Controlled hydrogenation of diphenylacetylene using alkylammonium formate

Article abstract of DOI:10.1016/j.tetlet.2017.08.054

A simple and straightforward semihydrogenation of alkyne to alkene with triethanolamine and formic acid in the presence of PdCl₂ has been described. Although hydrogenation using formic acid as a hydrogenation source has been used in combination with amines previously, few reports are available concerning the associated reactivity. We demonstrated that reactivity changes depending on the type of amine used in the hydrogenation. Further, this reaction requires no strict time control, making it a useful tool in organic synthesis.

Full text of DOI:10.1016/j.tetlet.2017.08.054

Accepted Manuscript
Controlled hydrogenation of diphenylacetylene using alkylammonium formate
Hideyuki Suzuki, Ikkyu Satoh, Hiromi Nishioka, Yasuo Takeuchi
PII:
S0040-4039(17)31061-4
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.08.054
TETL 49244
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
29 June 2017
18 August 2017
22 August 2017
Please cite this article as: Suzuki, H., Satoh, I., Nishioka, H., Takeuchi, Y., Controlled hydrogenation of
diphenylacetylene using alkylammonium formate, Tetrahedron Letters (2017), doi: http://dx.doi.org/10.1016/
j.tetlet.2017.08.054
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Controlled hydrogenation of
diphenylacetylene using alkylammonium
formate
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Hideyuki Suzuki, Ikkyu Satoh, Hiromi Nishioka, Yasuo Takeuchi

1
Tetrahedron Letters
Controlled hydrogenation of diphenylacetylene using alkylammonium formate
Hideyuki Suzuki a, Ikkyu Satohb, Hiromi Nishioka a and Yasuo Takeuchia,
a Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-Naka, Kita-
ku, Okayama 700-8530, Japan
b Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A simple and straightforward semihydrogenation of alkyne to alkene with triethanolamine and
formic acid in the presence of PdCl2 has been described. Although hydrogenation using formic
acid as a hydrogenation source has been used in combination with amines previously, few
reports are available concerning the associated reactivity. We demonstrated that reactivity
changes depending on the type of amine used in the hydrogenation. Further, this reaction
requires no strict time control, making it a useful tool in organic synthesis.
Available online
Keywords:
Semihydrogenation
Amine
2009 Elsevier Ltd. All rights reserved.
Formic acid
Palladium catalyst
Hydrogenation is widely used not only in laboratories but also
in industry as a synthetic method.1–4 The process uses H2 gas,
HCl aq., formic acid, and alcohol as hydrogen sources in the
presence of a metal catalyst such as Pd, Pt, Fe, Sn, Ru, Rh, and
Ir.5–9 Although reactivity is usually controlled by the choice of
ligand and additives, semihydrogenation of alkynes to alkenes
remains a challenging and important issue. For instance, the
classical approach using Lindlar catalysts suffers from selectivity
issues of terminal alkynes and time control.10–13 The reactivity of
hydrogenation using Lindlar catalysts is reduced through the
addition of quinoline. However, there are few reports concerning
controlling its reactivity through the addition of an appropriate
amine. Recently, Sajiki and co-workers reported control of
hydrogenation reactivity by changing the Pd carrier;
semihydrogenation of alkynes was achieved using Pd/BN and
diethylenetriamine.12 Although most of these reactions use H2 gas
as the hydrogen source, the advantage of using formic acid is that
it is easy to adjust its equivalent amount in the reaction. Using
formic acid, the reaction mechanism and isomerization from the
cis to the trans forms of the semihydrogenated products have
been reported.14–17 Hydrogenation using formic acid as the
hydrogen source in conjunction with amines such as ammonia,18
trimethylamine,18–20 and tributylamine21 have been described, but
few reports on the associated reactivity are available. In the
hydrogenation of carbonyl groups using amine-formic acid salts,
for example, we found that the reactivity changes greatly
depending on the type of amine.22, 23 As a next step, our present
focus concerns the semihydrogenation of alkynes with these
results in mind.
To determine the optimal reaction conditions for the
semihydrogenation of alkynes, we first examined the
hydrogenation of diphenylacetylene (1) with triethanolamine (5
eq.), formic acid (5 eq.), and Pd catalyst (5 mol%) in DMF at 30
C (Table 1). When Lindlar catalyst and Pd(OAc)2 were used,
cis-stilbene (2) was obtained but in low yields (entries 1 and 2).
Although we found that the reaction with PdCl2 afforded 2 :
trans-stilbene (3) = 14.5:1 in 93% yield, PdCl2(CH3CN)2 and
PdCl2(PPh3)2 did not promote the reaction (entries 3–5). In the
case of 20 eq. of triethanolamine and formic acid (entry 6), the
yields of 2 and 3 were similar to those obtained in entry 3. The
selectivity of 2 decreased at 50 C (entry 7). When the choice of
solvent was screened, acceleration of the reaction yet reduction in
selectivity were observed when methanol was used (entry 8). In
contrast, the reaction proceeded sluggishly in MeCN, THF,
AcOEt, and CHCl3 under the same conditions (entries 9–12).
Overall, it is clear that the yield can be improved by selecting the
solvent according to the reactivity of the substrate.
Table 1 Optimization of the reaction conditions.
Yield (%)a
Entry
1
Pd
Solvent
DMF
2
3
4
1
Lindlar catalyst
36
0
0
64
———
 Corresponding author. Tel.: +81-86-251-7964; fax: +81-86-251-7964; e-mail: take@pharm.okayama-u.ac.jp (Y. Takeuchi).

2
3
Pd(OAc)2
PdCl2
DMF
DMF
DMF
DMF
DMF
DMF
MeOH
MeCN
THF
23
87
34
7
1
6
4
3
67
0
6
7
0
0
8
98
4
0
4
PdCl2(CH3CN)2
PdCl2(PPh3)2
PdCl2
2
1
62
91
0
67
16
5
0
0
6b
7c
8
85
74
7
6
4
8
9
0
0
98
37
0
0
PdCl2
14
35
2
8
0
PdCl2
53
2
0
41
18
9
PdCl2
32
29
15
0
62
64
79
100
10
11
12
PdCl2
2
1
10
54
9
34
0
PdCl2
AcOEt
0
2
PdCl2
CHCl3
0
0
11
12
75
81
4
8
18
4
0
0
a Determined by 1H NMR analysis of crude reaction mixture.
b 20 eq. of triethanolamine and formic acid were used.
c The reaction was carried out at 50 C
13
14
3
7
7
85
34
0
0
In general, amines suppress the catalytic activity of palladium
by a coordination effect. We also know that PdCl2 is not reduced
without amine in preliminary experiments. To further investigate
the effect of amine on hydrogenation, various amines were
examined (Table 2). Although hydrogenation using ammonia
hardly proceeded, 1,2-diphenylethene (4) was the major product
when 1 and 2 amines, such as alkylamine and an amine with
the 2-hydroxyethyl group, were used (entries 1–6). Since the
reactions using triethylamine and tributylamine generally
progressed more slowly than the reactions using 2 amines, the
corresponding semihydrogenated products were obtained in
57
15
16b
17
77
0
6
0
0
13
97
0
0
0
0
97
moderate
yields
(entries
7,
9).
Notably,
when
18
0
0
0
0
0
0
0
0
0
98
97
98
diisopropylethylamine was used, which is a bulky 3 amine, 4
was afforded in 98% yield (entry 8). When 3 amines with a 2-
hydroxyethyl group were used, semihydrogenated compound 3
was obtained as the major product as a result of a diminished
reaction rate (entries 10–12). As seen in Table 2, cyclic
complexes composed of an aminoethanol structure and palladium
effectively controlled hydrogenation and achieved selectivity.
Indeed, even when a cyclic amine containing a morpholine
structure was used, a tendency similar to that using an acyclic
amine was confirmed (entries 13–15). In the case of DABCO, 4
was obtained quantitatively despite being a tertiary amine (entry
16). The aromatic amine elicited high inhibition of palladium and
hydrogenation did not proceed at all.
19 b
20 b
a Determined by 1H NMR analysis of the crude reaction mixture.
b Hydrogenation was performed with 20 eq. amine.
Kobayashi and co-workers have reported the effect of reaction
time on the hydrogenation of diphenylacetylene using H2 gas
with Lindlar catalyst.13 In this case, although the Lindlar catalyst
Table 2 Effect of amines on hydrogenation.
showed high selectivity, the formation of
4 increased
dramatically by extending the reaction time. At present, we
investigated the effect of reaction time on the hydrogenation of 1
using triethanolamine (5 eq.), formic acid (5 eq.), and PdCl2 (5
mol%) (Figure 1). As seen, the yield of 2 reached 87% after 24 h
and over-hydrogenation of 2 scarcely progressed even after 48 h.
In contrast, the yield of 3 hardly changed from 8 h after the start
of the reaction. Overall, these results indicate that this type of
hydrogenation does not require strict time control.
Yield (%)a
Entry
1
Amine
2
3
4
1
6
0
0
88
2
3
4
5
9
0
0
0
9
0
0
0
79
95
95
93
0
0
0
0

4
Tetrahedron
d Recovered 61% of starting material.
e Recovered 66% of starting material.
In conclusion, we have demonstrated that the type of amine
changes the reactivity of hydrogenation in the presence of
palladium catalyst and formic acid. In this system, the reaction
rate varied greatly depending on the type of solvent, indicating
that the reaction rate can be adjusted straightforwardly. This
experimental procedure is simple and requires no strict time
control, highlighting its utility as an effective tool in organic
synthesis.
Figure 1. Effect of reaction time on hydrogenation
References and notes
1.
2.
3.
4.
5.
6.
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Wang D.; Astruc D. Chem. Rev. 2015, 115, 6621–6686.
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Vol’pin E. M.; Kukolev P. V.; Chernyshev O. V.; Kolomnikov S.
I. Tetrahedron Lett. 1971, 12, 4435–4438.
Finally, we investigated the substrate scope with a 24 h
reaction time for various alkynes (Table 3). Depending on the
reactivity of the compound, it is possible to adjust the reaction
rate by changing the conditions such as the amount of Pd
catalyst, the type of solvent, and temperature. 1-Phenyl-1-hexyne
(5) and 1,1-diphenyl-2-propyn-1-ol (6) were successfully
transformed into their corresponding semihydrogenated products
in high yield and selectivity (entries 1, 2). In DMF, 6-dodecyne
(7) afforded the corresponding alkane in quantitative yield (entry
3), whereas it gave semihydrogenated products in high yield and
selectivity in AcOEt (entry 4). Semihydrogenation could be
achieved because the reaction rate was reduced by the effect of
AcOEt. Although the reactions of ester compounds produced
only alkenes in low yield over 24 h, it would be possible to
improve the yield by prolonging the reaction time (entries 5–7).
7.
8.
9.
Shen R.; Chen T.; Zhao Y.; Qiu R.; Zhou Y.; Yin S.; Wang X.;
Goto M.; Han L.-B. J. Am. Chem. Soc. 2011, 133, 17037–17044.
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Y; Sajiki H. J. Mol. Catal. A: Chem. 2009, 307, 77–87.
11. Sajiki H.; Mori S.; Ohkubo T.; Ikawa T.; Kume A.; Maegawa T.;
Monguchi Y. Chem. Eur. J. 2008, 14, 5109–5111.
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H. Adv. Synth. Catal. 2012, 354, 1264–1268.
13. Nishio R.; Sugiura M.; Kobayashi S. Org. Biomol. Chem., 2006,
4, 992–995.
14. Tani K.; Ono N.; Okamoto S.; Sato F. J. Chem. Soc., Chem.
Commun. 1993, 386–387.
Table 3 Reaction of various alkynes.
15. Yu J.; Spencer B. J. Chem. Commun. 1998, 1935–1936.
16. Yu J.; Spencer B. J. Chem. Commun., 1998, 1103–1104.
17. Leitner W.; Brown M. J.; Brunner H. J. Am. Chem. Soc., 1993,
115, 152–159.
18. Ram S.; Ehrenkaufer E. R. Synethesis, 1988, 91–94.
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20. Fujii A.; Hashiguchi S.; Uematsu N.; Ikariya T.; Noyori R. J. Am.
Chem. Soc. 1996, 118, 2521–2522.
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7769–7770.
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3686–3688.
Temp.
(C)
PdCl2
(mol%)
Yield %
Entry
1
Substrate
Solv.
DMF
(cis:trans)a
5
5
30
30
84 (13:1)
90
5
6
2
DMF
3
4
5
5
DMF
30
50
0b
23. Suzuki H.; Yoshioka S.; Igesaka A.; Nishioka H.; Takeuchi Y.
Tetrahedron 2013, 69, 6399–6403.
7
8
AcOEt
90 (21.5:1)
24. (Table 1 entry 3): To a solution of triethanolamine (5 eq.) and
formic acid (5 eq.) in DMF (5 mL) was added diphenylacetylene
(1) (178 mg, 1.00 mmol) and PdCl2 (5 mol%) at r.t. and the
reaction mixture was stirred at the same temperature for 24 h
under argon atmosphere. The mixture was poured into brine (10
mL) and extracted with Et2O (510 mL). The organic layer was
washed with H2O (50 mL), brine (50 mL) and dried with MgSO4.
The solvent was removed under reduced pressure to give crude
reaction mixture. Yield was directly determined by 1H NMR
spectroscopy.
5
10
DMF
30
49 (48:1)c
6
7
5
DMF
50
50
34 (4.7:1)d
30 (100:0)e
9
20
AcOEt
a Determined by 1H NMR analysis of the crude mixture.
b Over-hydrogenated product was obtained in 100% yield.
c Recovered 46% of starting material.

Highlights
 Semihydrogenation of alkyne to alkene was
discussed using diphenylacetylene.
 Use of triethanolamine in DMF gave the best
yield and selectivity.
 This method was applicable to other alkynes