Rhodium or palladium-catalyzed cascade aryl addition/ intramolecular lactonization of phthalaldehyde with potassium organotrifluoroborates to access 3-arylphthalides

Article abstract of DOI:10.1002/adsc.201000741

An efficient rhodium-catalyzed lactonization of phthalaldehyde with potassium organotrifluoroborates to access 3-arylphthalides has been developed. Moreover, palladium is a also good catalyst for such transformation.

Full text of DOI:10.1002/adsc.201000741

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DOI: 10.1002/adsc.201000741
Rhodium or Palladium-Catalyzed Cascade Aryl Addition/
Intramolecular Lactonization of Phthalaldehyde with
Potassium Organotrifluoroborates to Access 3-Arylphthalides
Fang Luo,a Shen Pan,a Changduo Pan,b Pengcheng Qian,a and Jiang Chenga,*
a
College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325000, Peopleꢀs Republic of China
Fax : (+86)-577-5699-8939; e-mail: jiangcheng@wzu.edu.cn
Wenzhou Institute of Industry & Science, Wenzhou 325000, Peopleꢀs Republic of China
b
Received: September 29, 2010; Revised: December 2, 2010; Published online: February 8, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000741.
Abstract: An efficient rhodium-catalyzed lactoniza-
tion of phthalaldehyde with potassium organotri-
fluoroborates to access 3-arylphthalides has been
developed. Moreover, palladium is a also good cata-
lyst for such transformation.
Organoboron compounds and particularly boronic
acids are known as useful reagents for carbon-carbon
bond formation with various electrophiles in the pres-
ence of transition metals.[7] Although having advan-
tages such as low toxicity and easy manipulation, bor-
onic acids often dimerize and trimerize to form bor-
onic acids anhydrides and boroxines,[8] which make
difficulties in the direct purification and in the deter-
mination of the exact stoichiometry of the reactions.
Recently, potassium organotrifluoroborates due to
their superior features such as higher air- and mois-
ture-stability,[9] have been focused as alternatives to
Keywords: 3-arylphthalides; palladium; phthalalde-
hyde; potassium organotrifluoroborates; rhodium
Phthalide (isobenzofuranone) frameworks are present boronic acid derivatives that easily undergo protode-
in a large number of natural products and biologically boronation.[10] Over the past decade, the transition
active compounds.[1] Thus, significant efforts have metal-catalyzed arylation reactions of aldehydes with
been focused on synthesizing phthalides in the past organoboronic acids have attracted much attention.[11]
few decades.[2] The transition metal-catalyzed carbon- Nevertheless, the employment of potassium organotri-
carbon or carbon-heteroatom bond formation is a fluoroborates in transition metal-catalyzed 1,2-addi-
powerful tool in organic chemistry. However, less ex- tion of aldehydes is rare.[12] Based on the aforemen-
amples on the synthesis of 3-arylphthalides catalyzed tioned works, we envisioned to develop the reaction
by transition metals have been developed.[3] Recently, of phthalaldehyde with potassium organotrifluorobo-
Onomura demonstrated the palladium-catalyzed ary- rates to access 3-substituted phthalides using the tran-
lation of methyl 2-formylbenzoate with organoboronic sition metal-catalyzed 1,2-addition of aldehyde as the
acids for the synthesis of 3-arylphthalides.[4] Subse- key step (Scheme 1).
quently, Hu demonstrated the rhodium-catalyzed ad-
Initially, we chose phthalaldehyde 1 and potassium
dition of arylboronic acids to 2-formylbenzoates af- phenyltrifluoroborate 2a as the model substrates for
forded 3-substituted phthalides.[5] Very recently, we surveying the reaction parameters (Table 1). The
developed a cascade aryl addition/intramolecular lac- choice of solvent had an important effect on the reac-
tonization reaction of phthalaldehyde with boronic tion. 1,2-Dichloroethane (DCE) turned out to be the
acids catalyzed by rhodium and palladium, respective- best and the solvents such as DMF and DMSO which
ly.[6] However, aryl-metal species were ultimately lim- have high solubility with H2O were totally ineffective.
ited to boronic acids in the aforementioned transfor- Bidentate phosphine ligands such as dppe and dppp,
mations using the transition metal-catalyzed 1,2-addi- showed better catalytic reactivity. The influence of
tion of aldehyde as the key step. Thus, the discovery bases was also investigated, and Li2CO3 was found to
of more catalytically active and practically advanta- be superior to some other bases such as K2CO3,
geous processes employing other reagents in such Na2CO3, NaHCO3, K3PO4 and CsF (Table 1, en-
transformation is highly desirable.
tries 13–19). Further study revealed that the source of
Rh had also some effect on the reaction and
320
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Adv. Synth. Catal. 2011, 353, 320 – 324

Rhodium or Palladium-Catalyzed Cascade Aryl Addition/Intramolecular Lactonization
worked well under the reaction conditions. The elec-
tronic properties of the substituents on the phenyl
ring of the potassium aryltrifluoroborate had a dra-
matic effect on the reaction. Electron-donating sub-
stituents at the phenyl ring of boronic acids were ben-
eficial for the transformation, whereas an electron-
withdrawing group decreased the efficiency (Table 2,
entries 2–7 vs. 8 and 9). The hindrance on the phenyl
ring of the potassium aryltrifluoroborate had some
effect on the reaction. For example, 93% of 3b was
isolated, while the yield of 3d was slightly decreased
to 84% (Table 2, entries 2 vs. 4). Under the standard
reaction conditions, the reaction conducted on a 3-
mmol scale formed the product 3a in 84% yield. In
comparison with our previous works, this procedure
reduced the amount of Rh source and delivered the
products in higher yields. Unfortunately, potassium
methyltrifluoroborate failed to deliver the product
Scheme 1. The synthesis of 3-arylphthalides using phthalade-
hyde.
[Rh
timization, we found that the best results were accom-
plished by using [Rh(cod)Cl]2, dppe, and Li2CO3 in liminary insight into reaction mechanism. When com-
DCE/H2O at 858C (Table 1, entry 20). pound 4 was subjected to the standard reaction condi-
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
Next, we turned our attention to investigate the tion, 3 was isolated in 87% yield. We reasoned the
scope of the potassium aryltrifluoroborate (Table 2). rhodium species A was the key intermediate for the
As expected, various potassium aryltrifluoroborates cascade reaction which was derived from the addition
Table 1. Screening of conditions for the Rh-catalyzed lactonization of phthalaldehyde with potassium phenyltrifluoroborates.
Entry
[Rh]
Ligand
Base
Solvent
Yield [%][a]
1
2
3
4
5
6
7
8
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
U
dppb
dppb
dppb
dppb
dppb
dppb
dppb
dppb
dppb
dppp
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
KHCO3
Na2CO3
K3PO4
NaHCO3
CsF
1,4-dioxane/H2O
toluene/H2O
xylene/H2O
DME/H2O
THF/H2O
48
48
47
58
39
69
62
<5
<5
58
11
10
71
68
67
52
27
<5
75
86
54
<5
DCE/H2O
CH2Cl2/H2O
DMF/H2O
DMSO/H2O
DCE/H2O
DCE/H2O
DCE/H2O
DCE/H2O
DCE/H2O
DCE/H2O
DCE/H2O
DCE/H2O
DCE/H2O
DCE/H2O
DCE/H2O
DCE/H2O
DCE/H2O
9
10
11
12
13
14
15
16
17
18
19
20
21
22
PACTHNGUTERNN(UG 1-nap)3
PPh3
dppe
dppe
dppe
dppe
dppe
dppe
dppe
dppe
dppe
dppe
Li2CO3
Li2CO3
Li2CO3
Li2CO3
RhACHTUGNTRENNNUG
[a]
Reaction conditions: 1 (0.2 mmol), 2a (0.3 mmol), Rh source (2.5 mol%), ligand (5 mol%), base (2.0 equiv.) in solvent/
H2O (2 mL) at 858C for 12 h. Isolated yield.
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321

Fang Luo et al.
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Table 2. Rh-catalyzed lactonization of phthalaldehyde with
potassium organotrifluoroborates.
Table 3. Screening conditions for the Pd-catalyzed lactoniza-
tion of phthalaldehyde with potassium phenyltrifluorobo-
rates.
Entry Ligand
Base
Solvent
Yield [%][a]
1
PG
DCE/H2O
<5
2
PN
1,4-dioxane/H2O 68
3
4
5
6
7
8
9
P
G
toluene/H2O
DME/H2O
THF/H2O
THF/H2O
THF/H2O
THF/H2O
68
69
80
<5
<5
<5
80
P
R
P
E
dppe
dppb
dppp
K2CO3
K2CO3
K2CO3
PACHTUNGTRENNUNG
10
11
12
P
PE
U
57
34
<5
[a]
Reaction conditions: 1 (0.2 mmol), 2a (0.4 mmol), PdCl2
(5 mol%), ligand (5 mol%), base (2.0 equiv.) in solvent/
H2O (2 mL) at 658C for 12 h. Isolated yield.
cies B. Ultimately, b-H elimination of intermediate B
delivers product 3 (Scheme 2).
Next, we tried to develop a palladium-catalyzed
lactonization of phthalaldehyde with potassium
organotrifluoroborates. When PdCl2 instead of
[Rh
of the product 3a’ was isolated. Fortunately, after re-
placing dppe with the bulky and electron-rich P(1-
ACHTUNGTRNEUN(NG cod)Cl]2 was subjected to the reaction, only 12%
ACHTUNGTRENNUNG
nap)3, 3a’ was isolated in 80% yield (Table 3). The re-
sults are shown in Table 4. Compared to the Rh-cata-
lyzed lactonization of phthalaldehyde with potassium
phenyltrifluoroborates, the yields were relatively
lower. The effect of the electronic properties and the
hindrance of the substituents on the phenyl ring of
the potassium aryltrifluoroborate were consistent with
those of the Rh-catalyzed procedure.
In summary, we have developed an efficient Rh-
catalyzed lactonization of phthalaldehyde with potas-
sium organotrifluoroborates to access 3-arylphtha-
lides. Meanwhile, palladium was also a good catalyst
for such transformation.
[a]
Reaction conditions: 1 (0.2 mmol), 2 (0.3 mmol), [Rh-
A
(2.5 mol%),
dppe
(5 mol%),
Li2CO3
(2.0 equiv.) in DCE/H2O=10/1 (2 mL) at 858C for 12 h.
Isolated yield.
The reaction was run on a 3-mmol scale.
Experimental Section
[b]
Typical Experimental Procedure for Rh-Catalyzed
Lactonization of Phthalaldehyde with Potassium
Organotrifluoroborates
of potassium aryltrifluoroborate to the C=O bond.
Then, insertion of intermediate A to the second alde-
Under air atmosphere, a mixture of phthalaldehyde 1
hyde carbonyl takes place to form the rhodium spe- (0.2 mmol), potassium organotrifluoroborate 2 (0.3 mmol),
322
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Adv. Synth. Catal. 2011, 353, 320 – 324

Rhodium or Palladium-Catalyzed Cascade Aryl Addition/Intramolecular Lactonization
Scheme 2. Possible mechanism.
purified by flash column chromatography (petroleum ether/
ethyl acetate) on silica gel to give the product.
3-Phenylisobenzofuran-1(3H)-one
(3a):[6]
Table 4. Pd-catalyzed lactonization of phthalaldehyde with
potassium organotrifluoroborates.
1H NMR
(500 MHz, CDCl3): d=7.89 (d, J=7.6 Hz, 1H), 7.59–7.56
(m, 1H), 7.50–7.47 (m, 1H), 7.32–7.29 (m, 3H), 7.27–7.25
(m, 1H), 7.21–7.18 (m, 2H), 6.33 (s, 1H); 13C NMR (125
MHZ, CDCl3): d=170.5, 149.7, 136.5, 134.3, 129.4, 129.3,
129.0, 127.0, 125.7, 125.6, 122.9, 82.7.
Acknowledgements
We thank the National Natural Science Foundation of China
(No. 20972115), and the Key Project of Chinese Ministry of
Education (No. 209054) for financial support.
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