Transition-metal-free semihydrogenation of diarylalkynes: Highly stereoselective synthesis of trans -alkenes using Na2S·9H 2O

Article abstract of DOI:10.1021/ol501137x

A highly stereoselective and efficient transition-metal-free semihydrogenation of internal alkynes to E-alkenes using cheap and green water as hydrogen donor is described. The reactions are conducted under convenient conditions and provide products in good to excellent yields, with broad substrate scope, including a variety of diarylalkynes.

Full text of DOI:10.1021/ol501137x

Letter
pubs.acs.org/OrgLett
Transition-Metal-Free Semihydrogenation of Diarylalkynes: Highly
Stereoselective Synthesis of trans-Alkenes Using Na2S·9H2O
Zhengwang Chen,* Miaoting Luo, Yuelu Wen, Guotian Luo, and Liangxian Liu*
Key Laboratory of Organo-Pharmaceutical Chemistry of Jiangxi Province, Gannan Normal University, Ganzhou 341000, P.R. China
S
* Supporting Information
ABSTRACT: A highly stereoselective and efficient transition-metal-free
semihydrogenation of internal alkynes to E-alkenes using cheap and green
water as hydrogen donor is described. The reactions are conducted under
convenient conditions and provide products in good to excellent yields, with
broad substrate scope, including a variety of diarylalkynes.
he selective semihydrogenation of alkynes to alkenes with
a defined Z- or E-configuration is an important trans-
However, the control experiment results showed that (E)-
diphenylethene could be obtained without addition of any
transition metals, which implies that it is a noncatalytic reaction.
As shown in Table 1, we then screened other factors of the
T
formation in organic chemistry.1 It has been widely used for the
synthesis of synthetic intermediates, natural products, fragran-
ces, and pharmaceuticals.2 Among the various efficient methods
to access Z-alkenes, Lindlar’s catalyst (Pd/CaCO3) and its
variants are the most popular choices.3 Over the past decades,
some other functional-group-tolerant catalytic Z-selective
semihydrogenation approaches have been developed.4 How-
ever, on the contrary, examples of semihydrogenation of
alkynes to E-alkenes have been rarely studied or reported. A
textbook example of a Birch-type reduction of alkynes by alkali
metals (Li, Na) in liquid ammonia is the traditional and
powerful protocol for obtaining E-alkene, but the harsh reaction
conditions damaged the functional group tolerance.5 Recently,
some catalytic systems for alkyne semihydrogenation to E-
alkenes have been explored. Among them, the transition-metal-
complex-containing Rh,6 Ru,7 Pd,8 Ir,9 Ni,10 and Fe11 have
proven to be useful for this transformation. However, these
transition-metal reagents still have some drawbacks, such as
high price, generation of toxic waste, and the need of an air-
sensitive or expensive ligand. From economical and environ-
mental viewpoints, it would be advantageous and quite
desirable to develop transition-metal-free systems for the
synthesis of alkenes from alkynes.12
Table 1. Optimization of Reaction Conditions for the
a
Synthesis of (E)-Diphenylethene
b
entry
solvent
temp (°C)
time (h)
yield (%)
1
2
3
4
5
DMSO
xylene
DMA
DMF
H2O
140
140
140
140
100
140
100
60
16
16
16
16
16
16
16
16
10
6
86
n.r.
93
96
trace
n.r.
70
c
6
DMF
DMF
DMF
DMF
DMF
DMF
DMF
7
8
trace
98 (96)
59
9
140
140
140
140
10
d
11
10
10
71
e
12
40
a
Reaction conditions: 1,2-diphenylethyne (0.25 mmol), sodium sulfide
b
Sodium sulfide nonahydrate is an inexpensive and safe
reducing agent, which has been widely used for the reduction of
aromatic nitro compounds to the corresponding anilines in
organic synthesis. Recently, we have reported a series of
transformations based on terminal alkynes and haloalkynes.13
As part of our continuing project on the functionalization of
alkynes, here we wish to present a highly stereoselective and
efficient method for the synthesis of a series of E-alkenes
containing a wide range of functional groups via Na2S·9H2O
reduction of diarylalkynes.
Our initial efforts were focused on the search for suitable
reaction conditions in dimethyl sulfoxide, where the reaction of
1,2-diphenylethyne (1a) with Na2S·9H2O was chosen as the
model reaction. We added different transition metals into the
reaction, assuming the reaction to be a catalytic process.
nonahydrate (1.2 equiv), and solvent (1.0 mL). Determined by GC.
Number in parentheses is isolated yield. Without sodium sulfide
c
d
nonahydrate. Sodium sulfide nonahydrate (2 equiv) was used.
e
Sodium sulfide nonahydrate (0.5 equiv) was used.
reaction including solvent, temperature and reaction time. We
found that the reaction showed a strong solvent dependence.
Among the solvents used, DMSO, DMA, and DMF were
proven appropriate (Table 1, entries 1−5). The reaction did
not proceed without sodium sulfide nonahydrate (Table 1,
entry 6). It is noteworthy that reaction temperatures are
Received: April 19, 2014
© XXXX American Chemical Society
A
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Organic Letters
Letter
essential to the transformation; the yields decreased drastically
at lower temperature (Table 1, entries 7 and 8). The optimal
reaction time is 10 h, and 2a could be obtained in 96% isolated
yield (Table 1, entries 9 and 10). Moreover, an increase or
decrease in the amount of Na2S·9H2O led to a decrease in the
yield (Table 1, entries 11 and 12). After some attempts, we
considered that the optimized reaction conditions are as
follows: 1a (0.25 mmol) with Na2S·9H2O (0.30 mmol) and
DMF (1 mL) at 140 °C for 10 h (Table 1, entry 9).
groups and hold enormous potential applications in organic
synthesis (Scheme 1, 2g−q). In the case of the diaryl alkyne
bearing a nitro group, the reduction proceeded simultaneously
at both the alkyne and nitro moieties (Scheme 1, 2r). Thienyl
and pyridyl derivatives were tolerant in this semihydrogenation
reaction (Scheme 1, 2s and 2t). To further explore its potential
application, we scaled up the reaction to a 10 mmol scale (1.78
g); the product could be formed in 93% yield (Scheme 1, 2a).
Continuing to investigate the reaction scope, we explored
various diarylalkynes for this process under the optimized
reaction conditions (Scheme 2). In general, most of the
With the optimized reaction conditions in hand, we set out
to test the generality of this reaction. As shown in Scheme 1,
Scheme 1. Na2S·9H2O Reduction of Internal Alkynes to the
Scheme 2. Na2S·9H2O Reduction of Diaryl Alkynes to the
a b
,
a,b
Corresponding E-Alkenes
Corresponding E-Alkenes
a
Reaction conditions: 1 (0.25 mmol), sodium sulfide nonahydrate (1.2
b
equiv), and DMF (1.0 mL) at 140 °C for 10 h. Isolated yield and the
ratio of Z/E isomers was above 98:2 determined by GC−MS.
substrates could afford the corresponding E-alkenes in good
yields. Furthermore, the yields were not affected when the
substituents were on the ortho-, meta-, and para-positions of the
phenyl ring (Scheme 2, 3e−g). The results indicated that
substituted aryl groups were perfectly tolerated (Scheme 2, 3a−
o). Interestingly, the five-membered cyclic ether reacted
smoothly rendering the target alkene in high yield (Scheme
2, 3b). Moreover, the dielectron-withdrawing group substituted
substrate gave 76% isolated yield (Scheme 2, 3i). In addition,
heterocyclic internal alkynes such as thienyl and pyridyl
derivatives provided the target products in excellent yields
(Scheme 2, 3m−o).
a
Reaction conditions: 1 (0.25 mmol), sodium sulfide nonahydrate (1.2
b
equiv), and DMF (1.0 mL) at 140 °C for 10 h. Isolated yield. The
c
ratio of Z/E isomers was above 98:2 as determined by GC−MS. 10
d
e
mmol scale of the reaction. Reacted for 20 h. Reacted for 24 h.
f
g
Reacted for 2 h. The raw material is 4-NO2-substituted
diphenylacetylene.
both electron-rich and electron-deficient substitutions on the
aromatic ring were compatible in the standard conditions
(Scheme 1, 2b−t). For most of the diarylalkynes 1, the reaction
proceeded smoothly to give the corresponding products in
good to excellent yields. The reaction conditions could be
compatible with a wide range of functional groups such as alkyl,
aryl, alkyloxy, hydroxyl, ester, amino, fluoro, chloro, formyl,
carbonyl, trifluoromethyl, cyano, and heteroaryl groups
(Scheme 1, 2b−t). Substitution at the ortho position of the
aromatic ring had some impact on the yield (Scheme 1, 2c).
The alkyne 1d bearing a bulky tert-butyl group afforded a high
yield of the desired alkene in a prolonged reaction time
(Scheme 1, 2d). Both strong electron-donating or -withdrawing
substituents on the phenyl ring had no significant influence on
the yields, especially reactive hydroxyl; amino and formyl
functionalities can be easily converted to various functional
Subsequently, 3-phenylpropiolic acid was reacted under the
standard conditions (Scheme 3). However, we were surprised
that thiophene 4a and thioamide 4b were formed instead of 3-
phenylacrylic acid.14 Both substituted thiophenes15 and
Scheme 3. Formation of Thiophene and Thioamide from
Phenylpropiolic Acid
B
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Letter
thioamides16 are ubiquitous in biologically active molecules and
have also been used as building blocks for biologically relevant
heterocyclic scaffolds. It is noteworthy that the amine moiety in
thioamide 4b comes from DMF.17
As shown in Scheme 4, (E)-1,2-dideuterioalkene was formed
in 73% yield when Na2S·9H2O was replaced by K2S and D2O.
It indicated that water acted as the hydrogen donor in the
transformation.
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Scheme 4. Investigation of the Hydrogen Source in the
Semihydrogenation Reaction
In summary, we developed a simple, efficient, and novel
transition-metal-free protocol for the formation of E-alkynes.
The semihydrogenation reaction was a highly stereoselective
reduction; only negligible amounts of Z-alkenes and over-
reduced alkanes were observed in GC−MS. The method
employed water as the hydrogen donor avoiding the use of a
potentially hazardous pressurized H2 atmosphere. Both
electron-donating and electron-withdrawing substitutions on
the aromatic ring were compatible under the standard
conditions. Importantly, the products with carbonyl, hydroxyl,
and amino groups can be utilized in several organic
transformations. Further studies to reveal the reaction
mechanism and extend the applications of this methodology
are currently underway in our labaratory.
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̈
ASSOCIATED CONTENT
■
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X.; Goto, M.; Han, L.-B. J. Am. Chem. Soc. 2011, 133, 17037. (b) Luo,
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* Supporting Information
Typical experimental procedure and characterization for all
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
(9) Tani, K.; Iseki, A.; Yamagata, T. Chem. Commun. 1999, 1821.
AUTHOR INFORMATION
Corresponding Authors
(10) Reyes-Sanchez, A.; Canavera-Buelvas, F.; Barrios-Francisco, R.;
́
̃
■
Cifuentes-Vaca, O. L.; Flores-Alamo, M.; García, J. J. Organometallics
2011, 30, 3340. (b) Chen, T.; Xiao, J.; Zhou, Y.; Yin, S.; Han, L.-B. J.
Organomet. Chem. 2014, 749, 51.
*E-mail: chenzwang@126.com.
*E-mail: lxliu@xmu.edu.cn.
Notes
(11) Srimani, D.; Diskin-Posner, Y.; Ben-David, Y.; Milstein, D.
Angew. Chem., Int. Ed. 2013, 52, 14131.
́
́ ́
z, A.; Papai, I.; Nieger, M.; Leskela,
̈
(12) Chernichenko, K.; Madaras
M.; Repo, T. Nat. Chem. 2013, 5, 718.
The authors declare no competing financial interest.
(13) (a) Chen, Z.; Li, J.; Jiang, H.; Zhu, S.; Li, Y.; Qi, C. Org. Lett.
2010, 12, 3262. (b) Chen, Z.; Zeng, W.; Jiang, H.; Liu, L. Org. Lett.
2012, 14, 5385. (c) Chen, Z.; Jiang, H.; Wang, A.; Yang, S. J. Org.
Chem. 2010, 75, 6700. (d) Chen, Z.; Jiang, H.; Li, Y.; Qi, C. Chem.
Commun. 2010, 46, 8049. (e) Chen, Z.-W.; Jiang, H.-F.; Pan, X.-Y.;
He, Z.-J. Tetrahedron 2011, 67, 5920. (f) Chen, Z.-W.; Ye, D.-N.; Qian,
Y.-P.; Liu, L.-X. Tetrahedron 2013, 69, 6116. (g) Chen, Z.-W.; Ye, D.-
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ACKNOWLEDGMENTS
We thank the NSFC (21202023, 21162001, and 21161001) for
financial support.
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