Rhodium-catalyzed intramolecular hydroacylation of 5- and 6-alkynals: Convenient synthesis of α-alkylidenecycloalkanones and cycloalkenones

Article abstract of DOI:10.1002/chem.200400679

A novel intramolecular hydroacylation of 5- and 6-alkynals leading to α-alkylidenecycloalkanones was accomplished by using cationic a rhodium(I)/BINAP complex. For all cyclizations described, a single (E)-olefin isomer was obtained. At elevated temperature, hydroacylation and double bond migration of 5- and 6-alkynals proceeded in a one-pot reaction to give cycloalkenones. An intramolecular hydroacylation of a 7-alkynal was unsuccessful. This method represents an attractive new route to highly functionalized α-alkylidenecycloalkanones and cycloalkenones.

Full text of DOI:10.1002/chem.200400679

FULL PAPER
Rhodium-Catalyzed Intramolecular Hydroacylation of 5- and 6-Alkynals:
Convenient Synthesis of a-Alkylidenecycloalkanones and Cycloalkenones
[a]
Kenzo Takeishi,Koudai Sugishima,Kaori Sasaki,and Ken Tanaka*
Abstract: A novel intramolecular hydroacylation of 5- and 6-alkynals leading to a-
alkylidenecycloalkanones was accomplished by using cationic a rhodium(i)/BINAP
complex. For all cyclizations described, a single (E)-olefin isomer was obtained. At
elevated temperature, hydroacylation and double bond migration of 5- and 6-alky-
nals proceeded in a one-pot reaction to give cycloalkenones. An intramolecular
hydroacylation of a 7-alkynal was unsuccessful. This method represents an attrac-
tive new route to highly functionalized a-alkylidenecycloalkanones and cycloalke-
nones.
Keywords: aldehydes
·
alkynes
·
·
cyclization
rhodium
·
hydroacylation
Introduction
moiety because of alternative reactivity of these substrates.[4]
Extension of this method to the synthesis of larger cyclic
compounds was accomplished by the use of 4,6-dienals or
cyclopropyl-4-alkenals as reaction substrates.[5,6] Synthesis of
cycloheptenones was carried out by rhodium-catalyzed in-
tramolecular hydroacylation of 4,6-dienals;[5a] the synthesis
of cyclooctenones was carried out by rhodium-catalyzed in-
tramolecular hydroacylation of 5-cyclopropyl-4-alkenals.[5b]
The corresponding reaction of 4-alkynals to generate cy-
clopentenones is an attractive route for their synthesis. Re-
cently, intramolecular trans hydroacylation of 4-alkynals was
developed by using a cationic rhodium(i)/dppe complex
(Scheme 2).[7,8] This result prompted our investigation into
whether the intramolecular hydroacylation of 5-alkynals can
proceed using cationic rhodium(i) complex. As one example
of an intramolecular hydroacylation of 5-alkynals, Nicolaou
et al. observed an unexpected intramolecular hydroacylation
of a tricyclic 5-alkynal to generate a tetracyclic cyclohexe-
none (78% yield based on 50% conversion) while attempt-
ing to decarbonylate an aldehyde with stoichiometric
amount of [RhCl(PPh3)3].[9] Murai et al. observed formation
of an ethylidenecyclopentanone as a by-product (13%
yield) while attempting cyclocarbonylation of a 5-heptynal
to a bicyclic a,b-unsaturated g-butyrolactone with CO and
catalytic amounts of [Ru3(CO)12].[10] Narasaka et al. also ac-
complished the synthesis of a-alkylidenecycloalkanones by
rhodium(i)-catalyzed acylation of alkynes with acylsilanes.[11]
However, no general method for intramolecular hydroacyla-
tion of 5-alkynals has been developed to date. This paper
describes the general protocol for intramolecular cis-hydroa-
cylation of 5- and 6-alkynals, which leads to a-alkylidenecy-
cloalkanones using a cationic rhodium(i)/BINAP complex.
Rhodium-catalyzed intramolecular hydroacylation of 4-alke-
nals is a well established method for the preparation of cy-
clopentanones.[1–3] However, hydroacylation of alkenals to
cycloalkanones is limited to 4-alkenals: it is not applicable
to 5-alkenals. In fact, Larock et al. noted that 5-hexenal fur-
nishes 2-methylcyclopentanone in only 19% yield and a sig-
nificant amount of decarbonylation occurs (Scheme 1).[2b]
Only one report for the intramolecular hydroacylation of
5-alkenal to generate cyclohexanone was reported, though it
turned out to be sensitive to substitution of the alkene
Scheme 1. Rhodium-catalyzed intramolecular hydroacylation of 4- and 5-
alkenals.
[a] K. Takeishi, K. Sugishima, K. Sasaki, Prof. Dr. K. Tanaka
Department of Applied Chemistry, Graduate School of Engineering
Tokyo University of Agriculture and Technology
Koganei, Tokyo 184-8588 (Japan)
Fax : (+81)2-388-7037
E-mail: tanaka-k@cc.tuat.ac.jp
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author: selected
1H NMR spectra.
Chem. Eur. J. 2004, 10, 5681 – 5688
DOI: 10.1002/chem.200400679
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5681

FULL PAPER
Table 1. Cationic rhodium(i)/BINAP complex-catalyzed intramolecular
hydroacylation of 5-alkynals.
Entry
1
5-Alkynal
Product
Yield [%][a]
78
Scheme 2. Rhodium-catalyzed intramolecular hydroacylation of 4-alky-
nals.
2
3
75
94
Results and Discussion
We first examined the reaction of 4-methyl-5-decynal (1) in
the presence of 10% [Rh(dppe)]BF4 in acetone at room
temperature, which currently appears to be the best condi-
tion for the intramolecular hydroacylation of 4-alkynals
(Scheme 2),[7] although the reaction was extremely sluggish.
The increase in reaction temperature (508C) led to an un-
identified complex mixture, which included decarbonylated
by-products. Although the reaction was sluggish, the use of
CH2Cl2 as a solvent suppressed the formation of decarbony-
lated by-products (Scheme 3). Moreover, very small
amounts of a cyclized product, 3-methyl-2-pentylidenecyclo-
pentanone (2), were detected. When 4-alkynals were treated
with [Rh(dppe)]BF4 in CH2Cl2, self [4+2] annulation to
generate cyclohexenones proceeded in high yields. The use
of coordinationg solvents such as acetone and CH3CN effi-
ciently suppressed undesired self-coupling.[12] After examin-
ing various phosphine ligands, we discovered that the same
reaction conducted in the presence of 10% [Rh(binap)]BF4
in CH2Cl2 at room temperature cleanly furnished the cy-
clized product 2 in 84% yield (Scheme 3). This result con-
trasts with the reaction of 4-alkynals with [Rh(binap)]BF4 in
CH2Cl2, which furnishes dienals via carbonyl migration
(Scheme 2).[13] No reaction was observed by using neutral
rhodium(i) complexes, while alkynal 1 was recovered un-
changed.
4
5
6
7
84
82
57
56
10
[a] Isolated yield.
which furnishes cyclopentenones and cyclobutanones (Sche-
me 4).[8b] In all cyclizations a single (E)-olefin isomer was
produced; however, 6-alkyl propargylic ether furnished cy-
clopentenone as a by-product.
Scheme 4. Reaction of 3-methoxy-4-alkynals with [Rh(binap)]BF4.
Not only 5-alkynals, but also 6-alkynals (Table 2) afforded
the corresponding a-alkylidenecyclohexanones in high
yields with single (E)-olefin isomer. Both 6-aryl and 6-alkyl-
6-alkynals afforded the corresponding a-alkylidenecyclopen-
tanones (entries 1 and 2). The substitution at the 4 and 5 po-
sitions were tolerated (entries 3 and 4). The cyclohexenone
was obtained as a by-product in the case of 7-phenyl-6-alky-
nal.
Because the cycloalkenons were obtained as by-products,
we anticipated that tandem hydroacylation/double-bond mi-
gration would occur at elevated temperature. Indeed, when
the reactions of 5-alkynals were conducted at 808C, the cy-
clopentenones were obtained in good yield via tandem hy-
Scheme 3. Rhodium-catalyzed intramolecular hydroacylation of 5-alky-
nals.
A series of 5-alkynals was subjected to the above optimal
reaction conditions (see also Table 1). Both 6-aryl and 6-
alkyl-5-alkynals cleanly afforded the corresponding a-alkyli-
denecyclopentanones in high yields (entries 1–3). The reac-
tion tolerates substituents at the 3 and 4 positions (entries 4
and 5). The cyclization of the labile secondary propargylic
ethers also proceeded (entries 6 and 7). This result contrasts
the reaction of 3-methoxy-4-alkynals with [Rh(binap)]BF4,
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Chem. Eur. J. 2004, 10, 5681 – 5688

Rhodium-Catalyzed Intramolecular Hydroacylation
5681 – 5688
Table 2. Cationic rhodium(i)/BINAP complex-catalyzed intramolecular
hydroacylation of 6-alkynals.
The double-bond migration of 6-alkynals also proceeded
(Table 4), but the presence of substituents at the 4 and 5 po-
sitions prohibited the double-bond migration (entries 3 and
4).
Table 4. Cationic rhodium(i)/BINAP complex-catalyzed intramolecular
tandem hydroacylation/double bond migration of 6-alkynals.
Entry
1
6-Alkynal
Product
Yield [%][a]
56
5
Entry
1
6-Alkynal
Product
Yield [%][a]
41
2
3
74
2
3
76
0
77
91
4
4
0
[a] Isolated yield.
[a] Isolated yield.
droacylation/double-bond migration (Table 3). This reaction
enabled the synthesis of a,b-disubstituted cyclopentenones
(entries 4, 6, and 7), such as dihydrojasmone (entry 4).
Although the reaction of 7-alkynal 3 was also investigat-
ed, no reaction was observed even at 808C and the alkynal
3 was recovered unchanged (Scheme 5).
Table 3. Cationic rhodium(i)/BINAP complex-catalyzed intramolecular
tandem hydroacylation/double-bond migration of 5-Alkynals.
Entry
1
5-Alkynal
Product
Yield [%][a]
60
Scheme 5. Reaction of 7-alkynal with rhodium(i)+/BINAP complex.
Scheme 6 depicts a plausible mechanism of this novel cyc-
lization.[14,15] We believe that the rhodium(i) catalyst oxida-
2
3
59
84
À
tively inserts into the aldehyde C H bond, affording a rho-
dium acyl hydride A. cis-Addition of the rhodium hydride
to the metal-bound alkyne then provides the rhodium metal-
lacycle B. Reductive elimination furnishes the a-alkylidene-
cycloalkanones and regenerates the rhodium(i) catalyst. Al-
ternatively, the catalytic cycle can be elucidated as the fol-
lowing: a cis addition of the acyl rhodium to the alkyne pro-
vides the rhodium vinyl hydride C followed by reductive
elimination. Murai et al. proposed the formation of the eth-
ylidene cyclopentanone via a reductive elimination from a
ruthenium–vinyl hydride.[10] At elevated temperature, rhodi-
um-catalyzed double bond migration of the a-alkylidenecy-
cloalkanones proceeded to give cycloalkenones.
4
83
5
6
7
58
39
Consistent with these pathways, reaction of a deuterium-
labeled 5-alkynal 4 led to stereospecific incorporation of
deuterium in the b position of the a-alkylidenecyclopenta-
none 5 (Scheme 7), and rhodium catalyst is essential for the
double-bond migration (Scheme 8). Although the transfor-
62[b]
[a] Isolated yield. [b] At 508C.
Chem. Eur. J. 2004, 10, 5681 – 5688
www.chemeurj.org
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K. Tanaka et al.
FULL PAPER
Experimental Section
General: 1H NMR spectra were recorded on either 300 MHz (JEOL AL
300) or 400 MHz (JEOL AL 400) at 258C and are referenced to residual
solvent downfield from tetramethylsilane (see Supporting Information).
13C NMR spectra were obtained with complete proton decoupling on
either 75 MHz (JEOL AL 300) or 100 MHz (JEOL AL 400) at 258C.
2H NMR spectra were obtained with complete proton decoupling on
61 MHz (JEOL AL 400) at 258C. Infrared spectra were obtained on a
JASCO A-302 IR. HRMS were collected on JEOL JMS 700. Anhydrous
CH2Cl2 was obtained from Aldrich (No. 27099-7) and used as received.
Anhydrous (CH2Cl)2 was obtained from Alrich (No. 28450-5) and used
as received. THF and CH2Cl2 was dried over MS 4 Š for the synthesis of
substrates. CuI (99.999%, Aldrich) was used as received. All other re-
agents and solvents were obtained from commercial sources, and used as
received. All reactions were carried out under an atmosphere of nitrogen
or argon in oven-dried glassware with magnetic stirring, unless otherwise
indicated.
Scheme 6. Proposed reaction mechanism for formation of a-alkylidenecy-
cloalkanones and cycloalkenones.
General procedure 1—Preparation of 4-alkynals: nBuLi (1.58 m in
hexane, 15.0 mL, 23.7 mmol) was added to a stirred solution of 1-dode-
cyne (5.2 mL, 24.3 mmol) in THF (63 mL) at À108C, and the resulting
mixture was stirred at À108C for 30 min. CuI (99.999%, 5.02 g,
26.4 mmol) was added, and the resulting mixture was stirred at À108C
for 1.5 h. After cooling to À788C, TMSI (3.4 mL, 23.9 mmol) was added,
and the resulting mixture was stirred at À788C for 5 min. Acrolein
(1.6 mL, 23.9 mmol) was added at À788C, and the resulting mixture was
stirred at À458C for 2 h, and then stirred at RT overnight. The reaction
was quenched by the addition of saturated aqueous NH4Cl and extracted
with Et2O. The organic layer was washed with 5% Na2S2O3 and brine,
dried over Na2SO4, and concentrated. To complete hydrolysis, a solution
of the residue in THF (250 mL) was treated with aqueous 10% HCl
(56 mL) at RT for 1 h. Saturated aqueous NaHCO3 was added slowly to
neutralize acid and then extracted with Et2O. The combined organic ex-
tracts were washed with 5% Na2S2O3 and brine, dried over Na2SO4, and
concentrated. The residue was purified by silica gel chromatography
(hexane/EtOAc 50:1), which furnished pentadec-4-ynal (3.84 g,
17.3 mmol, 72%, not optimized) as a colorless oil.
Scheme 7. Deuterium labeling study.
mation of a-alkylidenecycloalkanones to cycloalkenones
was already reported using a stoichiometric amount of
[RhCl(PPh3)3] in the presence of a catalytic amount of trie-
thylsilane,[15] the present method enables this transformation
using a catalytic amount of rhodium(i) complex.
General procedure 2—Preparation of 4-alkynals: nBuLi (1.58 m in
hexane, 15.2 mL, 24.0 mmol) was added to a stirred solution of 1-octyne
(3.5 mL, 23.7 mmol) in THF (63 mL) at À108C, and the resulting mixture
was stirred at À108C for 20 min. CuI (99.999%, 5.03 g, 26.5 mmol) was
added, and the resulting mixture was stirred at À108C for 1 h. After cool-
ing to À788C, TMSI (3.4 mL, 23.9 mmol) was added, and the resulting
mixture was stirred at À788C for 5 min. 2-Methyl-2-propenal (2.0 mL,
24.2 mmol) was added at À788C, and the resulting mixture was stirred at
À458C for 2 h, and then stirred at RT overnight. The reaction was
quenched by the addition of saturated aqueous NH4Cl and extracted
with Et2O. The organic layer was washed once with 5% Na2S2O3 and
brine, dried over Na2SO4, and concentrated. The residue was purified by
silica gel chromatography (hexane/EtOAc 50:1), which furnished 2-meth-
ylundec-4-ynal (2.60 g, 14.4 mmol, 61%, not optimized) as a colorless oil.
Scheme 8. Rhodium-catalyzed double bond migration of a-alkylidenecy-
clopentanones to cyclopentenones.
Conclusion
In summary, we have established that a cationic rhodium(i)/
BINAP complex catalyzes a novel intramolecular hydroacy-
lation of 5- and 6-alkynals leading to a-alkylidenecycloalka-
nones. In addition, hydroacylation and double-bond migra-
tion of 5- and 6-alkynals proceeded in a one-pot reaction at
elevated temperature to give cycloalkenones. Hydroacyla-
tion of alkenals to cycloalkanones is limited to 4-alkenals,
but hydroacylation of alkynals is not limited to 4-alkynals: it
is applicable to 5- and 6-alkynals. Although the reaction of a
7-alkynal was investigated, no reaction was observed. We
believe that this method represents an attractive new route
to produce highly functionalized a-alkylidenecycloalkanones
and cycloalkenones. The endo-intramolecular hydroacylation
of 5- and 6-alkynals leading to medium-sized cycloalkenones
(cyclohexenones and cycloheptenones) is currently under-
way in our laboratory.
General procedure 3—Preparation of 5- and 6-alkynals: A lithium diiso-
propylamine solution consisting of nBuLi (1.58 m in hexane, 5.5 mL,
8.7 mmol) and diisopropylamine (1.3 mL, 9.3 mmol) in THF (15 mL) was
added under argon atmosphere to a cooled (À108C), stirred suspension
of (methoxymethyl)triphenylphosphonium chloride (3.09 g, 9.03 mmol) in
THF (15 mL). To the deep red solution was added a solution of penta-
dec-4-ynal (1.01 g, 4.50 mmol) in THF (15 mL). The resulting solution
was kept at À108C for 1 h and then diluted with saturated aqueous
NaHCO3 (45 mL). After extraction with Et2O, the combined organic
layers were dried over Na2SO4, filtered, and concentrated. The crude 1-
metoxy-1-hexadecen-5-yne was used without purification in the next step.
A solution of the 1-metoxy-1-hexadecen-5-yne in THF (30 mL) was treat-
ed with aqueous HCl (12 mL, 10%) at RT for 24 h. Saturated aqueous
NaHCO3 was added slowly to neutralize acid and then extracted with
Et2O. The combined organic extracts were washed with brine, dried over
Na2SO4, concentrated, and purified by silica gel chromatography
(hexane/EtOAc 50:1), which furnished hexadec-5-ynal (0.86 g,
3.64 mmol, 81%, not optimized) as a colorless oil.
5684
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Chem. Eur. J. 2004, 10, 5681 – 5688

Rhodium-Catalyzed Intramolecular Hydroacylation
5681 – 5688
Hexadec-5-ynal (Table 1,entry 3) : The title compound was prepared ac-
cording to the GP 1 and 3. 1H NMR (CDCl3, 300 MHz): d = 9.81 (t, J=
1.2 Hz, 1H), 2.57 (dt, J=6.9, 1.2 Hz, 2H), 2.23 (tt, J=6.9, 2.4 Hz, 2H),
2.13 (tt, J=6.9, 2.4 Hz, 2H), 1.81 (quint, J=6.9 Hz, 2H), 1.56–1.18 (m,
16H), 0.88 (t, J=7.2 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d = 202.1,
81.7, 78.6, 42.8, 31.9, 29.6, 29.5, 29.3, 29.1, 29.0, 28.9, 22.7, 21.6, 18.7, 18.2,
14.1; IR (neat): n˜ = 2920, 2860, 1720, 1440 cmÀ1; HRMS (EI): m/z: calcd
for C16H28O: 236.2140, found 236.2124 [M]+.
4-Methoxy-6-phenylhex-5-ynal (Table 1,entry 6) : DIBAL (0.95m in n-
hexane, 24.4 mL, 23.2 mmol) was added a solution of 3-cianopropionalde-
hyde dimethyl acetal (3.02 mL, 23.2 mmol) in CH2Cl2 (120 mL) at À788C
and the resulting mixture was stirred for 1 h. The resulting mixture was
warmed slowly to RT, and treated with excess saturated aqueous NH4Cl.
The reaction mixture was then diluted with water and extracted with
CH2Cl2. The organic layer was washed with water, dried over Na2SO4,
dried over Mg4SO4, and concentrated, which afforded crude 4,4-dime-
thoxybutyraldehyde (2.6 g, 19.6 mmol, 84%) as a pale yellow oil.
4-Methyldec-5-ynal (1) (Table 1,entry 4) : The title compound was pre-
pared as a colorless oil in 51% isolated yield (not optimized) from 3-
methylnon-4-ynal according to the GP 3. 3-Methylnon-4-ynal was pre-
pared as colorless oil in 39% isolated yield (not optimized) from croto-
naldehyde according to the GP 1. 1H NMR (CDCl3, 300 MHz): d = 9.81
(t, J=1.8 Hz, 1H), 2.65–2.54 (m, 2H), 2.54–2.38 (m, 1H), 2.14 (dt, J=
6.9, 2.1 Hz, 2H), 1.87–1.55 (m, 2H), 1.52–1.31 (m, 4H), 1.17 (d, J=
6.9 Hz, 3H), 0.91 (t, J=7.2 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d =
202.4, 83.3, 81.6, 42.0, 31.1, 29.4, 25.5, 21.9, 21.4, 18.3, 13.6; IR (neat):
nBuLi (1.58 m in n-hexane, 14.4 mL, 22.8 mmol) was added a solution of
phenylacetylene (3.13 mL, 28.5 mmol) in THF (64 mL) at 08C and the re-
sulting mixture was stirred for 0.5 h. A solution of crude 4,4-dimethoxy-
butyraldehyde (2.51 g, 19.0 mmol) in THF (16.0 mmol) was added, and
the mixture was stirred for 0.5 h. MeI (5.92 mL, 95.0 mmol) and DMSO
(56 mL) were added, and the resulting mixture was heated under reflux
at 808C for 1 h. The reaction mixture was then diluted with water and ex-
tracted with ether. The organic layer was washed with water and brine,
dried over Na2SO4, and concentrated. To the residue was added water
(17 mL) and AcOH (51 mL), and the resulting mixture was stirred at
808C for 1 h. The reaction mixture was diluted with water and extracted
with Et2O. The organic layer was washed with water and saturated aque-
ous NaHCO3, dried over Na2SO4, concentrated, and purified by chroma-
tography (hexane/EtOAc 10:1), which afforded 4-methoxydodec-5-ynal
(1.13 g, 5.56 mmol, 29%, not optimized) as a pale yellow oil. 1H NMR
(CDCl3, 300 MHz): d = 9.82 (t, J=1.5 Hz, 1H), 7.48–7.38 (m, 2H), 7.35–
7.28 (m, 3H), 4.26 (t, J=6.0 Hz, 1H), 3.46 (s, 3H), 2.69 (dt, J=7.1,
1.5 Hz, 2H), 2.15 (dt, J=7.1, 6.0 Hz, 2H); 13C NMR (CDCl3, 75 MHz):
d = 201.8, 131.7, 128.5, 128.30, 128.29, 98.9, 86.9, 70.5, 56.6, 39.7, 28.3; IR
(neat): n˜ = 3300, 2900, 1720, 1100, 760, 690 cmÀ1; HRMS (EI): m/z:
calcd for C13H14O2: 202.0994, found 202.0919 [M]+.
n˜
=
2860, 2720, 1715, 1370, 1320 cmÀ1; HRMS (EI): m/z: calcd for
C11H18O: 166.1358, found 166.1323 [M]+.
3-Methyldodec-5-ynal (Table 1,entry 5) : The title compound was pre-
pared as a colorless oil in 80% isolated yield (not optimized) from 2-
methylundec-4-ynal according to the GP 3. 2-Methylundec-4-ynal was
1
prepared according to the GP 2 to yield a colorless oil. H NMR (CDCl3,
300 MHz): d = 9.79 (t, J=2.4 Hz, 1H), 2.77–2.50 (m, 1H), 2.37–2.06 (m,
6H), 1.57–1.21 (m, 8H), 1.04 (d, J=6.3 Hz, 3H), 0.89 (t, J=7.2 Hz, 3H);
13C NMR (CDCl3, 75 MHz): d = 202.3, 82.5, 77.4, 49.8, 31.3, 29.0, 28.5,
28.0, 26.0, 22.5, 19.7, 18.7, 14.0; IR (neat): n˜ = 2920, 2870, 1720, 1375,
910, 730 cmÀ1; HRMS (EI): m/z: calcd for C13H22O: 194.1671, found
194.1665 [M]+.
6-Phenylhex-5-ynal (Table 1,entry 1) :[17] A solution of DMSO (3.3 mL,
46.5 mmol) in CH2Cl2 (20 mL) was added at À788C to a solution of
(COCl)2 (3.1 mL, 23.1 mmol) in CH2Cl2 (45 mL). The resulting mixture
was stirred at À788C for 15 min, and then a solution of the 6-phenylhex-
5-ynol[18] (3.06 g, 17.6 mmol) in CH2Cl2 (45 mL) was added at À788C.
The mixture was stirred at À788C for 1 h, and Et3N (18.3 mL) was added
after stirring at RT for 1 h. The reaction was quenched by the addition of
water and extracted with CH2Cl2. The organic layer was washed with sa-
turated aqueous NH4Cl, dried over Na2SO4, concentrated, and purified
by silica gel chromatography (hexane/EtOAc 50:1), which furnished 6-
phenylhex-5-ynal (2.42 g, 14.1 mmol, 80%, unoptimized) as a yellow oil.
1H NMR (CDCl3, 300 MHz): d = 9.85 (t, J=1.2 Hz, 1H), 7.46–7.34 (m,
2H), 7.33–7.21 (m, 3H), 2.66 (dt, J=7.2, 1.2 Hz, 2H), 2.50 (t, J=7.2 Hz,
2H), 1.94 (quint, J=7.2 Hz, 2H); 13C NMR (CDCl3, 75 MHz): d = 201.9,
131.5, 128.2, 127.7, 123.5, 88.9, 81.7, 42.8, 21.2, 18.8.
4-Methoxydodec-5-ynal (Table 1,entry 7) : The title compound was pre-
pared as a pale yellow oil in 6% isolated yield (not optimized) from 1-
octyne according to the procedure for 4-methoxy-6-phenylhex-5-ynal.
1H NMR (CDCl3, 300 MHz): d = 9.79 (t, J=1.8 Hz, 1H), 4.00 (tt, J=6.0,
1.8 Hz, 1H), 3.37 (s, 3H), 2.61 (dt, J=7.3, 1.8 Hz, 2H), 2.22 (dt, J=6.9,
1.8 Hz, 2H), 2.02 (dt, J=7.3, 6.0 Hz, 2H), 1.65–1.15 (m, 8H), 0.89 (t, J=
6.9 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d = 202.0, 87.4, 77.8, 70.2,
56.2, 39.7, 31.2, 28.6, 28.47, 28.46, 22.5, 18.6, 14.0; IR (neat): n˜ = 2900,
1720, 1440, 1330, 1100 cmÀ1
; HRMS (EI): m/z: calcd for C12H18O:
178.1358, found 178.1334 [MÀCH3OH]+.
7-Phenylhept-6-ynal (Table 2,entry 1) : The title compound was prepared
as a yellow oil in 49% isolated yield (not optimized) from 6-phenylhex-
5-ynal according to the GP 3. 1H NMR (CDCl3, 300 MHz): d = 9.80 (t,
J=1.8 Hz, 1H), 7.42–7.35 (m, 2H), 7.34–7.24 (m, 3H), 2.51 (dt, J=7.2,
1.8 Hz, 2H), 2.45 (t, J=6.9 Hz, 2H), 1.88–1.77 (m, 2H), 1.73–1.60 (m,
2H); 13C NMR (CDCl3, 75 MHz): d = 202.3, 131.5, 128.2, 127.6, 123.8,
89.4, 81.1, 43.4, 28.1, 21.3, 19.2; IR (neat): n˜ = 3260, 2920, 2710, 1720,
6-o-Tolylhex-5-ynal (Table 1,entry 2) : [PdCl2(PPh3)2] (0.35 g, 0.50 mmol)
was added to a solution of 2-iodotoluene (3.2 mL, 25.0 mmol) and 5-
hexyn-1-ol (3.3 mL, 29.9 mmol) in Et3N (100 mL). The mixture was then
stirred for 5 min, and CuI (70 mg, 0.37 mmol) was added. The resulting
mixture was heated under a nitrogen atmosphere at 508C for 2 h and stir-
red overnight at RT. The resulting mixture was filtered, concentrated,
and purified by silica gel chromatography (hexane/EtOAc 20:1), which
furnished 6-o-tolylhex-5-ynol (4.50 g, 23.9 mmol, 96%, not optimized) as
a yellow oil.
1600, 1490, 1440, 1070, 755, 695 cmÀ1
; HRMS (EI): m/z: calcd for
C13H14O: 186.1045, found 186.1048 [M]+.
Heptadec-6-ynal (Table 2,entry 2) : The title compound was prepared as
a colorless oil in 95% isolated yield (not optimized) from hexadec-5-ynal
according to the GP 3. 1H NMR (CDCl3, 300 MHz): d = 9.77 (t, J=
1.8 Hz, 1H), 2.46 (dt, J=7.5, 1.8 Hz, 2H), 2.26–2.05 (m, 4H), 1.83–1.66
(m, 2H), 1.60–1.15 (m, 18H), 0.88 (t, J=7.2 Hz, 3H); 13C NMR (CDCl3,
75 MHz): d = 202.4, 80.9, 79.2, 43.4, 31.9, 29.6, 29.5, 29.3, 29.12, 29.07,
28.9, 28.4, 22.6, 21.2, 18.7, 18.5, 14.1; IR (neat): n˜ = 2850, 2710, 1715,
1430 cmÀ1; HRMS (EI): m/z: calcd for C17H30O: 250.2297, found 250.2278
[M]+.
A solution of DMSO (1.7 mL, 24.0 mmol) in CH2Cl2 (25 mL) was added
at À788C to a solution of (COCl)2 (3.2 mL, 23.9 mmmol) in CH2Cl2
(50 mL). The resulting mixture was stirred at À788C for 15 min, and then
a
solution of the 6-o-tolylhex-5-ynol (3.12 g, 16.6 mmol) in CH2Cl2
(50 mL) was added at À788C. The mixture was stirred at À788C for 1 h,
and Et3N (12.0 mL) was added after stirring at RT for 1 h, the reaction
was quenched by the addition of water and extracted with CH2Cl2. The
organic layer was washed with saturated aqueous NH4Cl, dried over
Na2SO4, concentrated, and purified by silica gel chromatography
(hexane/EtOAc 50:1), which furnished 6-o-tolylhex-5-ynal (2.74 g,
5-Methylundec-6-ynal (Table 2,entry 3) : The title compound was pre-
pared as a pale yellow oil in 88% isolated yield (not optimized) from 4-
methyldec-5-ynal according to the GP 3. 1H NMR (CDCl3, 300 MHz):
d = 9.70 (t, J=2.1 Hz, 1H), 2.42–2.27 (m, 3H), 2.08 (dt, J=6.6, 2.1 Hz,
2H), 1.84–1.56 (m, 2H), 1.45–1.25 (m, 6H), 1.07 (d, J=6.9 Hz, 3H), 0.84
(t, J=6.9 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d = 202.6, 83.9, 80.9,
43.6, 36.6, 31.2, 25.8, 21.9, 21.5, 20.0, 18.4, 13.6; IR (neat): n˜ = 2920,
2710, 1720, 1440, 1330, 1250, 1095, 790, 740 cmÀ1; HRMS (EI): m/z: calcd
for C12H20O: 180.1514, found 180.1480 [M]+.
14.7 mmol, 89%, unoptimized) as
a
yellow oil. 1H NMR (CDCl3,
300 MHz): d = 9.84 (t, J=1.2 Hz, 1H), 7.39–7.32 (m, 1H), 7.20–7.15 (m,
2H), 7.15–7.05 (m, 1H), 2.68 (dt, J=6.9, 1.2 Hz, 2H), 2.54 (t, J=6.9 Hz,
2H), 2.41 (s, 3H), 1.95 (quint, J=6.9 Hz, 2H); 13C NMR (CDCl3,
75 MHz): d = 201.9, 139.9, 131.8, 129.3, 127.7, 125.5, 123.3, 92.6, 80.5,
42.8, 21.3, 20.7, 19.0; IR (neat): n˜ = 3230, 2890, 1705, 755 cmÀ1; HRMS
(EI): m/z: calcd for C13H14O: 186.1045, found 186.1039 [M]+.
4-Methyltridec-6-ynal (Table 2,entry 4) : The title compound was pre-
pared as a colorless oil in 33% isolated yield (not optimized) from 3-
methyldodec-5-ynal according to the GP 3. 1H NMR (CDCl3, 400 MHz):
Chem. Eur. J. 2004, 10, 5681 – 5688
www.chemeurj.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5685

K. Tanaka et al.
FULL PAPER
d = 9.77 (t, J=1.6 Hz, 1H), 2.49–2.42 (m, 2H), 2.18–2.09 (m, 5H), 1.83–
1.60 (m, 2H), 1.59–1.22 (m, 8H), 0.98 (d, J=6.8 Hz, 3H), 0.89 (t, J=
6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz): d = 202.4, 81.8, 77.8, 41.7,
32.4, 31.4, 29.1, 28.6, 27.9, 25.9, 22.6, 19.4, 18.8, 14.1; IR (neat): n˜ = 2900,
2860, 2720, 1720, 1440, 1380 cmÀ1; HRMS (EI): m/z: calcd for C14H24O:
208.1827, found 208.1813 [M]+.
129.8, 129.1, 128.6, 125.7, 38.0, 29.4, 20.5, 20.0; IR (neat): n˜ = 3400, 2920,
1700, 1620, 1600, 1460, 1400, 1200, 1180, 760 cmÀ1; HRMS (EI): m/z:
calcd for C13H14O: 186.1045, found 186.1044 [M]+.
(E)-2-Undecylidenecyclopentanone (Table 1,entry 3) :[20] The title com-
pound was prepared as a pale yellow oil in 94% isolated yield from hexa-
dec-5-ynal (118.5 mg, 0.501 mmol), BINAP (31.5 mg, 0.051 mmol) and
[Rh(cod)2]BF4 (20.5 mg, 0.050 mmol) according to the GP 4; reaction
8-Phenyloct-7-ynal (3) (Scheme 5): The title compound was prepared as
1
a yellow oil in 31% isolated yield (not optimized) from 7-phenylhept-6-
time: 40 min. H NMR (CDCl3, 300 MHz): d = 6.55 (tt, J=7.5, 2.7, 1H),
1
ynal according to the GP 3. H NMR (CDCl3, 300 MHz): d = 9.78 (t, J=
2.65–2.51 (m, 2H), 2.33 (t, J=7.5, 2H), 2.21–2.07 (m, 2H), 1.93 (quint,
J=7.5 Hz, 2H), 1.53–1.16 (m, 16H), 0.88 (t, J=6.9 Hz, 3H); 13C NMR
(CDCl3, 75 MHz): d = 207.0, 137.0, 136.2, 38.5, 31.8, 29.54, 29.46, 29.4,
29.32, 29.26, 29.2, 28.3, 26.6, 22.5, 19.7, 14.0.
1.8 Hz, 1H), 7.46–7.34 (m, 2H), 7.34–7.20 (m, 3H), 2.46 (dt, J=6.9,
1.8 Hz, 2H), 2.42 (t, J=6.9 Hz, 2H), 1.76–1.41 (m, 6H); 13C NMR
(CDCl3, 75 MHz): d = 202.6, 131.5, 128.2, 127.5, 123.9, 89.8, 80.8, 43.7,
(E)-3-Methyl-2-pentylidenecyclopentanone (2) (Table 1,entry 4) :[21] The
title compound was prepared as a colorless oil in 84% isolated yield
from 4-methyldec-5-ynal (83.1 mg, 0.500 mmol), BINAP (31.3 mg,
0.050 mmol) and [Rh(cod)2]BF4 (20.4 mg, 0.050 mmol) according to the
GP 4; reaction time: 1 h. 1H NMR (CDCl3, 300 MHz): d = 6.51 (dt, J=
2.0, 7.7 Hz, 1H), 3.15–2.98 (m, 1H), 2.50–2.11 (m, 4H), 1.93–2.19 (m,
1H), 1.78–1.62 (m, 1H), 1.51–1.28 (m, 4H), 1.15 (d, J=7.1 Hz, 3H),
0.91(t, J=7.1 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d = 207.4, 142.3,
136.7, 36.1, 33.0, 30.8, 28.7, 27.7, 22.5, 20.4, 13.8.
28.4, 28.3, 21.6, 19.2; IR (neat): n˜
= 3210, 2910, 2850, 1705, 760,
695 cmÀ1; HRMS (EI): m/z: calcd for C14H16O: 200.1201, found 200.1176
[M]+.
1-Deuterio-4-methyldec-5-ynal (4) (Scheme 7): Jones reagent (1.5 m;
3.1 mL, 4.7 mmol) was added at 08C to a solution of 4-methyldec-5-ynal
(700 mg, 4.21 mmol) in acetone (15 mL). The resulting mixture was stir-
red at 08C for 15 min, and then the reaction was quenched by the addi-
tion of 2-PrOH (3.8 mL) at 08C. The mixture was stirred at RT for
10 min and then concentrated. The resulting residue was diluted with
water and extracted with Et2O. The organic layer was concentrated, and
the product was purified by silica gel chromatography (hexane/EtOAc
10:1), which furnished 4-methyldec-5-ynoic acid (706 mg, 3.87 mmol,
92%, not optimized) as a colorless oil.
(E)-2-Heptylidene-4-methylcyclopentanone (Table 1,entry 5) : The title
compound was prepared as a yellow oil in 82% isolated yield from 3-
methyldodec-5-ynal
(97.4 mg,
0.501 mmol),
BINAP
(31.2 mg,
0.050 mmol) and [Rh(cod)2]BF4 (20.4 mg, 0.050 mmol) according to the
1
A solution of 4-methyldec-5-ynoic acid (706 mg, 3.87 mmol) in THF
(4.0 mL) was added at 08C to a stirred mixture of LiAlD4 (316 mg,
7.53 mmol) in THF (17 mL). The resulting mixture was stirred at reflux
for 45 min and then cooled to 08C. The reaction was then quenched by
the addition of water (1.0 mL), followed by stirring at 08C for 10 min.
The solution was dried over MgSO4, filtered through Celite, and concen-
trated to give the crude alcohol (375 mg) as a colorless oil.
GP 4; reaction time: 2 h. H NMR (CDCl3, 300 MHz): d = 6.59–6.49 (m,
1H), 2.84–2.71 (m, 1H), 2.49 (dd, J=17.4, 7.2 Hz, 1H), 2.37–2.04 (m,
4H), 1.98 (dd, J=17.4, 8.4 Hz, 1H), 1.52–1.18 (m, 8H), 1.12 (d, J=
6.3 Hz, 3H), 0.88 (t, J=6.9 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d =
206.9, 137.6, 136.3, 47.1, 35.2, 31.6, 29.6, 29.0, 28.4, 28.3, 22.6, 21.0, 14.0;
IR (neat): n˜ = 2950, 2900, 1720, 1650, 1440, 1180 cmÀ1; HRMS (EI): m/z:
calcd for C13H22O: 194.1671, found 194.1640 [M]+.
A solution of DMSO (0.35 mL, 4.9 mmol) in CH2Cl2 (3.0 mL) was added
at À788C to a solution of (COCl)2 (0.22 mL, 2.6 mmol) in CH2Cl2
(7.0 mL). The resulting mixture was stirred at À788C for 20 min, and
then a solution of the crude alcohol (375 mg) in CH2Cl2 (7.0 mL) was
added at À788C. The mixture was stirred at À788C for 1.5 h, and Et3N
(1.0 mL) was added. After 1 h of stirring RT, the reaction was quenched
by the addition of water and extracted with CH2Cl2. The organic layer
was washed with saturated aqueous NH4Cl, dried over Na2SO4, concen-
trated, and purified by silica gel chromatography (hexane/EtOAc 50:1),
which furnished 1-deuterio-4-methyldec-5-ynal (110 mg, 0.66 mmol, 30%,
not optimized) as a colorless oil. 1H NMR (CDCl3, 300 MHz): d = 2.71–
2.54 (m, 2H), 2.54–2.37 (m, 1H), 2.14 (dt, J=6.9, 2.1 Hz, 2H), 1.88–1.72
(m, 1H), 1.72–1.56 (m, 1H), 1.53–1.30 (m, 4H), 1.17 (d, J=6.9 Hz, 3H),
0.91 (t, J=6.9 Hz, 3H); 2H NMR (CDCl3, 61 MHz): d = 9.78 (s).
(E)-2-Benzylidene-3-methoxycyclopentanone (Table 1,entry 6) : The title
compound was prepared as a pale yellow oil in 57% isolated yield from
4-methoxy-6-phenylhex-5-ynal (101.1 mg, 0.500 mmol), BINAP (31.1 mg,
0.050 mmol) and [Rh(cod)2]BF4 (20.3 mg, 0.050 mmol) according to the
1
GP 4; reaction time: 15 h; reaction temperature: 258C. H NMR (CDCl3,
300 MHz): d = 7.72–7.53 (m, 2H), 7.52–7.34 (m, 3H), 4.76–4.66 (m, 1H),
3.46 (s, 3H), 2.62 (ddd, J=9.3, 12.3, 18.6 Hz, 1H), 2.47–2.22 (m, 2H),
2.04–1.80 (m, 1H); 13C NMR (CDCl3, 75 MHz): d = 206.4, 138.1, 136.1,
134.5, 131.0, 130.2, 128.8, 77.9, 55.3, 35.1, 25.0; IR (neat): n˜ = 2900, 1700,
1620, 1180, 1080, 760, 700 cmÀ1; HRMS (EI): m/z: calcd for C13H14O2:
202.0994, found 202.0966 [M]+.
(E)-2-Heptylidene-3-methoxycyclopentanone (Table 1,entry 7) : The title
compound was prepared as a pale yellow oil in 56% isolated yield from
4-methoxydodec-5-ynal (63.1 mg, 0.300 mmol), BINAP (18.7 mg,
0.030 mmol) and [Rh(cod)2]BF4 (12.2 mg, 0.030 mmol) according to the
GP 4; reaction time: 20 min; reaction temperature: 258C. 2-Heptyl-3-me-
thoxycyclopent-2-enone was also obtained in 10% isolated yield.
1H NMR (CDCl3, 300 MHz): d = 6.79 (dt, J=8.1, 1.5 Hz, 1H), 4.56–4.48
(m, 1H), 3.31 (s, 3H), 2.53 (ddd, J=9.0, 11.1, 18.3 Hz, 1H), 2.41–2.06 (m,
4H), 2.06–1.81 (m, 1H), 1.60–1.15 (m, 8H), 0.89 (t, J=6.9 Hz, 3H);
13C NMR (CDCl3, 75 MHz): d = 205.7, 142.3, 137.4, 76.9, 55.7, 35.5, 31.5,
29.5, 29.0, 28.5, 26.6, 22.4, 14.0; IR (neat): n˜ = 2900, 1720, 1640, 1460,
1180, 1080, 880 cmÀ1; HRMS (EI): m/z: calcd for C13H22O2: 210.1620,
General procedure 4—Intramolecular hydroacylation of 5- and 6-alky-
nals: Under an Ar atmosphere, BINAP (31.3 mg, 0.050 mmol) and
[Rh(cod)2]BF4 (20.4 mg, 0.050 mmol) were dissolved in CH2Cl2 (2.0 mL)
and the mixture was stirred for 15 min. H2 was introduced to the resulting
solution in Schlenk tube. After stirring for 1 h at RT, the resulting so-
lution was concentrated to dryness and dissolved in CH2Cl2 (1.5 mL).
The residue was added to a solution of 6-phenylhex-5-ynal (86.1 mg,
0.500 mmol) in CH2Cl2 (0.5 mL). The mixture was stirred at RT for 13 h.
The resulting solution was concentrated and purified by silica gel chro-
matography (hexane/EtOAc 20:1), which furnished (E)-2-benzylidenecy-
found 210.1643 [M]+.
[22]
clopentanone (67.3 mg, 0.391 mmol, 78%) as a yellow solid.
(E)-2-Benzylidenecyclohexanone (Table 2,entry 1)
:
The title com-
[19]
(E)-2-Benzylidenecyclopentanone (Table 1,entry 1)
:
m.p. 60–628C;
pound was prepared as a yellow solid in 56% isolated yield from 7-phe-
nylhept-6-ynal (93.1 mg, 0.500 mmol), BINAP (31.2 mg, 0.050 mmol) and
[Rh(cod)2]BF4 (20.5 mg, 0.050 mmol) according to the GP 4; reaction
time: 66 h. 2-Benzylcyclohex-2-enone was also obtained in 5% yield.
1H NMR (CDCl3, 300 MHz): d = 7.59–7.50 (m, 2H), 7.48–7.31 (m, 4H),
2.98 (dt, J=7.5, 2.7 Hz, 2H), 2.41 (t, J=7.5 Hz, 2H), 2.03 (quint, J=
7.5 Hz, 2H); 13C NMR (CDCl3, 75 MHz): d = 208.0, 136.0, 135.5, 132.2,
130.4, 129.3, 128.6, 37.7, 29.3, 20.1.
M.p. 36–398C ; 1H NMR (CDCl3, 300 MHz): d
= 7.50 (t, J=2.1 Hz,
1H), 7.44–7.23 (m, 5H), 2.84 (dt, J=7.2, 2.1 Hz, 2H), 2.54 (t, J=6.9 Hz,
2H), 2.02–1.86 (m, 2H), 1.82–1.70 (m, 2H); 13C NMR (CDCl3, 75 MHz):
d = 201.8, 136.6, 135.5, 130.2, 129.1, 128.5, 128.3, 40.3, 28.9, 23.8, 23.3.
(E)-2-(2-Methylbenzylidene)cyclopentanone (Table 1,entry 2) : The title
compound was prepared as a yellow solid in 75% isolated yield from 6-
o-tolylhex-5-ynal (93.2 mg, 0.500 mmol), BINAP (31.3 mg, 0.050 mmol),
and [Rh(cod)2]BF4 (20.4 mg, 0.050 mmol) according to the GP 4; reaction
time: 17 h. M.p. 67–688C ; 1H NMR (CDCl3, 300 MHz): d = 7.61 (t, J=
2.7 Hz, 1H), 7.47–7.40 (m, 1H), 7.30–7.18 (m, 3H), 2.90 (dt, J=7.5,
2.7 Hz, 2H), 2.42 (t, J=7.5 Hz, 2H), 2.41 (s, 3H), 1.99 (quint, J=7.5 Hz,
2H); 13C NMR (CDCl3, 75 MHz): d = 208.0, 138.9, 136.8, 134.3, 130.5,
(E)-2-Undecylidenecyclohexanone (Table 2,entry 2) : The title compound
was prepared as a colorless oil in 74% isolated yield from heptadec-6-
ynal (125.1 mg, 0.500 mmol), BINAP (31.2 mg, 0.050 mmol) and
[Rh(cod)2]BF4 (20.4 mg, 0.050 mmol) according to the GP 4; reaction
1
time: 4 h. H NMR (CDCl3, 300 MHz): d = 6.63 (tt, J=7.5, 2.4 Hz, 1H),
5686
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 5681 – 5688

Rhodium-Catalyzed Intramolecular Hydroacylation
5681 – 5688
2.53–2.38 (m, 4H), 2.14–2.03 (m, 2H), 1.91–1.68 (m, 4H), 1.51–1.18 (m,
16H), 0.88 (t, J=7.2 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d = 201.1,
139.8, 136.0, 40.1, 31.8, 29.54, 29.51, 29.4, 29.3, 28.4, 27.7, 26.6, 23.6, 23.3,
(m, 2H), 2.16 (t, J=7.6 Hz, 2H), 2.05 (s, 3H), 1.44–1.18 (m, 6H), 0.87 (t,
J=7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz): d = 209.4, 169.8, 140.6,
34.3, 31.8, 31.5, 28.1, 23.0, 22.5, 17.2, 14.0.
22.6, 14.1; IR (neat): n˜ = 2950, 2880, 1685, 1615, 1450, 1250, 1140 cmÀ1
HRMS (EI): m/z: calcd for C17H30O: 250.2297, found 250.2303 [M]+.
;
2-Heptyl-4-methylcyclopent-2-enone (Table 3,entry 5) : The title com-
pound was prepared as a pale yellow oil in 58% isolated yield from 3-
(E)-3-Methyl-2-pentylidenecyclohexanone (Table 2,entry 3) :[23] The title
methyldodec-5-ynal
(96.9 mg,
0.499 mmol),
BINAP
(31.2 mg,
0.050 mmol) and [Rh(cod)2]BF4 (20.3 mg, 0.050 mmol) according to the
GP 4; reaction time: 72 h; reaction temperature: 808C in (CH2Cl)2.
1H NMR (CDCl3, 400 MHz): d = 7.16 (s, 1H), 2.94–2.81 (m, 1H), 2.62
(dd, J=18.8, 6.4 Hz, 1H), 2.19–2.08 (m, 2H), 1.96 (dd, J=18.8, 2.0 Hz,
1H), 1.54–1.38 (m, 2H), 1.36–1.19 (m, 8H), 1.16 (d, J=7.2 Hz, 3H), 0.88
(t, J=6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz): d = 209.6, 162.4, 145.3,
43.3, 33.3, 31.8, 29.4, 29.1, 27.7, 24.6, 22.7, 20.4, 14.1; IR (neat): n˜ = 2920,
2860, 1700, 1450 cmÀ1; HRMS (EI): m/z: calcd for C13H22O: 194.1671
found 194.1667 [M]+.
compound was prepared as a colorless oil in 77% isolated yield from 5-
methylundec-6-ynal
(90.3 mg,
0.501 mmol),
BINAP
(31.2 mg,
0.050 mmol) and [Rh(cod)2]BF4 (20.5 mg, 0.050 mmol) according to the
GP 4; reaction time: 3 h. 1H NMR (CDCl3, 300 MHz): d = 6.46 (dt, J=
7.8, 0.9 Hz, 1H), 3.20–3.00 (m, 1H), 2.58–2.43 (m, 1H), 2.37–2.21 (m,
1H), 2.21–2.04 (m, 2H), 2.04–1.74 (m, 3H), 1.74–1.58 (m, 1H), 1.49–1.27
(m, 4H), 1.04 (d, J=7.2 Hz, 3H), 0.91 (t, J=7.2 Hz, 3H); 13C NMR
(CDCl3, 75 MHz): d = 202.3, 141.7, 138.9, 40.3, 30.9, 30.6, 30.3, 27.2,
22.5, 20.4, 18.7, 13.9.
2-Benzyl-3-methoxycyclopent-2-enone (Table 3,entry 6) : The title com-
pound was prepared as a pale yellow oil in 39% isolated yield from 4-
methoxy-6-phenylhex-5-ynal (101.1 mg, 0.500 mmol), BINAP (31.1 mg,
0.050 mmol) and [Rh(cod)2]BF4 (20.3 mg, 0.05 mmol) according to the
GP 4. The reaction was conducted in (CH2Cl)2 at 508C for 15 h, and then
808C for 11 h. 1H NMR (CDCl3, 300 MHz): d = 7.30–7.10 (m, 5H), 3.94
(s, 3H), 3.46 (s, 2H), 2.75–2.59 (m, 2H), 2.56–2.37 (m, 2H); 13C NMR
(CDCl3, 75 MHz): d = 204.1, 184.9, 140.2, 128.5, 128.2, 125.8, 120.0, 56.5,
33.4, 27.2, 24.6; IR (neat): n˜ = 3400, 2900, 1620, 1440, 1360, 1260, 1090,
720, 700 cmÀ1; HRMS (EI) calcd for C13H14O2: 202.0994, found 202.0969
[M]+.
(E)-2-Heptylidene-4-methylcyclohexanone (Table 2,entry 4)
compound was prepared as a colorless oil in 91% isolated yield from 4-
methyltridec-6-ynal (104.2 mg, 0.500 mmol), BINAP (31.2 mg,
: The title
0.050 mmol) and [Rh(cod)2]BF4 (20.3 mg, 0.050 mmol) according to the
GP 4. Reaction time: 24 h. 1H NMR (CDCl3, 300 MHz): d = 6.66–6.56
(m, 1H), 2.75–2.64 (m, 1H), 2.54 (ddd, J=18.0, 5.1, 3.3 Hz, 1H), 2.34
(ddd, J=18.0, 11.7, and 6.0 Hz, 1H), 2.19–1.75 (m, 5H), 1.57–1.16 (m,
9H), 1.06 (d, J=6.3 Hz, 3H), 0.88 (t, J=7.2 Hz, 3H); 13C NMR (CDCl3,
75 MHz): d = 201.1, 139.9, 135.4, 39.0, 35.1, 31.6, 31.2, 29.8, 29.1, 28.4,
27.7, 22.5, 21.6, 14.0; IR (neat): n˜ = 2880, 1685, 1615, 1450, 1295, 1250,
1120 cmÀ1; HRMS (EI): m/z: calcd for C14H24O: 208.1827, found 208.1822
[M]+.
2-Heptyl-3-methoxycyclopent-2-enone (Table 3,entry 7) : The title com-
pound was prepared as a pale yellow oil in 62% isolated yield from 4-
(E)-3-Methyl-2-(1-deuteriopentylidene)cyclopentanone (5) (Scheme 7):
The title compound was prepared as a colorless oil in 72% isolated yield
from 1-deuterio-4-Methyldec-5-ynal (50.4 mg, 0.301 mmol), BINAP
(18.7 mg, 0.030 mmol) and [Rh(cod)2]BF4 (12.3 mg, 0.030 mmol) accord-
ing to the GP 4; reaction time: 19 h. 1H NMR (CDCl3, 300 MHz): d =
3.15–3.00 (m, 1H), 2.50–2.12 (m, 4H), 2.10–1.94 (m, 1H), 1.74–1.61 (m,
1H), 1.52–1.27 (m, 4H), 1.15 (dd, J=6.9, 0.6 Hz, 3H), 0.91 (t, J=6.9 Hz,
methoxydodec-5-ynal (63.1 mg, 0.300 mmol),
BINAP
(18.7 mg,
0.030 mmol) and [Rh(cod)2]BF4 (12.2 mg, 0.03 mmol) according to the
GP 4; reaction time: 20 h; reaction temperature: 508C in (CH2Cl)2.
1H NMR (CDCl3, 300 MHz): d = 3.94 (s, 3H), 2.75–2.56 (m, 2H), 2.52–
2.35 (m, 2H), 2.11 (t, J=7.2 Hz, 2H), 1.46–1.15 (m, 10H), 0.87 (t, J=
6.6 Hz, 3H); 13C NMR (CDCl3, 75 Hz): d = 204.9, 184.5, 121.0, 56.2,
33.4, 31.8, 29.5, 29.1, 28.0, 24.4, 22.6, 21.2, 14.0; IR (neat): n˜ = 2900,
1680, 1620, 1460, 1360, 1250, 1080 cmÀ1; HRMS (EI): m/z: calcd for
C13H22O2: 210.1620, found 210.1644 [M]+.
2-Benzylcyclohex-2-enone (Table 4,entry 1) :[24] The title compound was
prepared as a yellow oil in 41% isolated yield from 7-phenylhept-6-ynal
(93.3 mg, 0.501 mmol), BINAP (31.2 mg, 0.050 mmol) and [Rh(cod)2]BF4
(20.3 mg, 0.050 mmol) according to the GP 4; reaction time: 19 h; reac-
tion temperature: 808C in (CH2Cl)2. 1H NMR (CDCl3, 300 MHz): d =
7.29–7.15 (m, 2H), 7.15–7.02 (m, 3H), 6.52–6.42 (m, 1H), 3.44 (s, 2H),
2.43–2.31 (m, 2H), 2.29–2.17 (m, 2H), 1.89 (quint, J=8.0 Hz, 2H);
13C NMR (CDCl3, 75 MHz): d = 198.9, 146.4, 139.6, 139.4, 129.1, 128.3,
126.0, 38.4, 35.3, 26.0, 23.0.
2
3H); H NMR (CDCl3, 61 MHz): d = 6.56 (s).
2-Benzylcyclopent-2-enone (Table 3,entry 1) :[24] The title compound was
prepared as a yellow oil in 60% isolated yield from 6-phenylhex-5-ynal
(86.1 mg, 0.500 mmol), BINAP (31.1 mg, 0.050 mmol) and [Rh(cod)2]BF4
(20.3 mg, 0.050 mmol) according to the GP 4; reaction time: 45.5 h; reac-
tion temperature: 808C in (CH2Cl)2. 1H NMR (CDCl3, 300 MHz): d =
7.39–7.08 (m, 6H), 3.49 (s, 2H), 2.62–2.48 (m, 2H), 2.48–2.35 (m, 2H);
13C NMR (CDCl3, 100 MHz): d = 208.9, 158.7, 145.9, 138.7, 128.8, 128.4,
126.2, 34.6, 31.3, 26.5.
2-(2-Methylbenzyl)cyclopent-2-enone (Table 3,entry 2) : The title com-
pound was prepared as a yellow oil in 59% isolated yield from 6-o-tolyl-
hex-5-ynal (93.1 mg, 0.500 mmol), BINAP (62.3 mg, 0.100 mmol) and
[Rh(cod)2]BF4 (40.6 mg, 0.100 mmol) according to the GP 4; reaction
time: 44.5 h; reaction temperature: 808C in (CH2Cl)2. 1H NMR (CDCl3,
300 MHz): d = 7.18–7.08 (m, 4H), 6.97–6.92 (m, 1H), 3.49–3.43 (m, 2H),
2.58–2.39 (m, 4H), 2.23 (s, 3H); 13C NMR (CDCl3, 75 MHz): d = 209.2,
158.6, 145.2, 137.0, 136.2, 130.2, 129.7, 126.5, 126.0, 34.6, 28.9, 26.4, 19.3;
2-Undecylcyclohex-2-enone (Table 4,entry 2) : The title compound was
prepared as a pale yellow oil in 76% isolated yield from heptadec-6-ynal
(125.3 mg,
0.500 mmol),
BINAP
(31.2 mg,
0.050 mmol)
and
[Rh(cod)2]BF4 (20.3 mg, 0.050 mmol) according to the GP 4; reaction
time: 17.5 h; reaction temperature: 808C in (CH2Cl)2. 1H NMR (CDCl3,
300 MHz): d = 6.81–6.59 (m, 1H), 2.52–2.26 (m, 4H), 2.23–2.09 (m, 2H),
2.05–1.89 (m, 2H), 1.49–1.13 (m, 18H), 0.88 (t, J=8.8 Hz, 3H); 13C NMR
(CDCl3, 75 MHz): d = 199.5, 144.7, 139.9, 38.6, 31.9, 29.61, 29.57, 29.55,
29.5, 29.43, 29.38, 29.3, 28.5, 26.0, 23.1, 22.6, 14.1; IR (neat): n˜ = 2910,
2850, 1700, 1420 cmÀ1; HRMS (EI): m/z: calcd for C17H30O: 250.2297
found 250.2294 [M]+.
IR (neat): n˜
C13H14O: 186.1045, found 186.0998 [M]+.
= ; HRMS (EI): m/z: calcd for
2910, 1690, 740 cmÀ1
2-Undecylcyclopent-2-enone (Table 3,entry 3) : The title compound was
prepared as a pale yellow oil in 84% isolated yield from hexadec-5-ynal
(118.3 mg,
0.500 mmol),
BINAP
(31.1 mg,
0.050 mmol)
and
[Rh(cod)2]BF4 (20.4 mg, 0.050 mmol) according to the GP 4; reaction
time: 19 h; reaction temperature: 808C in (CH2Cl)2. 1H NMR (CDCl3,
300 MHz): d = 7.36–7.27 (m, 1H), 2.64–2.49 (m, 2H), 2.46–2.32 (m, 2H),
2.24–2.10 (m, 2H), 1.56–1.18 (m, 18H), 0.88 (t, J=6.9 Hz, 3H); 13C NMR
(CDCl3, 75 MHz): d = 210.0, 157.2, 146.5, 34.5, 31.9, 29.59, 29.56, 29.5,
29.37, 29.36, 29.3, 27.7, 26.4, 24.7, 22.6, 14.1; IR (neat) 2900, 2850, 1670,
1440, 1370 cmÀ1; HRMS (EI): m/z: calcd for C16H28O: 236.2140 found
236.2110 [M]+.
Acknowledgement
This research was supported by Fujisawa Foundation and Banyu Pharma-
ceutical Company Award in Synthetic Organic Chemistry, Japan.
3-Methyl-2-pentylcyclopent-2-enone
(dihydrojasmone,
Table 3,
entry 4):[25] The title compound was prepared as a yellow oil in 83% iso-
lated yield from 4-methyldec-5-ynal (83.1 mg, 0.500 mmol), BINAP
(31.1 mg, 0.050 mmol) and [Rh(cod)2]BF4 (20.3 mg, 0.050 mmol) accord-
ing to the GP 4. Reaction time: 72 h. Reaction temperature: 808C in
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1
(CH2Cl)2. H NMR (CDCl3, 400 MHz): d = 2.55–2.45 (m, 2H), 2.41–2.30
Chem. Eur. J. 2004, 10, 5681 – 5688
www.chemeurj.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5687

K. Tanaka et al.
FULL PAPER
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Received: July 5, 2004
Published online: October 7, 2004
5688
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www.chemeurj.org
Chem. Eur. J. 2004, 10, 5681 – 5688