Palladium-catalyzed hydroformylation of terminal arylacetylenes with glyoxylic acid

Article abstract of DOI:10.1039/c7cc09629a

A simple, practical and governable palladium-catalyzed hydroformylation of terminal arylacetylenes has been disclosed. The reaction proceeds under syngas-free conditions, using readily available glyoxylic acid as the formyl source, under mild conditions, giving rise to a broad range of α,β-unsaturated aldehydes.

Full text of DOI:10.1039/c7cc09629a

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: S. Xu, X. Tao, L.
Cai, Y. Liu and W. Pu, Chem. Commun., 2018, DOI: 10.1039/C7CC09629A.
This is an Accepted Manuscript, which has been through the
Volume 52 Number
1 4 January 2016 Pages 1–216
Royal Society of Chemistry peer review process and has been
accepted for publication.
ChemComm
Accepted Manuscripts are published online shortly after
Chemical Communications
www.rsc.org/chemcomm
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1359-7345
COMMUNICATION
Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc3N@C2n (2n 68 and 80). Synthesis of the
first methanofullerene derivatives of Sc N@D5h-C80
=
3
rsc.li/chemcomm

Page 1 of 5
ChemComm
View Article Online
DOI: 10.1039/C7CC09629A
Journal Name
COMMUNICATION
Palladium-Catalyzed Hydroformylation of Terminal
Arylacetylenes with Glyoxylic Acid
Cite this: DOI: 10.1039/x0xx00000x
Yang Liu, Liangzhen Cai,* Sheng Xu,* Weiwen Pu and Xiaochun Tao*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
equipment is indispensable. In the meanwhile, the application of
A
simply practical and governable palladium-catalyzed
syngas based hydroformylation in the laboratory is limited by the
toxic CO and dangerous H2. Fortunately, in recent years, some new
formyl reagents such as formaldehyde,8 alcohols,9 formic acid10 and
2,2-diethoxyglyoxylic acid11 have been developed as alternative
resources of syngas in the hydroformylation of olefins. Actually,
there are few reports about the hydroformylation of alkynes
without syngas. Herein, we use the glyoxylic acid as the formyl
source and PdCl2(PPh3)2 as the catalyst with the very common
ligand 1,3-bis(diphenylphosphino)propane (dppp) and PPh3 to
achieve the hydroformylation of terminal arylacetylenes. This
reaction featured with high stereoselectivity that only E-enals can
be obtained (Scheme 1 B).
hydroformylation of terminal arylacetylenes has been disclosed.
The reaction processes under a syngas free condition, using
readily available glyoxylic acid as formyl source, featured with
mild conditions, giving arise to a broad way of α,β-unsaturated
aldehydes.
With the development of transition metal catalysis,
hydroformylation has become
a significant method for the
preparation of aldehydes. In the past few decades, the
hydroformylation of alkenes catalyzed by transition metals reacted
with syngas to form the corresponding aldehyde products has been
widely reported. 1 In contrast to facile hydroformylation of alkenes,
few successful examples of hydroformylation of alkynes have been
reported, despite the resulting α,β-unsaturated aldehydes are
valuable in synthesis. The hydroformylation of alkynes suffers with
poor chemoselectivity, and low yields due to the undesired reduced
side reaction via the formation of corresponding alkenes and
saturated aldehydes byproduct.2 During the past two decades,
some effective catalysts such as [Rh(CO)2(acac)]/Biphephos,3 the
A) Previous work: Hydroformylation of alkynes
R2
CHO
[Rh], [Ru] or [Pd]
high pressure of hazardoussyngas
R1
CO/H2
R1
R2
B) This work: Hydroformylation of terminal arylacetylenes
heterobimetallic catalyst [PdCl2(PCy3)2]/[Co2(CO)8]4 and
a
[Pd]
zwitterionic rhodium complex5 were developed to address these
problems. Recently, some effective Rh or Pd catalyst with specific
phosphine ligands6 have been successively reported (Scheme 1 A).
However, terminal alkynes are more easily hydrogenated than di-
substituted alkynes under syngas condition, and so only a few
successful examples has been reported7.
CHO
easy to operate without syngas
Ar
H
.
Ar
CHOCO2H H2O
Scheme 1. Overview of transition metal catalyzed hydroformylation of
alkynes.
Phenylacetylene was exploited as the model substrate for the
studies. Here, 6 mol % or 12 mol % phosphine ligands, 3 mol % of
PdCl2(PPh3)2 and 5.0 equivalents of glyoxylic acid were added in
DMF and heated to 80 oC for 2 hours with intense stirring. As shown
in (Table 1), the yield was greatly influenced by ligand, solvent and
Pd catalyst. Few aldehydes were observed without ligand (entry 3).
Most of the bidentate phosphine ligands such as dppe, dppp and
dppb are favorable for this reaction (entries 4-6). Instead, dppf and
monodentate ligands give low yields (entries 7-10). The screening of
solvent effect reveals that the larger polar amide is more favorable
Generally, hydroformylation reactions involving syngas must be
carried out under high pressures, so the special pressurization
School of Chemistry & Molecular Engineering, East China University of Science
and Technology, 130 Mei Long Road, Shanghai 200237, China.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1

ChemComm
Page 2 of 5
VJieowuArrtnicalelONnlainme e
COMMUNICATION
DOI: 10.1039/C7CC09629A
for the reaction, and DMF is superior to other solvents (entries 11- product N-(2-acetylphenyl) acetamide13 was obtained when N-(2-
16). The choice of Pd catalysts is also crucial. PdCl2(PPh3)2 was the ethynylphenyl)acetamide is used.
best catalyst and the yield dropped down when it was replaced by
Table 2. Substrate scopea,b
Pd(OAc)2 or Pd(PPh3)4 (entries 17,18). We found that additional 6
mol % PPh3 would provide high yield during substrate scope studies.
(entry 20)12.
Table 1. Studies of the Reaction conditionsa
Entry
Ligand
Catalyst
Solvent
Yield[%]b
1
—
Pd(PPh3)4
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMAc
NMP
THF
13
28
2
2
—
PdCl2(PPh3)2
Pd(OAc)2
3
—
4
dppb
dppe
dppp
dppf
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
Pd (OAc)2
72
79
81
15
11
9
5
6
7
8
PCy3
Xphos
P(o-Tol)3
dppp
dppp
dppp
dppp
dppp
dppp
dppp
dppp
—
9
10
11
12
13
14
15
16
17
18
19
20c
8
65
32
trace
0
Toluene
DCE
t-BuOH
DMF
DMF
DMF
DMF
0
0
12
20
0
Pd(PPh3)4
a
The reactions were carried out with 1 (2 mmol), PdCl2(PPh3)2 (0.06 mmol),
—
PPh3 (0.12 mmol), dppp (0.12 mmol), and CHOCOOH·H2O (10 mmol) in DMF (4
ml) at 80 for 2-4 h. b Isolated yields.
dppp+PPh3
PdCl2(PPh3)2
86 (72)d
a
The reactions were carried out with 1a (1 mmol), catalyst (0.03 mmol), ligand
(0.06 or 0.12 mmol, P:Pd = 4:1), and CHOCOOH·H2O (5 mmol) in solvent (2 ml)
A precise reaction mechanism is not clear at this moment, one
plausible catalytic cycle is depicted in Scheme 2. Initially, the
reaction of palladium complex 4 and CHOCOOH (3) lead to the
palladium species 5. The active cationic palladium hydride species
66b can be formed in situ via the releasing of CO2, which coordinate
with alkyne (1), followed by the insertion reaction and the vinyl
palladium intermediate 7 was formed, then insertion of CO into the
palladium-vinyl bond would provide acyl palladium complex 8.
Subsequently, the hydrogenolysis reaction with glyoxylic acid
should afford the desired aldehyde 2 and regenerate the palladium
species 5.
In order to gain more insight of the reaction mechanism, the
deuterium labeling experiments were carried out with 1-ethynyl-4-
methoxybenzene (1l), 3 mol % PdCl2(PPh3)2, 6 mol % dppp, 6 mol %
PPh3 , 5 equivalent CHOCOOD, and shown in reaction A (Scheme 3).
Aldehyde (2l’) was isolated in 20% yield with 72% D, 50% D and 56%
D at carbons 1, 2, 3 respectively, and there was 61% D at the
terminal carbon of the alkyne which was not fully converted.
Reaction B was carried out with the same condition as reaction A
b
c
at 80
for 2 h. Determined by HPLC analysis. 0.06 mmol dppp and 0.06
mmol PPh3 was added. d Isolated yield.
With these optimized reaction conditions in hands (Table 1, entry
20), we investigated the general scope and the limitations of this
synthetic protocol. As shown in Table 2, the hydroformylation can
be extended to a variety of terminal alkynes, and the corresponding
α,β-unsaturated aldehydes were isolated in 36-82% yield. It is found
that the substrates with electron-donating substituents are
beneficial to high product yields as well as the reducing time of
reaction. Comparatively, the electron-withdrawing substituents
such as CF3, COOMe and CN led to the low yields (2s, 2t and 2u),
and the reaction achieved maximum yields in about three hours.
The position of the substituent on the aryl ring also has a great
influence on the reaction. The hydroformylation yields of o-
methoxyphenylacetylene (2m) and o-chlorophenylacetylene (2f) are
higher than the corresponding p-substituted substrates (2l, 2e).
Exceptionally, aldehydes 2n and 2o can be obtained in higher yields
from their alkynyl substrates, but the corresponding hydration
J. Name., 2013, 00, 1-3 | 2
This journal is © The Royal Society of Chemistry 20xx

Page 3 of 5
Journal Name
ChemComm
View Article Online
DOI: 1C0.O10M39M/CU7CNCI0C9A62T9IOA N
except H2 atmosphere, the yield was 9% and the distribution of hydrogen of the alkyne was exchanged in deuterium-labelling
deuterium had
experiments. The deuterium at carbon 2 of aldehyde (2l’) should
come from the alkyne. And then, the hydrogenolysis reaction of
acyl palladium complex 8 with CHOCOOD should afford the
deuterium at carbon 1. When the reaction was carried out under H2
atmosphere, the coordinated CO on the active cationic palladium
hydride species 6 and the vinyl palladium intermediate 7 should be
hindered and the yield was reduced.
In conclusion, an effective palladium-catalyzed hydroformylation
of terminal alkynes with glyoxylic acid has been developed,
affording the synthetically valuable α,β-unsaturated aldehydes with
exclusive E-selectivity and wide functional tolerence. Future work
will focus on extension substrate scope of alkylated alkyne and
detailed mechanism studies. Advantageously, the reactions can be
performed easily in the laboratory with glassware instead of high-
pressure equipment.
Project supported by National Key R&D Program of China
(2017YFB0306701). We thank Professor Yifeng Chen and Professor
Jun Zhang for discussion.
Conflicts of interest
There are no conflicts to declare.
Scheme 2. Proposed catalytic cycle for this reaction.
Notes and references
not changed. In reaction C, the alkyne was replaced by
hydroformylation product (2l), other conditions were the same as
reaction A, and there was no deuterium in the product. More
1 (a) F. Agbossou, J.-F. Carpentier and A. Mortreux, Chem. Rev.,
1995, 95, 2485-2506; (b) S. H. Chikkali, J. I. van der Vlugt and J.
N. H. Reek, Coord. Chem. Rev., 2014, 262, 1-15; (c) P. Eilbracht,
L. Bärfacker, C. Buss, C. Hollmann, B. E. Kitsos-Rzychon, C. L.
Kranemann, T. Rische, R. Roggenbuck and A. Schmidt, Chem.
Rev., 1999, 99, 3329-3366; (d) F. Hebrard and P. Kalck, Chem.
Rev., 2009, 109, 4272-4282; (e) J. Klosin and C. R. Landis, Acc.
Chem. Res., 2007, 40, 1251-1259; (f) J. Pospech, I. Fleischer, R.
Franke, S. Buchholz and M. Beller, Angew. Chem., Int. Ed., 2013,
52, 2852-2872.
details are available in the ESI†.
2 K. Doyama, J. Takashi and S. Takahashi, Tetrahedron Lett., 1986,
27, 4497-4500.
3 J. R. Johnson, G. D. Cuny and S. L. Buchwald, Angew. Chem., Int.
Ed., 1995, 34, 1760-1761.
4 Y. Ishii, K. Miyashita, K. Kamita and M. Hidai, J. Am. Chem. Soc.,
1997, 119, 6448-6449.
5 (a) B. G. Van den Hoven and H. Alper, J. Org. Chem., 1999, 64,
3964-3968; (b) B. G. Van den Hoven and H. Alper, J. Org.
Chem., 1999, 64, 9640-9645.
6 (a) V. Agabekov, W. Seiche and B. Breit, Chem. Sci., 2013, 4,
2418-2422; (b) X. Fang, M. Zhang, R. Jackstell and M. Beller,
Angew. Chem., Int. Ed., 2013, 52, 4645-4649; (c) Z. Zhang, Q.
Wang, C. Chen, Z. Han, X. Q. Dong and X. Zhang, Org. Lett.,
2016, 18, 3290-3293.
7 (a) V. Agabekov, W. Seiche and B. Breit, Chem. Sci., 2013, 4,
2418-2422; (b) F. Goettmann, P. Le Floch and C. Sanchez,
Chem. Commun., 2006, 180-182.
8 (a) J. A. Fuentes, R. Pittaway and M. L. Clarke, Chem. – Eur. J.,
2015, 21, 10645-10649; (b) T. Morimoto, T. Fujii, K. Miyoshi, G.
Makado, H. Tanimoto, Y. Nishiyama and K. Kakiuchi, Org.
Biomol. Chem., 2015, 13, 4632-4636; (c) H. Ren and W. D. Wulff,
Org. Lett., 2013, 15, 242-245; (d) M. Rosales, A. González, B.
González, C. Moratinos, H. Pérez, J. Urdaneta and R. A.
Sánchez-Delgado, J. Organomet. Chem., 2005, 690, 3095-3098.
9 (a) S. H. Christensen, E. P. Olsen, J. Rosenbaum and R. Madsen,
Org. Biomol. Chem., 2015, 13, 938-945; (b)J. J. Verendel, M.
Nordlund and P. G. Andersson, ChemSusChem., 2013, 6, 426-
Scheme 3. Deuterium-Labelling experiments.
The deuterium at each carbon on aldehyde (2l’) can be explained
by the proposed catalytic cycle. When the reaction was carried out
in the presence of CHOCOOD, the hydrogen on the active cationic
palladium hydride species 6 can be exchanged by deuterium, which
leads to the deuterium at carbon 3 via insertion reaction. The
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3

ChemComm
Page 4 of 5
COMMUNICATION
VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C7CC09629A
429.
10 W. Ren, W. Chang, J. Dai, Y. Shi, J. Li and Y. Shi, J. Am. Chem.
Soc., 2016, 138, 14864-14867.
11 H. Huang, C. Yu, Y. Zhang, Y. Zhang, P. S. Mariano and W. Wang,
J. Am. Chem. Soc., 2017, 139, 9799-9802.
12 B. El Ali, G. Vasapollo and H. Alper, J. Org. Chem., 1993, 58,
4739-4741.
13 Z. Zhang, L. Wu, J. Liao, W. Wu, H. Jiang, J. Li and J. Li, J. Org.
Chem., 2015, 80, 7594-7603.
J. Name., 2013, 00, 1-3 | 4
This journal is © The Royal Society of Chemistry 20xx

Page 5 of 5
ChemComm
View Article Online
DOI: 10.1039/C7CC09629A
Palladium-Catalyzed Hydroformylation of Terminal Arylacetylenes
with Glyoxylic Acid
Yang Liu, Liangzhen Cai,* Sheng Xu,* Weiwen Pu and Xiaochun Tao*
H
O
PdCl2(PPh3)2
dppp, PPh3
Ar
O
O
+
H
Ar
H
H
DMF
21 examples
H
H
O




Syngas-free reaction condition
Use common ligands
Terminal alkyne substrates
Some researches for mechanism