Decarbonylative Sonogashira Cross-Coupling of Carboxylic Acids

Article abstract of DOI:10.1021/acs.orglett.1c01445

Decarbonylative Sonogashira cross-coupling of carboxylic acids by palladium catalysis is presented. The carboxylic acid is activated in situ by the formation of a mixed anhydride and further decarbonylates using the Pd(OAc)2/Xantphos system to provide an aryl-Pd intermediate, which is intercepted by alkynes to access the traditional Pd(0)/(II) cycle using carboxylic acids as ubiquitous and orthogonal electrophilic cross-coupling partners. The methodology efficiently constructs new C(sp2)-C(sp) bonds and can be applied to the derivatization of pharmaceuticals. Mechanistic studies give support to decarbonylation preceding transmetalation in this process.

Full text of DOI:10.1021/acs.orglett.1c01445

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Letter
Decarbonylative Sonogashira Cross-Coupling of Carboxylic Acids
Chengwei Liu and Michal Szostak*
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sı Supporting Information
ABSTRACT: Decarbonylative Sonogashira cross-coupling of
carboxylic acids by palladium catalysis is presented. The carboxylic
acid is activated in situ by the formation of a mixed anhydride and
further decarbonylates using the Pd(OAc) /Xantphos system to
2
provide an aryl−Pd intermediate, which is intercepted by alkynes
to access the traditional Pd(0)/(II) cycle using carboxylic acids as
2
ubiquitous and orthogonal electrophilic cross-coupling partners. The methodology efficiently constructs new C(sp )−C(sp) bonds
and can be applied to the derivatization of pharmaceuticals. Mechanistic studies give support to decarbonylation preceding
transmetalation in this process.
onogashira cross-coupling represents one of the most
coupling repertoire of carboxylic acids attractive for organic
12
S
widely utilized and powerful strategies for incorporating
synthesis.
In continuation of our studies on decarbonylative
1
alkynes into organic molecules. Recent surveys place
Sonogashira cross-coupling as the third most commonly used
8
a
8b
8c
8d
borylation, arylation, reduction, 9 phosphorylation, and
2
8e
cross-coupling method in industrial settings. In particular, the
heteroarylation of carboxylic acids, we became interested in
capacity of alkynes to function as an important functional
group on their own as well as participate in an array of
reactions as synthetic intermediates has resulted in the broad
the development of decarbonylative Sonogashira cross-
coupling of carboxylic acids (Figure 1). Herein, we present
the development of this method, including derivatization of
pharmaceuticals and mechanistic studies that give support to
decarbonylation preceding transmetalation in this process. The
identified catalyst system involves Pd(OAc)2 (5 mol
3
interest to establish new protocols to incorporate alkyne motifs
1,2
by Sonogashira cross-coupling.
Typical electrophilic substrates for Sonogashira cross-
coupling include aryl halides and pseudohalides, such as
%)/Xantphos (10 mol %) with piv O (1.5 equiv) and
2
1
,2
sulfonates, while more recent attention has focused on
iodonium salts, diazonium salts, phosphonium salts, and
sulfonium salts among other electrophiles by C−X, C−O,
4
C−N, C−P, and C−S cleavage. In this context, it is important
to note that while many exciting achievements have been made
using the Pd/Cu-co-catalyzed variant, including cross-coupling
5
of alkyl electrophiles, the Pd-catalyzed/Cu-free variant has
6
a−c
received increased attention.
Recently, C−H alkynylation
methods, in particular transformations enabled by directing
groups, have also been developed.
7
In this context, our laboratory has developed new methods
8
,9
for decarbonylative cross-coupling of carboxylic acids. In this
reaction manifold, carboxylic acid is activated in situ to form a
8a−e
mixed anhydride,
followed by selective oxidative addition
Figure 1. (a) Sonogashira cross-coupling. (b) This work: Sonogashira
cross-coupling of carboxylic acids by decarbonylation.
of the C(O)−OR bond to a low valent metal and
decarbonylation to furnish the traditional Ar−metal inter-
mediate using ubiquitous carboxylic acids as cross-coupling
1
0
partners. The particular value of this approach is that
carboxylic acids represent pervasive substrates in organic
Received: April 28, 2021
Published: June 7, 2021
1
1
synthesis and are derived from an orthogonal pool of
11
precursors to aryl halides and pseudohalides. The inherent
presence of carboxylic acids in pharmaceuticals, natural
products, and functional materials renders the growing cross-
©
2021 American Chemical Society
https://doi.org/10.1021/acs.orglett.1c01445
4
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Org. Lett. 2021, 23, 4726−4730

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Letter
a
DMAP (1.5 equiv), dioxane (0.25 M), 160 °C, 15 h, as
activators. Very recently, Chen and co-workers reported the
first study of the decarbonylative cross-coupling of carboxylic
Table 1. Optimization of the Cross-Coupling
13
acids with alkynes. The conditions reported using Pd (dba)
2
3
(
(
2.5 mol %), Xantphos (10 mol %), Ac O (1.5 equiv), DME
2
13
8a−e
0.10 M), 130 °C, 12 h. In our experience
piv O with or
2
without a Lewis base is superior to Ac O in promoting
selective decarbonylative coupling of carboxylic acids.
2
8
,10,11
entry
1
2
3
4
5
6
7
8
9
[Pd]
ligand
base
additive
piv O
yield (%)
In
−
−
−
−
DMAP
DMAP
DMAP
−
<2
<2
68
7
light of this development and our own studies, we considered it
2
b
piv O
appropriate to report our findings. The two catalytic systems
2
1
4
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
2
dppb
dppb
dppb
dppb
dppb
dppb
dppb
dppp
dppent
dppf
XantPhos
DPEPhos
BINAP
PCy3
piv O
2
should be considered complementary, while our study
excludes the direct decarbonylation of ynones as intermediates
in this process.
piv O
2
DMAP
−
<2
18
<2
<2
33
45
35
31
92
7
<2
<2
<2
<2
<2
47
58
74
70
13
77
87
30
42
37
24
3
Et N
piv O
Selected optimization results are presented in Table 1. After
extensive optimization, we identified the combined use of
3
2
py
piv O
2
Pd (dba)3
2
Na CO3
piv O
2
Pd(OAc) and Xantphos in dioxane at 160 °C as effective
2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
2
K CO3
piv O
2
catalytic promoters for the process (entries 1−19). Interest-
ingly, several phosphine ligands can be used, including dppb,
dppp, dppent, dppf; however, Xantphos proved most effective,
while monodentate phosphines were ineffective (entries 10−
1
1
1
1
1
0
1
2
3
4
DMAP
piv O
2
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
piv O
2
piv O
2
Pd(OAc)2
piv O
2
1
9). Out of several activators tested, such as Ac O, Boc O, and
2 2
Pd(OAc)2
piv O
2
piv O, the latter was identified as giving the best reactivity
2
8
,14
15
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
piv O
2
(
entries 20−22), in agreement with our previous studies.
It
1
1
1
1
2
2
2
2
6
7
8
9
0
1
2
3
piv O
2
is important to note that Cu is not required for this process
PCy Ph
piv O
2
2
(
entries 24−31), resulting in a Cu-free Sonogashira variant.
PPh3
piv O
2
Finally, we demonstrated that the reaction proceeds at
temperatures as low as 120 °C, demonstrating efficient
decarbonylation under these conditions (entry 33). Further-
DavePhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
piv O
2
Ac O
2
Boc O
2
more, the use of Pd(OAc) at 1 mol % resulted in a promising
2
c
piv O
2
4
5% yield for future reaction development (entry 35). Overall,
d
e
piv O
2
the catalytic system is complementary to the one developed by
Chen and co-workers. The use of large bite angle
1
3
24
piv O
2
f
2
5
piv O
2
phosphines, such as Xantphos (108°), promotes decarbon-
g
h
i
8a−e
26
piv O
2
ylation in the process.
2
2
2
3
3
3
3
3
3
7
8
9
0
1
2
3
4
5
piv O
2
Having identified optimal reaction conditions for the
coupling, we investigated the scope of this decarbonylative
process for the synthesis of alkynes (Scheme 1). As shown in
Scheme 1A, this method is successful with an array of aryl
carboxylic acids. Naphthyl-carboxylic acids (3a−3c) as well as
electronically differentiated benzoic acids (3d−3f) are well-
tolerated. Importantly, halides, such as chlorides, are
compatible with this process (3g), enabling derivatization by
standard cross-coupling technologies and showing comple-
mentarity of our catalytic system. As shown previously by
piv O
2
j
piv O
2
k
l
piv O
2
piv O
2
m
n
o
p
piv O
2
84
69
73
45
piv O
2
piv O
2
piv O
2
a
Conditions: 1-Np-CO H (1.0 equiv), alkyne (4.0 equiv), Pd(OAc)
2
2
8
a−e
(5 mol %), ligand (10 mol %), DMAP (1.5 equiv), piv O (1.5 equiv),
2
b c
us,
Br in this manifold. Furthermore, steric ortho-substitution,
such as Me (3h), CF (3i), and even sterically hindered Ph
the reactivity of carboxylic acids is comparable to Ar−
dioxane (0.25 M), 160 °C, 15 h. CuI (10 mol %). Alkyne (3.0
d
e
f
equiv). Alkyne (5.0 equiv). CuCl (10 mol %). CuBr (10 mol %).
g
h
i
j
3
CuI (10 mol %). CuCN (10 mol %). CuF (10 mol %). CuSO
2 4
k l m
(3j), is also possible. As expected, meta-substitution is well-
(
10 mol %). Cu(OAc) (10 mol %). Cu(OTf) (10 mol %). 140
2
2
n
o
p
tolerated (3k−3l). This method can also be used to cross-
couple heterocyclic carboxylic acids, such as thienyl-carboxylic
acids (3m−3n).
°C. 120 °C. Toluene. Pd(OAc) (1 mol %), Xantphos (2 mol %).
2
See Supporting Information (SI) for details.
Finally, the potential of the method in derivatization of
pharmaceuticals has been demonstrated in the direct
Sonogashira cross-coupling of Bexarotene, an antineoplastic
agent (3o). It is important to note that in contrast to oxidative
hexylacetylene, couple in high yields (3r). Sensitive alkyl
electrophiles that can be utilized in further functionalization,
such as halides, are also tolerated (3s). Finally, silyl-acetylenes,
such as (triisopropylsilyl)acetylene, can be used (3t), providing
access to terminal alkynes after deprotection. At the present
stage, heterocyclic acids, such as thienyl, are tolerated. 3-
Pyridyl carboxylic acid gave a lower but promising yield (20%).
Carbonyl groups, such as ketones, are tolerated in decarbon-
10,11
methods for cross-coupling of carboxylic acids,
this redox-
neutral manifold by decarbonylation does not require steric or
electronic bias to facilitate decarboxylation, resulting in a
general method.
Next, the scope of the alkyne component was briefly
investigated (Scheme 1B). As shown, the reaction is
compatible with electronically differentiated phenylacetylenes
8
−12
ylative coupling.
Mechanistic studies were conducted to gain insight into this
process (Scheme 2). Thus, intermolecular competition experi-
ments between differently substituted acid electrophiles
(3d′, 3p−3q). Furthermore, alkylacetylenes, such as cyclo-
4
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Letter
Scheme 1. Decarbonylative Sonogashira Cross-Coupling of Carboxylic Acidsa,b
a
Conditions: carboxylic acid (1.0 equiv), alkyne (4.0 equiv), Pd(OAc) (5 mol %), XantPhos (10 mol %), DMAP (1.5 equiv), piv O (1.5 equiv),
2
2
b
dioxane (0.20 M), 160 °C, 15 h. Isolated yields. See SI for details.
revealed that electron-deficient carboxylic acids are inherently
more reactive (Scheme 2A). Furthermore, sterically hindered
acid electrophiles are more reactive than unsubstituted benzoic
acids (Scheme 2B), which is consistent with decarbonylation
favored by the steric demand of acyl−Pd complexes. In
contrast, intermolecular competition experiments using differ-
ently substituted acetylenes revealed that electron-rich
acetylenes are more reactive (Scheme 2C). Next, we prepared
the mixed acyl anhydride 4 and subjected this compound to
the reaction conditions, resulting in the formation of the
decarbonylative cross-coupling product in 82% yield (Scheme
diphenylacetylene by alkyne dimerization as a minor reaction
pathway. Overall, these studies are consistent with decarbon-
ylation preceding transmetalation in the process.
In summary, we have developed palladium-catalyzed
decarbonylative Sonogashira cross-coupling of carboxylic
10
acids. The reaction is promoted by the Pd(OAc) /Xantphos
2
catalytic system and proceeds by a selective oxidative addition
of a mixed anhydride and decarbonylation. The reaction is
compatible with various carboxylic acids and alkynes, leading
2
to the facile formation of C(sp )−C(sp) bonds from
ubiquitous carboxylic acids. The potential of this method in
pharmaceutical derivatization has been demonstrated. Mech-
anistic studies support the pathway by direct decarbonylation/
transmetalation vs acyl cross-coupling/ynone decarbonylation.
The method expands the portfolio of decarbonylative trans-
formations of carboxylic acids as effective aryl electrophiles in
3
A). Furthermore, to test the potential of the direct
10
decarbonylation of ynones, compounds 5 and 6 were tested
as potential substrates, resulting in no conversion to the
desired products (Scheme 3B). We also note that subjecting
phenylacetylene to the reaction conditions results in 29% of
4
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Letter
Scheme 2. Mechanistic Studies
orcid.org/0000-0002-9650-9690;
Email: michal.szostak@rutgers.edu
Author
Chengwei Liu − Department of Chemistry, Rutgers University,
Newark, New Jersey 07102, United States; orcid.org/
0000-0003-1297-7188
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c01445
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the NIH (1R35GM133326, M.S.), the NSF
CAREER CHE-1650766, M.S.), and Rutgers University
M.S.). The Bruker 500 MHz spectrometer used in this
■
(
(
study was supported by the NSF-MRI (CHE-1229030).
Additional support was provided by the Rutgers Graduate
School in the form of a Dean’s Dissertation Fellowship.
REFERENCES
■
(
1) (a) Chinchilla, R.; Najera, C. The Sonogashira Reaction: A
Booming Methodology in Synthetic Organic Chemistry. Chem. Rev.
2
007, 107, 874−922. (b) Chinchilla, R.; Najera, C. Recent advances
in Sonogashira reactions. Chem. Soc. Rev. 2011, 40, 5084−5121.
2) (a) New Trends in Cross-Coupling; Colacot, T. J., Ed.; The Royal
(
Society of Chemistry: Cambridge, 2015. (b) Magano, J.; Dunetz, J. R.
Large-Scale Applications of Transition Metal-Catalyzed Couplings for
the Synthesis of Pharmaceuticals. Chem. Rev. 2011, 111, 2177−2250.
Scheme 3. Control Experiments
(
c) Torborg, C.; Beller, M. Recent Applications of Palladium-
Catalyzed Coupling Reactions in the Pharmaceutical, Agrochemical,
and Fine Chemical Industries. Adv. Synth. Catal. 2009, 351, 3027−
3
(
043.
3) (a) Chinchilla, R.; Najera, C. Chemicals from Alkynes with
Palladium Catalysts. Chem. Rev. 2014, 114, 1783−1826. (b) Modern
Alkyne Chemistry: Catalytic and Atom-Economic Transformations;
Trost, B. M., Li, C. J., Eds.; Wiley: Weinheim, 2015.
(4) For selected examples, see: (a) Hwang, L. K.; Na, Y.; Lee, J.; Do,
Y.; Chang, S. Tetraarylphosphonium Halides as Arylating Reagents in
Pd-Catalyzed Heck and Cross-Coupling Reactions. Angew. Chem., Int.
Ed. 2005, 44, 6166−6169. (b) Fabrizi, G.; Goggiamani, A.; Sferrazza,
A.; Cacchi, S. Sonogashira Cross-Coupling of Arenediazonium Salts.
Angew. Chem., Int. Ed. 2010, 49, 4067−4070. (c) Zhu, D.; Wu, Y.;
Wu, B.; Luo, B.; Ganesan, A.; Wu, F. H.; Pi, R.; Huang, P.; Wen, S.
Three-Component Pd/Cu-Catalyzed Cascade Reactions of Cyclic
Iodoniums, Alkynes, and Boronic Acids: An Approach to Methyl-
idenefluorenes. Org. Lett. 2014, 16, 2350−2353. (d) Tian, Z. Y.;
Wang, S. M.; Jia, S. J.; Song, H. X.; Zhang, C. P. Sonogashira Reaction
Using Arylsulfonium Salts as Cross-Coupling Partners. Org. Lett.
organic synthesis. Further studies on decarbonylative cross-
coupling of carboxylic acids are ongoing and will be reported in
due course.
2
(
017, 19, 5454−5457.
5) Eckhardt, M.; Fu, G. C. The First Applications of Carbene
Ligands in Cross-Couplings of Alkyl Electrophiles: Sonogashira
Reactions of Unactivated Alkyl Bromides and Iodides. J. Am. Chem.
Soc. 2003, 125, 13642−13643.
ASSOCIATED CONTENT
sı Supporting Information
■
*
(6) For excellent overviews, see: (a) Pu, X.; Li, H.; Colacot, T. J.
Heck Alkynylation (Copper-Free Sonogashira Coupling) of Aryl and
Heteroaryl Chlorides, Using Pd Complexes of t-Bu (p-NMe C H )P:
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c01445.
2
2
6
4
Understanding the Structure−Activity Relationships and Copper
Effects. J. Org. Chem. 2013, 78, 568−581. (b) Aufiero, M.; Proutiere,
F.; Schoenebeck, F. Redox Reactions in Palladium Catalysis: On the
Accelerating and/or Inhibiting Effects of Copper and Silver Salt
Additives in Cross-Coupling Chemistry Involving Electron-rich
Phosphine Ligands. Angew. Chem., Int. Ed. 2012, 51, 7226−7230.
For a recent mechanistic study, see: (c) Gazvoda, M.; Virant, M.;
Experimental details, characterization data (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Michal Szostak − Department of Chemistry, Rutgers
University, Newark, New Jersey 07102, United States;
Pinter, B.; Kosm
̌
rlj, J. Mechanism of copper-free Sonogashira reaction
4
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Letter
operates through palladium-palladium transmetallation. Nat. Commun.
018, 9, 4814.
7) He, J.; Wasa, M.; Chan, K. S. L.; Yu, J. Q. Palladium(0)-
2
(
3
Catalyzed Alkynylation of C(sp )−H Bonds. J. Am. Chem. Soc. 2013,
35, 3387−3390.
8) (a) Liu, C.; Ji, C. L.; Hong, X.; Szostak, M. Palladium-Catalyzed
1
(
Decarbonylative Borylation of Carboxylic Acids: Tuning Reaction
Selectivity by Computation. Angew. Chem., Int. Ed. 2018, 57, 16721−
1
6726. (b) Liu, C.; Ji, C. L.; Qin, Z. X.; Hong, X.; Szostak, M.
Synthesis of Biaryls via Decarbonylative Palladium-Catalyzed Suzuki-
Miyaura Cross-Coupling of Carboxylic Acids. iScience 2019, 19, 749−
7
59. (c) Liu, C.; Qin, Z. X.; Ji, C. L.; Hong, X.; Szostak, M. Highly-
Chemoselective Step-Down Reduction of Carboxylic Acids to
Aromatic Hydrocarbons via Palladium Catalysis. Chem. Sci. 2019,
1
0, 5736−5742. (d) Liu, C.; Ji, C. L.; Zhou, T.; Hong, X.; Szostak, M.
Decarbonylative Phosphorylation of Carboxylic Acids via Redox-
Neutral Palladium Catalysis. Org. Lett. 2019, 21, 9256−9261. (e) Liu,
C.; Ji, C. L.; Zhou, T.; Hong, X.; Szostak, M. Bimetallic Cooperative
Catalysis for Decarbonylative Heteroarylation of Carboxylic Acids via
C-O/C-H Coupling. Angew. Chem., Int. Ed. 2021, 60, 10690−10699.
(
9) For selected studies on decarbonylation from our laboratory, see:
(
a) Meng, G.; Szostak, M. General Olefin Synthesis by the Palladium-
Catalyzed Heck Reaction of Amides: Sterically Controlled Chemo-
selective N−C Activation. Angew. Chem., Int. Ed. 2015, 54, 14518−
1
4522. (b) Shi, S.; Meng, G.; Szostak, M. Synthesis of Biaryls through
Nickel-Catalyzed Suzuki-Miyaura Coupling of Amides by Carbon−
Nitrogen Bond Cleavage. Angew. Chem., Int. Ed. 2016, 55, 6959−
6963. (c) Liu, C.; Szostak, M. Decarbonylative Phosphorylation of
Amides by Palladium and Nickel Catalysis: The Hirao Cross-
Coupling of Amide Derivatives. Angew. Chem., Int. Ed. 2017, 56,
1
(
2718−12722.
10) Lu, H.; Yu, T. Y.; Xu, P. F.; Wei, H. Selective Decarbonylation
via Transition-Metal-Catalyzed Carbon−Carbon Bond Cleavage.
Chem. Rev. 2021, 121, 365.
(11) (a) Goossen, L. J.; Rodriguez, N.; Goossen, K. Carboxylic Acids
as Substrates in Homogeneous Catalysis. Angew. Chem., Int. Ed. 2008,
4
7, 3100−3120. (b) Qin, T.; Cornella, J.; Li, C.; Malins, L. R.;
Edwards, J. T.; Kawamura, S.; Maxwell, B. D.; Eastgate, M. D.; Baran,
P. S. A general alkyl-alkyl cross-coupling enabled by redox-active
esters and alkylzinc reagents. Science 2016, 352, 801−805.
(
12) For recent selected examples of decarbonylative coupling, see:
(
a) Pan, F.; Boursalian, G. B.; Ritter, T. Palladium-Catalyzed
Decarbonylative Difluoromethylation of Acid Chlorides at Room
Temperature. Angew. Chem., Int. Ed. 2018, 57, 16871−16876.
(
b) Keaveney, S. T.; Schoenebeck, F. Palladium-Catalyzed Decarbon-
ylative Trifluoromethylation of Acid Fluorides. Angew. Chem., Int. Ed.
2
018, 57, 4073−4077. (c) Malapit, C. A.; Bour, J. R.; Brigham, C. E.;
Sanford, M. S. Base- Free Nickel-Catalysed Decarbonylative Suzuki−
Miyaura Coupling of Acid Fluorides. Nature 2018, 563, 100−104.
(d) Muto, K.; Yamaguchi, J.; Musaev, D. G.; Itami, K. Decarbon-
ylative Organoboron Cross-Coupling of Esters by Nickel Catalysis.
Nat. Commun. 2015, 6, 7508. (e) Guo, L.; Srimontree, W.; Zhu, C.
Nickel-catalyzed Suzuki−Miyaura Cross-Couplings of Aldehydes. Nat.
Commun. 2019, 10, 1957. (f) Zhao, T.-T.; Xu, W.-H.; Zheng, Z.-J.;
Xu, P.-F.; Wei, H. Directed Decarbonylation of Unstrained Aryl
Ketones via Nickel-Catalyzed C−C Bond Cleavage. J. Am. Chem. Soc.
2
(
018, 140, 586−589.
13) Li, X.; Liu, L.; Huang, T.; Tang, Z.; Li, C.; Li, W.; Zhang, T.; Li,
Z.; Chen, T. Palladium-Catalyzed Decarbonylative Sonogashira
Coupling of Terminal Alkynes with Carboxylic Acids. Org. Lett.
2
(
021, 23, 3304.
14) The catalytic system developed in ref 13 involves Pd (dba)
2
3
(
2.5 mol%), Xantphos (10 mol%), Ac O (1.5 equiv), DME (0.10 M),
2
8
a−e
1
30 °C, 12 h. In our experience
the use of piv O with or without a
2
Lewis base is superior to Ac O in promoting selective decarbonylative
2
coupling of carboxylic acids activated in situ as mixed anhydrides.
4
730
https://doi.org/10.1021/acs.orglett.1c01445
Org. Lett. 2021, 23, 4726−4730