Powerful and Phosphine-Free Palladium-Catalyzed Selective Formylation of Aryl Halides with Formic Acid as CO Source

Article abstract of DOI:10.1007/s10562-020-03108-z

The phosphine-free palladium-based catalytic system Pd(OAC)₂/DABCO has been developed for the carbonylative transformations of aryl halides with formic acid. The DABCO acts as a base as well as N-donor ligand to coordinate with metal ions and stabilize Pd-catalytic sites during the reaction process. Using DCC as the activator of formic acid and PEG as the reaction media. The aryl halides have been conveniently transformed into the corresponding aldehydes in moderate to excellent yields. Graphic Abstract: An efficient catalytic system Pd(OAc)2/ DABCO/ DCC for selective carbonylation of aryl halides with formic acid is described.[Figure not available: see fulltext.].

Full text of DOI:10.1007/s10562-020-03108-z

Catalysis Letters
https://doi.org/10.1007/s10562-020-03108-z
Powerful and Phosphine‑Free Palladium‑Catalyzed Selective
Formylation of Aryl Halides with Formic Acid as CO Source
Elahe Molaei · Fatemeh Mohammadsaleh1 · Khodabakhsh Niknam1
1
Received: 10 November 2019 / Accepted: 9 January 2020
©
Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract
The phosphine-free palladium-based catalytic system Pd(OAC) /DABCO has been developed for the carbonylative
2
transformations of aryl halides with formic acid. The DABCO acts as a base as well as N-donor ligand to coordinate
with metal ions and stabilize Pd-catalytic sites during the reaction process. Using DCC as the activator of formic acid
and PEG as the reaction media. The aryl halides have been conveniently transformed into the corresponding aldehydes
in moderate to excellent yields.
Graphic Abstract
An eꢀcient catalytic system Pd(OAc)2/ DABCO/ DCC for selective carbonylation of aryl halides with formic acid is
described.
Keywords Carbonylation · Formic acid · Aldehyde · Catalyst · Palladium
1
Introduction
2]. Aromatic aldehydes play an important role in this class
of organic compounds and are one of the key synthetic
blocks in formation of various C−C and C−X bonds, many
natural products and pharmaceutical compounds [3, 4].
Recently, carbonylative transformations have already
become one of the most powerful methodologies for the
synthesis of carbonyl-containing compounds, and many
related research eꢁorts have been conducted toward this
objective [5, 6]. The terms ‘carbonylation’ and ‘carbon-
ylative’ are used specially for a large number of transfor-
mations that introduce carbon monoxide into organic and
inorganic substrates. Although, CO gas has been recog-
nized as one of the carbonyl sources and has an accept-
able position in industry [6], the high toxicity and gaseous
nature, prevent the applications of CO gas-based method-
ologies. Therefore, many synthetic studies have conducted
The value of carbonyl-containing chemicals in chemistry
and biology as critical structural units and important inter-
mediates in chemical transformations for a variety of natu-
ral and pharmaceutical products has inspired the develop-
ment of various synthetic methods for their preparation [1,
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s10562-020-03108-z) contains
supplementary material, which is available to authorized users.
*
Fatemeh Mohammadsaleh
f.mohammadsaleh@gmail.com
*
Khodabakhsh Niknam
niknam@pgu.ac.ir
1
Department of Chemistry, Faculty of Sciences, Persian Gulf
University, Bushehr 75169, Iran
Vol.:(0
1
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3

E. Molaei et al.
toward the developing new CO-free carbonylation meth-
ods [7–9]. Among the various carbonyl sources, formic
acid (HCOOH) has attracted much attention because it can
produce one molecule of CO during the reaction process
aldehydes could be synthesized via carbonylative reaction
of aryl halides with the in-situ generation of CO from
formic acid using DCC as the activator.
[
10].
Palladium-catalyzed carbonylation of aryl halides by
2 Results and Discussion
various carbonyl sources such as CO [11–13], CO [7],
2
Mo(CO) [14] Oxalic acid [8], N-formylsaccharin [15] and
Our carbonylation approach was initiated using iodo-
benzene 1a as the aryl halide. We examined the effect of
various reaction parameters such as solvent, temperature
and catalyst loading on the yields of a series of screening
experiments (Table 1). The solvent effect was studied
and the results suggested that the solvent system plays a
crucial role in this reaction system. Among the several
6
,
Formic acid [16, 17] is eꢀcient and straightforward alter-
native methodology for preparing carbonyl compounds. In
these reactions, generally, the use of phosphine ligands to
activate and stabilize the palladium species results in high
eꢀciency of catalyst. However, most phosphine ligands
are air-sensitive, not environmentally-friendly and require
a high palladium loading in carrying out the reaction, sig-
niꢂcantly limiting their applications. Therefore, there is a
great interest in making new and phosphine-free ligands,
and development of economic benign synthetic protocols
as an important and challenging goal in organic chemistry.
In continuation of our studies on the synthesis and
development of new and eꢀcient catalytic systems, herein
we introduce a phosphine-free Pd-based catalytic system
incorporating 1,4 diazabicyclo[2.2.2]octane (DABCO) for
the formic acid carbonylation of aryl halides, in which
DABCO acts as an inexpensive and stable base as well
as an excellent ligand to stabilize Pd species in the reac-
tion media (Scheme 1). In this reaction system, aromatic
tested solvents such as H O, EtOH, MeCN, polyethyl-
2
ene glycol (PEG) and mixed solvents EtOH/H O (1:1);
2
PEG gave the best result (Table 1, entries 1–5). Further
examination of different bases proved DABCO was the
best option in terms of efficiency (Table 1, entries 5–8).
The concentration of DABCO and DCC was also
examined in this reaction system, and these parameters
were found to be important in the reaction progress. As
shown in Table 1 (entries 9–11), the use of lower con-
centrations of DABCO and DCC gave a relatively lower
yield.
The reaction temperature and the catalyst loadings
were also studied in this reaction system. The yield of
Scheme 1 Diꢁerent formylation methods. 1 [20], 2 [16, 19], 3 [21]
1
3

Powerful and Phosphine-Free Palladium-Catalyzed Selective Formylation of Aryl Halides with…
Table 1 Optimization of the reaction conditions for the carbonylation coupling
Entry
Solvent
Base (2 equiv.)
DCC
Catalyst (mol%)
T [°C]
Yield [%]a
1
2
3
4
5
6
7
8
H O
EtOH
DABCO
DABCO
DABCO
DABCO
DABCO
–
2 equiv
2 equiv
2 equiv
2 equiv
2 equiv
2 equiv
2 equiv
2 equiv
2 equiv
–
1 equiv
2 equiv
2 equiv
2 equiv
2 equiv
2 equiv
2.7
2.7
2.7
2.7
2.7
2.7
2.7
2.7
2.7
2.7
2.7
2.7
1.7
0.9
–
100
Reꢃux
Reꢃux
Reꢃux
100
100
100
100
100
100
100
60
–
2
10
15
50
90
20
75
70
75
50
70
40
75
50
–
H O/EtOH (1:1)
2
CH CN
3
PEG-200
PEG-200
PEG-200
PEG-200
PEG-200
PEG-200
PEG-200
PEG-200
PEG-200
PEG-200
PEG-200
PEG-200
Et N
3
K CO
2
3
b
9
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
1
1
1
1
1
1
1
0
1
2
3
4
5
6
100
100
100
rt
2.7
Trace
Reaction conditions: iodobenzene (0.5 mmol), HCOOH (3.5 mmol), DCC, Pd(OAc) , base, solvent (3 mL), 3 h
2
a
GC yield
DABCO (1 equiv.)
b
the model reaction decreased when the reaction tempera-
ture was changed from 100 to 60 °C (Table 1, entry 12).
The optimal catalyst loading was found to be as low as
The electronic properties of aryl halides had signiꢂcant
inꢃuence on the resulting yields in this procedure. Electron-
rich aryl halides in comparison to electron-poor aryl hal-
ides showed better conversions in shorter reaction time. The
methoxy- and methyl-aryl iodides gave excellent yields, in
contrast the reaction of nitro-aryl iodides required longer
reaction times and aꢁorded lower yields.
2
.7 mol% (Table 1, entries 5, 13–15).
According to the extensive experimental results, the opti-
mized conditions were established as Pd(OAc) (2.7 mol%),
2
DABCO (2 equiv), DCC (2 equiv), HCOOH (7 equiv) in
PEG at 100 °C.
Steric eꢁects were also examined for this catalytic system
by treating 2-iodotoluene under optimized reaction condi-
tions. As shown in Scheme 2, the steric hindrance does not
have a signiꢂcant eꢁect on the yield. The 2-iodothiophene
and 2-bromopyridine were chosen as heteroaryl halides and
gave the corresponding aldehyde in good yields (Scheme 2,
9a and 10a).
We next explored the scope and limitations of this trans-
formation (Scheme 2). Various aryl iodides and bromides
reacted successfully under the optimal conditions to give
the corresponding aldehydes in moderate to excellent yields.
As shown in Scheme 2, the most of aryl iodides were
successfully converted to the corresponding aldehyde prod-
ucts with excellent yields. Aryl bromides also reacted in
this system to aꢁord the corresponding aromatic aldehydes
To date, several mechanisms for Pd-assisted formic
acid-based carbonylation reactions have been described in
the literatures. Wu et al. [16, 18] have reported the in-situ
generation of one molecule of carbon monoxide from the
reaction of formic acid with DCC as the activator, that this
CO-molecule forms an acyl-palladium intermediate in the
catalytic cycle. Sun et al. [19] have studied the hydrogen
(
Scheme 2. 10a and 1a). However, the reactivity of aryl bro-
mides was lower than aryl iodides. Aryl bromides required
longer reaction times and gave lower yields. Aryl chlorides
were inactive in this reaction system.
1
3

E. Molaei et al.
Scheme 2 Scope of aryl halides
in carbonylation coupling reac-
tion with HCOOH
O
X
+
Pd(OAc)2 (2.7mol%)
PEG, DABCO
H
HCO2H
R
R
o
DCC (2 equiv.), 100 C
X: I, Br
a
O
O
O
H
MeO
H
H
O N
2
MeO
1a (1.5h, 90%, X:I)
2a (2h, 85%, X:I)
3a (5h, 35%, X:I)
O
H
O
H
O
H
O N
2
6
a (2h, 93%, X:I)
5
a (3h, 87%, X:I)
4a (5h, 60%, X:I)
O
H
O
H
H
S
O
Br
8a (5h, 40%, X:I)
9
a (3h, 80%, X:I)
7a (2.5h, 91%, X:I)
O
O
H
H
H
N
MeO
1a (24h, 50%, X:Br)
O
5
a (24h, 0%, X:Cl)
1
0a (10h, 70%, X:Br)
aReaction conditions: aryl halide (0.5 mmol), HCOOH (3.5 mmol), DCC (1.0 mmol), Pd(OAc)
2
o
(
2.7 mol%), DABCO (2.0 equiv.), solvent (3 mL), 100 C.
source of the aldehyde products in the palladium-catalyzed
formylation reaction of aryl iodide with isotopically labeled
catalysts combined with the ligands promote the synthesis
of aldehydes from aryl halides. As shown in Table 2, the
most important advantages of this carbonylation method
are mild and phosphine-free conditions, availability, low
catalyst-loading, short reaction times and good yields. In
general, reaction condition, reaction rate, selectivity and
availability are important factors that must be considered
in this transformations.
reagent D -formic acid. They found that the hydrogen source
2
of the aldehyde group derived from formic acid.
Based on these reports and our experimental results, a
possible reaction mechanism was proposed. As shown in
the Scheme 3, the catalytic cycle begins with the oxida-
tive addition of aryl halide to the Pd(0) species, in which
the DABCO acted as both an eꢀcient base and a N-donor
excellent ligand to stabilize the Pd-catalytic sites.
Due to the increasing importance of carbonyl-contain-
ing compounds in many aspects, the design of high-yield-
ing and selective synthetic methodologies for preparation
of these compounds will be interesting to follow in the
near future.
The present catalytic method was compared with the
some procedures previously reported by other groups,
in which diꢁerent catalytic systems based on palladium
1
3

Powerful and Phosphine-Free Palladium-Catalyzed Selective Formylation of Aryl Halides with…
Scheme 3 Proposed mechanism
Pd(OAc) (DABCO)
2
2
of formylation reaction
DABCO:L
O
0
Pd (L)n
I
Ar
CO +
2
Ar
H
Oxidation-Addition
Reductive-Elimination
O
I
II O
H
PdII
Ar
Pd
Ar
Ln
O
Ln
HI
HCOOH
+
DCC
O
HCOOH
CO
II
Pd
I
Ar
Ln
Table 2 Comparison of catalytic systems with literature examples for the formylation of 4-iodotoluene via carbonylation rection
Entry
Catalyst
Reaction conditions
Yield (%) [Refs.]
1
2
3
Pd(OAc) (3 mol%)
PPh ,I , HCOOH, Et N, Toluene, 80 °C, 2 h
83 [19]
76 [16]
82 [22]
2
3
2
3
Pd(OAc) (3 mol%)
PCy , DCC, HCOOH, Et N, DMF, 80 °C, 10 h
2
3
3
Pd (dba) (0.025 equiv.)
Dppe, Et SiH, EtN(i-Pr) , Acetic Formic Anhydride, 60 °C,
3 2
2
3
4
8 h
4
5
PdCl (3.5 mol%)
Present work
SDPP, Fe(CO) , Et N, H O/DMF (1.3% v/v H O)
DABCO, DCC, HCOOH, PEG, 100 °C, 1.5 h
92 [23]
93
2
5
3
2
2
Acknowledgements We are thankful to Persian Gulf University
2.1 Experimental
Research Council for partial support of this work.
2.1.1 General Procedure for Carbonylation Reaction
Compliance with Ethical Standards
Aryl halide (0.5 mmol), Pd(OAc) (2.7 mol%), PEG
2
Conflict of interest All authors declare that they have no conꢃict of
interest associated with this publication. They also conꢂrm that the
manuscript has been read and approved by all 3 authors.
(
3.0 mL) and formic acid (3.5 mmol) were transferred
into a round-bottom flask. After, DABCO (1.0 mmol)
and DCC (1.0 mmol) were added to the reaction flask,
immediately sealed, and the mixture was stirred at
1
00 °C. After the reaction was completed the mixture
References
was diluted with CH Cl and filtered and concentrated.
2
2
1
.
Kollár L (2008) Modern carbonylation methods. Wiley,
Hoboken
The crude product was purified by column chromatog-
raphy on silica gel to afford the corresponding product.
1
3

E. Molaei et al.
2
.
Wu X-F, Fang X, Wu L, Jackstell R, Neumann H, Beller M
2014) Transition-metal-catalyzed. Carbonylation reactions
of olefins and alkynes: a personal account. Acc Chem Res
14. Hajipour A-R, Tavangar-Rizi Z, Iranpoor N (2016) Palladium-
catalyzed carbonylation of aryl halides: an eꢀcient, heterogene-
ous and phosphine-free catalytic system for aminocarbonylation
(
4
7(4):1041–1053
and alkoxycarbonylation employing Mo(CO) as a solid carbon
6
3
4
.
.
Dirksen A, Dawson PE (2008) Rapid oxime and hydrazone
ligations with aromatic aldehydes for biomolecular labeling.
Bioconjug Chem 19(12):2543–2548
monoxide source. RSC Adv 6(82):78468–78476
15. Ueda T, Konishi H, Manabe K (2013) Palladium-catalyzed
reductive carbonylation of aryl halides with N-formylsaccharin
as a CO source. Angew Chem Int Ed 52(33):8611–8615
16. Wu FP, Peng JB, Meng LS, Qi X, Wu XF (2017) Palladium-
catalyzed ligand-controlled selective synthesis of aldehydes
and acids from aryl halides and formic acid. ChemCatChem
9(16):3121–3124
Campos CA, Gianino JB, Pinkerton DM, Ashfeld BL (2011)
Aryl aldehydes as traceless dielectrophiles in bifunctional
titanocene-catalyzed propargylic C-X activations. Org Lett
1
3(20):5680–5683
5
6
.
.
Li Y, Hu Y, Wu X-F (2018) Non-noble metal-catalysed car-
bonylative transformations. Chem Soc Rev 47(1):172–194
Gautam P, Bhanage BM (2015) Recent advances in the
transition metal catalyzed carbonylation of alkynes, arenes
and aryl halides using CO surrogates. Catal Sci Technol
17. Qi X, Jiang LB, Li HP, Wu XF (2015) A convenient palla-
dium-catalyzed carbonylative suzuki coupling of aryl halides
with formic acid as the carbon monoxide source. Chemistry
21(49):17650–17656
5
(10):4663–4702
18. Wu F-P, Peng J-B, Qi X, Wu X-F (2017) Palladium-catalyzed
carbonylative transformation of organic halides with formic
acid as the coupling partner and CO source: synthesis of car-
boxylic acids. J Org Chem 82(18):9710–9714
7
8
9
.
.
.
Shimomaki K, Murata K, Martin R, Iwasawa N (2017) Visi-
ble-light-driven carboxylation of aryl halides by the combined
use of palladium and photoredox catalysts. J Am Chem Soc
1
39(28):9467–9470
19. Sun G, Lv X, Zhang Y, Lei M, Hu L (2017) Palladium-catalyzed
formylation of aryl iodides with HCOOH as CO source. Org
Lett 19(16):4235–4238
Shao C, Lu A, Wang X, Zhou B, Guan X, Zhang Y (2017)
Oxalic acid as the in situ carbon monoxide generator in pal-
ladium-catalyzed hydroxycarbonylation of arylhalides. Org
Biomol Chem 15(23):5033–5040
20. Neumann H, Kadyrov R, Wu XF, Beller M (2012) Palladium-
catalyzed reductive carbonylation of aryl bromides with phos-
phinite ligands. Chem Asian J 7(10):2213–2216
Di Nicola A, Arcadi A, Rossi L (2016) BMIm HCO : an ionic
3
liquid with carboxylating properties. Synthesis of carbamate
21. Huang H, Li X, Yu C, Zhang Y, Mariano PS, Wang W (2017)
Visible-Light-promoted nickel-and organic-dye-cocatalyzed
formylation reaction of aryl halides and triꢃates and vinyl bro-
mides with diethoxyacetic acid as a formyl equivalent. Angew
Chem Int Ed 56(6):1500–1505
esters from amines. New J Chem 40(12):9895–9898
1
0. Sang R, Kucmierczyk P, Dong K, Franke R, Neumann H,
Jackstell R, Beller M (2018) Palladium-catalyzed selective
generation of CO from formic acid for carbonylation of alk-
enes. J Am Chem Soc 140(15):5217–5223
22. Cacchi S, Fabrizi G, Goggiamani A (2004) Palladium-catalyzed
synthesis of aldehydes from aryl iodides and acetic formic
anhydride. J Comb Chem 6(5):692–694
1
1
1. Brennführer A, Neumann H, Beller M (2009) Palladium-cata-
lyzed carbonylation reactions of aryl halides and related com-
pounds. Angew Chem Int Ed 48(23):4114–4133
23. Iranpoor N, Firouzabadi H, Etemadi-Davan E, Rostami A,
Rajabi Moghadam K (2015) Palladium-catalysed reductive
carbonylation of aryl halides with iron pentacarbonyl for syn-
thesis of aromatic aldehydes and deuterated aldehydes. Appl
Organomet Chem 29(11):719–724
2. Molla RA, Iqubal MA, Ghosh K, Roy AS, Islam SM (2014)
Mesoporous poly-melamine-formaldehyde stabilized pal-
ladium nanoparticle (Pd@ mPMF) catalyzed mono and dou-
ble carbonylation of aryl halides with amines. RSC Adv.
4
(89):48177–48190
1
3. Ashꢂeld L, Barnard CF (2007) Reductive carbonylation−an
eꢀcient and practical catalytic route for the conversion of aryl
halides to aldehydes. Org Process Res Dev 11(1):39–43
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