Carbonylative Transformation of Allylarenes with CO Surrogates: Tunable Synthesis of 4-Arylbutanoic Acids, 2-Arylbutanoic Acids, and 4-Arylbutanals

Article abstract of DOI:10.1021/acs.orglett.9b02047

In this Communication, procedures for the selective synthesis of 4-arylbutanoic acids, 2-arylbutanoic acids, and 4-arylbutanals from the same allylbenzenes have been developed. With formic acid or TFBen as the CO surrogate, reactions proceed selectively and effectively under carbon monoxide gas-free conditions.

Full text of DOI:10.1021/acs.orglett.9b02047

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Carbonylative Transformation of Allylarenes with CO Surrogates:
Tunable Synthesis of 4‑Arylbutanoic Acids, 2‑Arylbutanoic Acids,
and 4‑Arylbutanals
Fu-Peng Wu,† Da Li,† Jin-Bao Peng,† and Xiao-Feng Wu*,†,‡
†Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, People’s Republic of China
‡Leibniz-Institut fu
̈
r Katalyse e. V. an der Universitat Rostock, Albert-Einstein-Straβe 29a, 18059 Rostock, Germany
̈
S
* Supporting Information
ABSTRACT: In this Communication, procedures for the selective synthesis
of 4-arylbutanoic acids, 2-arylbutanoic acids, and 4-arylbutanals from the
same allylbenzenes have been developed. With formic acid or TFBen as the
CO surrogate, reactions proceed selectively and effectively under carbon
monoxide gas-free conditions.
ransition-metal-catalyzed carbonylation reactions refer to
the organic transformations that incorporate a carbon
and TFBen5 as the solid CO source. Interestingly, by applying
T
PPh3 as the ligand and using toluene as the reaction media, 2-
phenylbutanoic acid can be isolated as the main product.
Moreover, a good yield of 4-phenylbutanal was formed by
using iridium as the catalyst instead of palladium.
Subsequently, several allylarenes were tested under our
conditions with PPh3 as the ligand (Scheme 1). Moderate
yields of 2-arylbutanoic acids can be formed in general. It is
important to mention that a significant amount of products
monoxide molecule into organic chemicals.1 After decades of
developments, these types of transformations have been well
accepted as powerful procedures for the production of
carbonyl-containing compounds. However, some challenges
are still remaining and need to be resolved. One of them is the
selectivity issues related to specific substrates, such as
allylarenes, which can theoretically generate three products
(Figure 1).2 The other one is the usage of carbon monoxide
a
Scheme 1. Synthesis of 2-Arylbutanoic Acids
Figure 1. Carbonylation of allylarene.
gas in most of the developed procedures, which is highly toxic,
flammable, and requires professional equipment. As expected,
this challenge has been noticed by chemists, and many CO
surrogates and technologies have been developed and explored
in various transformations.3 We have been attracted to this
topic as well. During the past several years, formic acid, TFBen,
C6O6, HCHO, DMF, and so on have been successfully
explored as CO sources in carbonylation reactions.4 In this
Communication, we report our new results on the carbon-
ylative transformation of allylarenes under CO gas-free
conditions. By modifying the catalytic system, 4-arylbutanoic
acids, 2-arylbutanoic acids, and 4-arylbutanals can be produced
in moderate to good yields from the same allylbenzenes.
To establish the catalytic systems, allylbenzene was chosen
as the model substrate, and systematic studies were carried out.
(For optimization details, see the Supporting Information.)
After systematic studies, we found that an excellent yield of 4-
phenylbutanoic acid can be obtained with good selectivity by
using [PdCl2(cinnamyl)]2/Xantphos as the catalytic system
a
Reaction condition: Allylbenzene (0.5 mmol), formic acid (5 mmol),
Pd(OAc)2 (2.5 mol %), PPh3 (20 mol %), toluene (2 mL), 100 °C, 20
h, isolated yields.
Received: June 14, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b02047
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Letter
a
Scheme 2. Synthesis of 4-Arylbutanoic Acids
a
Reaction conditions: Allylbenzene (0.5 mmol), formic acid (5 mmol), [PdCl2(cinnamyl)]2 (2.5 mol %), Xantphos (20 mol %), TFBen (1 equiv)
THF (2 mL), 100 °C, 30 h, isolated yields. The liner selectivity = (γ/(α + β)) and is given in brackets.
due to γ and β selectivity can be detected as well (α/(γ + β) =
3:2).
are suitable substrates here as well; 53−88% of the
corresponding products can be produced (Scheme 2, 2t−2w).
Because of the importance of aldehydes, the transformation
of allylarenes to the corresponding 4-arylbutanals was carried
out as well (Scheme 3). In this system, formic acid has been
used both as the CO source and the reductant. The
manipulation of carbon monoxide gas or hydrogen can be
absolutely avoided here. By using iridium as the catalyst and
Sphos (2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl) as
the ligand,6 various 4-arylbutanals were formed in moderate to
good yields from the corresponding substrates. Numbers of
functional groups are well tolerated. Here it is also important
to mention that compared with the other noble metals, iridium
Then, we focused our attention on the testing of substrates
for 4-arylbutanoic acid production (Scheme 2). As we
expected, good to excellent yields of the desired 4-arylbutanoic
acids can be produced from the corresponding substrates
under our standard conditions. Besides methyl, methoxy, and
chloride groups, esters and acetyl functional groups can be
tolerated as well (Scheme 2, 2p, 2q, 2x, 2y, 2z, and 2aa).
Additionally, 4-phenyl-1-butene and styrene were also tested
under our standard conditions; 90−93% yields of the target
acids were obtained (Scheme 2, 2r and 2s). Aliphatic alkenes
B
DOI: 10.1021/acs.orglett.9b02047
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a
Scheme 3. Synthesis of 4-Arylbutanals
a
Reaction condition: Allylbenzene (0.5 mmol), formic acid (2 mmol), [Ir(cod)Cl]2 (1.25 mol %), Sphos (6 mol %), DCC (1 mmol), CH3CN (2
mL), 90 °C, 24 h, isolated yields. The liner selectivity = (γ/(α + β)) and is given in brackets.
Scheme 4. Control Experiments
C
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catalysts are relatively rarely reported in carbonylative
transformations.7
concentrated in vacuo. The crude product was purified by
column chromatography on silica gel to afford the correspond-
ing product.
Control experiments were designed and performed to get
insight into the reaction pathway as well (Scheme 4). Under
our standard reaction conditions, 4-phenylbutanoic acid can
still be obtained as the main product when trans-β-
methylstyrene was applied as the substrate (Scheme 4, eq a).
13C-TFBen was prepared and tested, and 71% of carbonyl C13-
labeled 4-phenylbutanoic acid was formed to confirm the role
of TFBen as the CO source (Scheme 4, eq b). In the testing
with formic-d acid, no deuterated product could be detected
(Scheme 4, eq c). However, when we tested formic-d acid in
aldehyde synthesis, deuterated aldehyde was formed and
confirms the use of formic acid as the reductant (Scheme 4, eq
d).
In summary, we have studied the possibility for selective
carbonylative transformation of allylarenes in this Communi-
cation. On the basis of our systematic studies, procedures for
the selective synthesis of 4-arylbutanoic acids, 2-arylbutanoic
acids, and 4-arylbutanals from the same allylbenzenes have
been developed. With palladium or iridium as the catalyst and
using formic acid or TFBen as the CO surrogate, reactions
proceed selectively and effectively under carbon monoxide gas-
free conditions.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b02047.
General comments, general procedure, optimization
details, analytic data, and NMR spectra (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: xiao-feng.wu@catalysis.de
ORCID
Xiao-Feng Wu: 0000-0001-6622-3328
Funding
We acknowledge the financial support from the National
Natural Science Foundation of China (21772177, 21801225).
Notes
The authors declare no competing financial interest.
GENERAL PROCEDURES
■
REFERENCES
■
General Procedure for 4-Arylbutanoic Acid Synthesis
́
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[PdCl2(cinnamyl)]2 (6.5 mg, 2.5 mol %), Xantphos (28.9 mg,
10 mol %), and TFBen (105.0 mg, 1 mmol) were transferred
to a 15 mL tube that was filled with nitrogen. Allylbenzene (66
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quickly sealed with a screw-top septum cap and placed in a
heating block that was preheated to 100 °C. After a time
period of 20 h, the reaction vial was allowed to cool to room
temperature. The reaction vial was filtered with EtOAc and
concentrated in vacuo. The crude product was purified by
column chromatography on silica gel to afford the correspond-
ing product.
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General Procedure for 2-Arylbutanoic Acid Synthesis
Pd(OAc)2 (2.8 mg, 2.5 mol %), PPh3 (26.2 mg, 20 mol %),
and TFBen (105.0 mg, 1 mmol) were transferred to a 15 mL
tube that was filled with nitrogen. Allylbenzene (66 uL, 0.5
mmol), formic acid (190 uL, 5 mmol), and toluene (2 mL)
were added to the reaction tube. Then, the vial was quickly
sealed with a screw-top septum cap and placed in a heating
block that was preheated to 100 °C. After a time period of 20
h, the reaction vial was allowed to cool to room temperature.
The reaction vial was filtered with EtOAc and concentrated in
vacuo. The crude product was purified by column chromatog-
raphy on silica gel to afford the corresponding product.
General Procedure for 4-Arylbutanal Synthesis
[Ir(cod)Cl]2 (4.2 mg, 1.25 mol %), Sphos (12.3 mg, 6 mol %),
and DCC (206.1 mg, 1 mmol) were transferred to a 15 mL
tube that was filled with nitrogen. Allylbenzene (66 uL, 0.5
mmol), acetonitrile (2 mL), and formic acid (76 uL, 2 mmol)
were successively added to the reaction tube. Then, the vial
was quickly sealed with a screw-top septum cap and placed in a
heating block that was preheated to 90 °C. After a time period
of 24 h, the reaction vial was allowed to cool to room
temperature. The reaction vial was filtered with EtOAc and
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