Carboxylic phosphoric anhydrides as a new coupling partner in Pd-catalyzed coupling reactions: A new ketone synthesis

Article abstract of DOI:10.1055/s-2006-947345

The Pd-catalyzed cross-coupling reactions of carboxylic phosphoric anhydrides with organoboronic acids or organostannanes afforded the corresponding ketones. The intramolecular Heck reaction was successful with carboxylic phosphoric anhydrides as a coupling partner. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-947345

LETTER
1851
Carboxylic Phosphoric Anhydrides as a New Coupling Partner in
Pd-Catalyzed Coupling Reactions: A New Ketone Synthesis
P
K
d-Catalyze
d
Coup
y
ling of
C
arb
o
oxylic Phosp
u
horic Anhyd
n
rides g-Chan Lim, Young-Taek Hong, Sunggak Kim*
Center for Molecular Design and Synthesis and Department of Chemistry, School of Molecular Science (BK21), Korea Advanced Institute
of Science and Technology, Daejeon 305-701, Korea
Fax +82(42)8698370; E-mail: skim@kaist.ac.kr
Received 14 April 2006
We began our studies using benzimidic phosphoric an-
Abstract: The Pd-catalyzed cross-coupling reactions of carboxylic
hydride (1) as a coupling partner in the Suzuki reaction.
When 1 was treated with phenylboronic acid (2a) using
phosphoric anhydrides with organoboronic acids or organostan-
nanes afforded the corresponding ketones. The intramolecular Heck
reaction was successful with carboxylic phosphoric anhydrides as a
coupling partner.
Pd(PPh ) catalyst in refluxing toluene for five hours, no
3 4
reaction occurred and the starting material was recovered.
Additional reactions using vinyl boronic acid and vinyl
stannane under the similar conditions were unsuccessful.
Furthermore, somewhat surprisingly, the Pd-catalyzed
coupling of oxime phosphate 4 with 2a under the similar
conditions did not occur (Scheme 1).3
Key words: palladium, cross-coupling, ketone, Suzuki reaction,
Stille reaction
The cross-coupling reaction by palladium catalyst is a
powerful and widely used method for the formation of We next examined the feasibility of using a carboxylic
carbon–carbon bonds. Like Stille and Suzuki coupling,1 phosphoric mixed anhydride as a coupling partner in the
the substitution at vinylic carbon by palladium catalyst is Suzuki reaction (Scheme 2). Recently, it has been report-
extensively studied. Furthermore, the substitution at the ed that Pd-catalyzed cross-coupling reactions using car-
8
iminyl carbon and the iminyl nitrogen of oxime type com- boxylic derivatives such as carboxylic anhydrides, active
2
,3
9
10
pounds by Pd catalyst is already reported. But most esters, and thiol esters provided a ready access to a ke-
studies of these reactions are concentrated on halides and tone synthesis. When the reaction was initially carried out
triflates as coupling partners.
with 5a and 2a using Pd(PPh ) as a catalyst in the pres-
3 4
ence of Na CO in refluxing THF for 12 hours gave ben-
Vinylic phosphates are known to be an efficient coupling
partner in Pd-catalyzed coupling with organoaluminium
2
3
zophenone (6a) in 51% yield. To search for optimum
conditions, we screened several Pd catalysts and additives
and the experimental results are listed in Table 1. Among
4
5
compounds, organostannanes, and organoboronic ac-
6
ids. Furthermore, the phosphate compounds show higher
several ligands and bases tested in this study, Pd(OAc)2/
stability and efficiency in their preparation than their tri-
5
,7
PPh was better than Pd(PPh ) and a combination of PPh
3 3 4 3
flate counterparts. However, as far as we are aware, the
Pd-catalyzed substitutions at the carbonyl and iminyl car-
bon using the phosphate as a leaving group have not been
reported. Thus, we were curious about the possibility of
utilizing the phosphate leaving group in other Pd-cata-
lyzed cross-coupling reactions.
and Na CO gave the best result. The reaction was typical-
2
3
ly carried out with Pd(OAc) /PPh in the presence of
2
3
Na CO in THF at 60 °C for 12 hours.
2
3
O
O
Pd cat.
THF
O
+
Ph-B(OH)2
P(OEt)2
Ph
O
Ph
Ph
OBn
BnO
5a
2a
6a
Pd(PPh3)4
N
N
O
+
PhB(OH)2
P(OEt)2
Scheme 2
toluene, 5 h
Ph
Ph
Ph
Ph
N
O
1
2a
3a
In order to test the generality of the present method, we
performed additional experiments using structurally
different carboxylic phosphoric anhydrides and phenyl-
boronic acid derivatives under the similar conditions.
O
P(OEt)2
O
Pd(PPh3)4, LiCl
THF, 12 h
N
+
PhB(OH)2
4
2a
3b
The use of 2b afforded 6b in 63% yield. When the same
reaction was attempted in refluxing toluene for 12 hours,
the yield was increased to 85% (entry 2). A similar result
was also obtained with 2c (entry 3). However, toluene did
not always give better results than THF (entry 14). Gener-
ally, aromatic carboxylic anhydrides gave better yields
than aliphatic carboxylic anhydrides (Table 2).
Scheme 1
SYNLETT 2006, No. 12, pp 1851–1854
Advanced online publication: 24.07.2006
0
1
.0
8
.2
0
0
6
DOI: 10.1055/s-2006-947345; Art ID: U04106ST
©
Georg Thieme Verlag Stuttgart · New York

1
852
K.-C. Lim et al.
LETTER
Table 1 Pd-Catalyzed Ketone Synthesis with 5a and 2a
O
O
PdCl2(PPh3)2
O
P(OEt)2 + PhSnBu3
R1
=
O
Catalyst
Ligand
–
Base
Yield (%) of 6a
t-BuPh, 130 °C, 3 h
R1
Ph
5
7
6
Pd(PPh3)4
Pd(PPh3)4
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Na CO
51
40
55
34
33
92
33
64
31
2
3
R1
Ph (5a)
-MeOC6H4 (5b)
6a 95%
6b 45%
6c 79%
6d 41%
6e 75%
–
–
–
–
–
4
Naphthyl (5c)
PhCH2 (5d)
PPh3
BINAP
PCy3
PPh3
PPh3
PPh3
PPh3
c-Hex (5e)
Scheme 3
Na CO
2
3
K CO
The Stille-type reaction was briefly studied using tri-
butyl(phenyl)stannane (7). When the reaction was initial-
ly examined with 5a and 7 using Pd(PPh ) catalyst in the
2
3
Cs CO
2
3
3
4
Et N
presence of Na CO in refluxing toluene or in refluxing
3
2 3
THF, the desired ketone was obtained in 40% and 20%
yield, respectively. Additional experiments suggested that
PdCl (PPh ) was much more effective than Pd(PPh )
2
3 2
3 4
Table 2 Pd-Catalyzed Cross-Coupling of Carboxylic Phosphoric
Anhydride (5) and Boronic Acid (2)
and the best result was obtained by performing the
reaction using PdCl (PPh ) as a catalyst in refluxing tert-
2
3 2
O
O
O
butylbenzene without the addition of a base.
Pd(OAc)2, PPh3
Na2CO3
P(OEt)2
+
R2 B(OH)2
R1
O
R1
R2
As it can be seen in Scheme 3, when 5a,c,e were reacted
with 7 under similar conditions, the desired ketones were
obtained in high yields. But the use of 5b or 5d lowered
the yield significantly.
5
2
6
R1 = Ph (5a), 4-MeO-C6H4 (5b), Naphthyl (5c),
PhCH2 (5d), c-Hex (5e), Me (5f), t-Bu (5g)
R2 = Ph (2a), 4-Ph-C6H4 (2b), PhCH=CH (2c)
The present reaction would be initiated by oxidative addi-
tion of Pd(0) to 5 to form acylpalladium(II) complex 8 and
followed by transmetallation to form intermediate 9.
Finally, reductive elimination of 9 would give rise to
ketone 6 (Scheme 4).
Entry
R1
Ph
Ph
Ph
R2
Ph
Product Yield (%)a
11
1
2
3
4
5
6
7
8
9
6a
6b
6c
6d
6e
6f
92
4-PhC H
63 (85)
50 (72)
(92)
(81)
68
6
4
O
O
O
PhCH=CH
Ph
P(OEt)2
R1
R2
R1
O
4-MeOC H4
Pd(0)
6
6
5
4-MeOC H4
4-PhC H
6
6
4
Naphthyl
Naphthyl
Naphthyl
PhCH2
c-Hex
c-Hex
c-Hex
Me
Ph
4-PhC H
O
O
O
6g
6h
6i
65
6
4
P(OEt)2
R1
Pd O
R1
Pd R2
PhCH=CH
Ph
55
9
8
74
O
MO P(OEt)2
2
R M
1
1
1
1
1
1
0
1
2
3
4
5
6
Ph
6j
74
Scheme 4
4-PhC H
6k
6l
88
6
4
PhCH=CH
Ph
59
We briefly studied the feasibility of intra- and intermolec-
ular Heck-type reaction using carboxylic phosphoric
anhydrides as coupling partners. Treatment of 10 with
Pd(OAc) /PPh as a catalyst in the presence of Na CO in
6m
6n
6o
6p
75
Me
4-PhC H
67 (57)
(66)
(60)
6
4
2
3
2
3
t-Bu
Ph
4-PhC H
refluxing THF for eight hours afforded exo-a-methyleno-
cyclopentanone (11) in 41% yield (entry 1). To search for
optimum conditions, several reactions were carried out as
shown in Table 3. Among several bases as additive
examined in this study, Na CO gave the best results and
1
t-Bu
6
4
a
The numbers in the parentheses indicate the yield of the reaction
performed in toluene at 100 °C for 12 h.
2
3
acetonitrile was the solvent of choice. Pd(OAc) /PPh and
2
3
Pd(PPh ) were equally effective (entries 3 and 8).
3
4
Synlett 2006, No. 12, 1851–1854 © Thieme Stuttgart · New York

LETTER
Pd-Catalyzed Coupling of Carboxylic Phosphoric Anhydrides
1853
Table 3 Intramolecular Heck Reaction of 10
O
O
O
P(OEt)2
O
Pd catalyst
00 °C
1
10
11
Entry
Catalyst
Ligand
Base
Solvent
THFa
Yield (%)
41
1
2
3
4
5
6
7
8
9
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
PdCl (PPh )
PPh3
Na CO
2
3
3
PPh3
Et N
MeCNb
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
THF
75
3
PPh3
Na CO
81
2
PPh3
K CO
15
2
3
PPh3
Cs CO
10
2
3
BINAP
Na CO
49
2
3
3
3
3
3
P(o-tol)3
Na CO
63
2
–
–
–
–
–
–
Na CO
85
2
Na CO
62
2
1
1
1
1
0
1
2
3
6
Na CO
Toluene
MeCN
MeCN
MeCN
59
2
Et N
48
3
KF
49
Na CO
71
2
3 2
2
3
a
0 °C.
0 °C.
b
7
O
O
When intramolecular Heck reaction of 10 was carried out
O
Ph
Ph
Ph
Ph
P(OEt)2
with Pd(PPh ) and Na CO in refluxing acetonitrile for
3
4
2
3
O
Pd(PPh ) , Na CO
3
4
2
3
eight hours, 11 was isolated in 85% yield (entry 8). A
similar result was obtained with 12. However, reaction of
14 under the similar condition afforded 15 in 70% yield
(Scheme 5). Apparently, decarbonylation of acylpalladi-
um(II) intermediate followed by dehydropalladation
yielded 15. Furthermore, when intermolecular Heck reac-
tion was attempted as shown in Scheme 6, the desired
product 16 was not obtained and ethyl trans-cinnamate
MeCN, 100 °C, 8 h
1
2
13: 62%
15: 70%
O
O
Ph
P(OEt)2
O
Pd(PPh3)4, Na2CO3
MeCN, 100 °C, 8 h
Ph
1
4
(
17) was isolated due to decarbonylation of the acylpalla-
Scheme 5
1
2
dium intermediate.
In conclusion, we have found that the carboxylic phos-
phoric anhydride can be utilized as a new coupling partner
in the Suzuki and Stille reactions. Intramolecular Heck
reaction of the carboxylic phosphoric anhydrides was suc-
cessful, whereas intermolecular Heck reaction afforded
the decarbonylation product.
O
O
P(OEt)2
+
CO2Et
Ph
O
5a
O
Ph
CO2Et
Pd(PPh3)4, Na2CO3
MeCN, 100 °C
16
The Suzuki Coupling of 5a and 2a
To a solution of 5a (26 mg, 0.1 mmol) and 2a (19 mg, 0.15 mmol)
in THF (1.5 mL) were added Pd(OAc) (1 mg, 0.006 mmol), PPh
CO2Et
7: 53%
Ph
decarbonylation
1
2
3
(
4 mg, 0.014 mmol), and Na CO (21 mg, 0.2 mmol) at r.t. After the
2 3
Scheme 6
reaction mixture was stirred at 60 °C for 12 h, the solvent was evap-
orated under reduced pressure and the residue was subjected to
silica gel column chromatograph (EtOAc–hexane = 1:10) to afford
the commercially available product 6a (17 mg, 92%).
Synlett 2006, No. 12, 1851–1854 © Thieme Stuttgart · New York

1
854
K.-C. Lim et al.
LETTER
The Stille Coupling of 5a and 7
To a solution of 5a (52 mg, 0.2 mmol) and 7 (81 mL, 0.24 mmol) in
tert-butylbenzene (1 mL) was added PdCl (PPh ) (14 mg, 0.02
mmol) and the reaction mixture was stirred at 130 °C for 3 h. After
the removal of solvent under reduced pressure, the residue was
column chromatographed on silica gel (EtOAc–hexane = 1:10) to
give 6a (35 mg, 95%).
References
(
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2
3 2
(
2
(
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3
The Intramolecular Heck Reaction
Compound 10 (60 mg, 0.2 mmol), Pd(PPh ) (7 mg, 0.006 mmol)
(
(
(
(
3
4
2
and Na CO (42 mg, 0.4 mmol) were dissolved in MeCN (1 mL) at
2
3
r.t. After refluxed for 8 h at 100 °C, the reaction mixture was cooled
to r.t. and concentrated under reduced pressure. The residue was
column chromatographed on silica gel (EtOAc–hexane = 1:5) to
1
3 1
give previously reported product 11 (25 mg, 85%). H NMR (400
MHz, CDCl ): d = 3.73 (br, 2 H), 5.61 (m, 1 H), 6.34 (m, 1 H), 7.38
3
1465. (b) Silbert, L. S.; Konen, D. A. J. Org. Chem. 1971,
(
t, J = 7.6 Hz, 1 H), 7.47 (d, J = 7.6 Hz, 1 H), 7.57 (dt, J = 7.6, 1.3
1
3
36, 2162.
Hz, 1 H), 7.84 (d, J = 7.6 Hz, 1 H). C NMR (100 MHz, CDCl3):
d = 31.8, 119.2, 124.6, 126.3, 127.6, 134.8, 138.2, 143.3, 149.9,
(
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–
1
1
93.4. IR (polymer): 3071, 2910, 1705, 1643, 1610, 1584 cm .
+
HRMS: m/z calcd for C H O [M ]: 144.0575; found: 144.0576.
1
0
8
Acknowledgment
(
We thank the Center for Molecular Design and Synthesis (CMDS)
and BK21 program for financial support.
(
10) Liebeskind, L.; Srogl, J. J. Am. Chem. Soc. 2000, 122,
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1
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Synlett 2006, No. 12, 1851–1854 © Thieme Stuttgart · New York