Cooperative catalytic reactions using distinct transition-metal catalysts: Ruthenium- and copper-catalyzed enantioselective propargylic alkylation

Article abstract of DOI:10.1002/chem.201103892

The enantioselective propargylic alkylation of propargylic alcohols with β-ketoesters in the presence of a thiolate-bridged diruthenium complex and a copper complex as co-catalyst affords the corresponding propargylic alkylated products in excellent yields as a mixture of two diastereoisomers with high enantioselectivity (up to 95 % enantiomeric excess (ee)). The findings reported herein not only open up a new type of enantioselective propargylic substitution reaction, but also a new aspect of cooperative catalytic reactions using distinct transition metals to realize a useful transformation that cannot be achieved by a single catalyst. Copyright

Full text of DOI:10.1002/chem.201103892

FULL PAPER
DOI: 10.1002/chem.201103892
Cooperative Catalytic Reactions Using Distinct Transition-Metal Catalysts:
Ruthenium- and Copper-Catalyzed Enantioselective Propargylic Alkylation
Masahiro Ikeda, Yoshihiro Miyake, and Yoshiaki Nishibayashi*[a]
Abstract: The enantioselective propar-
gylic alkylation of propargylic alcohols
with b-ketoesters in the presence of a
thiolate-bridged diruthenium complex
and a copper complex as co-catalyst af-
fords the corresponding propargylic al-
kylated products in excellent yields as
a mixture of two diastereoisomers with
high enantioselectivity (up to 95%
enantiomeric excess (ee)). The findings
reported herein not only open up a
new type of enantioselective propargyl-
ic substitution reaction, but also a new
aspect of cooperative catalytic reac-
tions using distinct transition metals to
realize a useful transformation that
cannot be achieved by a single catalyst.
Keywords: allenylidene · coopera-
tive reaction · copper · propargylic
substitution reaction · ruthenium
Introduction
ported by our group[5] and van Maarseveenꢀs group.[6] Un-
fortunately, however, suitable nucleophiles are quite limited.
Quite recently, we found the ruthenium-catalyzed propar-
gylic alkylation of propargylic alcohols with enamines gener-
ated in situ from aldehydes and secondary amines as
carbon-centered nucleophiles to give the corresponding
propargylic alkylated products with high enantioselectivity
(up to 99% enantiomeric excess (ee)).[7] In this reaction
system, the transition-metal catalyst (ruthenium complex)
and the organocatalyst (secondary amine) activate the prop-
argylic alcohol and the aldehyde, respectively, and coopera-
tively promote the propargylic alkylation enantioselectively.
To realize a novel type of enantioselective propargylic al-
kylation, we decided to introduce another type of coopera-
tive catalytic reaction using distinct transition-metal cata-
lysts.[1,8] Surprisingly, cooperative catalytic reactions of nu-
cleophilic and electrophilic intermediates activated only by
distinct transition metals[8] are extremely rare, being even
less well explored than cooperative catalytic reactions using
a transition-metal catalyst and an organocatalyst.[2] In coop-
erative catalytic reactions, unexpected interactions, such as
redox processes between the respective transition-metal cat-
alysts as well as undesirable side reactions, need to be avoid-
ed so as to favor the target reactions. To avoid such difficul-
ties, compatibility between the respective catalysts first
needs to be established.
We have now found that ruthenium- and copper-catalyzed
propargylic alkylation of propargylic alcohols with b-ke-
toesters affords the corresponding propargylic alkylated
products in high yields with excellent enantioselectivities. In
the present reaction system, the transition-metal catalysts
(ruthenium and copper complexes) activate propargylic al-
cohols and b-ketoesters, respectively, thereby cooperatively
promoting the propargylic alkylation enantioselectively
(Scheme 1). In fact, we have delineated the precise roles of
the ruthenium–allenylidene complex and the b-ketoester ac-
tivated by the copper complex as key reactive intermediates.
In the field of organic chemistry, more efficient and valuable
synthetic methodologies for the highly enantioselective con-
struction of carbon-carbon bonds are still required because
of strong demands for operationally simple and environmen-
tally friendly reaction conditions to synthesize useful com-
pounds. Recently, the combination of distinct catalysts for
dual activation of distinct reacting partners[1,2] has emerged
as a new strategy for developing novel and valuable reac-
tions that are difficult or impossible by the use of single cat-
alysts. Moreover, the generation of byproducts is minimized
in these reaction systems because they do not require a stoi-
chiometric amount of activating reagent to activate the sub-
strates. However, as yet there have only been a few success-
ful examples because there is the potential for a multitude
of side reactions and different catalysts can mutually inter-
fere in each reaction step.
In sharp contrast to allylic substitution reactions catalyzed
by transition-metal complexes,[3] much less attention has
been paid to the corresponding propargylic substitution re-
actions, presumably because of their difficulty. To the best
of our knowledge, only two reaction systems have hitherto
been reported that enable the successful accomplishment of
enantioselective propargylic substitution reactions. One is
the ruthenium-catalyzed enantioselective propargylic substi-
tution reaction reported by our group.[4] The other is the
copper-catalyzed enantioselective propargylic amination re-
[a] M. Ikeda, Dr. Y. Miyake, Prof. Dr. Y. Nishibayashi
Institute of Engineering Innovation
School of Engineering, The University of Tokyo
Yayoi, Bunkyo-ku, Tokyo, 113-8656 (Japan)
Fax : (+81)3-5841-1175
E-mail: ynishiba@sogo.t.u-tokyo.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201103892.
Chem. Eur. J. 2012, 18, 3321 – 3328
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3321

Table 1. Enantioselective propargylic alkylation of 1-(1-naphthyl)-2-
propyn-1-ol (1a) with b-ketoester 2a.[a]
Entry
2a
[equiv]
4
T
[8C]
t
Yield
of 5a
[%][b]
anti/syn
ratio of
5a[c]
ee of
G
[h]
anti-5a
[%][d]
1
2
3
4
5
6
3.0
3.0
3.0
3.0
1.5
1.5
4a
4b
4c
4d
4a
4a
RT
RT
RT
RT
RT
À10
120
120
120
120
120
45
96
93
50
79
94
94
4:1
4:1
3:1
1:1
4:1
7:1
86
84[e]
10
54
86
93
Scheme 1. Cooperative catalytic reactions using distinct transition-metal
catalysts.
[a] All reactions of 1a (0.20 mmol) with 2a (0.30 mmol) were carried out
in the presence of 3a (0.010 mmol), Cu(OTf)2 (0.020 mmol), 4
(0.024 mmol), and NH4BF4 (0.020 mmol) in THF (4 mL). [b] Isolated
yield. [c] Determined by 1H NMR spectroscopy. [d] Determined by
HPLC. [e] The opposite absolute configuration (2S,3S) was found.
G
Enolates generated in situ from copper complexes[9,10] and
b-ketoesters have been used as carbon-centered nucleo-
philes, but successful examples have been limited to enantio-
selective addition reactions to carbonyls and related com-
pounds. Our findings reported herein constitute the first ap-
plication of these enolates to asymmetric substitution reac-
tions such as benzylic, allylic, and propargylic substitution
reactions. We believe that the method described in this arti-
cle represents a new type of enantioselective dual catalytic
reaction using a pair of distinct transition-metal catalysts.[1,8]
Our preliminary results are described herein.
plex with 4a as the co-catalysts. Typical results are shown in
Table 2. Similarly high enantioselectivity was observed when
1-(2-naphthyl)-2-propyn-1-ol (1b) was used as the substrate
(Table 2, entry 2). However, the enantioselectivity decreased
slightly when 1-phenyl-2-propyn-1-ol (1c) was used as the
substrate (Table 2, entry 3). Introduction of a methoxy or
methyl group at the para-position of a benzene ring on the
propargylic alcohol had little effect on the reactivity or the
Results and Discussion
Treatment of 1-(1-naphthyl)-2-propyn-1-ol (1a) with three
equivalents of ethyl 3-oxo-3-phenylpropanoate (2a) in the
presence of catalytic amounts of thiolate-bridged dirutheni-
um complex [Cp*RuCl
complex of Cu(OTf)2 with (4R,4’R,5S,5’S)-2,2’-(cyclopro-
pane-1,1-diyl)-bis(4,5-diphenyl-4,5-dihydrooxazole) (4a),
(m2-SiPr)]2 (Cp*=h5-C5Me5; 3a), a
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
Table 2. Enantioselective propargylic alkylations of propargylic alcohols
(1) with b-ketoester 2a.[a]
and NH4BF4 in THF at room temperature for 120 h gave
ethyl 2-benzoyl-3-(naphthalen-1-yl)-4-pentynoate (5a) in
96% isolated yield as a mixture of two diastereoisomers
(anti-5a/syn-5a=4:1) with 86% ee of anti-5a (Table 1,
entry 1). Other bis(oxazoline) ligands such as 4b worked ef-
fectively, but substantially lower diastereo- and enantioselec-
tivities were observed when 4c or 4d were used as bis(oxa-
zoline) ligands (Table 1, entries 2–4).[11] The use of only
1.5 equivalents of 2a with respect to 1a was sufficient to
promote the propargylic alkylation (Table 1, entry 5). The
reaction proceeded smoothly even at À108C, higher diaster-
eo- and enantioselectivities being observed (Table 1,
entry 6). Separately, we confirmed that the use of either 3a
or the copper complex alone did not promote the propargyl-
ic alkylation. These results indicated that 3a and the copper
complex acted cooperatively as catalysts to promote the cat-
alytic reaction enantioselectively.
Entry
1
Yield of
anti-5/
syn-5[c]
ee of
5[b] [%]
anti-5 [%][d]
1
2
3
4
5
6
7
8
9
R=1-naphthyl (1a)
R=2-naphthyl (1b)
R=Ph (1c)
R=p-MeOC6H4 (1d)
R=p-MeC6H4 (1e)
R=p-PhC6H4 (1 f)
R=o-MeOC6H4 (1g)
R=o-MeC6H4 (1h)
R=o,p-(MeO)2C6H3 (1i)
94 (5a)
90 (5b)
93 (5c)
91 (5d)
87 (5e)
89 (5 f)
98 (5g)
97 (5h)
92 (5i)
7:1
6:1
4:1
3:1
3:1
2:1
15:1
7:1
4:1
93
95
83
81
86
93
93
90
85
[a] All reactions of 1 (0.20 mmol) with 2a (0.30 mmol) were carried out
in the presence of 3a (0.010 mmol), Cu(OTf)2 (0.020 mmol), 4a
AHCTUNGTRENNUNG
(0.024 mmol), and NH4BF4 (0.020 mmol) at À108C in THF (4 mL) for
1
Next, propargylic alkylations of a variety of propargylic
alcohols were carried out by using 3a and the copper com-
45 h. [b] Isolated yield. [c] Determined by H NMR spectroscopy. [d] De-
termined by HPLC.
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Chem. Eur. J. 2012, 18, 3321 – 3328

Propargylic Alkylation by Cooperative Dual Catalysis by Ru and Cu Complexes
FULL PAPER
enantioselectivity for the propargylic alkylated products
(Table 2, entries 4 and 5), but higher enantioselectivity was
observed when a phenyl group was introduced at the para-
position of a benzene ring on the propargylic alcohol
(Table 2, entry 6). Interestingly, the introduction of a me-
thoxy or methyl group at the ortho-position of a benzene
ring on the propargylic alcohol substantially increased the
enantioselectivity (Table 2, entries 7–9). No reaction oc-
curred at all under the same conditions when 1-cyclohexyl-
2-propyn-1-ol was used as the substrate, indicating that the
presence of an aryl moiety at the propargylic position of 1 is
necessary to achieve the reaction.
ACHTUNGRTEN(NNUG OTf)2 with 2.4 equivalents of 4a together with 2 equivalents
of 1g in THF at À108C for 45 h gave 5a in 53% isolated
yield, based on 6, as a mixture of two diastereoisomers
(anti-5a/syn-5a=5:1; anti-5a (90% ee)), together with 5g in
62% isolated yield based on 1g, as shown in Scheme 2.[13]
Propargylic alkylations with other b-ketoesters also pro-
ceeded smoothly to give the corresponding propargylic alky-
lated products with high enantioselectivities. Typical results
are shown in Table 3. Reactions of 1a with benzyl 3-oxo-3-
phenylpropanoate (2b), methyl 3-oxo-3-phenylpropanoate
(2c), and ethyl 3-(4-methoxyphenyl)-3-oxopropanoate (2d)
under the same reaction conditions gave the corresponding
alkylated products with similar high enantioselectivities
(Table 3, entries 1–3). When other b-ketoesters such as ethyl
3-(naphthalen-1-yl)-3-oxopropanoate (2e), ethyl 3-(naphtha-
len-2-yl)-3-oxopropanoate (2 f), and ethyl 3-oxo-3-(p-tolyl)-
propanoate (2g) were used in place of 2a, the corresponding
propargylic alkylated products were obtained in similarly
high yields with high enantio- and diastereoselectivities
(Table 3, entries 4–6). The introduction of a chloro substitu-
ent at the para-position of the benzene ring appended to the
b-ketoester had little effect on the reactivity or the enantio-
selectivity for the propargylic alkylated product (Table 3,
entry 7). Reactions of other propargylic alcohols 1b and 1g,
as well as 1a, with various b-ketoesters also gave similarly
good results (Table 3, entries 8–10).
Scheme 2. Stoichiometric reaction of a ruthenium allenylidene complex
with a b-ketoester in the presence of a copper complex.
Furthermore, the reaction of 1a with 2a in the presence of
catalytic amounts of 6 and Cu
N
45 h afforded 5a in 86% yield as a mixture of two diastereo-
isomers (anti-5a/syn-5a=7:1; anti-5a (93% ee)). Separately,
we confirmed that no reaction at all occurred when a prop-
argylic alcohol bearing an internal alkyne moiety was sub-
jected to the same reaction conditions. Thus, these results
clearly indicated that the propargylic alkylation proceeded
via ruthenium–allenylidene complexes as key reactive inter-
mediates.[14]
A proposed reaction pathway is shown in Scheme 3. The
initial step is the formation of an allenylidene complex (B)
by the reaction of propargylic alcohol 1 with 3 via a vinyli-
dene complex (A). Subsequent attack of an enolate (E),
generated in situ from b-ketoester 2 and CuACTHNURGTNEUNG(OTf)2 bearing
We investigated the following stoichiometric and catalytic
reactions to gain insight into the reaction pathway. Treat-
ment of
4, upon the g-carbon of B results in the formation of anoth-
er vinylidene complex (D) via an alkynyl complex (C).
After transformation of the vinylidene complex D into the
corresponding p-alkyne complex, the alkylated product 5 is
formed by ligand exchange
a
ruthenium–allenylidene complex 6[12] with
4.5 equivalents of 2a in the presence of 2 equivalents of Cu-
Table 3. Enantioselective propargylic alkylations of propargylic alcohols (1) with b-ketoesters (2).[a]
with another molecule of prop-
argylic alcohol 1. As described
in our previous reports,[12] we
believe that the synergistic
effect between the two rutheni-
um atoms in the diruthenium
complex is also quite impor-
tant for promoting this catalyt-
ic reaction.
To obtain some information
on the enantioselective propar-
gylic alkylation, the stereo-
chemistry of the product 5b
was determined. After one re-
crystallization of anti-5b, enan-
tiomerically pure anti-5b was
isolated, and its absolute con-
figuration was determined as
(2R,3R) by X-ray analysis.[15]
Entry
1
2
Yield of
anti-5/
syn-5[c]
ee of
5[b] [%]
anti-5 [%][d]
1
2
3
4
5
6
7
8
9
R1 =1-naphthyl (1a)
R1 =1-naphthyl (1a)
R1 =1-naphthyl (1a)
R1 =1-naphthyl (1a)
R1 =1-naphthyl (1a)
R1 =1-naphthyl (1a)
R1 =1-naphthyl (1a)
R1 =2-naphthyl (1b)
R1 =o-MeOC6H4 (1g)
R1 =o-MeOC6H4 (1g)
R2 =Bn, R3 =Ph (2b)
95 (5j)
99 (5k)
97 (5l)
92 (5m)
96 (5n)
95 (5o)
94 (5p)
93 (5q)
98 (5r)
94 (5s)
5:1
4:1
6:1
12:1
10:1
10:1
3:1
6:1
7:1
6:1
91
86
89
90
92
94
86
92
91
92
R2 =Me, R3 =Ph (2c)
R2 =Et, R3 =p-MeOC6H4 (2d)
R2 =Et, R3 =1-naphthyl (2e)
R2 =Et, R3 =2-naphthyl (2 f)
R2 =Et, R3 =p-MeC6H4 (2g)
R2 =Et, R3 =p-ClC6H4 (2h)
R2 =Et, R3 =2-naphthyl (2 f)
R2 =Bn, R3 =Ph (2b)
10
R2 =Et, R3 =p-ClC6H4 (2h)
[a] All reactions of 1 (0.20 mmol) with 2 (0.30 mmol) were carried out in the presence of 3a (0.010 mmol), Cu-
(OTf)2 (0.020 mmol), 4a (0.024 mmol), and NH4BF4 (0.020 mmol) at À108C in THF (4 mL) for 45 h. [b] Isolat-
ed yield. [c] Determined by H NMR spectroscopy. [d] Determined by HPLC.
ACHTUNGTRENNUNG
1
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3323

Y. Nishibayashi et al.
kylated products in excellent yields as a mixture of two dia-
stereoisomers with high enantioselectivity (up to 95% ee).
This catalytic reaction is considered to represent a new type
of enantioselective propargylic substitution reaction,[17] in
which an enolate generated in situ from a copper complex
and a b-ketoester enantioselectively attacks the ruthenium–
allenylidene complex. In the present reaction system, the
transition-metal catalysts (ruthenium complex and copper
complex) activate propargylic alcohols and b-ketoesters, re-
spectively, and both catalysts act cooperatively and simulta-
neously to promote the propargylic alkylation enantioselec-
tively. We believe that the findings described herein will not
only open up a new type of enantioselective propargylic
substitution reaction, but also a new aspect of cooperative
catalytic reactions using distinct transition metals to achieve
more valuable transformations that cannot be realized by a
single catalyst. Further work is currently in progress to
apply this strategy to other reaction systems.
Scheme 3. Proposed reaction pathway for the propargylic alkylation of
propargylic alcohols with b-ketoesters.
Experimental Section
General methods: 1H NMR (270 MHz) and 13C NMR (67.8 MHz) spec-
tra were measured on a JEOL Excalibur 270 spectrometer using CDCl3
as solvent. HPLC analyses were performed on a Hitachi L-7100 appara-
tus equipped with a UV detector using 25 cmꢂ4.6 mm DAICEL Chiral-
cel OZ-H and OJ-H and Chiralpak AS-H, AD, IC, and ID columns. Ele-
mental analyses were performed at the Microanalytical Center of the
University of Tokyo. Mass spectra were measured on a JEOL JMS-700
mass spectrometer. All reactions were carried out under a dry nitrogen
atmosphere. Solvents were dried by the usual methods, then distilled
under N2 and degassed before use. Propargylic alcohols 1 were prepared
by reaction of the corresponding aldehydes with ethynylmagnesium bro-
mide (0.5m in THF). Thiolate-bridged diruthenium complexes 3 were
prepared according to our previously reported procedure.[12,18,19] Ethyl 3-
oxo-3-phenylpropanoate (2a) is a commercially available reagent. b-Ke-
toesters (2b–2h)[20] and optically pure bis(oxazoline) ligands 4[21] were
synthesized according to literature procedures.
To account for the enantioselective and diastereoselective
formation of (2R,3R)-5, we propose transition states be-
tween the ruthenium–allenylidene complex and the copper-
enolate complex as indicated in Scheme 4.[16] In this reaction
General procedure for the preparation of a propargylic alkylated product
(5) by the reaction of a propargylic alcohol (1) with a b-ketoester (2): A
typical experimental procedure for the reaction of 1-(1-naphthyl)-2-
propyn-1-ol (1a) with ethyl 3-oxo-3-phenylpropanoate (2a) was as fol-
lows. A 20 mL Schlenk flask was charged with (4R,4’R,5S,5’S)-2,2’-(cyclo-
propane-1,1-diyl)-bis(4,5-diphenyl-4,5-dihydrooxazole) (4a; 11.6 mg,
Scheme 4. Asymmetric induction of propargylic alkylation between alle-
nylidene and copper complexes.
0.024 mmol) and CuACTHNUGTRNEUNG(OTf)2 (7.2 mg, 0.020 mmol) under N2. The mixture
was stirred under vacuum for 2 h and then an atmosphere of N2 was ad-
mitted to the flask. Anhydrous THF (1.0 mL) was added and the solution
was stirred for 2 h. After cooling the reaction flask to À108C, a solution
of ethyl 3-oxo-3-phenylpropanoate (2a; 57.6 mg, 0.30 mmol) in anhy-
drous THF (3.0 mL) was added to the reaction mixture, and then
system, the distorted tetrahedral copper-enolate proposed
by Jørgensen and co-workers[10b] attacks the Si-face of the
allenylidene complex from the Re-face of the enolate, lead-
ing to carbon–carbon bond formation. We believe this to be
the first successful example of enantioselective propargyla-
tion of b-ketoesters with propargylic alcohols to give the
corresponding a-propargyl b-ketoesters with high enantiose-
lectivity.
[Cp*RuClACTHNUGTRNEG(UN m2-SiPr)]2 (3a; 6.9 mg, 0.010 mmol), NH4BF4 (2.1 mg,
0.020 mmol), and 1-(1-naphthyl)-2-propyn-1-ol (1a; 36.4 mg, 0.20 mmol)
were added successively under N2. The reaction flask was kept at À108C
for 45 h. After concentration of the reaction mixture under reduced pres-
sure, the residue was purified by column chromatography (SiO2; eluent:
hexane/ethyl acetate, 95:5 to 85:15) to give ethyl 2-benzoyl-3-(naphtha-
len-1-yl)-4-pentynoate (5a) as a colorless oil (67.1 mg, 0.188 mmol, 94%
isolated yield, anti-5a/syn-5a=7:1).
1
Data for 5a: anti-isomer: H NMR: d=8.38 (d, J=8.6 Hz, 1H), 8.08–8.11
Conclusion
(m, 2H), 7.42–7.88 (m, 9H), 5.48 (dd, J=10.5 and 2.7 Hz, 1H), 5.23 (d,
J=10.5 Hz, 1H), 3.68 (q, J=7.0 Hz, 2H), 2.18 (d, J=2.7 Hz, 1H),
0.68 ppm (t, J=7.0 Hz, 3H); syn-isomer: 1H NMR: d=8.41 (d, J=
8.6 Hz, 1H), 8.09–8.12 (m, 2H), 7.28–7.35 (m, 3H), 5.24 (d, J=10.0 Hz,
1H), 4.27 (q, J=7.0 Hz, 2H), 2.34 (d, J=2.7 Hz, 1H), 1.26 ppm (t, J=
We have found the ruthenium- and copper-catalyzed enan-
tioselective propargylic alkylation of propargylic alcohols
with b-ketoesters to give the corresponding propargylic al-
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Chem. Eur. J. 2012, 18, 3321 – 3328

Propargylic Alkylation by Cooperative Dual Catalysis by Ru and Cu Complexes
FULL PAPER
7.0 Hz, 3H); anti-isomer: 13C NMR: d=192.2, 166.6, 136.4, 134.0, 133.8,
133.6, 131.0, 128.93, 128.91, 128.7, 128.55, 126.6, 126.3, 125.8, 125.3,
123.59, 83.6, 71.9, 61.6, 59.7, 33.4, 13.6 ppm; syn-isomer: 13C NMR: d=
191.7, 167.4, 135.9, 134.1, 133.7, 130.7, 128.51, 128.49, 128.46, 126.4, 125.7,
125.2, 123.65, 83.3, 72.5, 62.0, 59.4, 33.6, 14.0 ppm; HRMS (EI): m/z:
calcd for C24H20O3 [M]: 356.1412; found: 356.1409. The optical purity of
5a was determined by HPLC analysis; DAICEL Chiralpak IC, hexane/
J=7.8 Hz, 2H), 4.82 (d, J=10.8 Hz, 1H), 4.62 (dd, J=10.8 and 2.4 Hz,
1H), 3.89 (qd, J=7.0 and 1.1 Hz, 2H), 2.33 (s, 3H), 2.13 (d, J=2.4 Hz,
1H), 0.96 ppm (t, J=7.0 Hz, 3H); syn-isomer: 1H NMR: d=7.86–7.90
(m, 2H), 7.47–7.54 (m, 1H), 7.27–7.41 (m, 4H), 7.03 (d, J=8.1 Hz, 2H),
4.83 (d, J=10.5 Hz, 1H), 4.70 (dd, J=10.5 and 2.4 Hz, 1H), 4.22 (qd, J=
7.2 and 3.2 Hz, 2H), 2.31 (d, J=2.4 Hz, 1H), 2.23 (s, 3H), 1.24 ppm (t,
J=7.2 Hz, 3H); anti-isomer: 13C NMR: d=192.2, 166.6, 137.5, 136.4,
134.7, 133.7, 129.30, 128.9, 128.72, 128.24, 83.8, 71.7, 61.6, 61.33, 36.9,
21.1, 13.7 ppm; syn-isomer: 13C NMR: d=191.7, 167.2, 137.1, 136.1, 135.1,
133.6, 129.25, 128.68, 128.6, 128.19, 83.7, 72.0, 62.0, 61.35, 36.7, 21.0,
14.0 ppm; HRMS (EI): m/z: calcd for C21H20O3 [M]: 320.1412; found:
320.1425. The optical purities of anti-5e and syn-5e were determined by
HPLC analysis; DAICEL Chiralpak IC, hexane/iPrOH=95:5, flow
iPrOH=97:3, flow rate=1.0 mLminÀ1
, l=254 nm; retention times:
17.0 min (anti-major) and 30.2 min (anti-minor), 93% ee (anti); 19.4 min
(syn-minor) and 23.9 min (syn-major), 1% ee (syn).
Ethyl 2-benzoyl-3-(naphthalen-2-yl)pent-4-ynoate (5b): Isolated yield
90% (anti-5b/syn-5b=6:1). A white solid. anti-isomer: 1H NMR: d=
8.11–8.14 (m, 2H), 7.81–7.88 (m, 4H), 7.46–7.65 (m, 6H), 4.96 (d, J=
10.5 Hz, 1H), 4.84 (dd, J=10.5 and 2.7 Hz, 1H), 3.83 (m, 2H), 2.19 (d,
J=2.7 Hz, 1H), 0.85 ppm (t, J=7.0 Hz, 3H); syn-isomer: 1H NMR: d=
7.33–7.74 (m, 6H), 4.25 (q, J=7.0 Hz, 2H), 2.37 (d, J=2.7 Hz, 1H),
1.26 ppm (t, J=7.0 Hz, 3H); anti-isomer: 13C NMR: d=192.1, 166.5,
136.4, 135.1, 133.8, 133.3, 132.8, 129.0, 128.8, 128.5, 127.87, 127.63, 127.55,
126.3, 126.1, 126.02, 83.6, 72.2, 61.7, 61.2, 37.4, 13.6 ppm; syn-isomer:
13C NMR: d=191.5, 167.2, 135.9, 135.4, 133.7, 133.2, 132.6, 128.64, 128.56,
128.41, 127.90, 127.7, 127.5, 125.99, 125.96, 83.4, 72.5, 62.0, 61.3, 37.1,
14.0 ppm; elemental analysis calcd (%) for C24H20O3: C 80.88, H 5.66;
found: C 80.87, H 5.86. The optical purities of anti-5b and syn-5b were
determined by HPLC analysis; DAICEL Chiralpak AD, hexane/iPrOH=
97:3, flow rate=0.25 mLminÀ1, l=254 nm; retention times for anti-5b:
75.3 min (minor) and 82.8 min (major), 95% ee; retention times for syn-
5b: 69.2 min (major) and 90.9 min (minor), 65% ee. Colorless needle-
shaped crystals of (2R,3R)-5b suitable for X-ray analysis were obtained
by recrystallization of 5b from methanol.
rate=1.0 mLminÀ1
, l=254 nm; retention times for anti-5e: 14.7 min
(major) and 27.1 min (minor), 86% ee; retention times for syn-5e:
12.8 min (minor) and 18.0 min (major), 43% ee.
Ethyl 3-[(1,1’-biphenyl)-4-yl]-2-benzoylpent-4-ynoate (5 f): Isolated yield
89% (anti-5 f/syn-5 f=2:1). A white solid. anti-isomer: 1H NMR: d=
8.10–8.13 (m, 2H), 7.30–7.65 (m, 12H), 4.88 (d, J=10.8 Hz, 1H), 4.72
(dd, J=10.8 and 2.7 Hz, 1H), 3.91 (q, J=7.0 Hz, 2H), 2.18 (d, J=2.7 Hz,
1H), 0.95 ppm (t, J=7.0 Hz, 3H); syn-isomer: 1H NMR: d=7.88 (m,
2H), 4.89 (d, J=10.5 Hz, 1H), 4.79 (dd, J=10.5 and 2.4 Hz, 1H), 4.24
(qd, J=7.0 and 2.7 Hz, 2H), 2.35 (d, J=2.4 Hz, 1H), 1.26 ppm (t, J=
7.0 Hz, 3H); anti-isomer: 13C NMR: d=192.1, 166.6, 140.7, 140.4, 136.8,
136.4, 133.8, 128.9, 128.78, 128.7, 127.34, 127.31, 127.04, 83.5, 72.0, 61.7,
61.2, 37.0, 13.7 ppm; syn-isomer: 13C NMR: d=191.7, 167.2, 140.6, 140.5,
137.1, 136.0, 133.7, 129.0, 128.75, 128.6, 127.4, 127.27, 126.99, 83.4, 72.3,
62.0, 61.3, 36.7, 14.0 ppm; elemental analysis calcd (%) for C26H22O3: C
81.65, H 5.80; found: C 81.56, H 5.95. The optical purities of anti-5 f and
syn-5 f were determined by HPLC analysis; DAICEL Chiralcel OJ-H,
Ethyl 2-benzoyl-3-phenylpent-4-ynoate (5c): Isolated yield 93% (anti-5c/
syn-5c=4:1). A colorless oil. anti-isomer: 1H NMR: d=8.08–8.11 (m,
2H), 7.32–7.64 (m, 8H), 4.84 (d, J=10.5 Hz, 1H), 4.66 (dd, J=10.5 and
2.4 Hz, 1H), 3.88 (q, J=7.0 Hz, 2H), 2.15 (d, J=2.4 Hz, 1H), 0.93 ppm
(t, J=7.0 Hz, 3H); syn-isomer: 1H NMR: d=7.84–7.88 (m, 2H), 7.14–
7.41 (m, 8H), 4.85 (d, J=10.5 Hz, 1H), 4.73 (dd, J=10.5 and 2.4 Hz,
1H), 4.22 (qd, J=7.0 and 2.4 Hz, 2H), 2.32 (d, J=2.4 Hz, 1H), 1.25 ppm
(t, J=7.0 Hz, 3H); anti-isomer: 13C NMR: d=192.1, 166.5, 137.7, 136.3,
133.8, 128.9, 128.7, 128.6, 128.4, 127.7, 83.6, 71.9, 61.6, 61.3, 37.2,
13.6 ppm; syn-isomer: 13C NMR: d=191.7, 167.1, 138.0, 136.0, 133.6,
128.55, 128.52, 128.3, 127.5, 83.4, 72.2, 61.9, 61.2, 37.1, 14.0 ppm; HRMS
(EI): m/z: calcd for C20H18O3 [M]: 306.1256; found: 306.1252. The optical
purities of anti-5c and syn-5c were determined by HPLC analysis;
hexane/iPrOH=97:3, flow rate=1.0 mLminÀ1
, l=254 nm; retention
times for anti-5 f: 68.1 min (minor) and 92.1 min (major), 93% ee; reten-
tion times for syn-5 f: 46.6 min (minor) and 53.2 min (major), 71% ee.
Ethyl 2-benzoyl-3-(2-methoxyphenyl)pent-4-ynoate (5g): Isolated yield
98% (anti-5g/syn-5g=15:1). A colorless oil. anti-isomer: 1H NMR: d=
8.01–8.06 (m, 2H), 7.53–7.61 (m, 1H), 7.39–7.51 (m, 3H), 7.21–7.28 (m,
1H), 6.88–6.94 (m, 2H), 5.16 (d, J=9.7 Hz, 1H), 4.95 (dd, J=9.7 and
2.7 Hz, 1H), 3.86–3.97 (m, 2H), 3.91 (s, 3H), 2.09 (d, J=2.7 Hz, 1H),
0.95 ppm (t, J=7.0 Hz, 3H); syn-isomer: 1H NMR: d=7.90–7.93 (m,
2H), 7.14–7.18 (m, 1H), 5.08 (d, J=8.6 Hz, 1H), 4.91 (dd, J=8.6 and
2.4 Hz, 1H), 4.14–4.21 (m, 2H), 3.82 (s, 3H), 2.27 (d, J=2.4 Hz, 1H),
1.19 ppm (t, J=7.0 Hz, 3H); anti-isomer: 13C NMR: d=192.8, 167.2,
157.1, 136.7, 133.5, 130.2, 129.0, 128.8, 128.6, 125.7, 120.8, 111.2, 83.3,
70.7, 61.4, 57.7, 55.7, 32.4, 13.7 ppm; syn-isomer: 13C NMR: d=192.9,
167.7, 156.5, 136.2, 133.4, 130.0, 128.54, 128.51, 120.7, 110.8, 71.5, 61.5,
57.8, 55.4, 14.0 ppm; HRMS (EI): m/z: calcd for C21H20O4 [M]: 336.1362;
found: 336.1359. The optical purities of anti-5g and syn-5g were deter-
mined by HPLC analysis; DAICEL Chiralpak IC, hexane/iPrOH=97:3,
flow rate=1.0 mLminÀ1, l=254 nm; retention times for anti-5g: 46.9 min
(major) and 82.7 min (minor), 93% ee; retention times for syn-5g:
57.8 min (major) and 73.1 min (minor), 44% ee.
DAICEL Chiralpak IC, hexane/iPrOH=97:3, flow rate=0.5 mLminÀ1
,
l=254 nm; retention times for anti-5c: 31.6 min (major) and 60.0 min
(minor), 83% ee; retention times for syn-5c: 27.5 min (minor) and
44.7 min (major), 55% ee.
Ethyl 2-benzoyl-3-(4-methoxyphenyl)pent-4-ynoate (5d): Isolated yield
91% (anti-5d/syn-5d=3:1). A colorless oil. anti-isomer: 1H NMR: d=
8.08–8.12 (m, 2H), 7.59–7.64 (m, 1H), 7.50–7.54 (m, 2H), 7.34–7.39 (m,
2H), 6.86–6.90 (m, 2H), 4.805 (d, J=10.8 Hz, 1H), 4.62 (dd, J=10.8 and
2.4 Hz, 1H), 3.90 (qd, J=7.0 and 1.4 Hz, 2H), 3.80 (s, 3H), 2.14 (d, J=
1
2.4 Hz, 1H), 0.97 ppm (t, J=7.0 Hz, 3H); syn-isomer: H NMR: d=7.86–
Ethyl 2-benzoyl-3-(o-tolyl)pent-4-ynoate (5h): Isolated yield 97% (anti-
5h/syn-5h=7:1). A colorless oil. anti-isomer: 1H NMR: d=8.12–8.16 (m,
2H), 7.44–7.65 (m, 4H), 7.15–7.24 (m, 3H), 5.05 (d, J=10.8 Hz, 1H),
4.91 (dd, J=10.8 and 2.4 Hz, 1H), 3.84 (q, J=7.0 Hz, 2H), 2.51 (s, 3H),
2.07 (d, J=2.4 Hz, 1H), 0.86 ppm (t, J=7.0 Hz, 3H); syn-isomer:
1H NMR: d=7.86–7.91 (m, 2H), 7.37–7.55 (m, 3H), 7.26–7.29 (m, 1H),
7.02–7.06 (m, 3H), 5.06 (d, J=10.8 Hz, 1H), 4.89 (dd, J=10.8 and
2.4 Hz, 1H), 4.24 (q, J=7.0 Hz, 2H), 2.52 (s, 3H), 2.25 (d, J=2.4 Hz,
1H), 1.25 ppm (t, J=7.0 Hz, 3H); anti-isomer: 13C NMR: d=192.2,
166.5, 136.4, 136.30, 136.0, 133.8, 130.9, 129.0, 128.7, 128.0, 127.6, 126.34,
83.7, 71.1, 61.6, 59.68, 33.1, 19.7, 13.5 ppm; syn-isomer: 13C NMR: d=
191.7, 167.4, 136.34, 136.2, 136.1, 133.6, 128.60, 128.58, 127.3, 127.1,
126.29, 83.5, 71.5, 62.0, 59.72, 33.0, 14.0 ppm; HRMS (EI): m/z: calcd for
C21H20O3 [M]: 320.1412; found: 320.1424. The optical purities of anti-5h
and syn-5h were determined by HPLC analysis; DAICEL Chiralpak IC,
7.89 (m, 2H), 7.47–7.54 (m, 1H), 7.30–7.41 (m, 4H), 6.73–6.76 (m, 2H),
4.812 (d, J=10.5 Hz, 1H), 4.69 (dd, J=10.5 and 2.4 Hz, 1H), 4.22 (qd,
J=7.0 and 2.4 Hz, 2H), 3.71 (s, 3H), 2.32 (d, J=2.4 Hz, 1H), 1.24 ppm
(t, J=7.0 Hz, 3H); anti-isomer: 13C NMR: d=192.2, 166.6, 159.1, 136.4,
133.8, 129.7, 129.49, 128.9, 128.72, 114.0, 83.9, 71.7, 61.6, 61.5, 55.3, 36.5,
13.7 ppm; syn-isomer: 13C NMR: d=191.8, 167.2, 158.8, 136.1, 133.6,
130.1, 129.45, 128.65, 128.6, 113.9, 83.7, 72.0, 61.9, 55.2, 36.3, 14.0 ppm;
HRMS (EI): m/z: calcd for C21H20O4 [M]: 336.1362; found: 336.1353. The
optical purities of anti-5d and syn-5d were determined by HPLC analy-
sis; DAICEL Chiralpak IC, hexane/iPrOH=97:3, flow rate=
1.0 mLminÀ1, l=254 nm; retention times for anti-5d: 29.6 min (major)
and 49.6 min (minor), 81% ee; retention times for syn-5d: 24.2 min
(minor) and 32.8 min (major), 59% ee.
Ethyl 2-benzoyl-3-(p-tolyl)pent-4-ynoate (5e): Isolated yield 87% (anti-
5e/syn-5e=3:1). A colorless oil. anti-isomer: 1H NMR: d=8.08–8.11 (m,
2H), 7.58–7.64 (m, 1H), 7.50–7.53 (m, 2H), 7.32–7.35 (m, 2H), 7.14 (d,
hexane/iPrOH=98:2, flow rate=0.5 mLminÀ1
,
l=254 nm; retention
Chem. Eur. J. 2012, 18, 3321 – 3328
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
3325

Y. Nishibayashi et al.
times for anti-5h: 21.8 min (major) and 27.1 min (minor), 90% ee; reten-
tion times for syn-5h: 20.3 min (major) and 32.3 min (minor), 3% ee.
59.0, 55.4, 33.6, 14.1 ppm; HRMS (EI): m/z: calcd for C25H22O4 [M]:
386.1518; found: 386.1523. The optical purities of anti-5l and syn-5l were
determined by HPLC analysis; DAICEL Chiralpak IC, hexane/iPrOH=
90:10, flow rate=0.5 mLminÀ1, l=254 nm; retention times for anti-5l:
38.8 min (major) and 84.0 min (minor), 89% ee; retention times for syn-
5l: 42.2 min (minor) and 62.0 min (major), 9% ee.
Ethyl 2-benzoyl-3-(2,4-dimethoxyphenyl)pent-4-ynoate (5i): Isolated
yield 92% (anti-5i/syn-5i=4:1). A colorless oil. anti-isomer: 1H NMR:
d=8.02–8.05 (m, 2H), 7.55–7.61 (m, 1H), 7.29–7.49 (m, 3H), 6.42–6.46
(m, 2H), 5.12 (d, J=10.0 Hz, 1H), 4.87 (dd, J=10.0 and 2.7 Hz, 1H),
3.93 (qd, J=7.0 and 1.1 Hz, 2H), 3.88 (s, 3H), 3.79 (s, 3H), 2.08 (d, J=
Ethyl 2-(1-naphthoyl)-3-(naphthalen-1-yl)pent-4-ynoate (5m): Isolated
1
2.7 Hz, 1H), 0.98 ppm (t, J=7.0 Hz, 3H); syn-isomer: H NMR: d=7.90–
yield 92% (anti-5m/syn-5m=12:1).
A
colorless oil. anti-isomer:
7.93 (m, 2H), 7.51–7.61 (m, 1H), 6.33 (d, J=2.4 Hz, 1H), 5.06 (d, J=
8.4 Hz, 1H), 4.82 (dd, J=8.4 and 2.7 Hz, 1H), 4.14–4.20 (m, 2H), 3.74 (s,
3H), 2.26 (d, J=2.7 Hz, 1H), 1.20 ppm (t, J=7.0 Hz, 3H); anti-isomer:
13C NMR: d=192.9, 167.2, 160.5, 158.0, 136.7, 133.5, 130.7, 128.8, 128.55,
118.1, 104.44, 99.0, 83.6, 70.4, 61.4, 57.87, 55.6, 55.34, 32.0, 13.7 ppm; syn-
isomer: 13C NMR: d=193.0, 167.8, 160.3, 157.4, 136.2, 133.4, 130.5,
128.56, 128.50, 118.2, 104.39, 98.8, 83.0, 71.2, 61.5, 57.90, 55.4, 55.30, 32.1,
14.0 ppm; HRMS (EI): m/z: calcd for C22H22O5 [M]: 366.1467; found:
366.1455. The optical purities of anti-5i and syn-5i were determined by
HPLC analysis; DAICEL Chiralpak IC, hexane/iPrOH=95:5, flow
1H NMR: d=8.71 (d, J=8.4 Hz, 1H), 8.39 (d, J=8.4 Hz, 1H), 7.38–8.04
(m, 12H), 5.55 (dd, J=10.3 and 2.4 Hz, 1H), 5.26 (d, J=10.3 Hz, 1H),
3.72 (q, J=7.0 Hz, 2H), 2.20 (d, J=2.4 Hz, 1H), 0.71 ppm (t, J=7.0 Hz,
1
3H); syn-isomer: H NMR: d=8.15 (d, J=8.4 Hz, 1H), 5.51 (dd, J=10.3
and 2.7 Hz, 1H), 5.38 (d, J=10.3 Hz, 1H), 4.24 (q, J=7.3 Hz, 2H), 2.37
(d, J=2.7 Hz, 1H), 1.20 ppm (t, J=7.3 Hz, 3H); anti-isomer: 13C NMR:
d=195.5, 166.7, 135.5, 134.0, 133.9, 133.6, 133.4, 130.9, 130.4, 128.9,
128.54, 128.52, 128.3, 128.2, 126.7, 126.5, 126.3, 125.9, 125.8, 125.3, 124.2,
123.5, 83.6, 72.4, 62.5, 61.58, 33.9, 13.4 ppm; syn-isomer: 13C NMR: d=
195.2, 167.4, 135.9, 134.1, 133.1, 131.1, 130.6, 129.9, 129.8, 128.7, 128.47,
128.1, 127.8, 127.7, 126.9, 126.43, 126.40, 125.7, 125.2, 124.0, 123.6, 83.4,
72.0, 61.9, 61.64, 14.0 ppm; HRMS (EI): m/z: calcd for C28H22O3 [M]:
406.1569; found: 406.1588. The optical purities of anti-5m and syn-5m
were determined by HPLC analysis; DAICEL Chiralcel OZ-H, hexane/
iPrOH=97:3, flow rate=0.5 mLminÀ1, l=254 nm; retention times for
anti-5m: 20.0 min (minor) and 24.5 min (major), 90% ee; retention times
for syn-5m: 22.0 min (minor) and 45.7 min (major), 78% ee.
rate=1.0 mLminÀ1
, l=254 nm; retention times for anti-5i: 49.6 min
(major) and 82.0 min (minor), 85% ee; retention times for syn-5i:
55.3 min (major) and 77.5 min (minor), 58% ee.
Benzyl 2-benzoyl-3-(naphthalen-1-yl)pent-4-ynoate (5j): Isolated yield
95% (anti-5j/syn-5j=5:1). A colorless oil. anti-isomer: 1H NMR: d=
8.35 (d, J=7.8 Hz, 1H), 8.06–8.09 (m, 2H), 7.74–7.88 (m, 2H), 7.07–7.65
(m, 10H), 6.70–6.73 (m, 2H), 5.49 (dd, J=10.4 and 2.7 Hz, 1H), 5.30 (d,
J=10.4, 1H), 4.64 (s, 2H), 2.17 ppm (d, J=2.7 Hz, 1H); syn-isomer:
1H NMR: d=8.37 (d, J=7.8 Hz, 1H), 5.28 (d, J=9.7 Hz, 1H), 5.22 (s,
2H), 2.26 ppm (d, J=2.4 Hz, 1H); anti-isomer: 13C NMR: d=192.0,
166.5, 136.4, 134.6, 134.09, 133.8, 133.4, 130.9, 128.9, 128.7, 128.6, 128.2,
128.0, 127.8, 126.4, 125.8, 125.3, 123.56, 83.5, 72.1, 67.2, 59.3, 33.6 ppm;
syn-isomer: 13C NMR: d=191.5, 167.3, 135.8, 135.1, 134.07, 133.6, 130.6,
128.51, 128.48, 128.43, 128.35, 128.3, 126.5, 125.7, 125.2, 123.58, 83.2, 72.6,
67.6, 59.4 ppm; HRMS (EI): m/z: calcd for C29H22O3 [M]: 418.1569;
found: 418.1556. The optical purities of anti-5j and syn-5j were deter-
mined by HPLC analysis; DAICEL Chiralcel OZ-H, hexane/iPrOH=
95:5, flow rate=1.0 mLminÀ1, l=254 nm; retention times for anti-5j:
9.6 min (minor) and 20.9 min (major), 91% ee; retention times for syn-
5j: 11.2 min (major) and 64.5 min (minor), 13% ee.
Ethyl 2-(2-naphthoyl)-3-(naphthalen-1-yl)pent-4-ynoate (5n): Isolated
1
yield 96% (anti-5n/syn-5n=10:1). A colorless oil. anti-isomer: H NMR:
d=8.58 (s, 1H), 8.42 (d, J=8.4 Hz, 1H), 8.16 (dd, J=8.4 and 1.6 Hz,
1H), 7.43–7.96 (m, 11H), 5.55 (dd, J=10.3 and 2.4 Hz, 1H), 5.39 (d, J=
10.3 Hz, 1H), 3.71 (q, J=7.3 Hz, 2H), 2.19 (d, J=2.4 Hz, 1H), 0.70 ppm
(t, J=7.3 Hz, 3H); syn-isomer: 1H NMR: d=8.48 (d, J=8.9 Hz, 1H),
8.38 (d, J=8.9 Hz, 1H), 7.28 (dd, J=8.1 and 7.3 Hz, 1H), 5.52 (dd, J=
10.3 and 2.4 Hz, 1H), 5.42 (d, J=10.3 Hz, 1H), 4.28 (qd, J=7.0 and
3.5 Hz, 2H), 2.37 (d, J=2.4 Hz, 1H), 1.27 ppm (t, J=7.0 Hz, 3H); anti-
isomer: 13C NMR: d=192.2, 166.8, 135.8, 134.1, 133.8, 133.6, 132.4, 131.1,
131.0, 129.8, 128.9, 128.7, 128.54, 127.7, 126.9, 126.6, 126.3, 125.8, 125.3,
124.2, 123.6, 83.6, 72.1, 61.6, 59.7, 33.5, 13.4 ppm; syn-isomer: 13C NMR:
d=191.6, 167.5, 135.6, 133.3, 132.2, 130.8, 130.7, 129.7, 128.8, 128.45,
128.4, 127.6, 126.8, 125.7, 125.2, 123.8, 123.7, 83.4, 72.5, 62.0, 59.4, 33.3,
14.1 ppm; HRMS (EI): m/z: calcd for C28H22O3 [M]: 406.1569; found:
406.1552. The optical purities of anti-5n and syn-5n were determined by
HPLC analysis; DAICEL Chiralpak AD, hexane/iPrOH=97:3, flow
Methyl 2-benzoyl-3-(naphthalen-1-yl)pent-4-ynoate (5k): Isolated yield
99% (anti-5k/syn-5k=4:1). A colorless oil. anti-isomer: 1H NMR: d=
8.36 (d, J=8.6 Hz, 1H), 8.06–8.09 (m, 2H), 7.42–7.89 (m, 9H), 5.48 (dd,
J=10.3 and 2.7 Hz, 1H), 5.23 (d, J=10.3 Hz, 1H), 3.25 (s, 3H), 2.18 ppm
(d, J=2.7 Hz, 1H); syn-isomer: 1H NMR: d=8.40 (d, J=8.6 Hz, 1H),
7.25–7.33 (m, 3H), 5.46 (dd, J=10.0 and 2.4 Hz, 1H), 5.28 (d, J=
10.0 Hz, 1H), 3.80 (s, 3H), 2.35 ppm (d, J=2.4 Hz, 1H); anti-isomer:
13C NMR: d=192.3, 167.1, 136.4, 134.08, 133.8, 133.47, 130.8, 129.0, 128.9,
128.8, 128.62, 126.6, 126.3, 125.8, 125.3, 123.4, 83.4, 72.2, 59.4, 52.5,
33.6 ppm; syn-isomer: 13C NMR: d=191.6, 167.9, 135.9, 134.09, 133.6,
133.48, 130.7, 128.56, 128.5, 126.4, 125.7, 125.2, 123.6, 83.3, 72.4, 59.3,
53.0, 33.8 ppm; HRMS (EI): m/z: calcd for C23H18O3 [M]: 342.1256;
found: 342.1254. The optical purities of anti-5k and syn-5k were deter-
mined by HPLC analysis; DAICEL Chiralpak IC, hexane/iPrOH=95:5,
rate=0.5 mLminÀ1
, l=254 nm; retention times for anti-5n: 65.9 min
(minor) and 73.5 min (major), 92% ee; retention times for syn-5n:
54.3 min (minor) and 115.2 min (major), 0% ee.
Ethyl 2-(4-methylbenzoyl)-3-(naphthalen-1-yl)pent-4-ynoate (5o): Isolat-
ed yield 95% (anti-5o/syn-5o=10:1).
A colorless oil. anti-isomer:
1H NMR: d=8.39 (d, J=8.4 Hz, 1H), 8.01 (d, J=8.4 Hz, 2H), 7.42–7.88
(m, 6H), 7.29 (d, J=8.1 Hz, 2H), 5.47 (dd, J=10.5 and 2.7 Hz, 1H), 5.21
(d, J=10.5 Hz, 1H), 3.66 (q, J=7.0 Hz, 2H), 2.42 (s, 3H), 2.16 (d, J=
2.7 Hz, 1H), 0.67 ppm (t, J=7.0 Hz, 3H); syn-isomer: 1H NMR: d=8.42
(d, J=8.4 Hz, 1H), 7.32 (d, J=8.1 Hz, 2H), 7.12 (d, J=8.1 Hz, 2H), 5.23
(d, J=10.0 Hz, 1H), 4.26 (qd, J=7.0 and 1.6 Hz, 2H), 2.33 (d, J=2.7 Hz,
1H), 2.32 (s, 3H), 1.27 ppm (t, J=7.0 Hz, 3H); anti-isomer: 13C NMR:
d=191.7, 166.7, 144.8, 134.0, 133.93, 133.7, 131.0, 129.5, 129.1, 128.9,
128.5, 126.6, 126.25, 125.74, 125.3, 123.6, 83.7, 71.8, 61.5, 59.6, 33.3, 21.7,
13.4 ppm; syn-isomer: 13C NMR: d=191.1, 167.5, 144.6, 134.1, 133.91,
133.8, 130.7, 129.2, 128.7, 128.4, 126.31, 125.69, 125.2, 123.7, 83.4, 72.4,
62.0, 59.2, 33.5, 21.6, 14.0 ppm; HRMS (EI): m/z: calcd for C25H22O3 [M]:
370.1569; found: 370.1568. The optical purities of anti-5o and syn-5o
were determined by HPLC analysis; DAICEL Chiralpak IC, hexane/
iPrOH=95:5, flow rate=1.0 mLminÀ1, l=254 nm; retention times for
anti-5o: 18.1 min (major) and 43.1 min (minor), 94% ee; retention times
for syn-5o: 20.1 min (minor) and 30.8 min (major), 3% ee.
flow rate=0.5 mLminÀ1
, l=254 nm; retention times for anti-5k:
29.2 min (major) and 45.0 min (minor), 86% ee; , retention times for syn-
5k: 32.6 min (minor) and 40.0 min (major), 0% ee.
Ethyl 2-(4-methoxybenzoyl)-3-(naphthalen-1-yl)pent-4-ynoate (5l): Iso-
lated yield 97% (anti-5l/syn-5l=6:1).
A colorless oil. anti-isomer:
1H NMR: d=8.39 (d, J=8.4 Hz, 1H), 8.10 (d, J=9.2 Hz, 2H), 7.42–7.88
(m, 6H), 6.96 (d, J=9.2 Hz, 2H), 5.48 (dd, J=10.5 and 2.4 Hz, 1H), 5.19
(d, J=10.5 Hz, 1H), 3.87 (s, 3H), 3.67 (q, J=7.0 Hz, 2H), 2.17 (d, J=
2.4 Hz, 1H), 0.67 ppm (t, J=7.0 Hz, 3H); syn-isomer: 1H NMR: d=8.43
(d, J=8.4 Hz, 1H), 7.31 (dd, J=8.1 and 7.3 Hz, 1H), 6.79 (d, J=9.2 Hz,
1H), 5.22 (d, J=10.5 Hz, 1H), 4.27 (qd, J=7.0 and 2.4 Hz, 2H), 3.79 (s,
3H), 2.33 (d, J=2.4 Hz, 1H), 1.28 ppm (t, J=7.0 Hz, 3H); anti-isomer:
13C NMR: d=190.5, 166.8, 164.1, 134.0, 133.8, 131.4, 131.01, 129.4, 128.9,
128.5, 126.5, 126.2, 125.74, 125.3, 123.7, 113.9, 83.8, 71.8, 61.5, 59.5, 55.5,
33.3, 13.4 ppm; syn-isomer: 13C NMR: d=189.8, 167.7, 163.9, 134.1, 133.9,
130.98, 130.8, 128.4, 126.3, 125.68, 125.2, 123.8, 113.7, 83.5, 72.3, 61.9,
Ethyl 2-(4-chlorobenzoyl)-3-(naphthalen-1-yl)pent-4-ynoate (5p): Isolat-
ed yield 94% (anti-5p/syn-5p=3:1).
A colorless oil. anti-isomer:
1H NMR: d=8.35 (d, J=8.9 Hz, 1H), 8.02 (d, J=8.9 Hz, 2H), 7.44–7.89
(m, 7H), 7.27 (d, J=8.9 Hz, 1H), 5.46 (dd, J=10.3 and 2.4 Hz, 1H), 5.16
3326
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Chem. Eur. J. 2012, 18, 3321 – 3328

Propargylic Alkylation by Cooperative Dual Catalysis by Ru and Cu Complexes
FULL PAPER
(d, J=10.3 Hz, 1H), 3.69 (q, J=7.0 Hz, 2H), 2.19 (d, J=2.4 Hz, 1H),
0.69 ppm (t, J=7.3 Hz, 3H); syn-isomer: 1H NMR: d=8.39 (d, J=
8.9 Hz, 1H), 7.42–7.81 (m, 9H), 7.31–7.34 (m, 1H), 5.43 (dd, J=10.3 and
2.4 Hz, 1H), 5.18 (d, J=10.3 Hz, 1H), 4.27 (qd, J=7.0 and 1.1 Hz, 2H),
2.35 (d, J=2.4 Hz, 1H), 1.28 ppm (t, J=7.3 Hz, 3H); anti-isomer:
13C NMR: d=191.2, 166.4, 140.4, 134.7, 134.0, 133.4, 130.9, 130.3, 129.1,
128.8, 128.62, 126.6, 126.37, 125.82, 125.3, 123.5, 83.5, 72.1, 61.7, 59.7,
33.3, 13.4 ppm; syn-isomer: 13C NMR: d=190.8, 167.2, 140.2, 134.2, 134.1,
133.5, 130.6, 129.8, 128.98, 128.96, 128.55, 126.41, 125.78, 125.2, 123.6,
83.1, 72.6, 62.2, 59.4, 33.7, 14.1 ppm; HRMS (EI): m/z: calcd for
C24H19ClO3 [M]: 390.1023; found: 390.1038. The optical purities of anti-
5p and syn-5p were determined by HPLC analysis; DAICEL Chiralpak
IC, hexane/iPrOH=97:3, flow rate=0.50 mLminÀ1, l=254 nm; retention
times for anti-5p: 25.0 min (major) and 38.7 min (minor), 86% ee; reten-
tion times for syn-5p: 26.8 min (minor) and 33.0 min (major), 4% ee.
iPrOH=95:5, flow rate=1.00 mLminÀ1, l=254 nm; retention times for
anti-5s: 15.4 min (major) and 19.0 min (minor), 92% ee; retention times
for syn-5s: 14.3 min (major) and 22.2 min (minor), 62% ee.
Preparation of allenylidene complex 6: Complex 3a (220.3 mg,
0.318 mmol), NH4BF4 (66.7 mg, 0.636 mmol), and anhydrous MgSO4
(440 mg) were placed in a 20 mL Schlenk flask under N2. Anhydrous di-
chloromethane (20 mL) was added, and then the mixture was magnetical-
ly stirred at room temperature. After the addition of 1a (115.9 mg,
0.636 mmol), the reaction flask was kept at room temperature for 4 h.
The solvent was then removed under reduced pressure and the residue
was recrystallized from dichloromethane/n-hexane to give dark-brown
crystals of 6·0.5CH2Cl2 (144.3 mg, 0.152 mmol, 48%) suitable for X-ray
crystallographic study. 1H NMR: d=9.89 (s, 1H), 8.70 (d, J=8.1 Hz,
1H), 8.28 (d, J=8.1 Hz, 1H), 8.10 (dd, J=7.6 and 1.1 Hz, 1H), 7.96 (d,
J=8.4 Hz, 1H), 7.80 (td, J=7.6 and 1.4 Hz, 1H), 7.59 (td, J=8.1 and
1.1 Hz, 1H), 7.51 (t, J=7.6 Hz, 1H), 4.42 (sept, J=6.8 Hz, 2H), 1.91 (s,
15H), 1.70 (s, 15H), 1.41 (d, J=6.8 Hz, 6H), 1.39 ppm (d, J=6.8 Hz,
6H); IR (KBr): =1927 cmÀ1 (s, C=C=C); elemental analysis calcd (%)
Ethyl 2-(2-naphthoyl)-3-(naphthalen-2-yl)pent-4-ynoate (5q): Isolated
yield 93% (anti-5q/syn-5q=6:1). A white solid. anti-isomer: 1H NMR:
d=8.67 (s, 1H), 8.17 (dd, J=8.6 and 1.9 Hz, 1H), 7.45–8.02 (m, 12H),
5.13 (d, J=10.8 Hz, 1H), 4.91 (dd, J=10.8 and 2.4 Hz, 1H), 3.75–3.91
(m, 2H), 2.19 (d, J=2.4 Hz, 1H), 0.86 ppm (t, J=7.0 Hz, 3H); syn-
isomer: 1H NMR: d=8.46 (s, 1H), 7.36–7.41 (m, 2H), 5.14 (d, J=
10.5 Hz, 1H), 4.99 (dd, J=10.5 and 2.4 Hz, 1H), 4.24–4.28 (m, 2H), 2.40
(d, J=2.4 Hz, 1H), 1.27 ppm (t, J=7.0 Hz, 3H); anti-isomer: 13C NMR:
d=192.0, 166.6, 135.9, 135.1, 133.7, 133.3, 132.9, 132.4, 131.2, 129.9, 129.0,
128.7, 128.5, 127.9, 127.8, 127.7, 127.6, 126.9, 126.3, 126.13, 126.06, 124.3,
83.6, 72.2, 61.7, 61.3, 37.5, 13.7 ppm; syn-isomer: 13C NMR: d=191.3,
167.3, 135.7, 135.5, 133.2, 132.6, 132.2, 130.9, 129.8, 128.9, 128.4, 127.5,
126.8, 126.0, 123.9, 83.5, 72.5, 62.1, 61.4, 37.2, 14.1 ppm; elemental analy-
sis calcd (%) for C28H22O3: C 82.74, H 5.46; found: C 82.56, H 5.72. The
optical purities of anti-5q and syn-5q were determined by HPLC analy-
sis; DAICEL Chiralpak AS-H, hexane/iPrOH=97:3, flow rate=
0.35 mLminÀ1, l=254 nm; retention times for anti-5q: 42.2 min (minor)
and 54.4 min (major), 92% ee; retention times for syn-5q: 33.9 min
(major) and 39.4 min (minor), 53% ee.
for C39H52BClF4Ru2S2·ACHTUNGTRENN(UNG CH2Cl2)0.5: C 49.84, H 5.61; found: C 49.75, H
5.72.
Stoichiometric reaction of complex 6 in the presence of 1g: A 20 mL
Schlenk flask was charged with 4a (41.5 mg, 0.0857 mmol) and Cu(OTf)2
ACHTUNGTRENNUNG
(25.8 mg, 0.0714 mmol) under N2. The mixture was stirred under vacuum
for 2 h and then an atmosphere of N2 was admitted to the flask. Anhy-
drous THF (1.0 mL) was added and the solution was stirred for 2 h.
After cooling the reaction flask to À108C, 2a (30.9 mg, 0.161 mmol) was
added to the reaction mixture, and then 6·0.5CH2Cl2 (34.0 mg,
0.0357 mmol) and a solution of 1g (11.6 mg, 0.0714 mmol) in anhydrous
THF (2 mL) were added successively under N2. The reaction flask was
kept at À108C for 45 h. After concentration of the reaction mixture
under reduced pressure, the residue was purified by column chromatog-
raphy (SiO2; eluent: hexane/ethyl acetate, 95:5 to 85:15) to give 5a as a
colorless oil (6.7 mg, 0.0188 mmol, 53% isolated yield, anti-5a/syn-5a=
5:1, anti-5a (90% ee), syn-5a (4% ee)) and 5g as a colorless oil (14.8 mg,
0.0440 mmol, 62% isolated yield, anti-5g/syn-5g=6:1, anti-5g (87% ee),
syn-5g (46% ee)).
Benzyl 2-benzoyl-3-(2-methoxyphenyl)pent-4-ynoate (5r): Isolated yield
98% (anti-5r/syn-5r=7:1). A colorless oil. anti-isomer: 1H NMR: d=
7.98–8.03 (m, 2H), 7.52–7.59 (m, 1H), 7.37–7.46 (m, 3H), 7.18–7.35 (m,
4H), 6.98–7.02 (m, 2H), 6.83–6.91 (m, 2H), 5.22 (d, J=9.7 Hz, 1H), 4.98
(dd, J=9.7 and 2.7 Hz, 1H), 4.89 (s, 2H), 3.82 (s, 3H), 2.09 ppm (d, J=
2.7 Hz, 1H); syn-isomer: 1H NMR: d=7.87–7.90 (m, 2H), 6.83 (m, 1H),
5.14 (s, 2H), 5.13 (d, J=7.8 Hz, 1H), 4.92 (dd, J=7.8 and 2.7 Hz, 1H),
3.80 (s, 3H), 2.23 ppm (d, J=2.7 Hz, 1H); anti-isomer: 13C NMR: d=
192.7, 167.1, 157.0, 136.7, 135.1, 133.5, 130.1, 128.8, 128.6, 128.3, 128.05,
127.9, 125.58, 120.78, 111.2, 83.2, 70.9, 67.0, 57.6, 55.6, 32.4 ppm; syn-
isomer: 13C NMR: d=192.8, 167.6, 156.4, 136.1, 135.2, 133.4, 130.0, 129.0,
128.53, 128.51, 128.2, 128.12, 125.62, 120.76, 110.8, 82.5, 71.8, 67.1, 57.8,
55.4, 32.5 ppm; HRMS (EI): m/z: calcd for C26H22O4 [M]: 398.1518;
found: 398.1516. The optical purities of anti-5r and syn-5r were deter-
mined by HPLC analysis; DAICEL Chiralcel OZ-H, hexane/iPrOH=
95:5, flow rate=1.0 mLminÀ1, l=254 nm; retention times for anti-5r:
15.0 min (minor) and 37.7 min (major), 91% ee; retention times for syn-
5r: 32.6 min (minor) and 96.5 min (major), 30% ee.
Stoichiometric reaction of complex 6:
charged with 4a (37.5 mg, 0.0782 mmol) and Cu
A
20 mL Schlenk flask was
(OTf)2 (23.6 mg,
AHCTUNGTRENNUNG
0.0651 mmol) under N2. The mixture was stirred under vacuum for 2 h
and then an atmosphere of N2 was admitted to the flask. Anhydrous
THF (1.0 mL) was added and the solution was stirred for 2 h. After cool-
ing the reaction flask to À108C, 2a (12.5 mg, 0.0651 mmol) was added to
the reaction mixture, and then 6·0.5CH2Cl2 (31.0 mg, 0.0326 mmol) was
added under N2. The reaction flask was kept at À108C for 45 h. The reac-
tion was then quenched by the addition of water (10 mL), and the result-
ing mixture was extracted with ethyl acetate (3ꢂ15 mL). The combined
organic layers were washed with brine and dried over anhydrous Na2SO4.
After concentration under reduced pressure, the residue was purified by
column chromatography (SiO2; eluent: hexane/ethyl acetate, 95:5 to
85:15) to give 5a as a colorless oil (1.2 mg, 0.0034 mmol, 10% isolated
yield, anti-5a/syn-5a=4:1, anti-5a (92% ee), syn-5a (6% ee)).
Ethyl
2-(4-chlorophenylcarbonyl)-3-(2-methoxyphenyl)pent-4-ynoate
(5s): Isolated yield 94% (anti-5s/syn-5s=6:1). A colorless oil. anti-
isomer: 1H NMR: d=7.96 (d, J=8.6 Hz, 2H), 7.36–7.45 (m, 3H), 7.22–
7.28 (m, 1H), 6.88–6.94 (m, 2H), 5.10 (d, J=9.5 Hz, 1H), 4.93 (dd, J=9.5
and 2.4 Hz, 1H), 3.93 (q, J=7.0 Hz, 2H), 3.91 (s, 3H), 2.11 (d, J=2.4 Hz,
1H), 0.97 ppm (t, J=7.0 Hz, 3H); syn-isomer: 1H NMR: d=7.85 (d, J=
8.9 Hz, 2H), 7.36–7.47 (m, 3H), 7.18–7.22 (m, 1H), 6.86–6.89 (m, 1H),
6.75–6.78 (m, 1H), 5.02 (d, J=8.4 Hz, 1H), 4.88 (dd, J=8.4 and 2.4 Hz,
1H), 4.18 (qd, J=7.0 and 2.4 Hz, 2H), 3.81 (s, 3H), 2.28 (d, J=2.4 Hz,
1H), 1.20 ppm (t, J=7.0 Hz, 3H); anti-isomer: 13C NMR: d=191.8,
167.0, 157.0, 140.0, 135.0, 130.2, 130.1, 129.1, 128.88, 125.46, 120.7, 111.2,
83.1, 70.9, 61.5, 57.5, 55.6, 32.4, 13.7 ppm; syn-isomer: 13C NMR: d=
167.5, 156.4, 139.9, 134.4, 129.92, 129.88, 128.90, 128.8, 125.50, 110.8, 82.5,
71.6, 61.6, 57.8, 55.4, 14.0 ppm; HRMS (EI): m/z: calcd for C21H19ClO4
[M]: 370.0972; found: 370.0963. The optical purities of anti-5s and syn-5s
were determined by HPLC analysis; DAICEL Chiralpak ID, hexane/
Acknowledgements
This work was supported by the Funding Program for Next Generation
World-Leading Researchers (GR025). We thank Dr. Akihito Yamano of
Rigaku Corporation for the X-ray diffraction analysis of (2R,3R)-5b.
M.I. is a recipient of a JSPS Predoctoral Fellowship for Young Scientists
and also acknowledges the Global COE program for Chemistry Innova-
tion.
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2a and 2 equiv of Cu
G
45 h gave 5a in 10% isolated yield based on 6. This low yield of 5a
is considered to be due to the difficulty with which the product 5a is
liberated from the vinylidene complex (D) because of the lack of
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[15] Crystallographic data for the structure reported in this paper have
been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC-857684 (anti-5b). These data
can be obtained free of charge from The Cambridge Crystallograph-
ic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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