Palladium-catalyzed aerobic oxidative coupling of acyl chlorides with arylboronic acids

Article abstract of DOI:10.1002/adsc.201100971

The first example of a palladium-catalyzed aerobic oxidative coupling of acyl chlorides with arylboronic acids has been developed, leading to a wide range of aryl benzoates in good to excellent yields. This catalytic system shows broad functional group tolerance. Preliminary mechanistic experiments using deuterium labeling showed that the oxygen atom was derived from dioxygen. Copyright

Full text of DOI:10.1002/adsc.201100971

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DOI: 10.1002/adsc.201100971
Palladium-Catalyzed Aerobic Oxidative Coupling of Acyl
Chlorides with Arylboronic Acids
Jiuxi Chen,a,c,* Yong Peng,a Miaochang Liu,a Jinchang Ding,a,b Weike Su,c
and Huayue Wua,*
a
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, Peopleꢀs Republic of China
Fax : (+86)-577-8836-8280; phone: (+86)-577-8836-8280; e-mail: jiuxichen@wzu.edu.cn or huayuewu@wuz.edu.cn
College of Light Industry, Wenzhou Vocational and Technical College, Wenzhou 325035, Peopleꢀs Republic of China
Key Laboratory of Pharmaceutical Engineering of Ministry of Education, College of Pharmaceutical Science, Zhejiang
b
c
University of Technology, Hangzhou 310014, Peopleꢀs Republic of China
Received: December 14, 2011; Revised: February 22, 2012; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201100971.
Abstract: The first example of a palladium-cata-
lyzed aerobic oxidative coupling of acyl chlorides
with arylboronic acids has been developed, leading
to a wide range of aryl benzoates in good to excel-
lent yields. This catalytic system shows broad func-
tional group tolerance. Preliminary mechanistic ex-
periments using deuterium labeling showed that the
oxygen atom was derived from dioxygen.
the coupling reaction of acyl chlorides with arylboron-
ic acids has been investigated deeply in the past,[8]
this kind of coupling using molecular oxygen as the
oxidant still remains a challenging research area. To
the best of our knowledge, there are no known re-
ports concerning palladium-catalyzed aerobic oxida-
tive coupling of acyl chlorides with arylboronic acids
using molecular oxygen in the literature. As part of
Keywords: acyl chlorides; aryl benzoates; arylbor-
onic acids; oxidative coupling; palladium
Scheme 1.
The transition metal-catalyzed aerobic oxidative cou-
pling reaction involving molecular oxygen is a funda- the continuing efforts in our laboratory towards the
mental chemical transformation, which not only ex- development of new reactions under participation of
tends the carbon chain length, but also introduces organoboron reagents,[6,9] we herein describe a new
new synthetically versatile groups. The combination route to aryl benzoates by palladium-catalyzed aero-
of using dioxygen as the terminal oxidant and as a re- bic oxidative coupling of acyl chorides with arylbor-
actant via dioxygen activation would substantially onic acids in the presence of dioxygen (Scheme 1).
broaden the field of cross-coupling and offer structur-
On the basis of our previous studies on aerobic oxi-
ally diverse products by the incorporation of an dative coupling reactions,[6,9b] we postulated that read-
oxygen atom into the organic framework from dioxy- ily available arylboronic acids could be used as cou-
gen.[1]
pling partners with acyl chlorides via aerobic oxida-
Aryl benzoates are common functionalities in many tive coupling by employing an appropriate oxidant.
biological and pharmaceutical molecules.[2] The tradi- As suggested by our previous work,[9b] we began our
tional routes to these compounds include esterifica- investigation by testing the reaction of benzoyl chlo-
tion,[3] transesterification reactions[4] and the Baeyer– ride (1a) with phenylboronic aicd (2a) using bis[(2-di-
Villiger oxidation reaction.[5] In 2008, we demonstrat- phenylphosphino)phenyl] ether (DPEphos) as ligand,
ed a palladium-catalyzed aromatic esterification of al- 1-methylpiperine as base, and O2 as oxidant in the
dehydes with organoboronic acids and dioxygen.[6] presence of catalytic amounts of palladium catalysts
Recently, Gois developed an efficient iron/NHC-cata- in dry THF. To our delight, a trace amount of the de-
lyzed aerobic oxidative aromatic esterification of al- sired phenyl benzoate (3aa) was detected by GC-MS.
dehydes with boronic acids.[7] On the other hand, al- After the base was switched to K2CO3, 3aa was isolat-
though a palladium-catalyzed synthesis of ketones by ed in 27% yield together with benzophenone (4aa) in
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Table 1. Screening for optimal reaction conditions.
[a]
Reaction conditions: 1a (0.4 mmol), 2a (1.2 mmol), Pd source (5 mol%), ligand (5 mol%), base (3 equiv.)
and dry solvent (3 mL), under O2, 608C, 24 h. GC yield (isolated yield in parentheses).
1a (0.4 mmol), 2a (0.4 mmol), 12 h.
1a (0.4 mmol), 2a (0.6 mmol), 12 h.
1a (0.4 mmol), 2a (0.8 mmol), 12 h.
[b]
[c]
[d]
41% yield (Table 1, entry 1). Among other palladium Other ligands were also tested, and none showed
catalysts used [e.g., PdCl2, Pd(OAc)2, NaPdCl4, better activities than DPEPhos (Table 1, entries 13–
Pd(PPh3)4, PdCl2A(PPh3)2, PdCl2A(MeCN)2, PdCl2 18). The choice of base was also vital to the success of
(PhCN)2, PdCl2A(dppf), PdCl2A(dppe), PdCl2A(cod), and the catalytic reaction. Screening revealed that the use
Pd(dba)2] Pd(dba)2 exhibited the highest catalytic re- of CsF as base achieved the best result. Other bases,
activity giving a 51% yield (Table 1, entries 2–12). including Na2CO3, NaHCO3, NaOAc, Cs2CO3, KF,
AHCTUNGTRENNUNG
A
N
CHTUNGTRENNUNG
A
E
N
CHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
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Palladium-Catalyzed Aerobic Oxidative Coupling of Acyl Chlorides with Arylboronic Acids
Table 2. Reaction of benzoyl chloride with arylboronic
Table 3. Reaction of acyl chlorides with phenylboronic
acids.[a]
acid.[a]
[a]
Reaction conditions: 1a (0.4 mmol),
2
(0.8 mmol),
Pd(dba)2 (5 mol%), DPEphos (5 mol%), CsF (3 equiv.)
ACHTUNGTRENNUNG
and xylene (3 mL), O2, 608C, 12 h. Isolated yields.
K3PO4, and DABCO, were less efficient for this trans-
formation (Table 1, entries 19–26). When the reaction
was performed in other solvents, the yield improved
significantly, with xylene being the best (Table 1, en-
tries 27–33). We were pleased to discover that only
when the changed to the ratio of 1a/2a did the yield
dramatically increase to an 88% isolated yield
[a]
Reaction conditions:
Pd(dba)2 (5 mol%), DPEphos (5 mol%), CsF (3 equiv.)
and xylene (3 mL), O2, 608C, 12 h. Isolated yields.
1
(0.4 mmol), 2a (0.8 mmol),
AHCTUNGTRENNUNG
(Table 1, entry 34). After extensive screening of dif- the substituents in ortho position, which indicated
ferent parameters (Table 1), the optimal reaction con- that the steric effects of substituents affected the
ditions were determined to be as follows: under an O2 yields of the reaction to some extent (Table 2, 1st and
atmosphere, Pd
phos (5 mol%) as the ligand, and CsF (3 equiv.) as (e.g., CF3, CHO, and CN) at the para position afford-
the base in xylene at 608C. ed a slightly lower yield of oxidative coupling prod-
ACHTUNGTRENNUNG(dba)2 (5 mol%) as the catalyst, DPE- 2nd row). Having an electron-withdrawing substituent
Under the optimized reaction conditions, the scope ucts 3ah, 3ai, and 3aj (Table 2, 3rd row). It should be
and generality of this aerobic oxidative coupling reac- specially mentioned that fluoro, chloro, and bromo
tion was explored (Table 2). Electron-rich arylboronic moieties (commonly used for cross-coupling reac-
acids with a methoxy or methyl group at either the tions) in arylboronic acids were all tolerated in our
para or meta position proved to be good substrates catalytic system (Table 2, 4th row) and provided
for this transformation, affording the corresponding a novel route to the targeted products 3ak, 3al, and
products in higher yields than those analogues bearing 3am in moderate to good yields, making further elab-
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Scheme 2. Control experiments.
orations of the corresponding biaryl products possible. gave the products 3ra and 3sa in 96% and 97% yields,
Bicycloboronic acids, such as biphenyl-4-ylboronic respectively. Cinnamoyl chloride (1t) was found to
acid, naphthalen-1-ylboronic acid, naphthalen-2-ylbor- couple with 2a efficiently and afforded the desired
onic acid were also good partners and coupled with product 3ta in 77% yield. However, the aliphatic
benzoyl chloride (1a) efficiently (Table 2, 5th row). chlorides, such as 2-phenylacetyl chloride (1u) and
However, treatment of an alkylboronic acid such as hexanoyl chloride (1v) gave relatively low yields.
methylboronic acid or cyclopropylboronic acid with
1a under the optimized conditions afforded only ments were carried out under the standard conditions
a trace amount of the desired products. as shown in Scheme 2. Reaction of benzoic acid with
To elucidate the mechanism, some control experi-
We next explored the effect of the oxidative cou- phenylboronic acid (2a) failed to deliver the desired
pling of phenylboronic acid with various acyl chlor- product 3aa under the same reaction conditions
ides under the standard conditions, and the results are [Scheme 2, Eq. (a)]. Phenol was not observed in the
summarized in Table 3. The electronic properties of absence of acyl chlorides under the standard reaction
the groups on the the phenyl ring moiety of aromatic conditions [Scheme 2, Eq. (b)]. Treatment of benzoyl
acyl chlorides had some effects on the reaction. Both chloride (1a) with phenylboronic acid (2a) in the pres-
electron-donating and electron-withdrawing substitu- ence of 3 equiv. of 18OH2 afforded 3aa in 81% yield
tents are tolerated in the reaction. Generally, acyl under the standard conditions [Scheme 2, Eq. (c)].
chlorides having an electron-donating substituent on There is no a detection of [18O]-3aa by GC-MS analy-
the aryl group gave a slightly higher yield of oxidative sis. In addition, the reaction failed to give the desired
coupling product. Steric effects of substituents had an product 3aa when the procedure was carried out
obvious impact on the yield of the reaction. An aro- under a N2 atmosphere. It was surprising to find that
matic acyl chloride (1d) bearing an ortho-methyl the reaction proceeded smoothly under an 18O2 at-
group, for example, was treated with 2a to afford mosphere to provide the desired product [18O]-3aa
a slightly lower yield of oxidative coupling product containing 18O in 83% yield [Scheme 2, Eq. (d)]. The
3da. The same phenomena were observed in the reac- 18O-atom-containing product [18O]-3aa was deter-
tion of 1a with aromatic acyl chlorides possessing mined by GC-MS and HR-MS (ESI) analysis. This
other groups in ortho position (e.g., OMe, Cl, and F). result confirmed that dioxygen took part in this reac-
Noteworthy is that 3,4,5-trimethoxybenzoyl chloride tion and was crucial for the transformation.
(1m) coupled with phenylboronic acid (2a) efficiently
A plausible mechanism for the aerobic oxidative
and afforded the desired product 3ma in 81% yield. coupling of acyl chlorides with arylboronic acids is
To our delight, 1-naphthoyl chloride (1p) and 2-naph- proposed in Scheme 3. Step (i) involves the reaction
thoyl chloride (1q) also underwent smoothly the oxi- of Pd
(dba)2 with 18O2 to afford
a
reactive
dative coupling with 2a, and afforded the correspond- [(h2-18O2)PdL2][10–12] species A in the presence of
ing products 3pa and 3qa in 75% and 90% yields, re- ligand. Step (ii) of the proposed catalytic cycle
spectively. Moreover, we were pleased to observe that involves the transmetalation between the Pd(II)
heterocyclic acyl chlorides, such as furan-2-carbonyl species A and ArB(OH)2 to generate the trans-
chloride (1r) and thiophene-2-carbonyl chloride (1s)
(18OH)L2][13] species B. Next, the formation of
ACHUTGTNRENNUG[ArPdACHTUTGNRENNUGN
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Palladium-Catalyzed Aerobic Oxidative Coupling of Acyl Chlorides with Arylboronic Acids
HR-MS (ESI): m/z=311.0890, calcd. for C16H16O5 (M+
Na)+: 311.0891.
Acknowledgements
We thank the National Natural Science Foundation of China
(Nos. 21102105 and 21172175) for financial support.
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Scheme 3. Plausible mechanism.
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Experimental Section
General Experimental Procedure for Palladium-
Catalyzed Aerobic Oxidative Coupling of Acyl
Chlorides with Arylboronic Acids
To a Schlenk tube were added acyl chloride 1 (0.4 mmol),
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(5 mol%), CsF (1.2 mmol) and dry xylene (3 mL). Then the
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À
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Palladium-Catalyzed Aerobic Oxidative Coupling of Acyl
Chlorides with Arylboronic Acids
7
Adv. Synth. Catal. 2012, 354, 1 – 7
Jiuxi Chen,* Yong Peng, Miaochang Liu, Jinchang Ding,
Weike Su, Huayue Wu*
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