Cooperative catalytic reactions using lewis acids and organocatalysts: Enantioselective propargylic alkylation of propargylic alcohols bearing an internal alkyne with aldehydes

Article abstract of DOI:10.1002/ejoc.201100044

The enantioselective propargylic alkylation of propargylic alcohols bearing an internal alkyne moiety with aldehydes in the presence of a metal salt as the Lewis acid and an optically active secondary amine as the co-catalyst has been found to give the corresponding propargylic alkylated products in high yields as a mixture of two diastereoisomers with high enantioselectivity. The enantioselective propargylic alkylation of propargylic alcohols bearing an internal alkyne moiety with aldehydes in the presence of a metal salt as the Lewis acid and an optically active secondary amine as the co-catalyst has been found to give the corresponding propargylic alkylated products in high yields as a mixture of two diastereoisomers with high enantioselectivity. Copyright

Full text of DOI:10.1002/ejoc.201100044

FULL PAPER
DOI: 10.1002/ejoc.201100044
Cooperative Catalytic Reactions Using Lewis Acids and Organocatalysts:
Enantioselective Propargylic Alkylation of Propargylic Alcohols Bearing an
Internal Alkyne with Aldehydes
Kazuki Motoyama,[a] Masahiro Ikeda,[a] Yoshihiro Miyake,[a] and Yoshiaki Nishibayashi*[a]
Dedicated to Prof. Sakae Uemura on the occasion of his 70th birthday
Keywords: Enantioselectivity / Alkylation / Lewis acids / Organocatalysis / Alkynes
The enantioselective propargylic alkylation of propargylic
alcohols bearing an internal alkyne moiety with aldehydes
in the presence of a metal salt as the Lewis acid and an op-
tically active secondary amine as the co-catalyst has been
found to give the corresponding propargylic alkylated prod-
ucts in high yields as a mixture of two diastereoisomers with
high enantioselectivity.
Introduction
Quite recently, we found that the enantioselective prop-
argylic alkylation of propargylic alcohols with aldehydes in
the presence of a thiolate-bridged diruthenium complex and
an optically active secondary amine as the co-catalyst pro-
vided the corresponding propargylic alkylated products in
excellent yields as a mixture of two diastereoisomers with
high enantioselectivity (up to 99%ee; Scheme 1).[1] This
catalytic reaction is considered to provide a new type of
enantioselective propargylic substitution reaction,[2] where
the enamines generated in situ from the aldehydes enantio-
selectively attack the γ-carbon atom of the ruthenium–
allenylidene complexes.[3] In this reaction system, both a
transition-metal catalyst (ruthenium complex) and an
organocatalyst[4] (secondary amine) activate the propargylic
alcohols and aldehydes, respectively, and both catalysts co-
operatively and simultaneously work to promote the pro-
pargylic alkylation enantioselectively.
In our cooperative catalytic system, available substrates
were strictly limited to propargylic alcohols bearing a ter-
minal alkyne moiety, because the reaction proceeded via
allenylidene complexes as reactive intermediates, which can
be produced only from this type of propargylic alcohol. On
the other hand, several research groups have already found
metal-catalyzed propargylic substitution reactions of
propargylic alcohols bearing an internal alkyne moiety with
Scheme 1. Cooperative catalytic propargylic alkylation of prop-
argylic alcohols bearing a terminal alkyne moiety with aldehydes
via ruthenium–allenylidene complexes as key intermediates.
[a] Institute of Engineering Innovation, School of Engineering,
The University of Tokyo,
various nucleophiles to give the corresponding propargylic-
substituted products in good to high yields with excellent
selectivity.[5,6] In these reaction systems, the metal com-
plexes work as Lewis acids, and the catalytic reactions pro-
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/ejoc.201100044.
Eur. J. Org. Chem. 2011, 2239–2246
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2239

K. Motoyama, M. Ikeda, Y. Miyake, Y. Nishibayashi
FULL PAPER
ceed via propargylic cations as reactive intermediates, al- Table 1. Catalytic propargylic alkylation of propargylic alcohols
bearing an internal alkyne moiety with aldehydes proceeding via
though a detailed reaction mechanism has not yet been
propargylic cations as reactive intermediates.
cleared until now.
As an extension of our continuous studies on enantiose-
lective propargylic substitution reactions, we envisaged a
cooperative catalytic reaction using Lewis acids and organo-
catalysts. In fact, we found that reactions of propargylic
alcohols bearing an internal alkyne moiety with aldehydes
in the presence of a Lewis acid and an optically active sec-
ondary amine as the co-catalyst gave the corresponding
propargylic alkylated products in high yields as a mixture
of two diastereoisomers with high enantioselectivity. We be-
lieve that the method described in this article may provide
a new type of dual catalytic reaction using both Lewis acids
and organocatalysts.[7] Typical results are described here.
Results and Discussion
Treatment of 1-(4-methoxyphenyl)-3-phenyl-2-propyn-1-
ol (1a) with 3-phenylpropanal (2a, 3 equiv.) in the presence
of a catalytic amount of InBr3 (20 mol-%) and (5S)-2,2,3-
Table 2. Catalytic propargylic alkylation of propargylic alcohols
bearing an internal alkyne moiety with aldehydes proceeding via
trimethyl-5-benzyl-4-imidazolidinone trifluoroacetic acid
(3a, 20 mol-%) in CH2Cl2 at 0 °C for 40 h gave 2-benzyl-3-
(4-methoxyphenyl)-5-phenyl-4-pentynal (4a) exclusively
(Table 1). 2-Benzyl-3-(4-methoxyphenyl)-5-phenyl-4-pen-
tyn-1-ol (5a) was isolated in 90% yield as a mixture of two
diastereoisomers (syn-5a/anti-5a = 1.1:1) with 93%ee of
syn-5a and 88%ee of anti-5a after reduction of 4a with
NaBH4 at 0 °C for 1 h. When other amines such as (5S)-
propargylic cations as reactive intermediates.
2,2,3-trimethyl-5-benzyl-4-imidazolidinone
monohydro-
chloride (3b) and (2S,5S)-2-tert-butyl-3-methyl-5-benzyl-4-
imidazolidinone trifluoroacetic acid (3c) were used in place
of 3a, the catalytic reaction did not proceed smoothly under
the same reaction conditions. No reaction occurred at all
when (S)-α,α-bis[3,5-bis(trifluoromethyl)phenyl]-2-pyrrol-
idine-methanol trimethylsilyl ether (3d), which worked as
an effective organocatalyst in our reaction system,[1] was
used in place of 3a.
[a] 3a (10 mol-%) was used. [b] For 160 h.
We carried out the catalytic reaction by using other
Lewis acids under the same reaction conditions (Table 2).
A similar result was obtained when InCl3 was used as the
Lewis acid. The catalytic reaction did not proceed smoothly propargylic alkylation. This result indicates that both InBr3
in the presence of a catalytic amount of BiCl3. It was pre- and 3a cooperatively worked as catalysts to promote the
viously reported that p-toluenesulfonic acid (TsOH) worked catalytic reaction enantioselectively.
as an effective catalyst toward the propargylic substitution
Next, propargylic alkylation of a variety of propargylic
reactions of propargylic alcohols bearing a terminal or an alcohols bearing an internal alkyne with 2a was carried out
internal alkyne moiety with various nucleophiles,[8] but by using InBr3 and 3a as co-catalysts. Typical results are
TsOH did not work at all as a catalyst for the cooperative shown in Table 3. Some mixtures of two diastereoisomers
catalytic reaction.
can be separated by column chromatography. The presence
A longer reaction time such as 160 h was necessary to of an electron-donating group such as a dimethylamino
complete the catalytic alkylation when the amounts of moiety on the propargylic benzene ring dramatically re-
InBr3 (10 mol-%) and 3a (10 mol-%) were decreased under duced the reaction time (Table 3, Entries 1–5). In contrast,
the same reaction conditions. Interestingly, a similar result no reaction occurred at all when a less electron-donating
was observed in the reaction with only 2 equiv. of 2a in the group such as a methyl moiety was introduced onto the
presence of catalytic amounts of InBr3 (20 mol-%) and 3a propargylic benzene ring (Table 3, Entry 6). These results
(20 mol-%) in CH2Cl2 at 0 °C for 40 h. Separately, we con- suggest that propargylic cations might be involved as reac-
firmed that the use of only InBr3 or 3a did not promote the tive intermediates.
2240
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2239–2246

Cooperative Catalytic Reactions Using Lewis Acids and Organocatalysts
Table 3. Cooperative enantioselective propargylic alkylation of
Table 4. Cooperative enantioselective propargylic alkylation of
propargylic alcohols 1 with aldehyde 2a.[a]
propargylic alcohol 1a with aldehydes 2.[a]
[a] All reactions of 1a (0.30 mmol) with aldehydes 2 (0.60 mmol)
were carried out in the presence of InBr3 (0.06 mmol) and 3a
(0.06 mmol) in CH2Cl2 (3 mL) at 0 °C. [b] Isolated yield of 5.
[c] Determined by HPLC (see the Supporting Information for ex-
perimental details).
[a] All reactions of 1 (0.30 mmol) with aldehyde 2a (0.60 mmol)
were carried out in the presence of InBr3 (0.06 mmol) and 3a
(0.06 mmol) in CH2Cl2 (3 mL) at 0 °C. [b] Isolated yield of 5.
[c] Determined by HPLC (see the Supporting Information for ex-
perimental details).
Subsequent attack of enamine C generated in situ from al-
dehyde 2 and amine 3a upon the propargylic cation of B
results in the formation of propargylic alkylated intermedi-
ate D. These results clearly indicate that the proposed reac-
tion pathway of propargylic alkylation is quite similar with
those of the benzylic alkylation[10] of benzylic alcohols and
the allylic alkylation[11] of allylic alcohols.
On the other hand, a variety of substituents such as alkyl
groups and the trimethylsilyl group can be introduced at
the terminal position of the propargylic alcohols. In fact,
similar results are observed in the reactions of 1-(4-meth-
oxyphenyl)-2-heptyn-1-ol (1g), 1-(4-methoxyphenyl)-4,4-di-
methyl-2-pentyn-1-ol (1h), and 1-(4-methoxyphenyl)-3-(tri-
methylsilyl)-2-propyn-1-ol (1i) (Table 3, Entries 7–9). In
contrast, the reaction of propargylic alcohol bearing a ter-
minal alkyne moiety, 1-(4-methoxyphenyl)-2-propyn-1-ol
(1j), did not proceed under the same conditions (Table 3,
Entry 10). These results indicate that only propargylic
alcohols bearing an internal alkyne moiety are available as
substrates toward the propargylic alkylation.
Propargylic alkylation of 1a with other aldehydes also
proceeded smoothly to give the corresponding propargylic
alkylated products with high enantioselectivity. Typical re-
sults are shown in Table 4. The reaction of 1a with 3-(4-
chloro)phenylpropanal (2b) under the same reaction condi-
tions gave the corresponding alkylated product with a sim-
ilar high enantioselectivity (Table 4, Entry 2). When other
aldehydes such as 3-cyclohexylpropanal (2c), heptanal (2d),
and 6-chlorohexanal (2e) were used in place of 3-aryl-
propanals, the corresponding propargylic alkylated prod-
ucts were obtained in high yields as a mixture of two dia-
stereoisomers with high enantioselectivity (Table 4, En-
tries 3–5). These results indicate that a variety of aldehydes
are available for the propargylic alkylation.
Scheme 2. Proposed reaction pathway for the propargylic alk-
ylation of propargylic alcohols bearing an internal alkyne moiety
with aldehydes proceeding via propargylic cations as reactive inter-
mediates.
To obtain some information on the enantioselective
A proposed reaction pathway is shown in Scheme 2. The propargylic alkylation, the stereochemistry of the desilyl-
initial step is the formation of propargylic cation B by the ated product of syn-5h was compared with that of the prop-
reaction of propargylic alcohol 1 with InBr3, after InBr3 is argylic alkylated product that was previously obtained from
weakly coordinated by the oxygen atom on propargylic the enantioselective propargylic alkylation of 1j with 2a.[1]
alcohol A. Similar reactive intermediates such as A and B This result indicates that the absolute configuration of syn-
were previously proposed in the alkylation of alcohols with 5h is (2R,3R). The information on the stereochemistry of
carbon-centered nucleophiles by Baba and co-workers.[9] the propargylic alkylated products supports that the asym-
Eur. J. Org. Chem. 2011, 2239–2246
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2241

K. Motoyama, M. Ikeda, Y. Miyake, Y. Nishibayashi
FULL PAPER
metric induction of the propargylic alkylation catalyzed by
3a was achieved in a similar manner with that by 3d, which
was proposed in a previous paper.[1] Thus, for the formation
of major products syn-5, the enamine is generated from the
chiral amine and the aldehyde attacks from the Si face of
the enamine upon the Re face of the propargylic cation,
leading to carbon–carbon bond formation (Scheme 3).
Conclusions
We have found that the enantioselective propargylic alk-
ylation of propargylic alcohols bearing an internal alkyne
moiety with aldehydes in the presence of InBr3 and an op-
tically active secondary amine as a co-catalyst gives the cor-
responding propargylic alkylated products in excellent
yields as a mixture of two diastereoisomers with high
enantioselectivity (up to 98%ee). Cozzi and co-workers
have already reported the allylic alkylation of allylic
alcohols with aldehydes by using InBr3 and optically active
secondary amines as co-catalysts,[11] but this catalytic reac-
tion is considered to provide a new type of enantioselective
propargylic substitution reaction,[1,2,13–15] where the en-
amines generated in situ from the aldehydes enantioselecti-
vely attack the propargylic cations as reactive intermediates.
In the present reaction system, both the Lewis acid catalyst
(InBr3 or FeCl3) and the organocatalyst (secondary amine)
activate the propargylic alcohols and aldehydes, respec-
tively, and both catalysts cooperatively and simultaneously
work to promote the propargylic alkylation enantioselec-
tively. We believe that the finding described in this article
will open up new aspects of dual catalytic reactions using
both organocatalysts and transition-metal catalysts and
also the enantioselective α-alkylation of aldehydes.[16,17]
Further work is currently in progress to apply this strategy
to other reaction systems and to clarify the scope and
limitations of the present propargylic alkylation.
Scheme 3. The conformation of enamines generated from amines
and aldehydes and the high enantioselectivity of propargylic alkyl-
ated products.
Finally, we investigated the cooperative catalytic reac-
tions by using FeCl3 in place of InBr3 as a Lewis acid be-
cause FeCl3 was reported to work as an effective catalyst
toward propargylic substitution reactions of propargylic
alcohols bearing an internal alkyne moiety with various nu-
cleophiles.[12] Propargylic alkylation of various propargylic
alcohols with some aldehydes proceeded smoothly to give
the corresponding propargylic alkylated products with high
enantioselectivity. Typical results are shown in Table 5.
However, slightly lower yields of the propargylic alkylated
products were observed in all cases when we compared
these results with those obtained by using InBr3.
Experimental Section
General Methods: 1H NMR (270 MHz) and 13C NMR (67.8 MHz)
spectra were measured with a JEOL Excalibur 270 spectrometer by
using CDCl3 as the solvent unless otherwise stated. HPLC analyses
were performed with Hitachi L-7100 and GL-7410 apparatuses
equipped with a UV detector by using a 25 cmϫ4.6 mm DAICEL
Chiralcel OD, OZ-H and Chiralpak AS-H, IC columns. Elemental
analyses were performed at Microanalytical Center of The Univer-
sity of Tokyo. Mass spectra were measured with a JEOL JMS-
700 mass spectrometer. All reactions were carried out under a dry
nitrogen atmosphere. Solvents were dried by the usual methods and
then distilled under N2 and degassed before use. Propargylic
alcohols 1 were prepared by reaction of the corresponding alde-
hydes with the corresponding lithium acetylide. Aldehydes 2a and
2d and optically pure secondary amines 3 are commercially avail-
able reagents. Aldehyde 2c was prepared by PCC oxidation of the
corresponding alcohol. Aldehydes 2b[18] and 2e[19] were synthesized
according to literature methods.
Table 5. Iron-catalyzed enantioselective propargylic alkylation of
propargylic alcohols 1 with aldehydes 2.[a]
Typical Procedure for Enantioselective Propargylic Alkylation of
Propargylic Alcohols with Aldehydes: In a 20-mL Schlenk flask was
placed InBr3 (21.3 mg, 0.06 mmol) under an atmosphere of N2. Af-
ter anhydrous dichloromethane (3.0 mL) was added, and the mix-
ture was magnetically stirred at 0 °C for 30 min. Compound 2a
(80.5 mg, 0.60 mmol) and 3a (19.9 mg, 0.06 mmol) were added to
the reaction mixture, and then 1a (71.5 mg, 0.30 mmol) was added
successively under an atmosphere of N2. The reaction flask was
kept at 0 °C for 40 h. Then, ethanol (3.0 mL) and NaBH4 (22.7 mg,
0.600 mmol) were added, and the mixture was magnetically stirred
at 0 °C for 1 h. The reaction was quenched by brine (10 mL), and
the resulting mixture was extracted with dichloromethane
[a] All reactions of 1 (0.30 mmol) with 2 (0.60 mmol) were carried
out in the presence of FeCl3 (0.06 mmol) and 3a (0.06 mmol) in
CH2Cl2 (3 mL) at 0 °C. [b] Isolated yield of 5. [c] Determined by
HPLC (see the Supporting Information for experimental details).
2242
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2239–2246

Cooperative Catalytic Reactions Using Lewis Acids and Organocatalysts
(3ϫ10 mL). The combined organic layer was dried with anhydrous
MgSO4. After concentration under reduced pressure, the resulting
residue was purified by column chromatography (SiO2; dichloro-
methane/hexane/ethyl acetate, 12:4:1) to give 2-benzyl-3-(4-meth-
oxyphenyl)-5-phenyl-4-pentyn-1-ol (5a) as a colorless oil (95.3 mg,
= 0.5 mL/min, λ = 254 nm): tR = 31.2 (minor), 44.0 (major) min;
93%ee. HPLC (anti-5c; DAICEL Chiralpak OD, hexane/iPrOH =
92:8, flow rate = 0.5 mL/min, λ = 254 nm): tR = 25.3 (major), 52.0
(minor) min; 88%ee.
2-Benzyl-3-(2,4-dimethoxyphenyl)-5-phenyl-4-pentyn-1-ol (5d): Iso-
1
0.267 mmol, 89% isolated yield, syn-5a/anti-5a = 1.1:1). H NMR
1
lated yield 54% (syn-5d/anti-5d = 1.2:1). Pale yellow oil. H NMR
(syn isomer): δ = 7.03–7.54 (m, 12 H), 6.86–6.93 (m, 2 H), 4.26 (d,
J = 5.9 Hz, 1 H), 3.78 (s, 3 H), 3.66 (dd, J = 10.8, 7.0 Hz, 1 H),
3.51 (dd, J = 10.9, 3.8 Hz, 1 H), 2.90 (dd, J = 13.6, 3.8 Hz, 1 H),
2.63 (dd, J = 14.0, 10.5 Hz, 1 H), 2.12–2.26 (m, 1 H), 1.68 (br. s, 1
(syn isomer): δ = 7.45–7.57 (m, 3 H), 7.12–7.36 (m, 8 H), 6.55 (dd,
J = 8.4, 2.4 Hz, 1 H), 6.49 (d, J = 2.4 Hz, 1 H), 4.51 (d, J = 7.3 Hz,
1 H), 3.85 (s, 3 H), 3.81 (s, 3 H) 3.49 (dd, J = 11.3, 5.1 Hz, 1 H),
3.40 (dd, J = 11.3, 3.2 Hz, 1 H), 3.09 (dd, J = 13.5, 3.2 Hz, 1 H),
2.76 (dd, J = 13.5, 11.1 Hz, 1 H), 2.05–2.17 (m, 1 H), 1.97 (br. s, 1
1
H) ppm. H NMR (anti isomer): δ = 6.82–6.89 (m, 2 H), 3.98 (d,
J = 5.4 Hz, 1 H), 3.76 (s, 3 H), 3.72–3.77 (m, 1 H), 3.59 (dd, J =
10.9, 5.1 Hz, 1 H), 2.85 (dd, J = 13.5, 7.6 Hz, 1 H), 2.79 (dd, J =
13.5, 7.6 Hz, 1 H) ppm. 13C NMR (syn isomer): δ = 158.45, 140.3,
132.1, 131.62, 129.10, 129.00, 128.28, 128.2, 127.9, 125.9, 123.5,
113.87, 89.6, 85.0, 62.6, 55.22, 49.7, 38.5, 33.6 ppm. 13C NMR (anti
isomer): δ = 158.49, 131.7, 131.59, 129.07, 129.05, 128.4, 128.26,
128.0, 126.1, 123.3, 113.85, 89.5, 85.1, 62.5, 55.20, 49.6, 38.2,
35.7 ppm. HRMS (EI): calcd. for C25H24O2 [M] 356.1776; found
356.1784. HPLC (syn-5a; DAICEL Chiralpak AS-H, hexane/
iPrOH = 95:5, flow rate = 1.0 mL/min, λ = 254 nm): tR = 38.5
(major), 69.0 (minor) min; 94%ee. HPLC (anti-5a; DAICEL Chi-
ralpak AS-H, hexane/iPrOH = 95:5, flow rate = 1.0 mL/min, λ =
254 nm): tR = 29.0 (major), 54.2 (minor) min; 88%ee.
1
H) ppm. H NMR (anti isomer): δ = 6.50–6.54 (m, 1 H), 6.42 (d,
J = 2.4 Hz, 1 H), 4.37 (d, J = 4.6 Hz, 1 H), 3.80 (s, 3 H), 3.71 (s,
1
3 H), 3.71 (dd, J = 11.3, 5.1 Hz, H), 3.55 (dd, J = 11.3, 5.4 Hz,
1H), 2.93 (dd, J = 13.8, 7.6 Hz, 1 H), 2.79 (dd, J = 13.8, 7.6 Hz, 1
H), 2.27–2.38 (m, 1 H) ppm. 13C NMR (syn isomer): δ = 159.93,
156.9, 141.0, 131.6, 130.2, 129.17, 128.23, 128.19, 127.8, 125.8,
123.7, 120.9, 104.9, 98.6, 90.8, 83.9, 63.2, 55.7, 55.4, 48.8, 34.4,
32.7 ppm. 13C NMR (anti isomer): δ = 159.86, 157.2, 140.5, 129.9,
129.21, 128.3, 127.9, 125.9, 123.5, 120.3, 104.3, 98.5, 90.0, 84.3,
62.1, 55.34, 55.31, 47.2, 36.0, 32.3 ppm. HRMS (EI): calcd. for
C26H26O3 [M] 386.1882; found 386.1877. HPLC (syn-5d; DAICEL
Chiralpak AS-H, hexane/iPrOH = 95:5, flow rate = 1.0 mL/min, λ
= 254 nm): tR = 29.0 (major), 50.3 (minor) min; 98%ee. HPLC
(anti-5d; DAICEL Chiralpak AS-H, hexane/iPrOH = 95:5, flow
2-Benzyl-3-[4-(dimethylamino)phenyl]-5-phenyl-4-pentyn-1-ol (5b):
Isolated yield 92% (syn-5b/anti-5b = 1:1.6). Pale yellow oil. 1H
rate
= 1.0 mL/min, λ = 254 nm): tR = 37.6 (major), 54.2
NMR (syn isomer): δ = 7.45–7.50 (m, 2 H), 7.10–7.37 (m, 10 H),
6.72–6.78 (m, 2 H), 4.18 (d, J = 5.9 Hz, 1 H), 3.60–3.66 (m, 1 H),
3.53 (dd, J = 11.1, 4.1 Hz, 1 H), 2.89–2.98 (m, 1 H), 2.94 (s, 6 H),
2.64 (dd, J = 14.0, 10.5 Hz, 1 H), 2.14–2.25 (m, 1 H), 1.62 (br. s, 1
(minor) min; 97%ee.
2-Benzyl-3-(2-methoxyphenyl)-5-phenyl-4-pentyn-1-ol (5e): Isolated
yield 18% (syn-5e/anti-5e = 1.0:1). Pale yellow oil. H NMR (syn
1
1
isomer): δ = 7.68 (dd, J = 7.6, 1.6 Hz, 1 H), 7.46–7.51 (m, 2 H),
7.12–7.34 (m, 9 H), 7.03 (dd, J = 7.4, 1.1 Hz, 1 H), 6.92 (dd, J =
8.4, 1.1 Hz, 1 H), 4.61 (d, J = 7.3 Hz, 1 H), 3.88 (s, 3 H), 3.46–3.59
(m, 1 H), 3.38 (dd, J = 11.6, 3.0 Hz, 1 H), 3.11 (dd, J = 13.5,
3.2 Hz, 1 H), 2.78 (dd, J = 13.5, 11.3 Hz, 1 H), 2.09–2.20 (m, 1 H),
2.03 (br. s, 1 H) ppm. 1H NMR (anti isomer): δ = 7.65 (dd, J =
7.6, 1.6 Hz, 1 H), 6.97 (dd, J = 7.6, 0.8 Hz, 1 H), 6.84 (dd, J = 8.1,
0.8 Hz, 1 H), 4.45 (d, J = 4.3 Hz, 1 H), 3.73 (s, 3 H), 3.69–3.73 (m,
1 H), 3.46–3.61 (m, 1 H), 2.94 (dd, J = 13.8, 7.6 Hz, 1 H), 2.82
(dd, J = 13.8, 7.6 Hz, 1 H), 2.31–2.42 (m, 1 H), 1.94 (br. s, 1
H) ppm. 13C NMR (syn isomer): δ = 156.0, 140.9, 140.5, 131.7,
129.8, 129.18, 128.25, 127.86, 125.8, 123.6, 121.2, 110.7, 90.5, 84.0,
62.0, 55.8, 48.8, 34.4, 33.2 ppm. 13C NMR (anti isomer): δ = 156.2,
129.5, 129.24, 128.6, 128.28, 128.2, 127.95, 126.0, 123.5, 120.7,
110.5, 89.7, 84.5, 63.2, 55.3, 47.1, 36.0, 32.8 ppm. HRMS (EI):
calcd. for C25H24O2 [M] 356.1776; found 356.1768. HPLC (syn-
5e; DAICEL Chiralpak OZ-H, hexane/iPrOH = 99:1, flow rate =
0.3 mL/min, λ = 254 nm): tR = 57.9 (minor), 130.0 (major) min;
81%ee. HPLC (anti-5e; DAICEL Chiralpak OZ-H, hexane/iPrOH
= 99:1, flow rate = 0.3 mL/min, λ = 254 nm): tR = 66.0 (major),
68.9 (minor) min; 79%ee.
H) ppm. H NMR (anti isomer): δ = 6.68–6.73 (m, 2 H), 3.95 (d,
J = 5.4 Hz, 1 H), 3.77 (dd, J = 11.3, 5.1 Hz, 1 H), 3.63 (dd, J =
11.3, 5.1 Hz, 1 H), 2.92 (s, 6 H), 2.88 (dd, J = 13.5, 7.3 Hz, 1 H),
2.79 (dd, J = 13.5, 7.6 Hz, 1 H) ppm. 13C NMR (syn isomer): δ =
149.6, 140.5, 131.7, 129.1, 128.8, 128.31, 128.25, 127.8, 127.5,
125.9, 123.7, 112.8, 90.3, 84.6, 62.81, 49.70, 40.74, 38.6, 33.9 ppm.
13C NMR (anti isomer): δ = 131.6, 129.2, 128.7, 128.4, 128.28,
127.9, 126.1, 123.6, 112.7, 90.0, 84.9, 62.77, 49.66, 40.68, 38.2,
35.9 ppm. HRMS (EI): calcd. for C26H27NO [M] 369.2093; found
369.2095. HPLC (syn-5b; DAICEL Chiralpak AS-H, hexane/
iPrOH = 93:7, flow rate = 0.5 mL/min, λ = 254 nm): tR = 44.7
(major), 70.3 (minor) min; 95%ee. HPLC (anti-5b; DAICEL Chi-
ralpak AS-H, hexane/iPrOH = 93:7, flow rate = 0.5 mL/min, λ =
254 nm): tR = 33.7 (major), 59.3 (minor) min; 96%ee.
2-Benzyl-3-(3,4-dimethoxyphenyl)-5-phenyl-4-pentyn-1-ol (5c): Iso-
1
lated yield 90% (syn-5c/anti-5c = 1.1:1). Pale yellow oil. H NMR
(syn isomer): δ = 7.46–7.53 (m, 2 H), 7.08–7.38 (m, 8 H), 7.10 (dd,
J = 8.0, 1.5 Hz, 1 H), 7.04 (dd, J = 8.8, 1.9 Hz, 1 H), 6.87 (d, J =
8.1 Hz, 1 H), 4.27 (d, J = 5.7 Hz, 1 H), 3.90 (s, 3 H), 3.88 (s, 3 H)
3.66 (dd, J = 10.9, 7.0 Hz, 1 H), 3.55 (dd, J = 10.9, 4.1 Hz, 1 H),
2.93 (dd, J = 13.8, 3.8 Hz, 1 H), 2.64 (dd, J = 13.8, 10.5 Hz, 1 H),
1
2.17–2.28 (m, 1 H), 1.63 (br. s, 1 H) ppm. H NMR (anti isomer):
2-Benzyl-3-(4-methoxyphenyl)-4-nonyn-1-ol (5f): Isolated yield 87%
δ = 7.44–7.51 (m, 2 H), 7.16–7.35 (m, 8 H), 6.91–6.98 (m, 2 H), (syn-5f/anti-5f = 1.0:1). Colorless oil. 1H NMR (syn isomer): δ =
6.83 (d, J = 8.1 Hz, 1 H), 3.99 (d, J = 5.7 Hz, 1 H), 3.87 (s, 3 H),
7.04–7.37 (m, 7 H), 6.86–6.91 (m, 2 H), 4.01 (dt, J = 5.7, 2.2 Hz,
1 H), 3.80 (s, 3 H), 3.58 (dd, J = 11.1, 7.0 Hz, 1 H), 3.49 (dd, J =
3.86 (s, 3 H), 3.80 (dd, J = 11.3, 4.9 Hz, 1 H), 3.63 (dd, J = 11.3,
4.9 Hz, 1 H), 2.86 (dd, J = 13.5, 7.3 Hz, 1 H), 2.79 (dd, J = 13.5, 11.1, 4.1 Hz, 1 H), 2.74–2.79 (m, 1 H), 2.54 (dd, J = 13.8, 10.5 Hz,
7.6 Hz, 1 H) ppm. 13C NMR (syn isomer): δ = 148.9, 147.9, 140.27, 1 H), 2.26–2.33 (m, 2 H), 1.99–2.13 (m, 1 H), 1.67 (br. s, 1 H),
132.6, 131.61, 129.0, 128.31, 128.28, 127.96, 126.0, 123.5, 120.3, 1.40–1.63 (m, 4 H), 0.95 (t, J = 7.3 Hz, 3 H) ppm. H NMR (anti
1
111.3, 111.1, 89.46, 85.1, 62.7, 55.9, 49.7, 39.0, 33.7 ppm. 13C NMR
(anti isomer): δ = 148.0, 140.29, 132.3, 131.57, 129.1, 128.4, 128.04,
126.1, 123.3, 120.2, 89.48, 85.2, 62.6, 49.6, 38.7, 35.8 ppm. HRMS
(EI): calcd. for C26H26O3 [M] 386.1882; found 386.1865. HPLC
(syn-5c; DAICEL Chiralpak OD, hexane/iPrOH = 92:8, flow rate
isomer): δ = 6.81–6.86 (m, 2 H), 3.78 (s, 3 H), 3.71 (dt, J = 4.6,
2.4 Hz, 1 H), 3.66–3.72 (m, 1 H), 3.52 (dd, J = 11.3, 4.9 Hz, 1 H),
2.71–2.85 (m, 2 H), 0.94 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR (syn
isomer): δ = 158.37, 140.6, 132.8, 129.07, 129.05, 128.3, 125.9,
113.8, 85.2, 79.6, 63.0, 55.28, 49.60, 38.2, 33.4, 31.21, 22.1, 18.58,
Eur. J. Org. Chem. 2011, 2239–2246
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2243

K. Motoyama, M. Ikeda, Y. Miyake, Y. Nishibayashi
FULL PAPER
13.64 ppm. 13C NMR (anti isomer): δ = 158.39, 140.5, 132.7,
129.12, 128.98, 128.4, 126.1, 85.5, 79.7, 62.7, 55.26, 49.57, 37.9,
(syn-5i; DAICEL Chiralpak OD, hexane/iPrOH = 95:5, flow rate
= 1.0 mL/min, λ = 254 nm): tR = 39.6 (major), 50.7 (minor) min;
36.0, 31.16, 18.55, 13.63 ppm. HRMS (EI): calcd. for C23H28O2 93%ee. HPLC (anti-5i; DAICEL Chiralpak OD, hexane/iPrOH =
[M] 336.2089; found 336.2093. HPLC (syn-5f; DAICEL Chiralpak
OD, hexane/iPrOH = 95:5, flow rate = 0.5 mL/min, λ = 254 nm): tR
= 22.6 (major), 27.0 (minor) min; 93%ee. HPLC (anti-5f; DAICEL
Chiralpak OD, hexane/iPrOH = 95:5, flow rate = 0.5 mL/min, λ =
254 nm): tR = 17.2 (major), 49.4 (minor) min; 87%ee.
95:5, flow rate = 1.0 mL/min, λ = 254 nm): tR = 29.7 (major), 85.0
(minor) min; 89%ee.
2-(Cyclohexylmethyl)-3-(4-methoxyphenyl)-5-phenyl-4-pentyn-1-ol
1
(5j): Isolated yield 93% (syn-5j/anti-5j = 1.1:1). Pale yellow oil. H
NMR (syn isomer): δ = 7.24–7.47 (m, 7 H), 6.85–6.91 (m, 2 H),
4.22 (d, J = 5.1 Hz, 1 H), 3.79 (s, 3 H), 3.72 (dd, J = 11.1, 7.7 Hz,
1 H), 3.65 (dd, J = 11.1, 4.1 Hz, 1 H), 1.92–2.11 (m, 1 H), 0.48–1.87
2-Benzyl-3-(4-methoxyphenyl)-6,6-dimethyl-4-heptyn-1-ol (5g): Iso-
lated yield 86% (syn-5g/anti-5g = 1.0:1). Colorless oil. 1H NMR
(syn isomer): δ = 7.10–7.36 (m, 5 H), 7.02–7.06 (m, 2 H), 6.86–6.91
(m, 2 H), 4.00 (d, J = 5.1 Hz, 1 H), 3.81 (s, 3 H), 3.59 (dd, J =
11.1, 6.8 Hz, 1 H), 3.52 (dd, J = 11.1, 4.1 Hz, 1 H), 2.72 (dd, J =
1
(m, 14 H) ppm. H NMR (anti isomer): δ = 4.00 (d, J = 5.7 Hz, 1
H), 3.75 (dd, J = 11.3, 4.3 Hz, 1 H), 3.61 (dd, J = 11.3, 5.4 Hz, 1
H), 1.92–2.11 (m, 1 H), 0.48–1.87 (m, 14 H) ppm. 13C NMR (syn
isomer): δ = 158.3, 132.2, 131.59, 129.07, 128.19, 127.8, 123.6,
13.8, 3.8 Hz, 1 H), 2.53 (dd, J = 13.8, 10.5 Hz, 1 H), 2.00–2.11 (m,
1
1 H), 1.64 (br. s, 1 H), 1.30 (s, 9 H) ppm. H NMR (anti isomer): 113.7, 89.8, 84.55, 64.2, 55.2, 44.5, 38.7, 35.1, 34.7, 34.4, 32.5, 26.5,
δ = 7.14–7.36 (m, 7 H), 6.82–6.87 (m, 2 H), 3.79 (s, 3 H), 3.70 (d,
J = 5.1 Hz, 1 H), 3.67 (dd, J = 11.3, 4.6 Hz, 1 H), 3.52 (dd, J =
11.3, 5.1 Hz, 1 H), 2.88–2.74 (m, 2 H) ppm. 13C NMR (syn isomer):
δ = 158.32, 140.6, 132.7, 129.0, 128.2, 125.8, 113.7, 94.1, 78.0, 63.2,
26.3, 26.1 ppm. 13C NMR (anti isomer): δ = 158.4, 132.1, 131.56,
129.13, 128.21, 127.9, 123.4, 113.8, 90.2, 84.47, 63.5, 44.0, 39.1,
36.9, 34.9, 33.7, 33.3, 26.6, 26.2 ppm. HRMS (EI): calcd. for
C25H30O2 [M] 362.2246; found 362.2262. HPLC (syn-5j; DAICEL
55.25, 49.7, 38.1, 33.1, 31.33, 27.6 ppm. 13C NMR (anti isomer): δ Chiralpak AS-H, hexane/iPrOH = 95:5, flow rate = 0.2 mL/min, λ
= 158.34, 140.5, 132.6, 129.1, 128.9, 128.4, 126.0, 94.4, 78.2, 62.8,
55.22, 49.6, 37.5, 36.1, 31.26, 27.7 ppm. HRMS (EI): calcd. for
C23H28O2 [M] 336.2089; found 336.2092. HPLC (syn-5g; DAICEL
Chiralpak IC, hexane/iPrOH = 95:5, flow rate = 0.5 mL/min, λ =
254 nm): tR = 14.2 (major), 28.1 (minor) min; 92%ee. HPLC (anti-
5g; DAICEL Chiralpak IC, hexane/iPrOH = 95:5, flow rate =
0.5 mL/min, λ = 254 nm): tR = 15.4 (major), 16.5 (minor) min;
85%ee.
= 254 nm): tR = 48.7 (major), 64.1 (minor) min; 87%ee. HPLC
(anti-5j; DAICEL Chiralpak AS-H, hexane/iPrOH 95:5,
flow rate = 0.2 mL/min, λ = 254 nm): tR = 42.4 (major), 53.0
(minor) min; 84%ee.
=
2-[1-(4-Methoxyphenyl)-3-phenyl-2-propynyl]heptan-1-ol (5k): Iso-
1
lated yield 91% (syn-5k/anti-5k = 1.1:1). Pale yellow oil. H NMR
(syn isomer): δ = 7.27–7.47 (m, 7 H), 6.85–6.91 (m, 2 H), 4.20 (d,
J = 5.4 Hz, 1 H), 3.80 (s, 3 H), 3.75 (dd, J = 10.8, 7.0 Hz, 1 H),
3.69 (dd, J = 10.8, 4.3 Hz, 1 H), 1.84–1.95 (m, 1 H), 1.64 (br. s, 1
2-Benzyl-3-(4-methoxyphenyl)-5-(trimethylsilyl)-4-pentyn-1-ol (5h):
Isolated yield 79% (syn-5h/anti-5h = 1.0:1). Colorless oil. 1H NMR
(syn isomer): δ = 7.05–7.36 (m, 7 H), 6.86–6.92 (m, 2 H), 4.05 (d,
J = 5.7 Hz, 1 H), 3.81 (s, 3 H), 3.58 (dd, J = 11.1, 6.8 Hz, 1 H),
3.49 (dd, J = 11.1, 4.1 Hz, 1 H), 2.79 (dd, J = 13.8, 3.8 Hz, 1 H),
2.56 (dd, J = 13.8, 10.5 Hz, 1 H), 2.02–2.15 (m, 1 H), 1.64 (br. s, 1
1
H), 1.08–1.53 (m, 8 H), 0.83 (t, J = 6.8 Hz, 3 H) ppm. H NMR
(anti isomer): δ = 4.01 (d, J = 5.9 Hz, 1 H), 3.78 (dd, J = 11.3,
4.6 Hz, 1 H), 3.66 (dd, J = 11.3, 5.3 Hz, 1 H), 1.13–1.54 (m, 8 H),
0.88 (t, J = 6.8 Hz, 3 H) ppm. 13C NMR (syn isomer): δ = 158.3,
132.4, 131.6, 129.07, 128.19, 127.8, 123.6, 113.7, 89.9, 84.4, 63.7,
55.2, 47.5, 38.7, 32.0, 27.02, 27.0, 22.47, 13.96 ppm. 13C NMR (anti
isomer): δ = 158.4, 132.2, 131.5, 129.10, 128.20, 127.9, 123.4, 113.8,
1
H), 0.23 (s, 9 H) ppm. H NMR (anti isomer): δ = 6.82–6.88 (m, 2
H), 3.79 (s, 3 H), 3.76 (d, J = 5.4 Hz, 1 H), 3.71 (dd, J = 11.3,
4.6 Hz, 1 H), 3.52 (dd, J = 11.3, 4.1 Hz, 1 H), 2.70–2.86 (m, 2 90.2, 84.5, 63.2, 47.2, 39.0, 29.1, 26.9, 22.53, 14.01 ppm. HRMS
H) ppm. 13C NMR (syn isomer): δ = 158.47, 140.35, 131.6, 129.07,
(EI): calcd. for C23H28O2 [M] 336.2089; found 336.2088. HPLC
129.02, 128.3, 125.9, 113.8, 106.6, 89.4, 62.65, 55.24, 49.46, 39.1,
(syn-5k; DAICEL Chiralpak IC, hexane/iPrOH = 95:5, flow rate =
33.3, 0.14 ppm. 13C NMR (anti isomer): δ = 158.50, 140.31, 131.4, 0.2 mL/min, λ = 254 nm): tR = 34.2 (major), 40.5 (minor) min;
129.06, 129.00, 128.4, 126.1, 106.7, 89.7, 62.57, 55.22, 49.48, 38.7,
35.8, 0.07 ppm. HRMS (EI): calcd. for C22H28O2Si [M] 352.1859;
found 352.1873. HPLC (syn-5h; DAICEL Chiralpak IC, hexane/
iPrOH = 99:1, flow rate = 0.3 mL/min, λ = 254 nm): tR = 33.3
(major), 56.9 (minor) min; 90%ee. HPLC (anti-5h; DAICEL Chi-
ralpak IC, hexane/iPrOH = 99:1, flow rate = 0.3 mL/min, λ =
254 nm): tR = 31.1 (major), 37.2 (minor) min; 83%ee.
85%ee. HPLC (anti-5k; DAICEL Chiralpak IC, hexane/iPrOH =
95:5, flow rate = 0.2 mL/min, λ = 254 nm): tR = 31.4 (major), 36.7
(minor) min; 82%ee.
6-Chloro-2-[1-(4-methoxyphenyl)-3-phenyl-2-propynyl]hexan-1-ol (5l):
Isolated yield 94% (syn-5l/anti-5l = 1.1:1). Pale yellow oil. 1H
NMR (syn isomer): δ = 7.42–7.47 (m, 2 H), 7.28–7.39 (m, 5 H),
6.86–6.91 (m, 2 H), 4.20 (d, J = 5.4 Hz, 1 H), 3.81 (s, 3 H), 3.76
2-(4-Chlorobenzyl)-3-(4-methoxyphenyl)-5-phenyl-4-pentyn-1-ol (5i): (dd, J = 11.1, 7.3 Hz, 1 H), 3.69 (dd, J = 11.1, 4.3 Hz, 1 H), 3.45
1
Isolated yield 92% (syn-5i/anti-5i = 1.2:1). Colorless oil. H NMR
(syn isomer): δ = 7.15–7.50 (m, 9 H), 6.99–7.04 (m, 2 H), 6.87–6.93
(m, 2 H), 4.24 (d, J = 5.9 Hz, 1 H), 3.81 (s, 3 H), 3.57–3.65 (m, 1
H), 3.50 (dd, J = 10.8, 4.1 Hz, 1 H), 2.86 (dd, J = 13.8, 4.1 Hz, 1
H), 2.63 (dd, J = 13.8, 10.3 Hz, 1 H), 2.09–2.20 (m, 1 H), 1.62 (br.
(t, J = 6.6 Hz, 2 H),1.85–1.96 (m, 1 H), 1.14–1.77 (m, 7 H) ppm.
1H NMR (anti isomer): δ = 4.01 (d, J = 5.9 Hz, 1 H), 3.80 (dd, J
= 11.1, 4.9 Hz, 1 H), 3.68 (dd, J = 11.1, 5.1 Hz, 1 H), 3.53 (t, J =
6.6 Hz, 2 H), 1.26–1.84 (m, 8 H) ppm. 13C NMR (syn isomer): δ =
158.4, 132.1, 131.58, 129.0, 128.23, 127.9, 123.5, 113.8, 89.6, 84.7,
63.6, 55.2, 47.3, 44.8, 38.7, 32.61, 26.3, 24.6 ppm. 13C NMR (anti
isomer): δ = 158.5, 131.9, 131.56, 129.1, 128.24, 128.0, 123.3, 113.9,
1
d, J = 17.0 Hz, 1 H) ppm. H NMR (anti isomer): δ = 7.15–7.50
(m, 11 H), 6.84–6.90 (m, 2 H), 3.95 (d, J = 5.7 Hz, 1 H), 3.79 (s, 3
H), 3.74–3.79 (m, 1 H), 3.55–3.65 (m, 1 H), 2.78–2.81 (m, 2 89.9, 84.5, 63.0, 47.1, 44.9, 38.9, 32.64, 28.4, 24.5 ppm. HRMS
H) ppm. 13C NMR (syn isomer): δ = 158.5, 138.79, 131.91, 131.7,
(EI): calcd. for C22H25ClO2 [M] 356.1543; found 356.1533. HPLC
131.64, 130.4, 129.1, 128.31, 128.28, 128.0, 123.4, 113.9, 89.4, (syn-5l; DAICEL Chiralpak IC, hexane/iPrOH = 98:2, flow rate =
85.15, 62.5, 55.27, 49.6, 38.6, 32.9 ppm. 13C NMR (anti isomer): δ 0.4 mL/min, λ = 254 nm): tR = 70.2 (major), 75.3 (minor) min;
= 158.6, 138.83, 131.86, 131.61, 131.57, 130.5, 129.0, 128.5, 128.4,
128.1, 123.2, 89.3, 85.22, 62.3, 55.26, 49.5, 38.2, 35.1 ppm. HRMS
(EI): calcd. for C25H23ClO2 [M] 390.1387; found 390.1393. HPLC
88%ee. HPLC (anti-5l; DAICEL Chiralpak IC, hexane/iPrOH =
98:2, flow rate = 0.4 mL/min, λ = 254 nm): tR = 57.6 (major), 61.1
(minor) min; 85%ee.
2244
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2239–2246

Cooperative Catalytic Reactions Using Lewis Acids and Organocatalysts
García-Tellado, Angew. Chem. 2010, 122, 1029; Angew. Chem.
Int. Ed. 2010, 49, 1013; d) C. Zhong, X. Shi, Eur. J. Org. Chem.
2010, 2999; e) M. Rueping, R. M. Koenigs, I. Atodiresei,
Chem. Eur. J. 2010, 16, 9350; for recent examples, see: f) B. G.
Jellerichs, J.-R. Kong, M. J. Krische, J. Am. Chem. Soc. 2003,
125, 7758; g) I. Ibrahem, A. Córdova, Angew. Chem. 2006, 118,
1986; Angew. Chem. Int. Ed. 2006, 45, 1952; h) M. Rueping,
A. P. Antonchick, C. Brinkmann, Angew. Chem. 2007, 119,
7027; Angew. Chem. Int. Ed. 2007, 46, 6903; i) S. Mukherjee,
B. List, J. Am. Chem. Soc. 2007, 129, 11336; j) K. Sorimachi,
M. Terada, J. Am. Chem. Soc. 2008, 130, 14452; k) I. Usui, S.
Schmidt, B. Breit, Org. Lett. 2009, 11, 1453; l) M. Terada, Y.
Toda, J. Am. Chem. Soc. 2009, 131, 6354; m) C. Li, B. Villa-
Marcos, J. Xiao, J. Am. Chem. Soc. 2009, 131, 6967; n) Z.-Y.
Han, H. Xiao, X.-H. Chen, L.-Z. Gong, J. Am. Chem. Soc.
2009, 131, 9182; o) Y. Lu, T. C. Johnstone, B. A. Arndtsen, J.
Am. Chem. Soc. 2009, 131, 11284; p) S. Belot, K. A. Vogt, C.
Besnard, N. Krause, A. Alexakis, Angew. Chem. 2009, 121,
9085; Angew. Chem. Int. Ed. 2009, 48, 8923; q) G.-L. Zhao, F.
Ullah, L. Deiana, S. Lin, Q. Zhang, J. Sun, I. Ibrahem, P.
Dziedzic, A. Córdova, Chem. Eur. J. 2010, 16, 1585; r) K. L.
Jensen, P. T. Franke, C. Arróniz, S. Kobbelgaard, K. A.
Jørgensen, Chem. Eur. J. 2010, 16, 1750; s) D. E. A. Raup, B.
Cardinal-David, D. Holte, K. A. Scheidt, Nat. Chem. 2010, 2,
766.
a) R. Sanz, A. Martínez, J. M. Álvarez-Gutiérrez, F. Rodríg-
uez, Eur. J. Org. Chem. 2006, 1383; b) R. Sanz, D. Miguel,
A. Martínez, J. M. Álvarez-Gutiérrez, F. Rodríguez, Org. Lett.
2007, 9, 727.
a) M. Yasuda, T. Saito, M. Ueba, A. Baba, Angew. Chem. 2004,
116, 1438; Angew. Chem. Int. Ed. 2004, 43, 1414; b) Y. Nishim-
oto, M. Kajioka, T. Saito, M. Yasuda, A. Baba, Chem. Com-
mun. 2008, 6396; c) Y. Nishimoto, Y. Onishi, M. Yasuda, A.
Baba, Angew. Chem. 2009, 121, 9295; Angew. Chem. Int. Ed.
2009, 48, 9131.
a) R. R. Shaikh, A. Mazzanti, M. Petrini, G. Bartoli, P. Mel-
chiorre, Angew. Chem. 2008, 120, 8835; Angew. Chem. Int. Ed.
2008, 47, 8707; b) P. G. Cozzi, F. Benfatti, L. Zoli, Angew.
Chem. 2009, 121, 1339; Angew. Chem. Int. Ed. 2009, 48, 1313.
M. G. Capdevila, F. Benfatti, L. Zoli, M. Stenta, P. G. Cozzi,
Chem. Eur. J. 2010, 16, 11237.
a) Z.-P. Zhan, J.-L. Yu, H.-J. Liu, Y.-Y. Cui, R.-F. Yang, W.-Z.
Yang, J.-P. Li, J. Org. Chem. 2006, 71, 8298; b) Z.-P. Zhan, Y.-
Y. Cui, H.-J. Liu, Tetrahedron Lett. 2006, 47, 9143; c) Z.-P.
Zhan, H.-J. Liu, Synlett 2006, 2278; d) Z.-P. Zhan, X.-B. Cai,
S.-P. Wang, J.-L. Yu, H.-J. Liu, Y.-Y. Cui, J. Org. Chem. 2007,
72, 9838.
a) G. Hattori, H. Matsuzawa, Y. Miyake, Y. Nishibayashi, An-
gew. Chem. 2008, 120, 3841; Angew. Chem. Int. Ed. 2008, 47,
3781; b) G. Hattori, A. Yoshida, Y. Miyake, Y. Nishibayashi,
J. Org. Chem. 2009, 74, 7603; c) G. Hattori, Y. Miyake, Y. Nish-
ibayashi, ChemCatChem 2010, 2, 155; d) G. Hattori, K. Sakata,
H. Matsuzawa, Y. Tanabe, Y. Miyake, Y. Nishibayashi, J. Am.
Chem. Soc. 2010, 132, 10592; e) A. Yoshida, M. Ikeda, G. Hat-
tori, Y. Miyake, Y. Nishibayashi, Org. Lett. 2011, 13, 592.
a) R. J. Detz, M. M. E. Delville, H. Hiemstra, J. H. van Maar-
seveen, Angew. Chem. 2008, 120, 3837; Angew. Chem. Int. Ed.
2008, 47, 3777; b) Prof. van Maarseveen and co-workers
achieved the first enantioselective propargylic amination and
presented a part of their results at the PAC-Symposium 2007
(March 1, 2007, Utrecht).
Supporting Information (see footnote on the first page of this arti-
cle): Copies of the NMR spectra and HPLC traces of the propar-
gylic alkylated products after reduction.
Acknowledgments
This work was supported by a Grant-in-Aid for Scientific Research
for Young Scientists (S) from the Ministry of Education, Culture,
Sports, Science and Technology, Japan (No. 19675002) and the
Funding Program for Next Generation World-Leading Researchers
(GR025). M. I. acknowledges the Global COE Program for Chem-
istry Innovation. Y. N. thanks Ube Industries, Ltd.
[1] M. Ikeda, Y. Miyake, Y. Nishibayashi, Angew. Chem. 2010, 122,
7447; Angew. Chem. Int. Ed. 2010, 49, 7289.
[2] a) Y. Inada, Y. Nishibayashi, S. Uemura, Angew. Chem. 2005,
117, 7893; Angew. Chem. Int. Ed. 2005, 44, 7715; b) H. Matsuz-
awa, M. Miyake, Y. Nishibayashi, Angew. Chem. 2007, 119,
6608; Angew. Chem. Int. Ed. 2007, 46, 6488; c) H. Matsuzawa,
K. Kanao, Y. Miyake, Y. Nishibayashi, Org. Lett. 2007, 9, 5561;
d) K. Kanao, H. Matsuzawa, Y. Miyake, Y. Nishibayashi, Syn-
thesis 2008, 3869; e) K. Fukamizu, Y. Miyake, Y. Nishibayashi,
J. Am. Chem. Soc. 2008, 130, 10498; f) K. Kanao, Y. Miyake,
Y. Nishibayashi, Organometallics 2009, 28, 2920; g) K. Kanao,
Y. Miyake, Y. Nishibayashi, Organometallics 2010, 29, 2126; h)
K. Kanao, Y. Tanabe, Y. Miyake, Y. Nishibayashi, Organome-
tallics 2010, 29, 2381.
[8]
[9]
[3] For recent reviews on transition-metal–allenylidene complexes,
see: a) C. Bruneau, P. H. Dixneuf, Angew. Chem. 2006, 118,
2232; Angew. Chem. Int. Ed. 2006, 45, 2176; b) C. Bruneau,
P. H. Dixneuf (Eds.), Metal Vinylidenes and Allenylidenes in
Catalysis: From Reactivity to Applications in Synthesis, Wiley-
VCH, Weinheim, 2008; c) V. Cadierno, J. Gimeno, Chem. Rev.
2009, 109, 3512.
[10]
[4] For recent reviews, see: a) A. Berkessel, H. Gröger (Eds.),
Asymmetric Organocatalysis, Wiley-VCH, Weinheim, 2005; b)
P. I. Dalko (Ed.), Enantioselective Organocatalysis, Wiley-VCH,
Weinheim, 2007; c) B. List (Ed.), Asymmetric Organocatalysis,
Springer, Heidelberg, 2010; d) S. Mukherjee, J. W. Yang, S.
Hoffmann, B. List, Chem. Rev. 2007, 107, 5471; e) D. Enders,
C. Grondal, M. R. M. Hüttl, Angew. Chem. 2007, 119, 1590;
Angew. Chem. Int. Ed. 2007, 46, 1570; f) A. Dondoni, A. Massi,
Angew. Chem. 2008, 120, 4716; Angew. Chem. Int. Ed. 2008,
47, 4638; g) P. Melchiorre, M. Marigo, A. Carlone, G. Bartoli,
Angew. Chem. 2008, 120, 6232; Angew. Chem. Int. Ed. 2008,
47, 6138; h) D. W. C. MacMillan, Nature 2008, 455, 304; i) S.
Bertelsen, K. A. Jørgensen, Chem. Soc. Rev. 2009, 38, 2178; j)
C. Grondal, M. Jeanty, D. Enders, Nat. Chem. 2010, 2, 167.
[5] For recent reviews, see: a) Y. Nishibayashi, S. Uemura, Curr.
Org. Chem. 2006, 10, 135; b) Y. Nishibayashi, S. Uemura, Com-
prehensive Organometallic Chemistry III (Eds.: R. H. Crabtree,
D. M. P. Mingos), Elsevier, Amsterdam, 2007, vol. 11, p. 123;
c) G. W. Kabalka, M.-L. Yao, Curr. Org. Synth. 2008, 5, 28; d)
N. Ljungdahl, N. Kann, Angew. Chem. 2009, 121, 652; Angew.
Chem. Int. Ed. 2009, 48, 642; e) Y. Miyake, S. Uemura, Y. Nish-
ibayashi, ChemCatChem 2009, 1, 342; f) R. J. Detz, H. Hiem-
stra, J. H. van Maarseveen, Eur. J. Org. Chem. 2009, 6263.
[6] a) Y. Inada, Y. Nishibayashi, M. Hidai, S. Uemura, J. Am.
Chem. Soc. 2002, 124, 15172; b) Y. Nishibayashi, Y. Inada, M.
Yoshikawa, M. Hidai, S. Uemura, Angew. Chem. 2003, 115,
1533; Angew. Chem. Int. Ed. 2003, 42, 1495; c) Y. Nishibayashi,
A. Shinoda, Y. Miyake, H. Matsuzawa, M. Sato, Angew. Chem.
2006, 118, 4953; Angew. Chem. Int. Ed. 2006, 45, 4835.
[7] A new type of dual catalytic reaction using both organocata-
lysts and metal catalysts has already been reported; for recent
reviews, see: a) Z. Shao, H. Zhang, Chem. Soc. Rev. 2009, 38,
2745; b) M. Klussmann, Angew. Chem. 2009, 121, 7260; Angew.
Chem. Int. Ed. 2009, 48, 7124; c) P. de Armas, D. Tejedor, F.
[11]
[12]
[13]
[14]
[15]
The copper-catalyzed enantioselective propargylic alkylation of
propargylic acetates with enamines was reported by using our
reaction system, where Cl-MeO-BIPHEP and BINAP worked
as good chiral ligands, see: P. Fang, X.-L. Hou, Org. Lett. 2009,
11, 4612.
For a recent review, see: A.-N. Alba, M. Viciano, R. Rios,
ChemCatChem 2009, 1, 437.
[16]
[17]
For recent examples, see: a) D. A. Nicewicz, D. W. C. MacMil-
lan, Science 2008, 322, 77; b) S. Belot, A. Massaro, A. Tenti,
Eur. J. Org. Chem. 2011, 2239–2246
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2245

K. Motoyama, M. Ikeda, Y. Miyake, Y. Nishibayashi
FULL PAPER
A. Mordini, A. Alexakis, Org. Lett. 2008, 10, 4557; c) J. Wu,
B. Ni, A. D. Headley, Org. Lett. 2009, 11, 3354; d) T. Itoh, H.
Ishikawa, Y. Hayashi, Org. Lett. 2009, 11, 3854; e) H. Yang,
R. G. Carter, J. Org. Chem. 2009, 74, 2246; f) M. Laars, K.
Ausmees, M. Uudsemaa, T. Tamm, T. Kanger, M. Lopp, J.
16, 12616; l) R. Husmann, M. Jörres, G. Raabe, C. Bolm,
Chem. Eur. J. 2010, 16, 12549; m) Y. K. Kang, S. M. Kim, D. Y.
Kim, J. Am. Chem. Soc. 2010, 132, 11847; n) H.-W. Shih,
M. N. V. Wal, R. L. Grange, D. W. C. MacMillan, J. Am.
Chem. Soc. 2010, 132, 13600.
Org. Chem. 2009, 74, 3772; g) Z. Zheng, B. L. Perkins, B. Ni, [18] a) S. R. Stauffer, J. F. Hartwig, J. Am. Chem. Soc. 2003, 125,
J. Am. Chem. Soc. 2010, 132, 50; h) A. Quintard, S. Belot, E.
Marchal, A. Alexakis, Eur. J. Org. Chem. 2010, 927; i) J. Xiao,
F.-X. Xu, Y.-P. Lu, T.-P. Loh, Org. Lett. 2010, 12, 1220; j) P.
Galzerano, D. Agostino, G. Bencivenni, L. Sambri, G. Bartoli,
P. Melchiorre, Chem. Eur. J. 2010, 16, 6069; k) H. Ishikawa, T.
Suzuki, H. Orita, T. Uchimaru, Y. Hayashi, Chem. Eur. J. 2010,
6977; b) B. M. Nestl, S. M. Glueck, M. Hall, W. Kroutil, R.
Stuermer, B. Hauer, K. Faber, Eur. J. Org. Chem. 2006, 4573.
[19] R. J. Fox, G. Lalic, R. G. Bergman, J. Am. Chem. Soc. 2007,
129, 14144.
Received: January 12, 2011
Published Online: March 1, 2011
2246
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2239–2246