Copper-catalyzed semihydrogenation of internal alkynes with molecular hydrogen

Article abstract of DOI:10.1021/acs.organomet.6b00126

A copper-catalyzed system using a commercially available simple N-heterocyclic carbene ligand under atmospheric pressure of H₂ (1 atm, balloon) enables the semihydrogenation of internal alkynes, which proceeds with high Z selectivity. Thus, this copper catalysis provides a useful method for the preparation of (Z)-alkenes from internal alkynes.

Full text of DOI:10.1021/acs.organomet.6b00126

Communication
pubs.acs.org/Organometallics
Copper-Catalyzed Semihydrogenation of Internal Alkynes with
Molecular Hydrogen
Takamichi Wakamatsu, Kazunori Nagao, Hirohisa Ohmiya,* and Masaya Sawamura*
Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan
S
* Supporting Information
ABSTRACT: A copper-catalyzed system using a commercially available simple N-
heterocyclic carbene ligand under atmospheric pressure of H2 (1 atm, balloon) enables
the semihydrogenation of internal alkynes, which proceeds with high Z selectivity. Thus,
this copper catalysis provides a useful method for the preparation of (Z)-alkenes from
internal alkynes.
he semihydrogenation of alkynes mediated by copper
hydride species is a useful method for the synthesis of
T
(Z)-alkenes, having the benefits of mild reaction conditions and
excellent chemoselectivities.1 Conventionally, phosphine-coor-
dinated hexameric copper hydride [CuH(PPh3)]6, the so-called
“Stryker’s reagent”,2 and a copper hydride species generated in
situ from hydrosilanes and a copper catalyst3 have been used
for this transformation. In view of the economic and
environmental issues, molecular hydrogen (H2) would be an
attractive alternative as a source of the copper hydride species.4
In fact, Cu2O-catalyzed semihydrogenation of terminal alkynes
under H2 pressure (20 atm) was reported more than 40 years
ago,5a but Cu catalysis for the semihydrogenation of internal
alkynes using H2 was not reported until independent studies by
Nakao and Teichert appeared recently.5b,c Nakao and co-
workers reported a semihydrogenation protocol using [(PPh3)-
CuCl]4 as a catalytic copper source together with a
substoichiometric LiOtBu base and a stoichiometric alcohol
additive as a proton source.5b The protocol introduced by
Teichert and co-workers employed an N-hydroxyalkyl NHC
(N-heterocyclic carbene) ligand under a high hydrogenation
pressure (100 atm).5c This protocol did not require an
exogenous proton source.
1a proceeded in 90% NMR yield with complete Z selectivity
(entry 1). The use of CuOAc instead of CuCl slightly decreased
the product yield (82%) (entry 2). No reaction occurred with
CuCl2 (entry 3). The use of a SIMes ligand gave a better
product yield (94%) (eq 1 and entry 4). Other NHC ligands
such as IMes (0%) and IPr (9%) were less effective (entries 5
and 6). Monodentate and bidentate phosphines were also
tested as ligands under otherwise identical conditions (entries
7−10). PCy3 gave a high product yield (86%) (entry 7). On the
other hand, the weaker electron donor ligand PPh3 was not
effective (entry 8). Bisphosphines such as Xantphos (61%) and
DCYPE (92%) were useful (entries 9 and 10).
The nature of the base had a strong impact on the product
yield (Table 1, entries 11−14).6 The use of the sterically
smaller base NaOMe instead of NaOtBu decreased the product
yield (entry 11). The use of NaOAc or LiOtBu resulted in no
reaction (entries 12 and 13). No reaction occurred in the
absence of NaOtBu base (entry 14).
Here, we disclose results of our independent work on the
development of copper-catalyzed semihydrogenation of internal
alkynes using molecular hydrogen.6 Use of a commercially
available simple NHC ligand and the effectiveness of hydrogen
gas at atmospheric pressure are practical merits of this protocol.
Specifically, the reaction of 6-dodecyne (1a) in the presence
of [(SIMes)CuCl] (10 mol %), which was prepared from CuCl
and SIMes,7 and NaOtBu (10 mol %) in octane/1,4-dioxane
(4/1) under atmospheric pressure of H2 (balloon) at 100 °C
(oil bath temp) for 12 h gave (Z)-6-dodecene (2a) in 84%
isolated yield (based on 2a; 94% NMR yield; complete
conversion of 1a) (eq 1). The NMR analysis of the crude
product confirmed the complete Z stereoselectivity and no
occurrence of overreduction.
The solvent had a marked influence on the product yield
(Table 1, entries 15−18). Replacing the mixed solvent system
octane/1,4-dioxane in the semihydrogenation of 1a with octane
caused a decrease in product yield (entry 15). No reaction
occurred with 1,4-dioxane (entry 16). The efficiency of 1,4-
Special Issue: Organometallics in Asia
Received: February 13, 2016
The effects of different reaction conditions are summarized
in Table 1. Even without the ligand, the semihydrogenation of
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.6b00126
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Organometallics
Communication
a
a
Table 1. Optimization of Reaction Conditions
Table 2. Semihydrogenation of Internal Alkynes
b
entry
Cu catalyst
CuCl
base
solvent
yield (%)
1
2
3
4
5
6
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOMe
NaOAc
LiOtBu
none
octane/dioxane
octane/dioxane
octane/dioxane
octane/dioxane
octane/dioxane
octane/dioxane
octane/dioxane
octane/dioxane
octane/dioxane
octane/dioxane
octane/dioxane
octane/dioxane
octane/dioxane
octane/dioxane
octane
90
CuOAc
82
CuCl2
0
[(SIMes)CuCl]
[(IMes)CuCl]
[(IPr)CuCl]
94 (84)
0
9
c
7
c
CuCl/PCy3
0
8
CuCl/PPh3
86
61
92
61
0
9
CuCl/Xantphos
CuCl/DCYPE
[(SIMes)CuCl]
[(SIMes)CuCl]
[(SIMes)CuCl]
[(SIMes)CuCl]
[(SIMes)CuCl]
[(SIMes)CuCl]
[(SIMes)CuCl]
[(SIMes)CuCl]
10
11
12
13
14
15
16
17
18
0
0
NaOtBu
NaOtBu
NaOtBu
NaOtBu
67
0
dioxane
toluene
58
14
DMF
a
The reaction was carried out with H2 (1 atm, balloon), 1a (0.5
mmol), catalyst (0.05 mmol), and base (0.05 mmol) in solvent (1.0
mL) at 100 °C (oil bath temperature) for 12 h.
b
1H NMR yield. The yield of isolated product is given in parentheses.
c
Bisphosphine (20 mol %).
dioxane as a cosolvent may reflect the higher solubility of the
active Cu species. Toluene was also useful, although the
product yield was moderate (entry 17). A significant reduction
in yield was observed for the reaction in DMF (entry 18).
Various internal alkynes were subjected to the copper-
catalyzed semihydrogenation. Results obtained with 10 mol %
of [(SIMes)CuCl] under atmospheric pressure of H2 (balloon)
in octane/1,4-dioxane at 100 °C are summarized in Table 2.
The sterically demanding cyclohexyl-substituted alkyne 1b was
converted into the corresponding (Z)-2b in 68% yield without
the formation of the E isomer and alkane (entry 1). The
semihydrogenation of 1c bearing a THP ether also proceeded
with complete Z selectivity (entry 2). The propargyl amine
derivative 1d underwent semihydrogenation with 87% Z
selectivity (entry 3).
1-Aryl-1-propynes 1e,f bearing a methoxy group at the ortho
or para positions of the aromatic rings reacted to afford the
corresponding (Z)-alkene products 2e,f, respectively, with high
selectivities (Table 2, entries 4 and 5). In the case of the
B
DOI: 10.1021/acs.organomet.6b00126
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Organometallics
Communication
Table 2. continued
available simple NHC ligand such as SIMes can be used, and a
protic additive is unnecessary. Thus, this copper catalysis
provides a useful method for the preparation of (Z)-alkenes
from internal alkynes.
a
The reaction was carried out with H2 (1 atm, balloon), 1 (0.5 mmol),
[(SIMes)CuCl] (0.05 mmol), and NaOtBu (0.05 mmol) in octane
(0.8 mL) and 1,4-dioxane (0.2 mL) at 100 °C (oil bath temperature)
b
c
1
for 12 h. Isolated yield. Determined by H NMR or GC analysis of
ASSOCIATED CONTENT
* Supporting Information
■
d
e
the crude product. CuCl was used instead of [(SIMes)CuCl]. The
S
overreduced alkane was observed (entry 4, 5%; entry 7, 10%; entry 12,
f
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.6b00126.
6%). 2-Allyl-1,3-dimethoxybenzene was observed (7%).
reaction of 1e, a small amount of alkane was formed (5%). The
reaction with 1,3-dimethoxy-2-(1-propyn-1-yl)benzene (1g)
occurred with complete stereoselectivity (entry 6). The
semihydrogenation of 1-aryl-1-decyne (1h) having an ester
group as a para substituent of the aromatic ring proceeded with
high stereoselectivity, while the alkane formation was more
significant (10% yield) (entry 7). The reaction of 1-aryl-1-
nonyne (1i) having a bromo group did not proceed at all (entry
8).
Diphenylacetylene (1j) afforded stilbene 2j with 92% Z
selectivity (Table 1, entry 9). The substitution of a NO2 or CN
group in 2j inhibited the reactions (entries 10 and 11). 2-
Phenyl-1-(pyridin-3-yl)acetylene (1m) also participated in the
semireduction with 90% Z selectivity and 6% alkane formation
(entry 12).
The reaction with aromatic or aliphatic terminal alkynes
resulted in no reactions (data not shown). Thus, the utility of
the present Cu-catalyzed protocol is limited to the reaction of
internal alkynes.
A possible catalytic cycle is shown in Figure 1. First, the
[(SIMes)CuCl] complex reacted with NaOtBu to form the
Experimental details and characterization data for all new
compounds (PDF)
AUTHOR INFORMATION
Corresponding Authors
*E-mail for H.O.: ohmiya@sci.hokudai.ac.jp.
*E-mail for M.S.: sawamura@sci.hokudai.ac.jp.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by Grants-in-Aid for Scientific
Research (B) (No. 15H03803), JSPS, to H.O. and by CREST
and ACT-C, JST, to M.S. Additionally, K.N. thanks JSPS for
scholarship support.
REFERENCES
■
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Figure 1. Possible reaction mechanism.
copper(I) alkoxide complex A. The reaction between A and H2
through σ-bond metathesis forms the copper(I) hydride species
B and tBuOH. Subsequently, B forms the Cu−alkyne π
complex C. Syn hydrocupration of the Cu−H bond across the
C−C triple bond in 1 occurs to give the alkenylcopper
intermediate D. Finally, the protonation of D by tBuOH, which
formed through a σ-bond metathesis between A and H2, affords
(Z)-2 and regenerates A. The minor production of (E)-2 is
likely due to the isomerization of (Z)-2 through the addition−
elimination of the copper hydride B.
In summary, we have developed a new protocol for
semihydrogenation of internal alkynes using a copper catalyst
and molecular hydrogen. This reaction proceeds under
atmospheric pressure of H2 (1 atm, balloon). A commercially
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(7) Abbreviations: SIMes, 1,3-bis(2,4,6-trimethylphenyl)imidazoli-
din-2-ylidene; IPr, 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene;
IMes, 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene.
D
DOI: 10.1021/acs.organomet.6b00126
Organometallics XXXX, XXX, XXX−XXX