Ruthenium-Catalyzed Propargylic Reduction of Propargylic Alcohols with Hantzsch Ester

Article abstract of DOI:10.1021/acs.organomet.0c00187

Ruthenium-catalyzed propargylic reduction of propargylic alcohols bearing a terminal alkyne moiety is accomplished by using Hantzsch ester as a nucleophilic hydride source. A variety of secondary and tertiary propargylic alcohols are reduced to the corresponding propargylic reduced products such as 1-alkynes in excellent yields. Some mechanistic studies indicate that ruthenium-allenylidene complexes may work as key reactive intermediates.

Full text of DOI:10.1021/acs.organomet.0c00187

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Article
Ruthenium-Catalyzed Propargylic Reduction of Propargylic Alcohols
with Hantzsch Ester
Haowei Ding, Ken Sakata,* Shogo Kuriyama, and Yoshiaki Nishibayashi*
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ABSTRACT: Ruthenium-catalyzed propargylic reduction of propargylic alcohols
bearing a terminal alkyne moiety is accomplished by using Hantzsch ester as a
nucleophilic hydride source. A variety of secondary and tertiary propargylic alcohols
are reduced to the corresponding propargylic reduced products such as 1-alkynes in
excellent yields. Some mechanistic studies indicate that ruthenium−allenylidene
complexes may work as key reactive intermediates.
In order to expand the utility of propargylic reduction, we
have explored the use of a new hydride source. As a result, we
have focused on Hantzsch ester, which can work as a formal
hydride donor accompanied by aromatization into the
corresponding pyridine.11 Hantzsch ester is well-known as a
bench-stable reagent and is very easy to prepare by a single
one-pot reaction from commercially available reagents. Very
recently, Sun and co-workers have reported enantioselective
propargylic reduction of propargylic alcohols with Hantzsch
esters using optically active phosphoric acid as an organo-
catalyst to give the corresponding propargylic reduced
products with a high enantioselectivity.12 However, unfortu-
nately, the use of a 4-hydroxyphenyl moiety at the propargylic
position of the propargylic alcohols is necessary because an
interaction between the phosphoric acid and a p-quinone
methide generated from the 4-hydroxyphenyl moiety at the
propargylic position of the propargylic alcohols plays an
important role in achieving the high enantioselectivity. As a
result, a synthetically useful methodology for propargylic
reduction of propargylic alcohols without a 4-hydroxyphenyl
moiety at the propargylic position with Hantzsch esters has not
been reported until now.
INTRODUCTION
■
Deoxygenation reactions, the removal of oxygen functional
groups from organic skeletons, are attractive molecular
transformations because of their broad utility. For example,
deoxygenation often serves as a key step to prepare
pharmaceuticals and bioactive compounds.1 Also, deoxygena-
tion processes have been extensively studied in relation to
biomass applications to convert naturally produced polyoxy-
genated compounds such as saccharides and lignin into useful
chemical feedstocks.2 Toward these applications, the direct
substitution process of a hydroxy group with a hydrogen atom
provides a simple and important synthetic strategy.
The substitution reaction system is a methodology of prime
importance in organic synthesis. Transition-metal-catalyzed
allylic substitution reactions have been widely examined since
the 1960s;3,4 however, catalytic propargylic substitution
reactions were relatively limited until 2000. In 2000, thiolate-
bridged diruthenium complexes as bioinspired catalysts were
reported to catalytically promote propargylic substitution
reactions of propargylic alcohols bearing a terminal alkyne
moiety with various carbon- and heteroatom-centered
nucleophiles to give the corresponding propargylic substituted
products in good to high yields with complete selectivity. In
this reaction system, ruthenium−allenylidene complexes were
found to work as key reactive intermediates.5,6 After our
milestone work, a variety of transition-metal-catalyzed
propargylic substitution reactions of propargylic alcohol
derivatives were reported by many research groups.7,8
On the basis of these research backgrounds, we have
envisaged a new type of propargylic reduction of propargylic
alcohols with Hantzsch ester in the presence of a catalytic
amount of thiolate-bridged diruthenium complexes. Here, we
report detailed results.
In the course of our continuous study, we previously
succeeded in propargylic substitution reactions with hydride
nucleophiles such as triethylsilane9a and isopropyl alcohol9b as
an effective deoxygenative reduction process. Separately,
gold-10a and calcium-catalyzed10b propargylic reduction of
propargylic alcohols bearing an internal alkyne moiety with
silanes as hydride sources were also reported to give the
corresponding propargylic reduced products.
Received: March 20, 2020
https://dx.doi.org/10.1021/acs.organomet.0c00187
© XXXX American Chemical Society
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RESULTS AND DISCUSSION
Scheme 1. Scope of Propargylic Reduction with Hantzsch
Ester
■
a
We investigated reactions of 1-([1,1′-biphenyl]-4-yl)prop-2-
yn-1-ol (2a) with Hantzsch ester (3) in the presence of
catalytic amounts of thiolate-bridged diruthenium complexes
(1) and NH4BF4 to afford 3-([1,1′-biphenyl]-4-yl)-1-propyne
(4a) as the corresponding propargylic reduced product.
Typical results are shown in Table 1. The reaction of 2a
a
Table 1. Screening the Reaction Conditions
b
a
entry
solvent
3 (equiv)
Ru complex 1 [mol %]
yield (%)
Reactions of 2 (0.25 mmol) with 3 (0.25 mmol) were carried out in
the presence of 1a (0.0125 mmol, 5 mol %) and NH4BF4 (0.025
mmol, 10 mol %) in THF (2.5 mL) at 60 °C for 6 h.
1
2
3
4
5
6
7
8
9
10
11
12
13
DME
DCM
DCE
Et2O
MeCN
toluene
THF
THF
THF
THF
THF
THF
THF
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.0
1.0
1.0
1.0
1.0
1a [10]
1a [10]
1a [10]
1a [10]
1a [10]
1a [10]
1a [10]
1b [10]
1a [10]
1a [5]
85
83
79
0
alcohols were suitable for this protocol, giving the desired
products in high to quantitative yields. Relatively, isolated
yields are generally lower than NMR yields due to the high
volatility of the propargylic reduced products. The presence of
both electron-withdrawing and -donating groups on the
benzene ring at the propargylic position was well tolerated to
give the products in high yields (4a−n). However, the
introduction of trifluoromethyl and dibromo groups to the
benzene ring at the propargylic position significantly decreased
the yields of the products to 43% and 63%, respectively (4i,n).
Naphthyl groups in place of phenyl groups at the propargylic
position were also tolerated in this protocol to give the desired
products in high yields (4o,p). It is noteworthy that tertiary
propargylic alcohols bearing two aryl groups at the propargylic
position were transformed successfully to afford the corre-
sponding 3,3-diaryl-1-alkynes in 66−80% yields (4q−t).
We also investigated the use of propargylic alcohols bearing
alkyl group(s) at the propargylic position under the same
reaction conditions. The reaction of 2-([1,1′-biphenyl]-4-
yl)but-3-yn-2-ol (2u) gave 3-([1,1′-biphenyl]-4-yl)-1-butyne
(4u) in 88% yield. This result is in sharp contrast to the
formation of the corresponding 1,3-enynes from reactions of
propargylic alcohols bearing only alkyl groups at the
propargylic position such as 1-ethynyl-4-phenylcyclohexanol
(2v) and 1-tetradecyn-3-ol (2w) (Scheme 2). These results
indicate that propargylic alcohols bearing only alkyl groups at
the propargylic position were not applicable in the current
reaction system.9a To demonstrate the potential of this
protocol in practical synthesis, we carried out a large-scale
reaction of 1 mmol of 2a under the same reaction conditions
to afford 4a in quantitative yield.
0
70
90
88
99
94
99
trace
0
c
1a [5]
1a [0.1]
none
a
Unless noted otherwise, reactions of 2a (0.25 mmol) with 3 were
carried out in the presence of 1 and NH4BF4 (0.025 mmol, 10 mol %)
in solvent (2.5 mL) at room temperature for 18 h. Isolated yields.
At 60 °C for 6 h.
b
c
with 1.5 equiv of 3 was carried out in the presence of 10 mol %
of the methanethiolate-bridged diruthenium complex
[Cp*RuCl(SMe)]2 (1a; Cp* = η5-C5Me5) and 10 mol % of
NH4BF4 at room temperature for 18 h. First, we used various
solvents such as 1,2-dimethoxyethane (DME), dichloro-
methane (DCM), 1,2-dichloroethane (DCE), diethyl ether,
acetonitrile, toluene, and THF. Among them, THF was proved
to be the optimal solvent (Table 1, entries 1−7). When the 2-
propanethiolate-bridged diruthenium complex [Cp*RuCl(Si-
Pr)]2 (1b) was used in place of 1a as a catalyst, the yield of 4a
decreased slightly (Table 1, entry 8). When the amount of 3
was reduced to 1.0 equiv, 4a was obtained quantitatively
(Table 1, entry 9). In contrast, reduction of the amount of 1a
to 5 mol % slightly decreased the yield of 4a (Table 1, entry
10). On the other hand, the reaction in the presence of 5 mol
% of 1a at 60 °C gave 4a quantitatively (Table 1, entry 11).
However, when the catalyst loading of 1a was reduced to 0.1
mol %, only a trace amount of 4a was observed (Table 1, entry
12). Separately, we confirmed that no reaction occurred in the
absence of catalyst together with recovery of 2a in 95% yield
(Table 1, entry 13).
In order to obtain a mechanistic insight, we examined the
reaction of a propargylic alcohol bearing an internal alkyne
moiety (2x) (Scheme 3). In this case, no target product was
observed at all, while 87% of the starting propargylic alcohol
was recovered. As mentioned in the Introduction, we
previously reported the propargylic reduction of propargylic
alcohols bearing an internal alkyne moiety with triethylsilane.9a
In sharp contrast to the previous reaction system, the present
With the optimized conditions (Table 1, entry 11) in hand,
the scope of propargylic alcohols was investigated. Typical
results are shown in Scheme 1. A variety of propargylic
B
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Scheme 2. Reactions of Propargylic Alcohols Bearing Alkyl
Group(s) at the Propargylic Position with Hantzsch Ester
Scheme 5. Catalytic Reaction of Ruthenium−Allenylidene
Complex 5 with Hantzsch Ester
Scheme 6. Deuterium-Labeling Experiment
propargylic reduced product 4a-d with selective deuterium
incorporation at the propargylic position in 98% yield. This
result indicates that the hydrogen atom at the propargylic
position was derived from the 4-position of the dihydropyr-
idine. We also examined a competitive reaction with a mixture
of 3 and 3-d2 with the ratio of 3 and 3-d2 being 1:1. In this
case, a mixture of 4a and 4a-d was obtained in 91% yield with a
ratio of 4a and 4a-d2 of 7:3 (Scheme 7). These results indicate
that the hydrogen transfer may be involved in the rate-limiting
step of the present reaction system.
Scheme 3. Reaction of 1,3-Diphenyl-1-propyn-3-ol (2x)
with Hantzsch Ester
reaction system successfully promoted the propargylic
reduction of propargylic alcohols bearing a terminal alkyne
moiety. The unique reactivity of the present reaction system
suggests that the present reactions proceed via ruthenium−
allenylidene complexes as key reactive intermediates.
Scheme 7. Reaction of 2a with a Mixture of 3 and 3-d2
To get information on the reaction pathway, we examined
the stoichiometric reaction of a ruthenium−allenylidene
complex. The allenylidene complex 5 was prepared and
isolated from the reaction of 1a with 1-(1-naphthyl)-2-
propyn-1-ol (2o) according to a previous report.13 The
isolated ruthenium−allenylidene complex 5 reacted with 10
equiv of 3 in the presence of another propargylic alcohol 2a at
room temperature for 18 h to afford the corresponding
propargylic reduced product 4o in 43% (NMR) yield together
with 4a in 56% (NMR) yield (Scheme 4). Furthermore, we
On the basis of our observations, a proposed reaction
pathway is shown in Scheme 8. The initial step is formation of
a vinylidene complex (A) from the reaction of 1a with a
propargylic alcohol, which was followed by the dehydration of
A to form an allenylidene complex (B). Subsequent hydride
transfer of the Hantzsch ester to the γ-C atom of the
allenylidene ligand in B results in the formation of another
Scheme 4. Stoichiometric Reaction of Ruthenium−
Allenylidene Complex 5 with Hantzsch Ester
Scheme 8. Plausible Reaction Pathway
examined the catalytic reaction of 2a with 1 equiv of 3 in the
presence of 5 mol % of 5 in THF at 60 °C for 6 h to give 4a in
quantitative yield (Scheme 5). These results of the
stoichiometric and catalytic reactions clearly indicate that
ruthenium−allenylidene complexes worked as key reactive
intermediates.
A deuterium-labeling experiment was carried out in order to
obtain mechanistic insight into the hydrogen atom transfer in
the present reaction system (Scheme 6). The reaction of 2a
with deuterated dihydropyridine 3-d2 gave the corresponding
C
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Figure 1. Gibbs energy diagram (ΔG) at the ωB97XD(IEF-PCM(tetrahydrofuran))/(SDD, 6-311++G**)//ωB97XD(IEF-PCM-
(tetrahydrofuran))/(SSD, 6-31G*) level of theory (298 K).
vinylidene complex (C). Then, vinylidene complex C is
transformed into a π-alkyne complex (D), which liberates the
corresponding propargylic reduced product by ligand exchange
with a propargylic alcohol to regenerate the starting vinylidene
complex A.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.organomet.0c00187.
■
sı
Experimental details, NMR spectra, and details of
theoretical calculations (PDF)
Cartesian coordinates of the calculated structures (XYZ)
The reaction pathway from B to C shown in Scheme 8 was
further examined by ωB97XD(IEF-PCM)-level DFT calcu-
lations (Figure 1). The complexation of the allenylidene
complex IA, which is formed by 1a and 2b, with Hantzsch ester
II gives the complex III (ΔG = 2.9 kcal/mol), where the H
atom in the Hantzsch ester weakly interacts with the γ-C atom
in the allenylidene. Then III is transformed into the complex
IV (ΔG = −12.4 kcal/mol), which consists of the acetylide
complex and pyridinium ion, through the transition state
TSIII−IV (ΔG = 10.8 kcal/mol). The charge of the pyridinium
ion fragment in IV is +1.24, showing that this step is the
hydride transfer. IV is easily decomposed into acetylide
complex V and pyridinium ion VI, and these two species
give the complex VII (ΔG = −15.5 kcal/mol). Proton transfer
from the pyridinium ion to the acetylide part via the transition
state TSVII−VIII (ΔG = −9.4 kcal/mol) results in the vinylidene
complex VIII (ΔG = −22.5 kcal/mol). The reaction barriers of
two steps, the hydride transfer (from III to TSIII−IV) and the
proton transfer (from VII to TSVII−VIII), are modest (7.9 and
6.1 kcal/mol, respectively), and the reaction pathway from the
allenylidene IA to the vinylidene IX is exothermic by 23.7 kcal/
mol. Thus, the reaction pathway proceeds smoothly.
AUTHOR INFORMATION
Corresponding Authors
■
Ken Sakata − Faculty of Pharmaceutical Sciences, Toho
University Miyama, Funabashi, Chiba 274-8510, Japan;
orcid.org/0000-0002-6920-0735; Email: ken.sakata@
phar.toho-u.ac.jp
Yoshiaki Nishibayashi − Department of Systems Innovation,
School of Engineering, The University of Tokyo, Tokyo 113-
8656, Japan; orcid.org/0000-0001-9739-9588;
Email: ynishiba@sys.t.u-tokyo.ac.jp
Authors
Haowei Ding − Department of Systems Innovation, School of
Engineering, The University of Tokyo, Tokyo 113-8656, Japan
Shogo Kuriyama − Department of Systems Innovation, School of
Engineering, The University of Tokyo, Tokyo 113-8656, Japan
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.organomet.0c00187
Notes
CONCLUSION
The authors declare no competing financial interest.
■
In summary, we have developed an efficient method for
propargylic reduction of propargylic alcohols bearing a
terminal alkyne moiety with Hantzsch ester in the presence
of a catalytic amount of a thiolate-bridged diruthenium
complex under mild reaction conditions. A variety of
secondary and tertiary propargylic alcohols were applicable
to this protocol to afford the desired products in high to
quantitative yields. Mechanistic studies based on experiments
and DFT calculations revealed a possible reaction pathway via
ruthenium−allenylidene complexes as key reactive intermedi-
ates. We believe that this method provides useful information
to design new types of propargylic substitution reactions,
including their enantioselective versions. Further studies are
currently in progress.
ACKNOWLEDGMENTS
■
The present project was supported by CREST, JST
(JPMJCR1541). We acknowledge Grants-in-Aid for Scientific
Research (Nos. JP17H01201, JP15H05798, JP18K19093, and
JP19K23645) from JSPS and MEXT.
REFERENCES
■
̈
(1) (a) Herrmann, J. M.; Konig, B. Reductive Deoxygenation of
Alcohols: Catalytic Methods Beyond Barton-McCombie Deoxygena-
tion. Eur. J. Org. Chem. 2013, 2013, 7017−7027. (b) Heravi, M. M.;
Bakhtiari, A.; Faghihi, Z. Applications of Barton-McCombie Reaction
in Total Syntheses. Curr. Org. Synth. 2014, 11, 787−823.
(2) (a) Vennestrøm, P. N. R.; Osmundsen, C. M.; Christensen, C.
H.; Taarning, E. Beyond Petrochemicals: The Renewable Chemicals
D
https://dx.doi.org/10.1021/acs.organomet.0c00187
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
Industry. Angew. Chem., Int. Ed. 2011, 50, 10502−10509. (b) Ruppert,
A. M.; Weinberg, K.; Palkovits, R. Hydrogenolysis Goes Bio: From
Carbohydrates and Sugar Alcohols to Platform Chemicals. Angew.
Chem., Int. Ed. 2012, 51, 2564−2601.
(3) (a) Trost, B. M.; van Vranken, D. L. Asymmetric Transition
Metal-Catalyzed Allylic Alkylations. Chem. Rev. 1996, 96, 395−422.
(b) Trost, B. M.; Crawley, M. L. Asymmetric Transition-Metal-
Catalyzed Allylic Alkylations: Applications in Total Synthesis. Chem.
Rev. 2003, 103, 2921−2944. (c) Hartwig, J. F. Organotransition Metal
Chemistry; University Science Books: 2010; Chapter 20.
(4) (a) Nakamura, K.; Ohno, A.; Oka, S. Reduction by a model of
NAD(P)H. 44. Transition metal catalyzed reduction of allylic acetate.
Tetrahedron Lett. 1983, 24, 3335−3336. (b) Hayashi, T.; Iwamura,
H.; Naito, M.; Matsumoto, Y.; Uozumi, Y.; Miki, M.; Yanagi, K.
Catalytic Asymmetric Reduction of Allylic Esters with Formic Acid
Catalyzed by Palladium-MOP Complexes. J. Am. Chem. Soc. 1994,
116, 775−776.
(5) (a) Miyake, Y.; Uemura, S.; Nishibayashi, Y. Catalytic
Propargylic Substitution Reactions. ChemCatChem 2009, 1, 342−
356. (b) Ljungdahl, N.; Kann, N. Transition-Metal-Catalyzed
Propargylic Substitution. Angew. Chem., Int. Ed. 2009, 48, 642−644.
(c) Detz, R. J.; Hiemstra, H.; van Maarseveen, J. H. Catalyzed
Propargylic Substitution. Eur. J. Org. Chem. 2009, 2009, 6263−6276.
(d) Ding, C.-H.; Hou, X.-L. Catalytic Asymmetric Propargylation.
Chem. Rev. 2011, 111, 1914−1937. (e) Sakata, K.; Nishibayashi, Y.
Mechanism and Reactivity of Catalytic Propargylic Substitution
Reactions via Metal-Allenylidene Intermediates: A Theoretical
Perspective. Catal. Sci. Technol. 2018, 8, 12−25.
(6) (a) Nishibayashi, Y.; Wakiji, I.; Hidai, M. Novel Propargylic
Substitution Reactions Catalyzed by Thiolate-Bridged Diruthenium
Complexes via Allenylidene Intermediates. J. Am. Chem. Soc. 2000,
122, 11019−11020. (b) Nishibayashi, Y.; Milton, M. D.; Inada, Y.;
Yoshikawa, M.; Wakiji, I.; Hidai, M.; Uemura, S. Ruthenium-
Catalyzed Propargylic Substitution Reactions of Propargylic Alcohols
with Oxygen-, Nitrogen-, and Phosphorus-Centered Nucleophiles.
Chem. - Eur. J. 2005, 11, 1433−1451. (c) Inada, Y.; Yoshikawa, M.;
Milton, M. D.; Nishibayashi, Y.; Uemura, S. Ruthenium-Catalyzed
Propargylation of Aromatic Compounds with Propargylic Alcohols.
Eur. J. Org. Chem. 2006, 2006, 881−890. (d) Tanabe, Y.; Kanao, K.;
Miyake, Y.; Nishibayashi, Y. Remarkable Effect of Halogens on
Catalytic Activities of Thiolato-Bridged Diruthenium Complexes in
Propargylic Substitution Reactions. Organometallics 2009, 28, 1138−
1142.
Chem. 2011, 2011, 2239−2246. (b) Qin, H.; Yamagiwa, N.;
Matsunaga, S.; Shibasaki, M. Bismuth-Catalyzed Direct Substitution
of the Hydroxy Group in Alcohols with Sulfonamides, Carbamates,
and Carboxamides. Angew. Chem., Int. Ed. 2007, 46, 409−413.
(c) Huang, X.; Wu, S.; Wu, W.; Li, P.; Fu, C.; Ma, S. Palladium-
Catalysed Formation of Vicinal All-Carbon Quaternary Centres via
Propargylation. Nat. Commun. 2016, 7, 12382.
(9) (a) Nishibayashi, Y.; Shinoda, A.; Miyake, Y.; Matsuzawa, H.;
Sato, M. Ruthenium-Catalyzed Propargylic Reduction of Propargylic
Alcohols with Silanes. Angew. Chem., Int. Ed. 2006, 45, 4835−4839.
(b) Yuki, M.; Miyake, Y.; Nishibayashi, Y. Preparation of Thiolate-
Bridged Dinuclear Ruthenium Complexes Bearing a Phosphine
Ligand and Application to Propargylic Reduction of Propargylic
Alcohols with 2-Propanol. Organometallics 2010, 29, 5994−6001.
(10) (a) Georgy, M.; Boucard, V.; Debleds, O.; Dal Zotto, C.;
Campagne, J.-M. Gold(III)-Catalyzed Direct Nucleophilic Substitu-
tion of Propargylic Alcohols. Tetrahedron 2009, 65, 1758−1766.
(b) Meyer, V. J.; Niggemann, M. Highly Chemoselective Calcium-
Catalyzed Propargylic Deoxygenation. Chem. - Eur. J. 2012, 18, 4687−
4691.
(11) (a) Ouellet, S. G.; Walji, A. M.; Macmillan, D. W. C.
Enantioselective Organocatalytic Transfer Hydrogenation Reactions
using Hantzsch Esters. Acc. Chem. Res. 2007, 40, 1327−1339.
(b) Zheng, C.; You, S.-L. Transfer Hydrogenation with Hantzsch
Esters and Related Organic Hydride Donors. Chem. Soc. Rev. 2012,
41, 2498−2518.
(12) Chen, M.; Sun, J. How Understanding the Role of an Additive
Can Lead to an Improved Synthetic Protocol without an Additive:
Organocatalytic Synthesis of Chiral Diarylmethyl Alkynes. Angew.
Chem., Int. Ed. 2017, 56, 11966−11970.
(13) Nishibayashi, Y.; Wakiji, I.; Ishii, Y.; Uemura, S.; Hidai, M.
Ruthenium-Catalyzed Propargylic Alkylation of Propargylic Alcohols
with Ketones: Straightforward Synthesis of γ-Keto Acetylenes. J. Am.
Chem. Soc. 2001, 123, 3393−3394.
(7) (a) Hattori, G.; Matsuzawa, H.; Miyake, Y.; Nishibayashi, Y.
Copper-Catalyzed Asymmetric Propargylic Substitution Reactions of
Propargylic Acetates with Amines. Angew. Chem., Int. Ed. 2008, 47,
3781−3783. (b) Detz, R. J.; Delville, M. M. E.; Hiemstra, H.; van
Maarseveen, J. H. Enantioselective Copper-Catalyzed Propargylic
Amination. Angew. Chem., Int. Ed. 2008, 47, 3777−3780. (c) Hattori,
G.; Sakata, K.; Matsuzawa, H.; Tanabe, Y.; Miyake, Y.; Nishibayashi,
Y. Copper-Catalyzed Enantioselective Propargylic Amination of
Propargylic Esters with Amines: Copper-Allenylidene Complexes as
Key Intermediates. J. Am. Chem. Soc. 2010, 132, 10592−10608.
(d) Detz, R. J.; Abiri, Z.; le Griel, R.; Hiemstra, H.; van Maarseveen, J.
H. Enantioselective Copper-Catalysed Propargylic Substitution:
Synthetic Scope Study and Application in Formal Total Syntheses
of (+)-Anisomycin and (−)-Cytoxazone. Chem. - Eur. J. 2011, 17,
5921−5930. (e) Nakajima, K.; Shibata, M.; Nishibayashi, Y. Copper-
Catalyzed Enantioselective Propargylic Etherification of Propargylic
Esters with Alcohols. J. Am. Chem. Soc. 2015, 137, 2472−2475.
(f) Tsuchida, K.; Senda, Y.; Nakajima, K.; Nishibayashi, Y.
Construction of Chiral Tri- and Tetra-Arylmethanes Bearing
Quaternary Carbon Centers: Copper-Catalyzed Enantioselective
Propargylation of Indoles with Propargylic Esters. Angew. Chem., Int.
Ed. 2016, 55, 9728−9732.
(8) (a) Motoyama, K.; Ikeda, M.; Miyake, Y.; Nishibayashi, Y.
Cooperative Catalytic Reactions Using Lewis Acids and Organo-
catalysts: Enantioselective Propargylic Alkylation of Propargylic
Alcohols Bearing an Internal Alkyne with Aldehydes. Eur. J. Org.
E
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