic acid under palladium catalysis yielded
biaryls 18 in good yields (Schemes 11–13). Ketones 18 were
converted into the corresponding ꢀ,ꢁ-unsaturated ketones 19
under similar conditions shown in Table 1. Fortunately, an
ester moiety survived during the nucleophilic addition reaction
of the allylaluminum reagent (Scheme 12).
PhB(OH)2 (1.2 mol. amt.)
Pd2(dba)3 (0.05 mol. amt.)
P(t–Bu)3 (0.15 mol. amt.)
KF (3.3 mol. amt.)
O
O
Cl
Ph
O
Cp*
Cp*
dioxane, reflux, 72 h
4e
18c 57%
AlMe2
(1.5 mol. amt.)
THF, –20 °C, 1 h
Ph
toluene, reflux
2 h
19c 86%
Scheme 13.
tained in CDCl3 with tetramethylsilane as an internal standard
or in C6D6. Chemical shifts (ꢃ) are in parts per million relative
to tetramethylsilane at 0.00 ppm for H and relative to CDCl3 at
1
This approach could be also applicable to the Heck reaction,
which requires basic conditions (Scheme 14).5
77.0 ppm for 13C in CDCl3 and relative to benzene at 7.16 ppm
for H and at 128.0 ppm for 13C in C6D6 unless otherwise noted.
1
Experimental
General. 1H NMR (500 MHz) and 13C NMR (125.7 MHz)
spectra were taken on a Varian UNITY INOVA 500 spectrometer
IR spectra were determined on a SHIMADZU FT-IR-8200PC
spectrometer. Mass spectra were determined on a JEOL Mstation
700 spectrometer. TLC analyses were performed on commercial
1
unless otherwise noted. H NMR and 13C NMR spectra were ob-
glass plates bearing 0.25-mm layer of Merck Silica gel 60F254.

M. Uemura et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 12 (2007) 2403
(Silica Gel 60N, hexane/ethyl acetate = 10:1) in 98% yield
(139 mg, 0.49 mmol).
styrene (2.0 mol. amt.)
Pd(OAc)2 (0.05 mol. amt.)
P(o–tolyl)3 (0.10 mol. amt.)
Et3N (3.0 mol. amt.)
O
O
General Procedure for Nucleophilic Addition Reaction of
Allylic Aluminum Reagent to Aliphatic Ketones and Acid-
Induced Cleavage Reaction (Scheme 7). A solution of dimeth-
ylaluminum chloride in hexane (1.04 mol dmꢂ3, 0.72 mL, 0.75
mmol) was added to a solution of 2-methyl-2-propenylmagnesium
chloride in THF (0.89 mol dmꢂ3, 0.84 mL, 0.75 mmol) at ꢂ20 ꢁC.
After the suspension was stirred for 10 min at ꢂ20 ꢁC, a solution
of 14a (131 mg, 0.50 mmol) in THF (2.5 mL) was added to the
mixture. The whole mixture was stirred for 1 h at ꢂ20 ꢁC. Hydro-
chloric acid (1 mol dmꢂ3) was added to quench the reaction. Ex-
traction with ethyl acetate and evaporation under reduced pressure
afforded the crude oil. The oil was passed through a pad of silica
gel with ethyl acetate, and the filtrate was concentrated in vacuo.
A solution of trichloroacetic acid in CH2Cl2 (0.1 mol dmꢂ3, 0.50
mL, 0.05 mmol) was added to a solution of the resulting oil in
CH2Cl2 (3.3 mL) at room temperature. The mixture was stirred
for 1 h at room temperature. After the reaction was quenched with
saturated aqueous NaHCO3, the mixture was extracted with ethyl
acetate. The combined organic layer was dried over anhydrous
Na2SO4 and concentrated in vacuo. Silica-gel column chromatog-
raphy (hexane/ethyl acetate = 20:1) and GPC purification (tol-
uene) provided heptyl 2-methyl-2-propenyl ketone (16b) (45.5
mg, 0.25 mmol, 50%).
Cp*
Cp*
DMF, 120 °C, 26 h
Br
4d
Ph
20 78%
O
AlMe2
(1.5 mol. amt.)
THF, –20 °C, 1 h
toluene, reflux
45 min
21 90%
Ph
Scheme 14.
Silica gel (Wakogel 200 mesh and Silica Gel 60N 40–100 mm,
spherical, neutral, Kanto Chemical Co., Ltd.) was used for column
chromatography. Gel permeation chromatography (GPC) was per-
formed by LC-908 (Japan Analytical Industry Ltd., two in-line
JAIGEL-2H, toluene, 7.8 mL minꢂ1, UV and RI detectors). The
analyses were carried out at the Elemental Analysis Center of
Kyoto University.
Unless otherwise noted, materials obtained from commercial
suppliers were used without further purification. THF and ether
were purchased from Kanto Chemical Co., stored under nitrogen,
and used as provided. 1,2,3,4,5-Pentamethyl-1,3-cyclopentadiene
was purchased from Kanto Chemical Co., and stored under argon.
General Procedure for Nucleophilic Addition Reaction of
Synthesis of 4-Biphenylyl 1,2,3,4,5-Pentamethyl-2,4-cyclo-
pentadienyl Ketone (18a).
A mixture of 4d (638 mg, 2.00
ꢀ
Cp Li to Aromatic Acid Chlorides (Table 1). A solution of
mmol), phenylboronic acid (293 mg, 2.40 mmol), Pd(OAc)2
(22.4 mg, 0.10 mmol), PPh3 (78.7 mg, 0.30 mmol), and Na2CO3
(254 mg, 2.40 mmol) in i-PrOH (8 mL) and H2O (4 mL) was heat-
ed at reflux for 3 h. The mixture was quenched with 1 mol dmꢂ3
HCl, and the mixture was extracted with ethyl acetate. The com-
bined organic layer was dried over anhydrous Na2SO4 and con-
centrated in vacuo to give a crude oil. The oil was purified by
chromatography on silica gel (hexane/ethyl acetate = 20:1) to
afford 18a (621 mg, 1.96 mmol, 98%).
Synthesis of Methyl 40-(1,2,3,4,5-Pentamethyl-2,4-cyclo-
pentadienylcarbonyl)biphenyl-4-carboxylate (18b). A mixture
of 4d (479 mg, 1.50 mmol), 4-methoxycarbonylphenylboronic acid
(324 mg, 1.80 mmol), Pd(OAc)2 (17.0 mg, 0.075 mmol), PPh3
(59.0 mg, 0.23 mmol), and CsF (547 mg, 3.60 mmol) in DME
(10 mL) was heated at reflux for 13 h. After the reaction was
quenched with water, the mixture was extracted with ethyl acetate.
The combined organic layer was dried over anhydrous Na2SO4
and concentrated in vacuo. Silica-gel column chromatography
(hexane/ethyl acetate = 20:1) provided 18b (530 mg, 1.41 mmol,
94%).
Synthesis of 3-Biphenylyl 1,2,3,4,5-Pentamethyl-2,4-cyclo-
pentadienyl Ketone (18c). A mixture of 4e (1.78 g, 6.48 mmol),
phenylboronic acid (949 mg, 7.78 mmol), Pd2(dba)3 (297 mg, 0.32
mmol), P(t-Bu)3 in hexane (1.0 mol dmꢂ3, 0.96 mL, 0.96 mmol),
and KF (1.24 g, 21.4 mmol) in dioxane (13 mL) was heated at re-
flux for 72 h. The reaction was quenched with 1 mol dmꢂ3 HCl,
and the mixture was extracted with ethyl acetate. The combined
organic layer was dried over anhydrous Na2SO4 and concentrated
in vacuo to give a crude oil. The oil was purified by chromatog-
raphy on silica gel (hexane/ethyl acetate = 80:1) to afford 18c
(1.16 g, 3.67 mmol, 57%).
n-BuLi in hexane (1.60 mol dmꢂ3, 1.38 mL, 2.20 mmol) was
added to a solution of 1,2,3,4,5-pentamethyl-1,3-cyclopentadiene
(0.38 mL, 2.40 mmol) in THF (20 mL) at 0 ꢁC. The mixture was
stirred for 30 min at the same temperature to generate a white sus-
pension of lithium pentamethylcyclopentadienide. After an addi-
tion of 3-chlorobenzoyl chloride (350 mg, 2.00 mmol) in THF
(1 mL), the mixture was stirred for an additional 30 min at 0 ꢁC.
The reaction was quenched with water, and the mixture was
extracted with ethyl acetate. The combined organic layer was
dried over anhydrous Na2SO4 and concentrated in vacuo to give
a crude oil. The oil was purified by chromatography on silica
gel (hexane/ethyl acetate = 40:1) to afford 3-chlorophenyl
1,2,3,4,5-pentamethyl-2,4-cyclopentadienyl ketone (4e) (536 mg,
1.95 mmol, 98%).
General Procedure for Nucleophilic Addition Reaction of
Allylaluminum Reagent to Aromatic Ketones and Thermal
Cleavage Reaction (Table 1). A solution of dimethylaluminum
chloride in hexane (1.04 mol dmꢂ3, 0.72 mL, 0.75 mmol) was
added to a solution of allylmagnesium bromide in Et2O (0.87
mol dmꢂ3, 0.86 mL, 0.75 mmol) at ꢂ20 ꢁC. After the mixture was
stirred for 10 min at the same temperature, 4e (137 mg, 0.50
mmol) in THF (2.5 mL) was added to the reaction mixture. The
mixture was stirred for 1 h at ꢂ20 ꢁC. The reaction mixture was
quenched with 1 mol dmꢂ3 HCl. The mixture was extracted with
ethyl acetate. The combined organic layer was dried over an-
hydrous Na2SO4 and concentrated in vacuo to give a crude oil.
The oil was filtered through a short pad of silica gel (ethyl ace-
tate), and the filtrate was concentrated in vacuo. The oil was used
for the next step without further purification. The resulting oil was
dissolved in toluene (5 mL) and heated at reflux for 1.5 h. The
mixture was concentrated and purified by chromatography on
silica gel (hexane/ethyl acetate = 20:1) and GPC (toluene) to af-
ford allyl 3-chlorophenyl ketone (8e) (59.1 mg, 0.33 mmol, 66%).
The crude 7a could be isolated by chromatography on silica gel
Synthesis of 1,2,3,4,5-Pentamethyl-2,4-cyclopentadienyl (E)-
4-Stilbenyl Ketone (20). A solution of 4d (319 mg, 1.00 mmol),
styrene (0.23 mL, 2.00 mmol), Pd(OAc)2 (11.2 mg, 0.050 mmol),
P(o-tolyl)3 (30.4 mg, 0.10 mmol), and Et3N (0.42 mL, 3.00 mmol)

2404 Bull. Chem. Soc. Jpn. Vol. 80, No. 12 (2007)
Synthesis of ꢀ,ꢁ-Unsaturated Ketones
in DMF (1.2 mL) was heated at 120 ꢁC for 26 h. After the reaction
was quenched with saturated NH4Cl, the mixture was extracted
with hexane–ethyl acetate (5:1). The combined organic layer
was dried over anhydrous Na2SO4 and concentrated in vacuo.
Silica-gel column chromatography (hexane/ethyl acetate = 40:1)
provided 20 (268 mg, 0.78 mmol, 78%).
Characterization Data. The spectral data of the products 8a,6
8b,7 8c,8 8d,9 8i,2a 12,10 and 16a11 can be found in the literature.
Ketone 8h is commercially available.
140.26, 143.68, 204.93; Found: C, 55.70; H, 5.18%. Calcd for
C17H19IO: C, 55.75; H, 5.23%; Mp 59.0–60.0 ꢁC.
1,2,3,4,5-Pentamethyl-2,4-cyclopentadienyl 2-Thienyl Ketone
(4h): IR (nujol) 1638 cmꢂ1 1H NMR (CDCl3) ꢃ 1.24 (s, 3H),
;
1.71 (d, J ¼ 0:5 Hz, 6H), 1.86 (d, J ¼ 0:5 Hz, 6H), 6.92 (dd, J ¼
5:0, 4.0 Hz, 1H), 7.37 (dd, J ¼ 5:0, 1.0 Hz, 1H), 7.54 (dd, J ¼ 4:0,
1.0 Hz, 1H); 13C NMR (CDCl3) ꢃ 10.53 (ꢃ2), 11.46 (ꢃ2), 17.63,
69.69, 127.07, 132.05, 132.13, 138.99 (ꢃ2), 139.50 (ꢃ2), 140.60,
193.31; Found: C, 72.96; H, 7.40%. Calcd for C15H18OS: C,
73.13; H, 7.36%; Mp 85.5–86.5 ꢁC.
2-Furyl 1,2,3,4,5-Pentamethyl-2,4-cyclopentadienyl Ketone
(4i): IR (nujol) 1653 cmꢂ1; 1H NMR (CDCl3) ꢃ 1.23 (s, 3H), 1.70
(s, 6H), 1.85 (s, 6H), 6.28–6.32 (m, 1H), 6.73–6.77 (m, 1H), 7.44–
7.49 (m, 1H); 13C NMR (CDCl3) ꢃ 10.48 (ꢃ2), 11.42 (ꢃ2), 17.51,
68.83, 111.51, 116.73, 137.91 (ꢃ2), 139.68 (ꢃ2), 145.90, 150.13,
189.08; Found: C, 77.95; H, 7.86%. Calcd for C15H18O2: C,
78.23; H, 7.88%; Mp 90.5–91.0 ꢁC.
1,2,3,4,5-Pentamethyl-2,4-cyclopentadienyl Phenyl Ketone
1H NMR (CDCl3) ꢃ 1.24 (s, 3H),
(4a): IR (nujol) 1669 cmꢂ1
;
1.68 (d, J ¼ 1:0 Hz, 6H), 1.83 (d, J ¼ 0:5 Hz, 6H), 7.20–7.25 (m,
2H), 7.36–7.41 (m, 1H), 7.50–7.54 (m, 2H); 13C NMR (CDCl3) ꢃ
10.60 (ꢃ2), 11.41 (ꢃ2), 19.19, 70.31, 127.32 (ꢃ2), 127.88 (ꢃ2),
131.86, 138.06 (ꢃ2), 138.23, 140.00 (ꢃ2), 202.37; Found: C,
84.85; H, 8.37%. Calcd for C17H20O: C, 84.96; H, 8.39%; Mp
45.0–45.5 ꢁC.
1,2,3,4,5-Pentamethyl-2,4-cyclopentadienyl 4-Trifluorometh-
ylphenyl Ketone (4b): IR (neat) 2921, 1674, 1325, 1169, 1130,
1068 cmꢂ1; 1H NMR (CDCl3) ꢃ 1.26 (s, 3H), 1.69 (s, 6H), 1.83 (s,
6H), 7.49 (d, J ¼ 8:0 Hz, 2H), 7.59 (d, J ¼ 8:0 Hz, 2H); 13C NMR
(CDCl3) ꢃ 10.57 (ꢃ2), 11.41 (ꢃ2), 18.64, 70.40, 123.71 (q, J ¼
272:5 Hz), 124.91 (q, J ¼ 3:9 Hz, ꢃ2), 127.47 (ꢃ2), 133.09 (q,
J ¼ 32:2 Hz), 138.99 (ꢃ2), 139.36 (ꢃ2), 141.10, 201.74; Found:
C, 69.88; H, 6.33%. Calcd for C18H19F3O: C, 70.12; H, 6.21%.
4-Methoxyphenyl 1,2,3,4,5-Pentamethyl-2,4-cyclopentadien-
1-(1,2,3,4,5-Pentamethyl-2,4-cyclopentadienyl)-1-phenyl-3-
buten-1-ol (7a): IR (neat) 2917, 1445, 1327, 1249, 992, 924,
1
761, 709 cmꢂ1; H NMR (C6D6) ꢃ 1.31 (s, 3H), 1.45 (d, J ¼ 1:5
Hz, 3H), 1.60 (d, J ¼ 1:0 Hz, 3H), 1.86 (s, 3H), 1.96 (s, 3H), 2.03
(s, 1H), 2.47 (dd, J ¼ 13:5, 10.0 Hz, 1H), 2.94 (ddt, J ¼ 13:5, 5.0,
1.5 Hz, 1H), 4.80 (ddt, J ¼ 10:0, 1.5, 0.5 Hz, 1H), 4.90–4.95 (m,
1H), 5.31 (dddd, J ¼ 17:5, 10.0, 10.0, 5.0 Hz, 1H), 6.99–7.13 (m,
3H), 7.27–7.33 (m, 2H); 13C NMR (C6D6) ꢃ 10.86, 11.14, 13.46,
13.72, 15.86, 41.86, 63.72, 78.51, 120.04, 126.56, 126.62 (ꢃ2),
126.65 (ꢃ2), 134.60, 135.65, 137.74, 138.66, 141.65, 143.85;
Found: C, 84.88; H, 9.58%. Calcd for C20H26O: C, 85.05; H,
9.28%.
yl Ketone (4c): IR (nujol) 1656, 1600, 1572, 1248, 1176 cmꢂ1
;
1H NMR (CDCl3) ꢃ 1.22 (s, 3H), 1.68 (d, J ¼ 0:5 Hz, 6H), 1.85
(d, J ¼ 0:5 Hz, 6H), 3.80 (s, 3H), 6.72 (d, J ¼ 9:0 Hz, 2H), 7.60
(d, J ¼ 9:0 Hz, 2H); 13C NMR (CDCl3) ꢃ 10.55 (ꢃ2), 11.37 (ꢃ2),
19.82, 55.14, 69.98, 113.01 (ꢃ2), 129.95 (ꢃ2), 130.64, 137.19
(ꢃ2), 140.94 (ꢃ2), 162.65, 199.93; Found: C, 79.78; H, 8.14%.
Calcd for C18H22O2: C, 79.97; H, 8.20%; Mp 135.0–136.0 ꢁC.
4-Bromophenyl 1,2,3,4,5-Pentamethyl-2,4-cyclopentadienyl
Allyl 3-Chlorophenyl Ketone (8e): IR (nujol) 1679 cmꢂ1
;
1H NMR (C6D6) ꢃ 3.08 (dt, J ¼ 6:5, 1.5 Hz, 2H), 4.93 (ddt, J ¼
17:0, 3.0, 1.5 Hz, 1H), 5.03 (ddt, J ¼ 10:5, 3.0, 1.5 Hz, 1H), 5.97
(ddt, J ¼ 17:0, 10.5, 6.5 Hz, 1H), 6.73 (t, J ¼ 8:0 Hz, 1H), 7.06–
7.09 (m, 1H), 7.43–7.48 (m, 1H), 7.74–7.78 (m, 1H); 13C NMR
(C6D6) ꢃ 43.07, 118.30, 126.33, 128.54, 129.93, 131.23, 132.69,
134.87, 138.48, 195.29; Found: C, 66.70; H, 5.07%. Calcd for
C10H9ClO: C, 66.49; H, 5.02%; Mp 32.0–33.0 ꢁC.
1
Ketone (4d): IR (nujol) 1652, 1582 cmꢂ1; H NMR (CDCl3) ꢃ
1.23 (s, 3H), 1.67 (d, J ¼ 1:0 Hz, 6H), 1.83 (s, 6H), 7.35–7.38 (m,
2H), 7.40–7.43 (m, 2H); 13C NMR (CDCl3) ꢃ 10.54 (ꢃ2), 11.38
(ꢃ2), 19.09, 70.17, 126.75, 129.00 (ꢃ2), 131.10 (ꢃ2), 136.65,
138.27 (ꢃ2), 139.92 (ꢃ2), 201.08; Found: C, 63.88; H, 5.98%.
Calcd for C17H19OBr: C, 63.96; H, 6.00%; Mp 58.0–59.0 ꢁC.
3-Chlorophenyl 1,2,3,4,5-Pentamethyl-2,4-cyclopentadienyl
Ketone (4e): IR (neat) 2972, 2916, 2855, 1674, 1668, 1569,
Heptyl 1,2,3,4,5-Pentamethyl-2,4-cyclopentadienyl Ketone
1
(14a): IR (neat) 2928, 1701 cmꢂ1; H NMR (CDCl3) ꢃ 0.86 (t,
J ¼ 7:0 Hz, 3H), 1.09 (s, 3H), 1.67 (s, 6H), 1.84 (s, 6H), 1.13–1.42
(m, 10H), 1.84 (t, J ¼ 7:5 Hz, 2H); 13C NMR (CDCl3) ꢃ 10.39
(ꢃ2), 11.41 (ꢃ2), 14.07, 14.70, 22.61, 24.03, 29.00, 29.20, 31.67,
34.63, 71.33, 136.98 (ꢃ2), 139.38 (ꢃ2), 210.42; Found: C, 82.14;
H, 11.24%. Calcd for C18H30O: C, 82.38; H, 11.52%.
1
1443, 1230, 974 cmꢂ1; H NMR (CDCl3) ꢃ 1.23 (s, 3H), 1.68 (s,
6H), 1.84 (s, 6H), 7.16 (t, J ¼ 8:0 Hz, 1H), 7.33–7.42 (m, 2H),
7.51 (t, J ¼ 2:0 Hz, 1H); 13C NMR (CDCl3) ꢃ 10.61 (ꢃ2), 11.42
(ꢃ2), 18.78, 70.35, 125.36, 127.56, 129.23, 131.77, 133.86,
138.75 (ꢃ2), 139.50, 139.67 (ꢃ2), 201.09; Found: C, 74.04; H,
7.25%. Calcd for C17H19ClO: C, 74.31; H, 6.97%.
1,2,3,4,5-Pentamethyl-2,4-cyclopentadienyl o-Tolyl Ketone
;
(4f): IR (nujol) 1681 cmꢂ1 1H NMR (CDCl3) ꢃ 1.27 (s, 3H),
1.69 (d, J ¼ 1:0 Hz, 6H), 1.77 (d, J ¼ 0:5 Hz, 6H), 2.32 (s, 3H),
6.89–6.95 (m, 2H), 7.11–7.15 (m, 1H), 7.16–7.20 (m, 1H);
13C NMR (CDCl3) ꢃ 10.47 (ꢃ2), 11.36 (ꢃ2), 18.24, 20.47, 71.07,
124.69, 125.12, 129.66, 130.92, 135.44, 138.51 (ꢃ2), 138.57
(ꢃ2), 139.09, 206.12; Found: C, 84.71; H, 8.68%. Calcd for
C18H22O: C, 84.99; H, 8.72%; Mp 36.0–37.0 ꢁC.
2-Iodophenyl 1,2,3,4,5-Pentamethyl-2,4-cyclopentadienyl
Ketone (4g): IR (nujol) 1684 cmꢂ1; 1H NMR (CDCl3) ꢃ 1.32 (s,
3H), 1.76 (s, 12H), 6.86 (dd, J ¼ 8:0, 1.5 Hz, 1H), 6.97 (dt, J ¼
8:0, 1.5 Hz, 1H), 7.08 (dt, J ¼ 8:0, 1.0 Hz, 1H), 7.83 (dd, J ¼ 8:0,
1.0 Hz, 1H); 13C NMR (CDCl3) ꢃ 10.79 (ꢃ2), 11.37 (ꢃ2), 17.75,
70.77, 91.66, 125.43, 126.91, 130.85, 137.96 (ꢃ2), 139.26 (ꢃ2),
Cyclohexyl 1,2,3,4,5-Pentamethyl-2,4-cyclopentadienyl
Ketone (14b): IR (neat) 2931, 2856, 1695, 1448, 989 cmꢂ1
;
1H NMR (CDCl3) ꢃ 0.99–1.67 (m, 10H), 1.08 (s, 3H), 1.69 (d, J ¼
1:0 Hz, 6H), 1.86 (d, J ¼ 0:5 Hz, 6H), 2.05 (tt, J ¼ 11:5, 3.5 Hz,
1H); 13C NMR (CDCl3) ꢃ 10.94 (ꢃ2), 11.44 (ꢃ2), 14.62, 25.67
(ꢃ2), 25.71, 30.01 (ꢃ2), 43.22, 71.67, 136.55 (ꢃ2), 139.94 (ꢃ2),
213.51; Found: C, 82.58; H, 10.90%. Calcd for C17H26O: C,
82.87; H, 10.64%.
Heptyl 2-Methyl-2-propenyl Ketone (16b): IR (neat) 2929,
1717, 1649, 1458, 1376, 894 cmꢂ1; 1H NMR (C6D6) ꢃ 0.89 (t, J ¼
7:0 Hz, 3H), 1.10–1.30 (m, 8H), 1.46–1.55 (m, 2H), 1.66 (s, 3H),
2.07 (t, J ¼ 7:0 Hz, 2H), 2.77 (d, J ¼ 1:0 Hz, 2H), 4.70–4.74 (m,
1H), 4.82–4.86 (m, 1H); 13C NMR (C6D6) ꢃ 14.27, 22.59, 22.98,
23.96, 29.45, 29.48, 32.04, 41.67, 52.09, 114.48, 140.01, 206.43;
Found: C, 79.32; H, 12.37%. Calcd for C12H22O: C, 79.06; H,
12.16%.
4-Biphenylyl 1,2,3,4,5-Pentamethyl-2,4-cyclopentadienyl
1
Ketone (18a): IR (nujol) 1653 cmꢂ1; HNMR (CDCl3) ꢃ 1.27 (s,

M. Uemura et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 12 (2007) 2405
3H), 1.72 (s, 6H), 1.87 (s, 6H), 7.33–7.38 (m, 1H), 7.41–7.49 (m,
4H), 7.56–7.59 (m, 2H), 7.62–7.66 (m, 2H); 13C NMR (CDCl3) ꢃ
10.66 (ꢃ2), 11.46 (ꢃ2), 19.38, 70.30, 126.56 (ꢃ2), 127.06 (ꢃ2),
127.84, 128.06 (ꢃ2), 128.78 (ꢃ2), 136.78, 137.96 (ꢃ2), 140.08,
140.26 (ꢃ2), 144.50, 201.67; Found: C, 87.24; H, 7.68%. Calcd
for C23H24O: C, 87.30; H, 7.64%; Mp 90.0–91.0 ꢁC.
Methyl 40-(1,2,3,4,5-Pentamethyl-2,4-cyclopentadienylcar-
bonyl)biphenyl-4-carboxylate (18b): IR (nujol) 1722, 1663,
1604, 1277, 1108 cmꢂ1; 1H NMR (CDCl3) ꢃ 1.26 (s, 3H), 1.71 (s,
6H), 1.86 (s, 6H), 3.93 (s, 3H), 7.48–7.51 (m, 2H), 7.62–7.66 (m,
4H), 8.07–8.11 (m, 2H); 13C NMR (CDCl3) ꢃ 10.66 (ꢃ2), 11.47
(ꢃ2), 19.26, 52.17, 70.35, 126.79 (ꢃ2), 127.02 (ꢃ2), 128.12 (ꢃ2),
129.39, 130.10 (ꢃ2), 137.57, 138.18 (ꢃ2), 140.13 (ꢃ2), 143.18,
144.50, 166.85, 201.66; Found: C, 79.89; H, 7.02%. Calcd for
C25H26O3: C, 80.18; H, 7.00%; Mp 123.0–124.0 ꢁC.
201.31; Found: C, 87.41; H, 7.76%. Calcd for C25H26O: C, 87.68;
H, 7.65%; Mp 106.0–107.0 ꢁC.
Allyl (E)-4-Stilbenyl Ketone (21): IR (nujol) 1685, 969, 818,
722 cmꢂ1
;
1H NMR (CDCl3) ꢃ 3.77 (d, J ¼ 6:5 Hz, 2H), 5.20–
5.28 (m, 2H), 6.10 (ddt, J ¼ 17:0, 10.5, 6.5 Hz, 1H), 7.14 (d, J ¼
16:5 Hz, 1H), 7.24 (d, J ¼ 16:5 Hz, 1H), 7.31 (t, J ¼ 7:5 Hz, 1H),
7.39 (t, J ¼ 7:5 Hz, 2H), 7.55 (d, J ¼ 7:5 Hz, 2H), 7.60 (d, J ¼
8:5 Hz, 2H), 7.97 (d, J ¼ 8:5 Hz, 2H); 13C NMR (CDCl3) ꢃ 43.40,
118.68, 126.50 (ꢃ2), 126.79 (ꢃ2), 127.35, 128.30, 128.76 (ꢃ2),
128.81 (ꢃ2), 131.12, 131.48, 135.27, 136.62, 142.03, 197.30;
Found: C, 86.93; H, 6.62%. Calcd for C18H16O: C, 87.06; H,
6.49%; Mp 105.0–106.0 ꢁC.
This work was supported by Grants-in-Aid for Scientific
Research, Young Scientists, and COE Research from the Min-
istry of Education, Culture, Sports, Science and Technology,
Japan. M.U. acknowledges JSPS for financial support.
3-Biphenylyl 1,2,3,4,5-Pentamethyl-2,4-cyclopentadienyl
Ketone (18c): IR (neat): 2918, 1668, 1451, 1218, 971, 760,
1
697 cmꢂ1; H NMR (CDCl3) ꢃ 1.29 (s, 3H), 1.73 (s, 6H), 1.88 (s,
6H), 7.31–7.38 (m, 2H), 7.42–7.46 (m, 2H), 7.48–7.53 (m, 2H),
7.56–7.60 (m, 1H), 7.64–7.67 (m, 1H), 7.86–7.89 (m, 1H);
13C NMR (CDCl3) ꢃ 10.67 (ꢃ2), 11.47 (ꢃ2), 19.28, 70.39, 126.20,
126.35, 126.77 (ꢃ2), 127.45, 128.44, 128.75 (ꢃ2), 130.37, 137.99
(ꢃ2), 138.43, 140.36, 140.53 (ꢃ3), 201.98; HRMS Found:
316.1826. Calcd for C23H24O: 316.1827.
References
1
a) K. Yagi, H. Yorimitsu, K. Oshima, Tetrahedron Lett.
2005, 46, 4831. b) M. Uemura, H. Yorimitsu, K. Oshima, Tetra-
hedron Lett. 2006, 47, 163. c) M. Uemura, K. Yagi, M. Iwasaki,
K. Nomura, H. Yorimitsu, K. Oshima, Tetrahedron 2006, 62,
3523. d) M. Uemura, H. Yorimitsu, K. Oshima, Chem. Lett.
2006, 35, 408. e) M. Iwasaki, E. Morita, M. Uemura, H.
Yorimitsu, K. Oshima, Synlett 2007, 167.
Allyl 4-Biphenylyl Ketone (19a):
IR (nujol) 1684 cmꢂ1
;
1H NMR (CDCl3) ꢃ 3.80 (dt, J ¼ 7:0, 1.5 Hz, 2H), 5.25 (ddt, J ¼
17:0, 3.0, 1.5 Hz, 1H), 5.26 (ddt, J ¼ 10:5, 3.0, 1.5 Hz, 1H), 6.12
(ddt, J ¼ 17:0, 10.5, 7.0 Hz, 1H), 7.39–7.43 (m, 1H), 7.45–7.50
(m, 2H), 7.62–7.65 (m, 2H), 7.68–7.71 (m, 2H), 8.03–8.07 (m,
2H); 13C NMR (CDCl3) ꢃ 43.52, 118.76, 127.27 (ꢃ4), 128.25,
128.89 (ꢃ2), 128.95 (ꢃ2), 131.10, 135.25, 139.84, 145.86,
197.62; Found: C, 86.15; H, 6.55%. Calcd for C16H14O: C, 86.45;
H, 6.35%; Mp 69.5–70.0 ꢁC.
2
a) M. Gohain, B. J. Gogoi, D. Brajapati, J. S. Sandhu, New
J. Chem. 2003, 27, 1038. b) M. Yasuda, M. Tsuchida, A. Baba,
Chem. Commun. 1998, 563. c) S. Inaba, R. D. Rieke, J. Org.
Chem. 1985, 50, 1373. d) M. Onaka, T. Goto, T. Mukaiyama,
Chem. Lett. 1979, 1438. e) J. S. Yadav, B. V. S. Reddy, M. S.
Reddy, G. Parimala, Synthesis 2003, 2390. f) Y. Liu, Y. Zhang,
Tetrahedron Lett. 2004, 45, 1295. g) A. S.-Y. Lee, L.-S. Lin,
Tetrahedron Lett. 2000, 41, 8803. h) B. Baruah, A. Boruah, D.
Prajapati, J. S. Sandhu, Tetrahedron Lett. 1996, 37, 9087. i) P.
Methyl 40-(3-Butenoyl)biphenyl-4-carboxylate (19b):
IR
(nujol) 1723, 1677, 1610 cmꢂ1; H NMR (CDCl3) ꢃ 3.80 (dt, J ¼
6:5, 1.5 Hz, 2H), 3.95 (s, 3H), 5.24 (ddt, J ¼ 17:0, 2.5, 1.0 Hz,
1H), 5.26 (ddt, J ¼ 10:5, 2.5, 1.0 Hz, 1H), 6.11 (ddt, J ¼ 17:0,
10.5, 6.5 Hz, 1H), 7.66–7.74 (m, 4H), 8.03–8.08 (m, 2H), 8.11–
8.15 (m, 2H); 13C NMR (CDCl3) ꢃ 43.52, 52.21, 118.86, 127.20
(ꢃ2), 127.46 (ꢃ2), 128.94 (ꢃ2), 129.74, 130.20 (ꢃ2), 130.90,
135.86, 144.11, 144.49, 166.73, 197.50; Found: C, 76.87; H,
5.74%. Calcd for C18H16O3: C, 77.12; H, 5.75%; Mp 139.0–
140.0 ꢁC.
1
´
Marceau, L. Gautreau, F. Beguin, G. Guillaumet, J. Organomet.
Chem. 1991, 403, 21. j) R. Calas, J. Dunogues, J.-P. Pillot, C.
Biran, F. Pisciotti, B. Arreguy, J. Organomet. Chem. 1975, 85,
149.
3
The reaction of 4a with 1.5 molar amount of an allylalumi-
num reagent, which was prepared from allyltributyltin, n-BuLi,
and dimethylaluminum chloride, at ꢂ20 ꢁC for 1 h also afforded
the 3-butenyl alcohol 7a in 84% yield.
Allyl 3-Biphenylyl Ketone (19c): IR (neat) 3032, 1687, 1598,
1478, 1452, 1418, 1296, 1188, 921 cmꢂ1
;
1H NMR (CDCl3) ꢃ
4
a) N. Miyaura, Top. Curr. Chem. 2002, 219, 11. b) A.
3.82 (dt, J ¼ 7:0, 1.5 Hz, 2H), 5.25 (ddt, J ¼ 17:0, 3.5, 1.5 Hz,
1H), 5.27 (ddt, J ¼ 10:5, 3.5, 1.5 Hz, 1H), 6.13 (ddt, J ¼ 17:0,
10.5, 7.0 Hz, 1H), 7.37–7.42 (m, 1H), 7.46–7.50 (m, 2H), 7.52–
7.57 (m, 1H), 7.60–7.64 (m, 2H), 7.77–7.82 (m, 1H), 7.94–7.96
(m, 1H), 8.19–8.21 (m, 1H); 13C NMR (CDCl3) ꢃ 43.58, 118.80,
126.95, 127.08, 127.16 (ꢃ2), 127.80, 128.91 (ꢃ2), 129.06,
131.00, 131.78, 137.04, 140.12, 141.75, 197.95; Found: C, 86.57;
H, 6.54%. Calcd for C16H14O: C, 86.45; H, 6.35%.
Suzuki, H. C. Brown, Organic Synthesis via Boranes, Aldrich,
Milwaukee, WI, 2003, Vol. 3. c) N. Miyaura, A. Suzuki, Chem.
Rev. 1995, 95, 2457.
5
a) N. J. Whitcombe, K. K. Hii, S. E. Gibson, Tetrahedron
2001, 57, 7449. b) I. P. Beletskaya, A. V. Cheprakov, Chem. Rev.
2000, 100, 3009. c) R. F. Heck, Acc. Chem. Res. 1979, 12, 146.
6
7
F.-X. Felpin, J. Lebreton, J. Org. Chem. 2002, 67, 9192.
P. H. Toy, B. Dhanabalasingam, M. Newcomb, I. H.
1,2,3,4,5-Pentamethyl-2,4-cyclopentadienyl (E)-4-Stilbenyl
1
Hanna, P. F. Hollenberg, J. Org. Chem. 1997, 62, 9114.
8
Ketone (20): IR (nujol) 1661, 1604 cmꢂ1; H NMR (CDCl3) ꢃ
´
G. Blay, I. Fernandez, P. Formentin, B. Monje, J. R. Pedro,
1.25 (s, 3H), 1.70 (d, J ¼ 1:0 Hz, 6H), 1.86 (d, J ¼ 0:5 Hz, 6H),
7.04 (d, J ¼ 16:5 Hz, 1H), 7.14 (d, J ¼ 16:5 Hz, 1H), 7.25–7.30
(m, 1H), 7.34–7.39 (m, 4H), 7.48–7.52 (m, 2H), 7.54–7.58 (m,
2H); 13C NMR (CDCl3) ꢃ 10.64 (ꢃ2), 11.45 (ꢃ2), 19.42, 70.29,
125.97 (ꢃ2), 126.68 (ꢃ2), 127.75, 128.05, 128.07 (ꢃ2), 128.73
(ꢃ2), 130.54, 136.91, 136.98, 137.90 (ꢃ2), 140.35 (ꢃ2), 140.84,
R. Ruiz, Tetrahedron 2001, 57, 1075.
P. Jones, P. Knochel, J. Org. Chem. 1999, 64, 186.
10 R. D. Rieke, W. R. Klein, T.-C. Wu, J. Org. Chem. 1993,
58, 2492.
11 E. Ruba, C. Gemel, C. Slugovc, K. Mereiter, R. Schmid,
¨
K. Kirchner, Organometallics 1999, 18, 2275.
9