Cationic P(OPh)3- or PPh3-rhodium(I) complex-catalyzed isomerizations of 5-alkynals to δ-alkynyl ketones, cyclopent-1-enyl ketones, and cyclohexenones

Article abstract of DOI:10.1002/ejoc.200700550

We have developed catalytic isomerizations of 5-alkynals to γ-alkynyl ketones and cyclopent-1-enyl ketones using [Rh{P(OPh)₃} ₂]BF₄ as a catalyst. Cu(OTf)₂ and AgBF ₄ are also effective catalysts for

Full text of DOI:10.1002/ejoc.200700550

FULL PAPER
DOI: 10.1002/ejoc.200700550
Cationic P(OPh)3- or PPh3-Rhodium(I) Complex-Catalyzed Isomerizations of
5-Alkynals to δ-Alkynyl Ketones, Cyclopent-1-enyl Ketones, and
Cyclohexenones
Ken Tanaka,*[a] Kaori Sasaki,[a] Kenzo Takeishi,[a] and Masao Hirano[a]
Keywords: Aldehydes / Ketones / Alkynes / Rhodium / Catalysis
We have developed catalytic isomerizations of 5-alkynals to
γ-alkynyl ketones and cyclopent-1-enyl ketones using
[Rh{P(OPh)3}2]BF4 as a catalyst. Cu(OTf)2 and AgBF4 are also
effective catalysts for the formation of γ-alkynyl ketones. The
substituents at the 4-positions in 5-alkynals play important
roles in the selection of two different isomerization pathways.
The first catalytic endo/trans hydroacylation of acyclic 5-al-
kynals leading to cyclohexenones was also developed with
[Rh(PPh3)2]BF4 as a catalyst. Crossover deuterium-labeling
studies indicated that these isomerization reactions proceed
intramolecularly.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
Rhodium-catalyzed intramolecular hydroacylation of 4-
alkenals, first discovered by Sakai and co-workers in 1972,
is well established method for the preparation of cyclo-
pentanones.[1–3] However, the intramolecular hydroacyl-
ation of 5-alkenals to generate cyclohexanones is not a ge-
neral method, being restricted to cyclic substrates.[4,5] In
2001, the corresponding reactions of 4-alkynals to generate
cyclopentenones through intramolecular endo/trans hydro-
acylation were developed using a cationic dppe-rhodium(I)
complex in acetone [dppe = 1,2-bis(diphenylphosphanyl)-
ethane, see Scheme 1].[6a] The effects of ligands and substit-
uents on the cationic rhodium(I) complex-catalyzed trans-
formations of 4-alkynals were then thoroughly examined,
which revealed that the use of dppe as a ligand furnishes
cyclopentenones[6a] or [4+2] annulation products[6b] de-
pending on the solvents used, and that the use of BINAP
[2,2Ј-bis(diphenylphosphanyl)-1,1Ј-binaphthyl] as a ligand
furnishes cyclopentenones,[6c,6d] cyclobutanones,[6d] or dien-
als,[6e] depending on the substituents at the 3-positions
(Scheme 1).[6]
Scheme 1. Effect of ligands and substituents on cationic rhodium(I)
complex-catalyzed transformations of 4-alkynals.
(80 °C), a tandem exo/cis hydroacylation-double bond mi-
gration to generate cyclopentenones proceeds in high yield
(Scheme 2).
Unlike that of 5-alkenals, the intramolecular exo/cis
hydroacylation of 5-alkynals to generate α-alkylidenecyclo-
pentanones can proceed at room temp. in high yield
through the use of a cationic rhodium(I)/BINAP complex
as a catalyst (Scheme 2).[7,8] At elevated temperature
Scheme 2. RhI+/BINAP-catalyzed reactions of 5-alkynals.
[a] Department of Applied Chemistry, Graduate School of Engi-
neering, Tokyo University of Agriculture and Technology
Koganei, Tokyo 184-8588, Japan
However, the effects of ligands and substituents on the
cationic rhodium(I) complex-catalyzed transformations of
5-alkynals have not been thoroughly examined. In this pa-
per, we describe cationic P(OPh)3- or PPh3-rhodium(I)
complex-catalyzed isomerizations of 5-alkynals to γ-alkynyl
Fax: +81-42-388-7037
E-mail: tanaka-k@cc.tuat.ac.jp
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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ketones, cyclopent-1-enyl ketones, and cyclohexenones, re- (Entries 11–15), AgBF4 showed the highest catalytic ac-
vealing that the substituents at the 4-positions and the tivity (Entry 11). Brønsted acids did not catalyze this isom-
choice of ligands determine the selectivity among the three erization reaction at all (Entries 16 and 17).
products.[9]
Table 1. Screening of catalysts for isomerization of 5-alkynal 1a to
γ-alkynyl ketone 3a.
Results and Discussion
Cationic P(OPh)3-Rhodium(I) Complex-Catalyzed
Isomerization of 5-Alkynals to δ-Alkynyl Ketones
In order to examine the effects of substituents at the 4-
positions of 5-alkynals in cationic rhodium(I)/BINAP com-
plex-catalyzed intramolecular hydroacylation, the reaction
of 6-alkyl-4-methoxy-5-alkynal 1a with 10 mol-% [Rh-
(BINAP)]BF4 in CH2Cl2 at room temp. was conducted, fur-
nishing the corresponding exo/cis hydroacylation product
2a in 77% yield (Scheme 3). To our surprise, though, the
reaction of 6-phenyl-4-methoxy-5-alkynal 1b provided not
the expected α-alkylidenecyclopentanone 2b, but γ-alkynyl
ketone 3b in 47% yield (Scheme 3).
Scheme 3. RhI+/BINAP-catalyzed reactions of 4-methoxy-5-
alkynals.
The use of various cationic rhodium(I)/phosphane cata-
[a] Rh catalysts were generated in situ from [Rh(cod)2]BF4 or
lysts to promote the isomerization of 1a to γ-alkynyl ketone
[Rh(nbd)2]BF4, ligand, and H2. [b] Isolated yield. [c] Solvent:
3a was examined, as shown in Table 1. The use of bidentate
phosphane ligands did not furnish 3a at all (Entries 1–3).
On the other hand, the use of 10 mol-% [Rh(PPh3)2]BF4
CH3CN.
The reactions of a series of 4-alkyl-4-methoxy-5-alkynals
catalyzed endo/trans hydroacylation of 1a to give cyclohex- were investigated in the presence of 10 mol-% [Rh(P-
enone 4a in 30% yield (Entry 4). Fortunately, a cationic (OPh)3)2]BF4, Cu(OTf)2, or AgBF4 at room temp. as shown
rhodium(I)/electron-deficient monodentate phosphane or in Table 2. The 6-alkyl- and 6-phenyl-5-alkynals 1a–c all
phosphite complex catalyzed the isomerization of 1a to 3a cleanly afforded the corresponding γ-alkynyl ketones 3a–c
(Entries 5 and 6). Especially, the use of 10 mol-% in good yields (Entries 1, 3, 5, 7, and 8). Although the yield
[Rh(P(OPh)3)2]BF4 gave 3a in 77% yield (Entry 6). We an- of the ketone 3a was reduced, 5 mol-% Rh, Cu, or Ag cata-
ticipated that this isomerization reaction might proceed lyst can be used (Entries 2, 4, and 6). Although the reaction
through activation of alkynes and aldehydes by complex- of 6-trimethylsilyl-5-alkynal 1d in the presence of
ation to electrophilic transition metal complexes. Indeed, [Rh(P(OPh)3)2]BF4 did not proceed even at elevated tem-
catalytic cycloisomerizations of alkynyl carbonyl com- perature (80 °C, Entry 9), the use of Cu(OTf)2 or AgBF4 at
pounds leading to a variety of cyclic compounds through 80 °C gave the desired ketone 3d in low yields (Entries 10
the use of a range of electrophilic transition metal com- and 11). The scope of 4-alkyl substituents was also investi-
plexes have been developed.[10–12] However, the correspond- gated. Not only methyl-, but also n-propyl- and isopropyl-
ing reactions of γ-alkynyl carbonyl compounds, including substituted 5-alkynals 1e and 1f can be used for this reac-
5-alkynals, have hardly been explored.[13] Accordingly, tion (Entries 12 and 13).
other electrophilic transition metal complexes, which are
In order to clarify the stereochemical course of this isom-
frequently used for activation of alkynyl carbonyl com- erization, the reactions of enantioenriched 4-methoxy-5-al-
pounds, were also examined. Although the use of 10 mol-% kynals were examined. The reaction of enantioenriched 4-
[14a]
PdCl2,[11c,12l–12o] PtCl2,[12c] and SbF5
led to unidentified methoxy-5-alkynal (–)-1b (18% ee), prepared through the
[12i,12j]
mixtures (Entries 7–9), the use of 10 mol-% Cu(OTf)2
kinetic resolution of racemic 1b by treatment with 10 mol-
and AgBF4[15a] gave 3a in 69% and 70% yields, respectively % [Rh((R)-BINAP)]BF4 at room temp.,[16] proceeded in the
(Entries 10 and 11). Among the silver(I) salts examined presence of 10 mol-% [Rh(P(OPh)3)2]BF4 at room temp. to
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Rhodium(I)-Catalyzed 5-Alkynal Isomerizations
Table 2. RhI+/P(OPh)3, Cu(OTf)2, or AgBF4-catalyzed isomeriza-
tion of 5-alkynals to γ-alkynylketones.[a]
Scheme 4. RhI+/P(OPh)3-catalyzed isomerization of enantio-en-
riched 4-methoxy-5-alkynal (–)-1b to γ-alkynyl ketone (+)-3b.
Figure 1. Unsuitable alkynals for RhI+/P(OPh)3-catalyzed isomer-
ization to alkynyl ketones.
presence of 10 mol-% [Rh(P(OPh)3)2]BF4 at room temp. led
to the corresponding cyclic acetal
(Scheme 5).
6 in 74% yield
Scheme 5. RhI+/P(OPh)3-catalyzed reaction of 4-methoxyaldehyde
5 to give cyclic acetal 6.
Although no reaction was observed when 4-methoxydo-
dec-5-ynal (1g) was treated in the presence of 10 mol-%
[Rh(P(OPh)3)2]BF4 at room temp., we anticipated that an
exchange reaction between formyl hydrogen and propar-
gylic hydrogen might proceed in place of that between for-
myl hydrogen and propargylic alkyl group. Indeed, deute-
rium–hydrogen exchange between formyl deuterium and
propargylic hydrogen proceeded slowly in the reaction of 1-
deuteriated 4-methoxydodec-5-ynal ([D]-1g, Scheme 6).
[a] Reactions were conducted with [Rh(P(OPh)3)2]BF4
(0.050 mmol), 1 (0.50 mmol), and CH2Cl2 (2.0 mL) at room temp.
[b] Isolated yield. [c] Catalyst: 5 mol-%. [d] Catalyst: Cu(OTf)2. Sol-
vent: CH3CN. [e] Catalyst: AgBF4 (0.030 mmol), 1 (0.30 mmol).
[f] At 80 °C.
give (+)-3b with 5% ee, which revealed that the partial race-
mization of the stereocenter occurs during the isomeriza-
tion (Scheme 4).
Although the isomerization of 4-methoxy-5-alkynals to
γ-alkynyl ketones proceeds in good yield, the corresponding
reactions of a 5-methoxy-6-alkynal, a 3-methoxy-4-alkynal,
and a 3-oxa-5-alkynal in the presence of 10 mol-%
[Rh(P(OPh)3)2]BF4 at room temp. led to mixtures of un-
identified products (Figure 1).
Scheme 6. RhI+/P(OPh)3-catalyzed deuterium–hydrogen exchange
The existence of an alkyne moiety is essential for the
isomerization. The reaction of 4-methoxyaldehyde 5 in the reaction.
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K. Tanaka, K. Sasaki, K. Takeishi, M. Hirano
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Scheme 7 depicts a possible mechanism for the formation pargylic position of γ-alkynylketone [D]-3a, while no deute-
of γ-alkynyl ketone 3. We believe that the coordination of rium crossover between γ-alkynyl ketones [D]-3a and 3e was
a transition metal complex could lead to acyclic cationic observed (Scheme 8).
intermediate A. An exchange reaction between alkyl group
In order to confirm the activation of alkynes and alde-
(R2) and formyl hydrogen would proceed via either the hydes by complexation to electrophilic transition metal
monocoordinated intermediate B or the biscoordinated in- complexes, 13C NMR spectroscopic analysis of 5-alkynal 1d
termediate C to form γ-alkynyl ketone 3 and regenerate the in the presence of AgBF4 was investigated. In the presence
transition metal complex. Alternatively, the coordination of of 50 mol-% AgBF4 at room temp., both carbonyl and al-
an electrophilic transition metal complex could induce an kyne carbon signals disappeared, but the methoxy carbon
attack of a carbonyl oxygen onto an alkyne through an signal was unchanged.[18] In the presence of 100 mol-%
endo pathway, leading to cyclic vinylmetal complex D.[17] AgBF4 at room temp., complete isomerization to γ-alkynyl
An exchange reaction between R2 and formyl hydrogen ketone 3d took place (Figure 2). These results demonstrated
would then proceed via the oxygen-stabilized cationic inter- that transition metal complexes may activate both carbonyl
mediate E to form the γ-alkynyl ketone 3. The intermediate and triple bond in the isomerization reaction.
C may be partially involved in this isomerization, which
would account for the partial racemization of the stereocen-
ter.
Figure 2. 13C NMR spectroscopic analysis of 5-alkynal 1d in the
presence of AgBF4 (numbers in parentheses are the chemical shifts
of the isomerization product 3d).
Cationic P(OPh)3-Rhodium(I) Complex-Catalyzed
Isomerization of 5-Alkynals to Cyclopent-1-enyl Ketones
As cationic rhodium(I)/electron-deficient monodentate
phosphane complexes catalyze the isomerization of 4-meth-
Table 3. Screening of catalysts for isomerization of 5-alkynal 1h to
cyclopent-1-enyl ketone 7h.
Scheme 7. Possible mechanism for isomerization of 4-methoxy-5-
alkynals 1 to γ-alkynyl ketones 3.
Consistently with this pathway, a crossover deuterium-
labeling experiment of a 1:1 mixture of deuterated 5-alkynal
[D]-1a and nondeuterated 5-alkynal 1e in the presence of
10 mol-% [Rh(P(OPh)3)2]BF4 revealed that the deuterium
in [D]-1a was stereospecifically incorporated into the pro-
[a] Rh catalysts were generated in situ from [Rh(cod)2]BF4 or
[Rh(nbd)2]BF4, ligand, and H2. [b] NMR yield. [c] Isolated yield.
[d] Solvent: CH3CN.
Scheme 8. Crossover deuterium-labeling experiment.
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Rhodium(I)-Catalyzed 5-Alkynal Isomerizations
oxy-5-alkynals to γ-alkynyl ketones, the reaction of 5-alky- corresponding cyclopent-1-enyl ketones 7h and 7i in good
nal 1h, bearing no methoxy group at the 4-position, in the yields (Entries 1 and 2), but 3-alkyl-5-alkynal 1j and 5-alky-
presence of 10 mol-% [Rh(P(OPh)3)2]BF4 was also exam- nals 1k–m, bearing no substituents at either 3- or 4-posi-
ined. Interestingly, the intramolecular addition of aldehyde tions, afforded the corresponding cyclopent-1-enyl ketones
to alkyne proceeded in CH2Cl2 at 40 °C to give cyclopent- 7j–m in low to moderate yields (Entries 3–6). Not only 5-
1-enyl ketone 7h in moderate yield (Table 3, Entry 1).[14,15] alkynals 1h–m, but also 6-alkynal 8 could also cyclize to
The use of (p-F3CC6H4)3P as a ligand decreased the yield give cyclohex-1-enyl ketone 9, although the yield was low
of 7h (Entry 2). The use of PPh3 and BINAP as ligands (Entry 7).
furnished endo/trans and exo/cis hydroacylation products 4h
Scheme 9 depicts a possible mechanism for the rhodium-
and 2h, which was similar to the reactions of 4-methoxy-5- catalyzed intramolecular addition of aldehyde to alkyne. We
alkynals (Entries 3 and 4). Other electrophilic transition believe that the formation of cyclopent-1-enyl ketone 7 may
metal complexes and Brønsted acids were also examined, proceed through an oxete intermediate F, as has also been
[14a]
but none was effective (Entries 8–15). Although SbF5
proposed in the case of previously reported metal-catalyzed
and AgI salts[15a] are known to catalyze the addition of al- inter- and intramolecular addition of aldehydes to al-
dehyde to alkyne, they did not catalyze the isomerization of kynes.[14,15]
1h to 7h (Entries 11 and 13).
Thus, the reactions of a series of 5-alkynals in the pres-
ence of 10 mol-% [Rh(P(OPh)3)2]BF4 were investigated as
shown in Table 4. 4-Alkyl-5-alkynals 1h and 1i afforded the
Table 4. RhI+/P(OPh)3-catalyzed isomerizations of 5- and 6-alkyn-
als to 1-cycloalkenyl ketones.[a]
Scheme 9. Possible mechanism for isomerization of 5-alkynals to
cyclopent-1-enyl ketones.
The reaction of 1-deuteriated 5-alkynal [D]-1h led to ste-
reospecific incorporation of the deuterium into the vinylic
position of cyclopent-1-enyl ketone [D]-7h, which is consis-
tent with the mechanism proposed above (Scheme 10).
Scheme 10. Deuterium labeling study.
Cationic PPh3-Rhodium(I) Complex-Catalyzed
Isomerization of 5-Alkynals to Cyclohexenones
As shown in Table 1 and Table 3, the combined use of a
cationic rhodium catalyst with PPh3 and BINAP as ligands
could furnish endo/trans and exo/cis hydroacylation prod-
ucts. As an example of intramolecular endo/trans hydroacyl-
ation of a 5-alkynal to generate a cyclohexenone, Nicolaou
and co-workers observed an unexpected hydroacylation of
a tricyclic 5-alkynal to generate a tetracyclic cyclohexenone
(78% yield based on 50% conversion) while attempting to
decarbonylate an aldehyde in the presence of a stoichiomet-
ric amount of RhCl(PPh3)3.[19] However, rigidity of the sub-
strates is crucial for the success of their reaction and the
method cannot be applicable to acyclic 5-alkynals.
Accordingly, we thoroughly examined the reaction of
acyclic 5-alkynal 1k, bearing no substituent at either 3- or
4-positions, in the presence of 10 mol-% cationic rhodi-
um(I)/phosphane complexes at room temp. to promote the
endo/trans hydroacylation (Table 5). The use of PPh3 as a
[a] Reactions were conducted with [Rh(P(OPh)3)2]BF4
(0.050 mmol) and either 1 or 8 (0.50 mmol), in (CH2Cl)2 (2.0 mL)
at 50 °C. [b] Isolated yield. [c] At 80 °C.
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ligand furnished both endo/trans and exo/cis hydroacylation Table 6. RhI+/PPh3-catalyzed isomerizations of 5-alkynals to cyclo-
hexenones.[a]
products 4k and 2k, with 4k being obtained as the major
product (Entry 1). The use of 3 equiv. of PPh3 relative to
rhodium lowered the yield of 4k (Entry 2). Other mono-
dentate phosphane ligands with different electronic and ste-
ric characters, such as o-Tol3P, (p-F3CC6H4)3P, (p-Me-
OC6H4)3P, and nBu3P, also lowered the yield of 4k. The use
of bisphosphane ligands [dppm: bis(diphenylphosphanyl)-
methane, dppe, and dppp: 1,3-bis(diphenylphosphanyl)-
propane], which have small P–M–P natural bite angles, fur-
nished no hydroacylation products (Entries 3–5). On the
other hand, the use of bisphosphane ligands [dppb: 1,4-
bis(diphenylphosphanyl)butane, dppf: 1,1Ј-bis(diphenyl-
phosphanyl)ferrocene, and BINAP], which have large P–M–
P natural bite angles, furnished exo/cis hydroacylation
product 2k, but no endo/trans hydroacylation product 4k
was obtained (Entries 6–8).
Table 5. Screening of catalysts for isomerization of 5-alkynal 1k to
cyclohexenone 4k.
[a] Reactions were conducted with [Rh(PPh3)2]BF4 (0.050 mmol),
1 (0.50 mmol), and CH2Cl2 (2.0 mL) at room temp. [b] Isolated
yield. [c] At 80 °C. [d] Catalyst: 20 mol-%.
acylation-isomerization product 10 was obtained in 23%
yield at elevated temperature (80 °C),[7] no endo/trans hy-
droacylation product was obtained (Scheme 11).
[a] Rh catalysts were generated in situ from [Rh(cod)2]BF4 or
[Rh(nbd)2]BF4, ligand, and H2. [b] NMR yield. [c] Isolated yield.
Scheme 11. RhI+/PPh3-catalyzed reaction of a 6-alkynal.
Next, the cationic rhodium(I)/PPh3 catalyst system was
applied to the transformation of 4-alkynal 11. In this case,
employment of 4 equiv. of PPh3 relative to rhodium and
elevated temperature (80 °C) are effective, and the corre-
sponding endo/trans hydroacylation product 12 was ob-
tained in 63% yield (Scheme 12).
A series of 5-alkynals was subjected to the above optimal
reaction conditions as shown in Table 6. The reaction of 6-
alkyl-5-alkynal 1k afforded the corresponding cyclohex-
enone 4k in good yield at room temp. (Entry 1), but the
reaction of 6-aryl-5-alkynal 1l required elevated tempera-
ture (80 °C) and the product yield was lower than that of
1k (Entry 2). Not only linear 5-alkynal 1k, but also
branched 5-alkynal 1h, bearing a substituent at the 4-posi-
tion, also furnished the corresponding cyclohexenone 4h,
although a lower yield was observed (Entry 3). The cycliza-
tions of the coordinating propargylic ethers 1a and 1c pref-
erentially furnished endo/trans hydroacylation products,
similarly to the cyclizations of 4-alkynals possessing propar-
gylic ether moieties (Entries 4 and 5).[6c]
Scheme 12. RhI+/PPh3-catalyzed reaction of 4-alkynal.
Scheme 13 depicts a possible mechanism for the intramo-
The reaction of 6-alkynal 8 in the presence of 10 mol-% lecular endo/trans hydroacylation of 5-alkynals 1.[20] We
[Rh(PPh3)2]BF4 was also investigated at room temp., but it propose that the rhodium(I) catalyst oxidatively inserts into
was extremely sluggish. Although tandem exo/cis hydro- the aldehyde C–H bond, affording the rhodium acyl hydride
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Rhodium(I)-Catalyzed 5-Alkynal Isomerizations
G. endo/trans addition of the rhodium hydride to the metal- [Rh(PPh3)2]BF4 as a catalyst. Crossover deuterium-labeling
bound alkyne then provides seven-membered rhodium studies indicated that these isomerization reactions proceed
metallacycle H. Reductive elimination furnishes cyclohex- intramolecularly.
enones 4 and regenerates the rhodium(I) catalyst.
Scheme 13. Possible mechanism for trans hydroacylation of 5-alky-
nals to give cyclohexenones.
Scheme 15. Effect of ligands and substituents in cationic rhodium-
(I) complex-catalyzed transformations of 5-alkynals.
Consistently with the proposed reaction pathway, a
crossover experiment with the 1:1 mixture of deuterium-
labeled 5-alkynal [D]-1h and 5-alkynal 1k furnished deuter-
ated cyclized products ([D]-4h and [D]-2h) and nondeuter-
ated cyclized products (4k and 2k) exclusively. Stereospec-
ific incorporation of the deuterium into the β positions of
both cyclohexenone [D]-4h and α-alkylidenecyclopentanone
[D]-2h was also observed (Scheme 14).[20]
Experimental Section
1
General Methods: H NMR spectra were recorded on a 300 MHz
instrument (JEOL AL 300). 13C NMR spectra were obtained with
complete proton decoupling at 75 MHz (JEOL AL 300). HRMS
data were obtained on a JEOL JMS-700 instrument. Infrared spec-
tra were obtained on a JASCO A-302. Anhydrous CH2Cl2 (No.
27,099-7) and anhydrous (CH2Cl)2 (No. 28,450–5) were obtained
from Aldrich and used as received. Solvents for the synthesis of
substrates were dried with molecular sieves (4 Å) prior to use. All
other reagents were obtained from commercial sources and used as
received. All reactions were carried out under argon or nitrogen in
oven-dried glassware with magnetic stirring.
Starting Materials: Alkynals 1h, 1j, 1k, 1l, 1m, 8, [D]-1h, and 11
were synthesized by literature procedures.[7]
Alkynal 1a: nBuLi (1.58  in n-hexane, 23 mL, 36 mmol) was added
at 0 °C to a solution of hex-1-yne (5.2 mL, 46 mmol) in THF
(120 mL), and the resulting solution was stirred at 0 °C for 0.5 h.
1,1-Dimethoxybutan-3-one was added at 0 °C, and the system was
stirred at room temp. for 0.5 h. MeI (9.4 mL, 0.15 mol) and DMSO
(90 mL) were added, and the resulting mixture was stirred at 80 °C
for 1 h. The reaction mixture was then diluted with water and ex-
tracted with Et2O. The organic layer was washed with water and
brine, dried with Na2SO4, and concentrated. Water (35 mL) and
AcOH (100 mL) were added to the residue, and the resulting mix-
ture was stirred at 80 °C for 0.5 h. The reaction mixture was diluted
with water and extracted with Et2O. The organic layer was washed
with saturated aqueous Na2CO3, dried with Na2SO4, and concen-
trated, which afforded crude 3-methoxy-3-methylnon-4-ynal
(5.1 g).
Scheme 14. Crossover deuterium-labeling experiment.
Conclusions
In conclusion, we have determined the effects of ligands
and substituents in the cationic rhodium(I) complex-cata-
lyzed transformations of 5-alkynals as summarized in
Scheme 15. A catalytic isomerization of 4-alkyl-4-methoxy-
5-alkynals to γ-alkynyl ketones proceeded in the presence A lithium diisopropylamide solution consisting of nBuLi (1.58  in
n-hexane, 34 mL, 54 mmol) and diisopropylamine (8.0 mL,
57 mmol) in THF (65 mL) was added to a cooled (–10 °C) and
stirred suspension of (methoxymethyl)triphenylphosphonium chlo-
ride (19.4 g, 56.6 mmol) in THF (61 mL). A solution of crude 3-
methoxy-3-methylnon-4-ynal (5.1 g) in THF (55 mL) was added to
the deep red solution, which was kept at –10 °C for 1 h and then
diluted with saturated aqueous NaHCO3. After extraction with
Et2O, the combined organic layers were dried with Na2SO4, fil-
tered, and concentrated. A solution of the residue in THF (375 mL)
was treated at room temp. with aqueous HCl (10%, 75 mL) for
of [Rh(P(OPh)3)2]BF4 as a catalyst. Cu(OTf)2 and AgBF4
are also effective catalysts for this isomerization. In the case
of 5-alkynals having no 4-methoxy substituent, an intramo-
lecular addition of aldehyde to alkyne proceeded in the
presence of [Rh(P(OPh)3)2]BF4 as a catalyst to give cy-
clopent-1-enyl ketones. The substituents at the 4-positions
of 5-alkynals play important roles in the selection of two
isomerization pathways. The first catalytic endo/trans hy-
droacylation of acyclic 5-alkynals leading to monocyclic cy-
clohexenones was also developed in the presence of 24 h. Saturated aqueous NaHCO3 was added slowly to neutralize
Eur. J. Org. Chem. 2007, 5675–5685
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5681

K. Tanaka, K. Sasaki, K. Takeishi, M. Hirano
FULL PAPER
HCl and then extracted with Et2O. The combined organic extracts
were then washed with brine, dried with Na2SO4, concentrated, and
purified on a silica gel column chromatography (hexane/EtOAc,
15:1), which furnished 1a (5.2 g, 26 mmol, 48% yield) as a pale
yellow oil. 1H NMR (CDCl3, 300 MHz): δ = 9.78 (t, J = 1.5 Hz, 1
H), 3.30 (s, 3 H), 2.75–2.50 (m, 2 H), 2.21 (t, J = 6.9 Hz, 2 H),
with Na2SO4, and concentrated. Water (5 mL) and AcOH (15 mL)
were added to the residue, and the resulting mixture was stirred at
60 °C for 1 h. The reaction mixture was diluted with water and
extracted with Et2O. The organic layer was washed with saturated
aqueous Na2CO3, dried with Na2SO4, and concentrated, which af-
forded 1f (1.1 g, 4.9 mmol, 94% yield) as a pale yellow oil. 1H
2.10–1.88 (m, 2 H), 1.58–1.30 (m, 4 H), 1.39 (s, 3 H), 0.92 (t, J = NMR (CDCl3, 300 MHz): δ = 9.79 (t, J = 1.5 Hz, 1 H), 3.27 (s, 3
7.2 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 202.4, 86.7,
H), 2.70–2.48 (m, 2 H), 2.24 (t, J = 6.9 Hz, 2 H), 2.10–1.83 (m, 3
79.9, 72.8, 51.2, 39.6, 34.5, 30.7, 25.8, 21.9, 18.2, 13.5 ppm. IR H), 1.58–1.33 (m, 4 H), 1.01 (d, J = 6.9 Hz, 3 H), 0.92 (t, J =
(neat): ν = 3350, 2900, 1720, 1080 cm–1. HRMS: (EI) calcd. for
7.2 Hz, 3 H), 0.92 (d, J = 6.9 Hz, 3 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 202.7, 88.4, 79.5, 51.2, 39.2, 33.9, 30.9, 27.2, 22.0,
˜
C12H20O2: 196.1463; found: 196.1426 [M]+.
18.3, 18.0, 16.6, 13.7 ppm. IR (neat): ν = 2900, 1690, 1070 cm–1.
˜
Alkynal 1b: The title compound was prepared from phenylacetylene
by the procedure for 1a. Pale yellow oil. 1H NMR (CDCl3,
300 MHz): δ = 9.83 (t, J = 1.5 Hz, 1 H), 7.45–7.37 (m, 2 H), 7.48–
7.28 (m, 3 H), 3.40 (s, 3 H), 2.82–2.59 (m, 2 H), 2.12 (dt, J = 7.5,
1.5 Hz, 2 H), 1.52 (s, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ =
202.3, 131.7, 128.5, 128.3, 122.4, 89.1, 86.2, 73.2, 51.6, 39.5, 34.4,
HRMS (EI): calcd. for C10H15O2: 167.1071; found: 167.1030 [M –
C4H9]+.
Alkynal 1e: The title compound was prepared from 1-(1,3-dioxolan-
2-yl)hexan-3-one[21] by the procedure for 1f. 1-(1,3-Dioxolan-2-yl)-
hexan-3-one was prepared from 2-(2-bromoethyl)-1,3-dioxolane
and butyryl chloride by the procedure for 1f. Pale yellow oil. 1H
NMR (CDCl3, 300 MHz): δ = 9.78 (t, J = 1.8 Hz, 1 H), 3.28 (s, 3
H), 2.71–2.45 (m, 2 H), 2.22 (t, J = 6.9 Hz, 2 H), 1.96 (t, J =
7.2 Hz, 2 H), 1.72–1.30 (m, 8 H), 0.93 (t, J = 7.2 Hz, 3 H), 0.92 (t,
J = 6.6 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 202.6,
87.7, 79.5, 75.9, 51.1, 40.5, 39.4, 31.3, 30.8, 21.9, 18.3, 17.3, 14.3,
25.6 ppm. IR (neat): ν = 2900, 1720, 1440, 1370, 1260, 1180, 880,
˜
760, 690 cm–1. HRMS (EI): calcd. for C14H16O2: 216.1150; found:
216.1160 [M]+.
Alkynal 1c: The title compound was prepared from 5-chloropent-
1
1-yne by the procedure for 1a. Pale yellow oil. H NMR (CDCl3,
300 MHz): δ = 9.78 (t, J = 1.8 Hz, 1 H), 3.65 (t, J = 6.6 Hz, 2 H),
3.30 (s, 3 H), 2.72–2.49 (m, 2 H), 2.42 (t, J = 6.6 Hz, 2 H), 2.09–
1.90 (m, 4 H), 1.69 (s, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ
= 202.1, 84.6, 81.2, 72.8, 51.4, 43.6, 39.5, 34.5, 31.3, 25.8, 16.1 ppm.
13.6 ppm. IR (neat): ν = 3300, 2900, 1700, 1420, 1280, 1080 cm–1.
˜
HRMS (EI): calcd. for C10H15O2: 167.1071; found: 167.1030 [M –
C4H9]+.
IR (neat): ν = 2900, 1720, 1430, 1370, 1270, 1180, 1150, 1080 cm–1.
˜
Alkynal (–)-1b: (R)-BINAP (49.8 mg, 0.080 mmol) and [Rh(cod)2]-
BF4 (32.5 mg, 0.080 mmol) were dissolved in CH2Cl2 (2.0 mL) and
the mixture was stirred at room temp. for 5 min. H2 was introduced
into the resulting solution through a Schlenk tube. After stirring at
room temp. for 1 h, the resulting solution was concentrated to dry-
ness. Alkynal 1b (173.0 mg, 0.800 mmol) was added to the residue
by using CH2Cl2 (3.5 mL). The mixture was stirred at room temp.
for 2 h. The resulting solution was concentrated and purified on
a silica gel column (hexane/EtOAc, 20:1) to give (–)-1b (57.7 mg,
0.267 mmol, 33% yield, 18% ee) as a colorless oil. [α]2D5 = –0.84 (c
= 1.615 in Et2O, 18% ee). GC: Chiraldex B-DM column, 150 °C
isothermal, retention times: 28.9 min (minor isomer) and 30.0 min
(major isomer).
HRMS (EI): calcd. for C10H14ClO2: 201.0682; found: 201.0678
[M – CH3]+.
Alkynal 1d: The title compound was prepared from (trimethylsilyl)-
acetylene by the procedure for 1a. Pale yellow oil. 1H NMR
(CDCl3, 300 MHz): δ = 9.79 (m, 1 H), 3.32 (s, 3 H), 2.75–2.50 (m,
2 H), 2.01 (dt, J = 1.8, 7.8 Hz, 2 H), 1.40 (s, 3 H), 0.19 (s, 9 H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 202.0, 105.4, 90.6, 72.9, 51.4,
39.4, 34.2, 25.5, –0.03 ppm. IR (neat): ν = 3350, 2950, 1720, 1250,
˜
1080, 840, 760 cm–1. HRMS (EI): calcd. for C10H17O2Si: 197.0998;
found: 197.0953 [M – CH3]+.
Alkynal 1f: A solution of 2-(2-bromoethyl)-1,3-dioxolane (12.5 g,
69 mmol) in THF (20 mL) was added to a stirred suspension of
magnesium (3.0 g, 69 mmol) in THF (80 mL) and the reaction mix-
ture was stirred at room temp. for 30 min. The solution was cooled
to 0 °C, CuBr powder (9.3 g, 65 mmol) was added, and the re-
sulting mixture was stirred at 5–15 °C for 20 min. After cooling to
–70 °C, a solution of isobutyryl chloride (5.8 mL, 55 mmol) in THF
(100 mL) was added over 15 min, and the reaction mixture was
stirred at –70 °C for an additional 1 h. The reaction mixture was
warmed to room temp. and stirred at room temp. for 18 h. The
mixture was poured into an ice-cold solution of aqueous HCl (2 ,
200 mL) and was extracted with Et2O (3ϫ 100 mL). The combined
organic layers were dried with Na2SO4, concentrated, and purified
on a silica gel column (hexane/EtOAc, 5:1) to give 1-(1,3-dioxolan-
2-yl)-4-methylpentan-3-one (3.0 g, 17.6 mmol, 32% yield) as a pale
yellow oil.
Aldehyde 5: The Grignard reagent prepared from bromobenzene
(7.41 g, 47.2 mmol) and Mg (1.30 g, 52.0 mmol) in THF (15 mL)
was added dropwise at room temp. to a solution of 1,1-dimeth-
oxybutan-3-one (4.00 g, 30.3 mmol) in THF (30 mL), and the re-
sulting mixture was stirred at room temp. for 1 h. MeI (9.4 mL,
152 mmol) and DMSO (91 mL) were added, and the resulting mix-
ture was stirred at 80 °C for 1 h. The reaction was quenched with
saturated aqueous NH4Cl and extracted with Et2O. The organic
layer was washed with brine, dried with Na2SO4, and concentrated.
Water (30 mL) and AcOH (88 mL) were added to the residue, and
the resulting mixture was stirred at 80 °C for 0.5 h. The reaction
mixture was diluted with water and extracted with Et2O. The or-
ganic layer was washed with saturated aqueous Na2CO3, dried with
Na2SO4, and concentrated, which afforded the crude aldehyde
(4.6 g).
nBuLi (1.58  in n-hexane, 8.4 mL, 13 mmol) was added at 0 °C to
a solution of hex-1-yne (2.0 mL, 16.5 mmol) in THF (45 mL), and
the resulting solution was stirred at 0 °C for 0.5 h. A solution of 1-
(1,3-dioxolan-2-yl)-4-methylpentan-3-one (1.9 g, 11 mmol) in THF
(10 mL) was added at 0 °C, and the mixture was stirred at room
temp. for 0.5 h. MeI (3.4 mL, 55 mmol) and DMSO (34 mL) were
added, and the resulting mixture was stirred at 80 °C for 1 h. The
reaction mixture was then diluted with water and extracted with
Et2O. The organic layer was washed with water and brine, dried
A lithium diisopropylamide solution consisting of nBuLi (1.58  in
hexane, 30.9 mL, 48.8 mmol) and diisopropylamine (7.3 mL,
51 mmol) in THF (56 mL) was added to a cooled (–10 °C) suspen-
sion of (methoxymethyl)triphenylphosphonium chloride (17.6 g,
51.4 mmol) in THF (56 mL). A solution of the crude aldehyde
(4.6 g) in THF (56 mL) was added to the deep red solution. The
resulting solution was kept at –10 °C for 1 h and then diluted with
saturated aqueous NaHCO3. After extraction with Et2O, the or-
5682
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5675–5685

Rhodium(I)-Catalyzed 5-Alkynal Isomerizations
ganic layer was dried with Na2SO4 and concentrated to afford the
crude enol ether. A solution of the crude enol ether in THF
(206 mL) was treated with aqueous HCl (10%, 47 mL) at room
temp. for 3 h. Saturated aqueous NaHCO3 was added slowly to
neutralize the acid, and the system was extracted with Et2O. The
organic layer was washed with brine, dried with Na2SO4, concen-
trated, and purified on a silica gel column (hexane/EtOAc, 10:1),
which furnished 5 (0.93 g, 4.7 mmol, 16% yield) as a pale yellow
oil. 1H NMR (CDCl3, 300 MHz): δ = 9.67 (t, J = 1.8 Hz, 1 H),
7.49–7.25 (m, 5 H), 3.11 (s, 3 H), 2.48–2.29 (m, 2 H), 2.16–1.99 (m,
2 H), 1.55 (s, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 202.0,
128.6, 127.5, 126.2, 125.8, 65.8, 55.3, 50.4, 23.8, 15.2 ppm. IR
solved in CH2Cl2 (1.0 mL) and the mixture was stirred at room
temp. for 5 min. Alkynal 1a (58.9 mg, 0.300 mmol) was added to
the mixture in CH2Cl2 (1.0 mL) and stirred at room temp. for 14 h.
The resulting solution was concentrated and purified by silica gel
preparative TLC (hexane/EtOAc, 5:1) to give 3a (37.6 mg,
0.192 mmol, 64% yield) as a colorless oil.
1
Ketone 3a: Yield 77% (76 mg). H NMR (CDCl3, 300 MHz): δ =
3.98 (tt, J = 1.8, 6.3 Hz, 1 H), 3.36 (s, 3 H), 2.61 (t, J = 7.2 Hz, 2
H), 2.22 (dt, J = 1.8, 6.9 Hz, 2 H), 2.16 (s, 3 H), 2.00–1.90 (m, 2
H), 1.56–1.30 (m, 4 H), 0.92 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 208.2, 86.8, 77.9, 70.1, 56.1, 39.0, 30.6, 29.9,
29.6, 21.8, 18.2, 13.4 ppm. IR (neat): ν = 2920, 1700, 1340,
˜
(neat): ν = 3424, 2978, 2934, 1720, 1660, 1494, 1446, 1122, 1073,
˜
1100 cm–1. HRMS (EI): calcd. for C8H13O: 125.0966; found:
765, 701, 472 cm–1. HRMS (EI): calcd. for C9H11O: 135.0810;
125.0926 [M – CH2CH2COMe]+.
found: 135.0796 [M – CH2CH2CHO]+.
1
Ketone 3b: Yield 71% (71 mg). Pale yellow oil. H NMR (CDCl3,
Alkynal [D]-1g: The title compound was prepared from 4-methoxy-
dodec-5-ynal (1g)[21] by following the procedure for the synthesis of
1-deuterio-4-methyldec-5-ynal ([D]-1h).[7] Colorless oil. 1H NMR
(CDCl3, 300 MHz): δ = 4.01 (tt, J = 6.0, 1.8 Hz, 1 H), 3.37 (s, 3
H), 2.61 (t, J = 6.6 Hz, 2 H), 2.22 (dt, J = 7.2, 1.8 Hz, 2 H), 2.03
(q, J = 7.2 Hz, 2 H), 1.57–1.44 (m, 2 H), 1.44–1.21 (m, 6 H), 0.89
(t, J = 6.9 Hz, 3 H) ppm. 2H NMR (CHCl3, 61 MHz): δ = 9.81
(s) ppm.
300 MHz): δ = 7.47–7.41 (m, 2 H), 7.34–7.29 (m, 3 H), 4.24 (t, J
= 6.0 Hz, 1 H), 3.45 (s, 3 H), 2.70 (t, J = 7.5 Hz, 2 H), 2.18 (s, 3
H), 2.12–2.04 (m, 2 H) ppm. 13C NMR (CDCl3, 75 MHz): δ =
208.2, 131.6, 128.4, 128.2, 122.4, 87.1, 86.2, 70.4, 56.5, 38.9, 30.0,
29.4 ppm. IR (neat): ν = 2900, 1700, 1340, 1160, 1100, 960, 760,
˜
700 cm–1. HRMS (EI): calcd. for C14H16O2: 216.1150; found:
216.1072 [M]+.
1
Alkynal [D]-1a: The title compound was prepared from 4-methoxy-
4-methyldec-5-ynal (1a) by following the procedure for the synthe-
sis of 1-deuterio-4-methyldec-5-ynal ([D]-1h).[7] Colorless oil. 1H
NMR (CDCl3, 300 MHz): δ = 3.30 (s, 3 H), 2.75–2.50 (m, 2 H),
2.21 (t, J = 6.9 Hz, 2 H), 2.10–1.88 (m, 2 H), 1.58–1.41 (m, 4 H),
1.39 (s, 3 H), 0.92 (t, J = 7.2 Hz, 3 H) ppm. 2H NMR (CHCl3,
61 MHz): δ = 9.81 (s) ppm.
Ketone 3c: Yield 74% (80 mg). Pale yellow oil. H NMR (CDCl3,
300 MHz): δ = 3.99 (tt, J = 1.8 and 6.1 Hz, 1 H), 3.66 (t, J =
6.2 Hz, 2 H), 3.37 (s, 3 H), 2.61 (t, J = 7.2 Hz, 2 H), 2.44 (dt, J =
1.8, 7.0 Hz, 2 H), 2.17 (s, 3 H), 2.05–1.85 (m, 4 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 208.2, 84.7, 79.2, 70.1, 56.3, 43.6, 39.0, 31.2,
30.0, 29.5, 16.1 ppm. IR (neat): ν = 2900, 1700, 1340, 1100 cm–1.
˜
HRMS (EI): calcd. for C11H17ClO2: 216.0917; found: 216.0860
[M]+.
Alkynal 1i: The title compound was prepared from oct-1-yne and
hept-2-enal by following the procedure for the synthesis of 4-
methyldec-5-ynal (1h).[7] Colorless oil. 1H NMR (CDCl3,
300 MHz): δ = 9.81 (t, J = 1.8 Hz, 1 H), 2.72–2.49 (m, 2 H), 2.39–
2.26 (m, 1 H), 2.15 (dt, J = 7.2, 1.8 Hz, 2 H), 1.88–1.74 (m, 1 H),
1.71–1.58 (m, 1 H), 1.54–1.29 (m, 14 H), 0.90 (t, J = 7.2 Hz, 3 H),
0.89 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ =
202.5, 82.6, 82.3 42.1, 35.2, 31.31, 31.29, 29.6, 29.0, 28.5, 27.7, 22.6,
Ketone 3d: Yield 24% (25 mg). Colorless oil. 1H NMR (CDCl3,
300 MHz): δ = 3.98 (t, J = 6.3 Hz, 1 H), 3.37 (s, 3 H), 2.61 (t, J =
6.3 Hz, 2 H), 2.15 (s, 3 H), 1.96 (q, J = 6.3 Hz, 2 H), 0.17 (s, 9
H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 208.1, 103.6, 91.1, 70.4,
56.4, 38.9, 30.0, 29.2, 0.1 ppm. IR (neat): ν = 2900, 1700, 1340,
˜
1240, 1090, 840, 760 cm–1. HRMS (EI): calcd. for C10H17O2Si:
197.0998; found: 197.0939 [M – CH3]+.
22.5, 18.7, 14.0 ppm. IR (neat): ν = 2900, 2860, 2720, 1720, 1440,
˜
Ketone 3e: Yield 43% (48 mg). Colorless oil. 1H NMR (CDCl3,
300 MHz): δ = 3.98 (tt, J = 1.8 and 6.3 Hz, 1 H), 3.36 (s, 3 H),
2.58 (t, J = 7.5 Hz, 2 H), 2.40 (t, J = 7.2 Hz, 2 H), 2.22 (dt, J =
1.8, 6.9 Hz, 2 H), 1.95 (q, J = 7.5 Hz, 2 H), 1.61 (sextet, J = 7.2 Hz,
2 H), 1.53–1.32 (m, 4 H), 0.91 (t, J = 7.2 Hz, 6 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 210.5, 86.9, 78.0, 70.3, 56.1, 44.8, 38.0, 30.7,
1380 cm–1. HRMS (EI): calcd. for C16H28O: 236.2140; found:
236.2124 [M]+.
Representative Procedure for Isomerization of Alkynals: (Using Rh
catalyst: Table 2, Entry 1): (PhO)3P (31.0 mg, 0.10 mmol) and
[Rh(cod)2]BF4 (20.3 mg, 0.050 mmol) were dissolved in CH2Cl2
(2.0 mL) and the mixture was stirred at room temp. for 0.5 h. H2
was introduced into the resulting solution through a Schlenk tube.
After stirring at room temp. for 1 h, the resulting solution was con-
centrated to dryness. Alkynal 1a (98.1 mg, 0.500 mmol) was added
to the residue in CH2Cl2 (2.0 mL). The mixture was stirred at room
temp. for 16 h. The resulting solution was concentrated and puri-
fied by silica gel preparative TLC (hexane/EtOAc, 5:1) to give 3a
(75.5 mg, 0.385 mmol, 77% yield) as a colorless oil.
29.6, 21.8, 18.3, 17.2, 13.7, 13.5 ppm. IR (neat): ν = 2900, 1700,
˜
1320, 1100 cm–1. HRMS (EI): calcd. for C14H24O2: 224.1776;
found: 224.1721 [M]+.
1
Ketone 3f: Yield 57% (64 mg). Pale yellow oil. H NMR (CDCl3,
300 MHz): δ = 3.98 (tt, J = 1.8, 6.0 Hz, 1 H), 3.37 (s, 3 H), 2.69–
2.51 (m, 3 H), 2.23 (dt, J = 1.8, 6.9 Hz, 2 H), 2.00–1.89 (m, 2 H),
1.54–1.33 (m, 4 H), 1.10 (d, J = 7.2 Hz, 6 H), 0.91 (t, J = 7.2 Hz,
3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 214.2, 78.1, 70.4, 56.2,
40.9, 35.7, 30.7, 29.7, 21.9, 18.32, 18.25, 18.2, 13.6 ppm. IR (neat):
Representative Procedure for Isomerization of Alkynals with Cu Cat-
alyst (see Table 2, Entry 3): Cu(OTf)2 (18.1 mg, 0.050 mmol) was
dissolved in CH3CN (1.0 mL) and the mixture was stirred at room
temp. for 5 min. Alkynal 1a (98.1 mg, 0.500 mmol) was added to
the mixture in CH3CN (1.0 mL) and the system was stirred at room
temp. for 15 h. The resulting solution was concentrated and puri-
fied by silica gel preparative TLC (hexane/EtOAc, 5:1) to give 3a
(68.1 mg, 0.347 mmol, 69% yield) as a colorless oil.
ν = 2900, 1700, 1440, 1320, 1180, 1100, 1020, 960 cm–1. HRMS
˜
(EI): calcd. for C14H24O2: 224.1776; found: 224.1755 [M]+.
Cyclopentanone 2a (Scheme 3): Yield 77% (76 mg). BINAP was
used as a ligand. 1H NMR (CDCl3, 300 MHz): δ = 6.78 (t, J =
7.2 Hz, 1 H), 3.17 (s, 3 H), 2.56–1.95 (m, 5 H), 1.90–1.75 (m, 1 H),
1.50 (s, 3 H), 1.55–1.20 (m, 4 H), 0.93 (t, J = 7.2 Hz, 3 H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 205.1, 142.6, 138.2, 81.8, 50.3,
Representative Procedure for Isomerization of Alkynals with Ag Cat-
alyst (see Table 2, Entry 5): AgBF4 (5.84 mg, 0.030 mmol) was dis-
35.9, 31.1, 30.8, 27.2, 25.6, 22.5, 13.8 ppm. IR (neat): ν = 2900,
˜
Eur. J. Org. Chem. 2007, 5675–5685
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5683

K. Tanaka, K. Sasaki, K. Takeishi, M. Hirano
FULL PAPER
1720, 1640, 1500, 1440, 1220, 1180, 1080, 1040, 820, 720 cm–1.
Representative Procedure for Isomerization of Alkynals (Table 6, En-
try 1): Under Ar, PPh3 (26.2 mg, 0.10 mmol) and [Rh(cod)2]BF4
(20.3 mg, 0.050 mmol) were dissolved in CH2Cl2 (2.0 mL) and the
mixture was stirred at room temp. for 0.5 h. H2 was introduced into
the resulting solution through a Schlenk tube. After stirring at
room temp. for 1 h, the resulting solution was concentrated to dry-
ness. A CH2Cl2 (2.0 mL) solution of 1k (118.2 mg, 0.500 mmol)
was added to the residue. The mixture was stirred at room temp.
for 93 h. The resulting solution was concentrated and purified by
silica gel preparative TLC (hexane/EtOAc, 20:1) to give 4k
(63.4 mg, 0.268 mmol, 54% yield) as a colorless oil and 2k
(35.7 mg, 0.151 mmol, 30% yield) as a colorless oil.
HRMS (EI): calcd. for C12H20O2: 196.1463; found: 196.1458 [M]+.
Ketone (+)-3b: Yield 51% (24 mg). [α]2D5 = +1.44 (c = 1.615 in Et2O,
5% ee). HPLC: CHIRALCEL OD-H, hexane/iPrOH (99:1),
1.0 mLmin–1, retention times: 11.5 min (major isomer) and
12.9 min (minor isomer).
Isomerization of 5-Alkynal [D]-1g (Scheme 6): The reaction of deu-
terium labeled 5-alkynal [D]-1g was conducted according to the
procedure for 1a. The ratios of X = H/Y = H were determined by
1H NMR integration of 9.78 ppm/4.00 ppm.
Ketone [D]-3a: Yield 72% (18 mg). Colorless oil. 1H NMR (CDCl3,
300 MHz): δ = 3.36 (s, 3 H), 2.61 (t, J = 7.2 Hz, 2 H), 2.22 (t, J =
6.6 Hz, 2 H), 2.16 (s, 3 H), 1.94 (t, J = 7.2 Hz, 2 H), 1.30–1.59 (m,
Cyclohexenone 4a: Yield 30% (29 mg). Pale yellow oil. 1H NMR
(CDCl3, 300 MHz): δ = 6.48 (s, 1 H), 3.28 (s, 3 H), 2.64 (ddd, J =
11.4, 6.9, 4.8 Hz, 1 H), 2.47–2.33 (m, 1 H), 2.33–2.07 (m, 3 H),
1.95–1.82 (m, 1 H), 1.45–1.23 (m, 4 H), 1.38 (s, 3 H), 0.90 (t, J =
6.9 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 198.7, 148.0,
140.1, 73.1, 50.3, 35.1, 32.6, 30.4, 28.9, 24.0, 22.4, 13.9 ppm. IR
2
4 H), 0.91 (t, J = 6.6 Hz, 3 H) ppm. H NMR (CHCl3, 61 MHz):
δ = 3.96 (s) ppm.
1
Ketone 7h: Yield 62% (52 mg). Pale yellow oil. H NMR (CDCl3,
(neat): ν = 2850, 1660, 1420, 1350, 1050 cm–1. HRMS (EI): calcd.
300 MHz): δ = 6.69–6.63 (m, 1 H), 3.11–2.97 (m, 1 H), 2.72–2.50
(m, 3 H), 2.50–2.32 (m, 1 H), 2.21–2.04 (m, 1 H), 1.67–1.46 (m, 3
H), 1.41–1.23 (m, 2 H), 1.07 (d, J = 6.9 Hz, 3 H), 0.91 (t, J =
7.2 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 199.4, 150.0,
142.5, 38.9, 38.2, 31.9, 31.7, 26.9, 22.4, 19.6, 13.8 ppm. IR (neat):
˜
for C12H20O2: 196.1463; found: 196.1425 [M]+.
Cyclohexenone 4c: Yield 46% (45 mg). Pale yellow oil. 1H NMR
(CDCl3, 300 MHz): δ = 6.58 (s, 1 H), 3.52 (t, J = 6.6 Hz, 2 H),
3.29 (s, 3 H), 2.65 (ddd, J = 16.8, 6.6, 4.8 Hz, 1 H), 2.49–2.18 (m,
4 H), 2.00–1.80 (m, 3 H), 1.39 (s, 3 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 198.4, 149.4, 138.3, 73.0, 50.3, 44.4, 35.0, 32.7, 31.0,
ν = 2890, 1660, 1440, 1360 cm–1. HRMS (EI): calcd. for C H O:
˜
11 18
166.1358; found: 166.1393 [M]+.
1
Ketone 7i: Yield 71% (84 mg). Pale yellow oil. H NMR (CDCl3,
26.9, 23.8 ppm. IR (neat): ν = 2870, 1660, 1420, 1360, 1260, 1180,
˜
1050, 860, 720 cm–1. HRMS (EI): calcd. for C11H17ClO2: 216.0917;
found: 216.0869 [M]+.
300 MHz): δ = 6.70–6.64 (m, 1 H), 3.03–2.90 (m, 1 H), 2.69–2.31
(m, 3 H), 2.11–1.95 (m, 1 H), 1.73–1.53 (m, 4 H), 1.42–1.15 (m, 12
H), 0.88 (t, J = 6.9 Hz, 6 H) ppm. 13C NMR (CDCl3, 75 MHz): δ
= 199.6, 149.0, 142.9, 43.5, 39.3, 33.1, 32.1, 31.7, 29.7, 29.0, 28.9,
Cyclohexenone [D]-4h: Yield 25% (21 mg). Pale yellow oil. 1H
NMR (CDCl3, 300 MHz): δ = 2.62–2.24 (m, 3 H), 2.24–1.97 (m, 3
H), 1.70–1.50 (m, 1 H), 1.46–1.19 (m, 4 H), 1.13 (d, J = 7.2 Hz, 3
H), 0.90 (t, J = 6.9 Hz, 3 H) ppm.
Cyclohexenone [D]-2h: Yield 22% (18 mg). Pale yellow oil. 1H
NMR (CDCl3, 300 MHz): δ = 3.15–2.98 (m, 1 H), 2.50–2.11 (m, 4
H), 2.19–1.93 (m, 1 H), 1.78–1.62 (m, 1 H), 1.51–1.28 (m, 4 H),
1.15 (d, J = 7.1 Hz, 3 H), 0.91 (t, J = 7.1 Hz, 3 H) ppm.
24.7, 22.9, 22.5, 14.12, 14.05 ppm. IR (neat): ν = 2880, 1660, 1455,
˜
1375 cm–1. HRMS (EI): calcd. for C16H28O: 236.2140; found:
236.2119 [M]+.
1
Ketone 7j: Yield 47% (46 mg). Pale yellow oil. H NMR (CDCl3,
400 MHz): δ = 6.68–6.59 (m, 1 H), 2.77–2.67 (m, 2 H), 2.63 (t, J
= 7.6 Hz, 2 H), 2.49–2.35 (m, 1 H), 2.20–2.09 (m, 2 H), 1.65–1.54
(m, 2 H), 1.38–1.20 (m, 6 H), 1.05 (d, J = 6.8 Hz, 3 H), 0.88 (t, J
= 6.8 Hz, 3 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 199.5,
144.7, 142.0, 42.0, 38.9, 38.8, 31.8, 31.7, 29.1, 24.7, 22.6, 21.5,
Supporting Information (see also the footnote on the first page of
this article): Compound characterization data of all known com-
1
pounds (6, 7l, 7m, 4k, 2k, 4l, 2l, 4h, 2h, 10, and 12) and H NMR
14.1 ppm. IR (neat): ν = 2940, 1660, 1425, 1375 cm–1. HRMS (EI):
˜
spectra of all new compounds (1a, 1b, 1c, 1d, 1e, 1f, 1i, 2a, 3a, 3b,
3c, 3d, 3e, 3f, 4a, 4c, 5, 7h, 7i, 7j, and 7k).
calcd. for C13H22O: 194.1671; found: 194.1643 [M]+.
1
Ketone 7k: Yield 43% (51 mg). Pale yellow oil. H NMR (CDCl3,
300 MHz): δ = 6.77–6.67 (m, 1 H), 2.64 (t, J = 7.5 Hz, 2 H), 2.60–
2.49 (m, 4 H), 1.92 (quint, J = 7.5 Hz, 2 H), 1.67–1.53 (m, 2 H),
1.38–1.16 (m, 14 H), 0.88 (t, J = 6.3 Hz, 3 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 199.5, 145.7, 143.0, 39.0, 33.8, 31.8, 30.6,
29.52, 29.46, 29.42, 29.37, 29.3, 24.7, 22.7, 22.6, 14.1 ppm. IR
Acknowledgments
This work was partly supported by the Fujisawa Foundation,
Kyowa Hakko Kogyo Co., Ltd., Japan, and a Grant-in-Aid for
Scientific Research on Priority Areas from the Ministry of Educa-
tion, Culture, Sports, Science and Technology, Japan (No.
19028015, Chemistry of Concerto Catalysis).
(neat): ν = 2870, 1660, 1440, 1360 cm–1. HRMS (EI): calcd. for
˜
C16H28O: 236.2140; found: 236.2093 [M]+.
Ketone 9: Yield 19% (24 mg). Colorless oil. 1H NMR (CDCl3,
300 MHz): δ = 6.94–6.84 (m, 1 H), 2.61 (t, J = 7.2 Hz, 2 H), 2.30–
2.17 (m, 4 H), 1.71–1.50 (m, 6 H), 1.39–1.12 (m, 14 H), 0.88 (t, J
= 6.9 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 201.9, 139.4,
139.2, 37.0, 31.7, 29.6, 29.49, 29.45, 29.3, 26.0, 24.9, 23.1, 22.7,
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˜
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Ketone [D]-7h: Yield 46% (19 mg). Pale yellow oil. 1H NMR
(CDCl3, 300 MHz): δ = 3.12–2.97 (m, 1 H), 2.69–2.51 (m, 3 H),
2.49–2.35 (m, 1 H), 2.20–2.04 (m, 1 H), 1.66–1.47 (m, 3 H), 1.33
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5684
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5675–5685

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Received: June 15, 2007
Published Online: August 31, 2007
Eur. J. Org. Chem. 2007, 5675–5685
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5685