Palladium-catalyzed direct conversion of carboxylic acids into ketones with organoboronic acids promoted by anhydride activators

Article abstract of DOI:10.1246/bcsj.75.1333

A new type of catalytic process to convert carboxylic acids and organoboron compounds into unsymmetrical ketones in one-pot under mild and neutral conditions was presented. The method allowed the use of an α, β-unsatuarted carboxylic acids such as trans-c

Full text of DOI:10.1246/bcsj.75.1333

Bull. Chem.
Soc. Jpn.
75
6
© 2002 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 75, 1333–1345 (2002) 1333
The Chemical
Society of Ja-
pan
The Chemical
Society of Ja-
pan
OB
Palladium-Catalyzed Direct Conversion of Carboxylic Acids into
Ketones with Organoboronic Acids Promoted by Anhydride Activators
Novel Pd-Catalyzed Ketone Synthesis
R. Kakino et al.
6
15
Ryuki Kakino, Hirohisa Narahashi, Isao Shimizu, and Akio Yamamoto*
2002
1333
1345
BCSJA8
0009-2673
01398
11
Department of Applied Chemistry, Graduate School of Science and Engineering and Advanced Research Institute for
Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555
(Received November 5, 2001)
5
2001
1
25
2002
Various carboxylic acids are catalytically converted into ketones on treatment with organoboron compounds in the
presence of activators and palladium catalysts. Detailed examination of factors influencing the yield of ketone formation
revealed the following characteristics of the reactions: (a) Palladium complexes containing tertiary phosphine ligands,
particularly triphenylphosphine and tricyclohexylphosphine, are most effective among the palladium complexes; (b) Di-
oxane and THF are suitable as the solvent; (c) Dimethyl dicarbonate is required as the activator to obtain ketones in high
yields. The process provides a general, versatile, synthetic method to produce various symmetrical and unsymmetrical
ketones with aromatic, aliphatic, and heterocyclic groups. The mechanism proposed for the catalytic process involves (i)
exchange reaction of the carboxylic acid employed with dimethyl dicarbonate added as the activator to form a mixed an-
hydride of the carboxylic acid and mono methyl ester of carbonic acid; (ii) oxidative addition of the mixed anhydride to
zerovalent palladium species to give an (acyl)(methyl carbonato)palladium species; (iii) decarboxylation of the methyl
carbonato ligand to give (acyl)(methoxo)palladium species; (iv) transmetallation of the (acyl)(methoxo)palladium spe-
cies with an arylboronic acid to give an (acyl)(aryl)palladium species; and (v) reductive elimination of the (acyl)(ar-
yl)palladium species to liberate the coupling product of the acyl and aryl ligands with regeneration of the Pd(0) species.
Not only homogeneous catalyst systems but also heterogeneous systems were found to give ketones under mild condi-
tions. On the basis of the present study involving the acyl(methoxo)palladium complexes generated in the reaction mix-
ture of carboxylic acids with dimethyl dicarbonate on reaction with Pd(0) complexes, we also developed a new catalytic
process to convert carboxylic acids with terminal alkynes into α, β-alkynyl ketones under similar conditions.
3.2.1
4.10
Among palladium-catalyzed processes to perform the C–C
bond formation in organic synthesis,1 cross-coupling reactions
of aryl and alkenyl halides with various organometallic com-
pounds of non-transition metals2 have provided useful method-
ology in organic synthesis together with arylation of olefins
(Mizoroki–Heck processes).3 However, both processes entail
intrinsic problems of using organic halides as substrates for
preparation of products without halogen. Thus finding more
atom-efficient methodology is needed for reducing waste. We
have been concerned with development of an alternative meth-
od to replace organic halides with oxygen-containing com-
pounds as the starting compounds on the basis of the informa-
tion gained in examination of the C–O bond cleavage process-
es promoted by transition metal complexes.4
Scheme 1. Cleavage of C–O bond in aryl trifluoroacetates
and carboxylic anhydrides.
In previous studies we have found that aryl trifluoroacetates5
and carboxylic anhydrides6 readily undergo the oxidative addi-
tion reaction to afford acylpalladium carboxylate and aryloxide
complexes (Scheme 1).
As another direction of application of the concept of the C–
O bond cleavage to give acylpalladium complexes, we con-
ceived of the conversion of the acylpalladium intermediates
into ketones. Having found that the acylpalladium complexes
react with arylboronic acids to produce ketones, we could de-
velop a new catalytic method of synthesizing unsymmetrical
ketones from carboxylic anhydrides using arylboronic acids as
arylation reagents (Eq. 2).7
The acylpalladium carboxylate complexes were found to re-
act with molecular hydrogen, releasing aldehydes and carbox-
ylic acids. Utilizing the behavior of the acylpalladium com-
plexes to release aldehyde we could develop a palladium-cata-
lyzed process to synthesize aldehydes and carboxylic acids
from carboxylic anhydrides (Eq. 1).6
(1)
(2)

1334 Bull. Chem. Soc. Jpn., 75, No. 6 (2002)
Novel Pd-Catalyzed Ketone Synthesis
Utilization of the ready cleavage of the C–O bond in aryl
perfluoroalkanecarboxylates combined with transmetallation
using arylboronic acids also led to the catalytic synthesis of
fluorine-containing unsymmetrical ketones.8
These catalytic processes have provided new routes to alde-
hydes and ketones starting from carboxylic anhydrides. How-
ever, these processes still include shortcomings such as the
need for prior preparations of anhydrides.
Our studies on reactions of different carboxylic anhydrides
with Pd(0) complexes revealed that the acyl unit of less steric
demand in anhydrides showed higher reactivity in their oxida-
tive addition process to give the acylpalladium intermediate.
On the basis of such information, we have developed a catalyt-
ic process of synthesizing aldehydes directly from carboxylic
acids without prior preparation of carboxylic anhydrides (Eq.
3).9
matic ketones, are generally carried out by using more than a
stoichiometric amount of anhydrous aluminum trichloride as a
Lewis acid. From an industrial point of view, the reaction is
less desirable because of the highly corrosive conditions and
the concomitant formation of a large amount of waste. In addi-
tion, Friedel–Crafts reactions display ortho and para selectivity
and are not suitable for preparation of aryl ketones with a meta
substituent. Reaction of organometallic reagents of electrop-
ositive metals such as lithium and magnesium with carboxylic
acid derivatives provides a convenient laboratory method for
the synthesis of ketones,15 but the reactions have to be carried
out at low temperature to avoid the formation of the tertiary al-
cohols. In addition, the process and Friedel–Crafts acylation
reactions generally require the prior preparation of more reac-
tive carboxylic acid derivatives such as acid chlorides, acid an-
hydrides, and amides. Carboxylic acid themselves are not usu-
ally employed as the materials for these reactions.14,15
Some methods for synthesis of ketones from carboxylic acid
themselves are known.16 However, most of these reactions
have limitations in their applicability and some of the process-
es are not environmentally benign or need to be performed un-
der drastic experimental conditions.
Recently palladium-catalyzed cross-coupling reactions have
gained considerable attention as routes to ketones.15 Among
these palladium-catalyzed cross-coupling processes, the proto-
col using organoboron compounds (Suzuki–Miyaura pro-
cess)17 has proved useful in giving the desired ketones.7,8,18,19
The process usually gives the coupling products in high yields,
tolerates functional groups, and shows excellent stereochemis-
try. In addition, most organoboron compounds are nontoxic,
inert to air and moisture, thermally stable, and can be recrystal-
lized from water or alcohols.
(3)
The concept for realizing the palladium-catalyzed direct
conversion of a carboxylic acid into an aldehyde is based on
the utilization of an exchange process of a carboxylic acid with
a carboxylic anhydride of less reactivity, such as pivalic anhy-
dride (2,2-dimethylpropanoic anhydride). Addition of the
bulky pivalic anhydride to the carboxylic acid would lead to
the mixture of mixed anhydride and symmetrical anhydrides.
The less hindered acyl unit in the anhydride produced from the
exchange reaction would react preferentially with Pd(0) com-
plex to undergo the selective acyl-O bond cleavage to generate
the acylpalladium complex that reacts preferentially with hy-
drogen liberating the aldehyde from the carboxylic acid em-
ployed.
In fact, by adding pivalic anhydride to the reaction system
containing the carboxylic acid and the palladium catalyst un-
der hydrogen pressure, we could obtain aldehydes in high
yields selectively in a one-pot process under mild conditions.9
The success of using pivalic anhydride as an activator in
combination with carboxylic acids to form mixed anhydrides
to accomplish the selective C–O bond cleavage of the carboxy-
lic acids prompted us examine the applicability of a similar
strategy to ketone synthesis.
Representative palladium-catalyzed preparative methods of
ketones are (i) carbonylative cross-coupling of haloarenes with
organoboron compounds18 and (ii) cross-coupling reaction of
acyl halides with various organoboron compounds.19 Howev-
er, these methods also entail problems with the requirement of
prior preparation of alkyl or acyl halides and the necessity of
using a stoichiometric amount of a base. Thus these processes
are not applicable to the synthesis of ketones sensitive to a
base, besides the inherent environmental problems and low
atom efficiency.
Ketones occupy pivotal positions as intermediates in organic
synthesis as well as end products for various commercial uses.
Although quite a variety of synthetic methods are available,
most methods entail some shortcomings in efficiency and leave
some room for improvement from the environmental view-
point. For example, palladium-catalyzed oxidation of olefins
(Wacker oxidation) has been extensively used for production
of ketones in laboratory synthesis as well as in industrial pro-
cesses.10 However, applicable olefins are limited and regiose-
lectivity of ketones obtained leaves a problem. Many useful
reactions are known in partial oxidation of secondary alcohols
to ketones, such as the Swern oxidation,11 and oxidation by
heavy metal salts such as PCC12 and MnO2.13 However, in
these processes stoichiometric amounts of oxidizing agents are
required, with concomitant formation of undesirable by-prod-
uct(s). The Friedel–Crafts acylation reactions,14 which are
among the most important processes for the synthesis of aro-
Another new route to ketone synthesis without using a base
has been recently developed by Liebeskind.20 The process pro-
vides a convenient new route to ketones although requirements
of the prior synthesis of thioesters21,22 and of addition of a sto-
ichiometric amount of copper carboxylate leave room for im-
provement.
We have recently reported in a communication that carboxy-
lic acid themselves can be catalytically converted into the cor-
responding ketones, usually in excellent yields, on treatment
with arylboronic acids in the presence of dimethyl dicarbonate
and palladium catalysts (Eq. 4).23
(4)
In the present paper, we summarize the full details of the
catalytic process and discuss the applicability of the process.

R. Kakino et al.
Bull. Chem. Soc. Jpn., 75, No. 6 (2002) 1335
Results
Catalytic Processes to Prepare Ketones from Carboxylic
Acids and Organoboron Compounds. Before attempting
the direct conversion of carboxylic acids into ketones using
arylboronic acids, we examined relative reactivities of the acyl
units in a mixed anhydride having one bulky acyl and the other
less bulky aroyl units, as we briefly mentioned in the previous
report on catalytic conversion of carboxylic anhydrides into
ketones.7 Treatment of pivalic p-toluic anhydride with 1.2 mol
amt. of phenylboronic acid in the presence of [Pd(PPh3)4] at
80 °C for 24 hours yielded 4-methylbenzophenone and 2,2-
dimethylpropiophenone in 80% and 10% yields, respectively
(Eq. 5).
Scheme 2. Catalytic cycle for the formation of ketones.
(5)
Yields of ketones are influenced by various factors including
the nature of catalyst, solvent, temperature, activator, and sub-
strate (carboxylic acids as well as organoboron compounds).
We examined the effect of each of these factors on the ketone
yields.
The result suggests that the less bulky acyl part in the mixed
anhydride reacted preferentially with the palladium complex in
the catalytic system.
(a) Examination of Catalyst Systems. Various palladium
catalysts with tertiary phosphine ligands proved effective in
synthesizing ketones. Table 1 summarizes activities of various
palladium catalysts in reactions of p-toluic acid with 1.2 mol
amt. of phenylboronic acid at 80 °C in dioxane in the presence
of 3 mol amt. of pivalic anhydride per p-toluic acid.
On the basis of the above result, we designed a catalytic pro-
cess to convert carboxylic acids with organoboron compounds
into ketones by combining the exchange process of the carbox-
ylic acids with a less reactive, bulky carboxylic anhydride such
as pivalic anhydride, as shown in Scheme 2.
The conceived catalytic process consists of several elemen-
tary processes: (i) the mixture of carboxylic acid and pivalic
anhydride undergoes exchange of the acyl entities to give a
mixed anhydride;24 (ii) oxidative addition of the mixed anhy-
dride to a zerovalent palladium complex A with the regioselec-
tive C–O bond cleavage gives acyl(trimethylacetato)palladium
species B; (iii) transmetallation of B with an arylboronic acid
gives an acyl(aryl)palladium species C; and (iv) reductive
elimination of the acyl and the aryl ligands produces ketone as
the coupling product regenerating the Pd(0) species, which fur-
ther carries the catalytic cycle. In fact, treatment of p-toluic
acid with phenylboronic acid at 80 °C in dioxane in the pres-
ence of pivalic anhydride and 0.05 molar amount of
[Pd(PPh3)4] per p-toluic acid for 24 h gave 73% yield of 4-
methylbenzophenone (Eq. 6).
Among various palladium complexes examined, [Pd-
(PCy3)2] having bulky and electron-donating tricyclohexy-
lphosphine ligands proved to serve as the most effective cata-
lyst for the ketone synthesis when pivalic anhydride was em-
ployed as the activator (Run 2). The triphenylphosphine-coor-
dinated Pd(0) complex, [Pd(PPh3)4], also demonstrated a com-
parable activity (Run 1). Although Pd(0) is considered to serve
as the active species in the catalytic system, it is not necessary
to use a phosphine-coordinated palladium(0) complex itself as
the catalyst.25 Use of palladium(Ⅱ) acetate in combination
with three to four molar amounts of PPh3 per Pd(OAc)2 gave
good yields of 4-methylbenzophenone (Runs 4 and 5), but fur-
ther increase in the amount of triphenylphosphine seems to
have some inhibition effect (Run 3). Decrease in the amount
of PPh3 below two molar amounts per palladium acetate
caused a decrease in the ketone yield (Run 6). The system us-
ing [Pd(dba)2] in combination with 3 to 4 mol amt. of PPh3
(Runs 7 and 8) showed less activity than the system using
Pd(OAc)2 and PPh3. Palladium(Ⅱ) acetate in combination with
monodentate tertiary phosphines such as tri-p-methoxyphe-
nylphosphine and tributylphosphine were moderately effective
(Runs 9 and 11). The presence of four molar amounts of ter-
tiary phosphine ligand such as tri-2-furylphosphine caused a
lower yield of the ketone (Run 10).
(6)
Employment of ditertiary phosphine ligand such as 1,1ꢀ-

1336 Bull. Chem. Soc. Jpn., 75, No. 6 (2002)
Novel Pd-Catalyzed Ketone Synthesis
Table 1. Effect of Homogeneous Catalysts on the Cross-
Coupling Reaction of p-Toluic Acid with Phenylboronic
Acid in the Presence of (tBuCO)2O
Table 2. Effects of Solvents and Temperature on the Cross-
Coupling Reactions of p-Toluic Acid with Phenylboronic
Acid in the Presence of (tBuCO)2O
Ruma)
Pd-catalyst
Yield/%b)
Ruma)
Temp/°C
Solvent
Yield/%b)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
[Pd(PPh3)4]
[Pd(PCy3)2]
73
80
58
67
64
25
34
37
60
11
42
46
7
1
2
3
4
5
6
7
8
9
r. t.
60
80
100
reflux
reflux
80
dioxane
dioxane
dioxane
dioxane
THF
acetone
toluene
NMPc)
hexane
5
47
73
71
68
44
38
47
5
Pd(OAc)2 + 5PPh3
Pd(OAc)2 + 4PPh3
Pd(OAc)2 + 3PPh3
Pd(OAc)2 + 2PPh3
[Pd(dba)2] + 4PPh3
[Pd(dba)2] + 3PPh3
Pd(OAc)2 + 4P(p-MeOC6H4)3
Pd(OAc)2 + 4P(2-furyl)3
Pd(OAc)2 + 2PnBu3
[Pd(dba)2] + 1DPPFc)
Pd(OAc)2
80
reflux
a) Typical conditions: a mixture containing p-toluic acid (1
mmol), phenylboronic acid (1.2 mmol), pivalic anhydride
(3.0 mmol), [Pd(PPh3)4] (0.05 mmol), and solvent (5 cm3)
was stirred in a Schlenk tube under argon for 24 h.
b) Determined by GC using nC14H30 as an internal standard.
c) N-methyl-2-pyrrolidinone.
[Pd(dba)2]
0
a) Typical conditions: a mixture containing p-toluic acid (1
mmol), phenylboronic acid (1.2 mmol), pivalic anhydride
(3.0 mmol), palladium catalyst (0.05 mmol), and dioxane
(5 cm3) was stirred in a Schlenk tube under argon at 80 °C
for 24 h.
Table 3. Effects of Activator on the Cross-Coupling Reac-
tion of Heptanoic Acid with Phenylboronic Acid
b) Determined by GC using nC14H30 as an internal standard.
c) DPPF is 1, 1ꢀ-bis (diphenylphosphino) ferrocene.
bis(diphenylphosphino)ferrocene (DPPF) with Pd(OAc)2 also
gave a moderate yield of the ketone (Run 12). Palladium com-
plexes such as Pd(OAc)2 and [Pd(dba)2] without tertiary phos-
phine ligands showed poor or no catalytic activity in the cata-
lyst systems (Runs 13 and 14).
(b) Effects of Solvent and Temperature. Table 2 shows
the effects of reaction temperature and of solvents employed.
The reaction catalyzed by [Pd(PPh3)4] was slow at room tem-
perature in dioxane (Run 1). Raising the reaction temperature
to 60 °C and to 80 °C gave higher yields of ketone, whereas at
the still higher temperature of 100 °C a slight decrease in the
yield was noted (Runs 2 – 4).
Runs 5 – 9 show the effects of variation of solvents in the
catalytic reaction. Higher yields can be obtained when diox-
ane or THF was employed as a solvent (Runs 3 – 5). Employ-
ment of acetone, toluene and 1-methyl-2-pyrrolidinone (NMP)
gave moderate yields (Runs 6 – 8), whereas hexane was not
suitable as solvent (Run 9).
(c) Effects of Activator. We next examined the effects of
various activators for the ketone synthesis from hexanoic acid
and phenylboronic acid in the presence of [Pd(PPh3)4] at 80 °C
in dioxane (Table 3). Acetic anhydride was much less effective
than pivalic anhydride as the activator (Run 2). We found that
dialkyl dicarbontes are better promoters of the catalytic reac-
tion than pivalic anhydride. Di-t-butyl dicarbonate gave a rea-
sonably high yield of ketone (Run 3), but dimethyl dicarbonate
was found particularly suitable for the reaction, giving the ke-
Ruma)
Activator
(tBuCO)2O
Ac2O
Mol amt.
C6H13COPh/%b)
1
2
3
4
5
6
3
3
3
3
1.2
1
83
12
67
95
95
75
(tBuOCO)2O
(MeOCO)2O
(MeOCO)2O
(MeOCO)2O
a) Typical conditions: a mixture containing hexanoic acid
(1 mmol), phenylboronic acid (1.2 mmol), activator (1.0–
3.0 mmol), [Pd(PPh3)4] (0.02 mmol), and dioxane (5 cm3)
was stirred in a Schlenk tube under argon at 80 °C for 24 h.
b) Determined by GC using nC14H30 as an internal standard.
tone in 95% (Run 4). Use of dimethyl dicarbonate had the oth-
er advantage that use of a large excess was not necessary, as
was the case with pivalic anhydride in the ketone synthesis.
The amount of dimethyl dicarbonate could be reduced to 1.2
mol amt. per carboxylic acid without affecting the product
yield (Run 5). Further decrease to equimolar ratio of the acti-
vator/carboxylic acid caused some drop in the ketone yield,
giving 75% of the ketone (Run 6).
(d) Examination of Amounts of Catalysts.
Next we
probed the necessary amount of the catalyst required for cross-
coupling reaction of heptanoic acid with phenylboronic acid in
the presence of dimethyl dicarbonate (Table 4). An excellent

R. Kakino et al.
Bull. Chem. Soc. Jpn., 75, No. 6 (2002) 1337
Table 4. Influence of the Amount of Catalyst on the Cross-
Coupling Reaction of Heptanoic Acid with Phenylboronic
Acid
Table 5. Synthesis of Unsymmetrical Ketones by the Palla-
dium-Catalyzed Cross-Coupling of Carboxylic Acids with
Organoboronic Acids in the Presence of Dimethyl Dicar-
bonate
Ruma)
Pd/C6H13COOH
C6H13COPh/%b)
TONc)
Entrya) R1
R2
Yield/%b)
1
2
3
4
0.02
0.01
0.005
0.001
94
92
94
70
47
92
188
700
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Ph
Ph
Ph
Ph
Ph
Ph
p-MeC6H4
Ph
Ph
p-MeOC6H4
p-F3CC6H4
m-MeC6H4
Ph
Ph
Ph
Ph
97
96 (86)
97
(88)
(99)
(88)
98
96
97
98
(85)
(85)
99 (88)
85
56
40
96
52
20
p-MeOC6H4
p-MeC6H4
p-ClC6H4
p-F3CC6H4
p-HCOC6H4
p-NCC6H4
p-O2NC6H4
Ph
a) Typical conditions: a mixture containing hexanoic acid
(1 mmol), phenylboronic acid (1.2 mmol), dimethyl dicar-
bonate (1.5 mmol), [Pd(PPh3)4] (0.01–0.02 mmol), and
dioxane (5 cm3) was stirred in a Schlenk tube under argon
at 80 °C for 24 h.
b) Determined by GC using nC14H30 as an internal standard.
c) TON = Turn over number.
Ph
m-MeC6H4
3-furan
2-thiophene
3-pyridine
trans-PhCHwCH
Ph
trans-PhCHwCH
nC6H13
Ph
Ph
Ph
iPr
tBu
a) Typical conditions: a mixture containing carboxylic acid
(1 mmol), organoboronic acid (1.2 mmol), dimethyl dicar-
bonate (1.2 mmol), [Pd(PPh3)4] (0.01 mmol), and dioxane
(5 cm3) was stirred in a Schlenk tube under argon at 80 °C
for 6 h. b) GC yields based on carboxylic acid. The iso-
lated yields are in the parentheses.
of dimethyl dicarbonate. The present process is applicable to a
large variety of substrates, including aromatic, heterocyclic,
and aliphatic carboxylic acids, in combination with organobo-
ron compounds, giving ketones in excellent yields. The pro-
cess is tolerant of carboxylic acids having various functional
groups. Benzoic acid derivatives having methoxy, methyl,
formyl, trifluoromethyl, cyano, and nitro groups at the para po-
sitions can be catalytically converted into the corresponding
ketones in excellent yields on treatment with arylboronic acids
in the presence of dimethyl dicarbonate and [Pd(PPh3)4] (Runs
2 – 10). p-Chlorobenzoic acid was transformed selectively
into p-chlorobenzophenone without undergoing the C–Cl bond
cleavage (Run 4).26
Friedel–Crafts acylation generally displays ortho and para
selectivity and is not suitable for preparation of aryl ketones
with a meta substituent.14 With the present method, on the oth-
er hand, 3, 3ꢀ-dimethyl benzophenone was selectively obtained
in an excellent yield in the reaction of m-toluic acid and m-
tolylboronic acid (Runs 11).
Fig. 1. Time course of the coupling reaction of C6H13COOH
with PhB(OH)2 catalyzed by [Pd (PPh3)4] carried out at 80
°C in dioxane in the presence of dimethyl dicarbonate.
yield of the ketone was obtained when the molar amount of
[Pd(PPh3)4] used per heptanoic acid was lowered to 0.005
(Run 3), but further decrease in the amount of [Pd(PPh3)4] was
found to give a lower yield of ketone (Run 4).
(e) Time Course. Figure 1 exhibits a typical time course
in the reaction of heptanoic acid with phenylboronic acid in the
presence of dimethyl dicarbonate in dioxane carried out at 80
°C. Use of [Pd(PPh3)4] as a catalyst converted heptanoic acid
into heptanophenone almost completely within 2 h, as shown
in Fig. 1.
Heteroatoms which coordinate to transition metals often re-
tard the cross-coupling reaction of organometallics. However,
heterocyclic carboxylic acids such as 2-thiophenecarboxylic
acid, 3-furoic acid, and nicotinic acid readily coupled with
phenylboronic acid under standardized conditions to give the
(f) Scope and Limitation. Table 5 summarizes represen-
tative examples of the palladium-catalyzed ketone synthesis
from carboxylic acids and organoboronic acids in the presence

1338 Bull. Chem. Soc. Jpn., 75, No. 6 (2002)
Novel Pd-Catalyzed Ketone Synthesis
corresponding ketones in good yields (Runs 12 – 14). trans-
Cinnamic acid having the double bond that may interact with
the palladium center could be also used, although the yield was
moderate (Run 15). The presence of CwC bond on the side of
organoboronic acid also hinders preparation of ketones (Run
16).
dioxaborinane30 was found less effective as the arylating re-
agents (Eq. 10).
Various aliphatic carboxylic acids such as heptanoic acid are
converted smoothly into heptanophenone in combination with
phenylboronic acid (Run 17), whereas a bulky aliphatic car-
boxylic acid such as 2, 2-dimethylpropionic acid and 2-meth-
ylpropionic acid resulted in low to moderate yields, probably
due to the lower reactivity of their mixed anhydride in oxida-
tive addition to a Pd(0) species (Runs 18 and 19).27
(9)
Aromatic and aliphatic dicarboxylic acids could also be
converted into diketones in the catalytic process. As shown in
Eqs. 7 and 8, terephthalic acid and azelaic acid were converted
into the corresponding diketones in moderate to excellent
yields on treatment with phenylboronic acid in the presence of
dimethyl dicarbonate and [Pd(PPh3)4].
(10)
(g) Application to Heterogeneous Systems. Recently, the
effect of addition of ligands not only to homogeneous catalyst
systems but also to heterogeneous catalysts to control the reac-
tion courses is attracting increasing attention.31 Heterogeneous
catalysts possess obvious advantages over the homogeneous
systems in ease of separation of the catalysts and the product.
The yield of ketone is influenced by nature and the amount of
the phosphine ligands added to the heterogeneous catalysts.
Development of the catalytic activity of the heterogeneous cat-
alyst was favored at higher temperatures, as shown in Table 6.
The commercially available heterogeneous palladium cata-
lysts such as palladium deposited on barium sulfate (unre-
duced samples) without added tertiary phosphine ligands did
not catalyze the ketone synthesis (Run 1). Addition of triphe-
nylphosphine to Pd/BaSO4, however, developed the catalytic
activities (Runs 2–13). Reactions carried out at 90 °C and un-
der reflux conditions in dioxane afforded benzophenone in
good yields (Runs 3 and 4), whereas the reaction carried out at
70 °C gave a lower yield (Run 2). A less polar solvent such as
toluene was also found effective (Run 5). Among the tertiary
phosphine ligands examined, triphenylphosphine gave the
highest yields. Use of more electron-rich tertiary phosphine
ligands than PPh3 such as tris(p-methoxyphenyl)phosphine or
less electron-rich ligands like tri-2-furylphosphine resulted in
decrease in the yield of the ketone (Runs 6 and 7). The amount
of PPh3 contained in the catalytic systems also affected the cat-
alytic activity. Addition of PPh3 up to 4 mol amt./palladium
caused improvement in the yield of the ketone, whereas further
increase in the amounts of the ligand added showed an adverse
effect (Runs 8–13).
(7)
(8)
If the reaction could be applied to α-keto acids, we might
find a new route to α-diketone synthesis. However, the reac-
tion of benzoylformic acid with p-tolylboronic acid gave 4-me-
thylbenzophenone as the major product without giving the ex-
pected α-diketone (Eq. 9). The result suggests that decarbon-
ylation of the (phenylglyoxyl)palladium intermediate occurred
to give a (benzoyl)palladium intermediate that further under-
went transmetallation with p-tolylboronic acid to produce 4-
methylbenzophenone.28
Organoboron compounds other than organoboronic acids
were also examined. Employment of sodium tetraphenylbo-
rate29 in a quantity somewhat higher than equimolar amount in
combination with the benzoic acid gave benzophenone in 96%
yield. A moderately high yield of benzophenone (72%) from
benzoic acid was obtained even when 0.3 molar amount of
NaBPh4 per benzoic acid was employed in the presence of
[Pd(PPh3)4], the result indicating that three phenyl groups in
NaBPh4 were used in the transfer process. 2-Phenyl-1, 3, 2-
Discussion
Reaction Mechanism. On the basis of our fundamental
studies on the C–O bond cleavage of carboxylic anhydrides
with Pd(0) complexes and further information on reactivity of
an isolated acylpalladium complex with organoboronic acid,7

R. Kakino et al.
Bull. Chem. Soc. Jpn., 75, No. 6 (2002) 1339
Table 6. Effect of Heterogeneous Catalysts on the Cross-
Coupling Reaction of Benzoic Acid with Phenylboronic
Acid in the Presence of (MeOCO)2O
Table 7. Reactivity of p-Substituted Phenylboronic Acids
Relative to Phenylboronic Acid and Their Hammett Sub-
stituent Values
Ruma)
Ligand
Temp
Yield/%b)
1
2
3
None
90
70
90
reflux
90
90
90
90
90
90
trace
52
82
80
81
20
52
65
76
88
81
77
49
Y
Hammettσp
P(Y)/P(H)a)
log (P(Y)/P(H))
15 mol% PPh3
15 mol% PPh3
15 mol% PPh3
15 mol% PPh3
15 mol% P (2-furyl)3
15 mol% P (p-MeOC6H4)3
5 mol% PPh3
10 mol% PPh3
20 mol% PPh3
25 mol% PPh3
30 mol% PPh3
35 mol% PPh3
Meo
Me
H
Cl
CF3
−0.27
−0.17
0
0.23
0.54
0.62
0.72
1
2.0
2.1
−0.21
−0.14
0
0.30
0.32
4
5c)
6
7
8
9
10
11
12
13
a) Determined by GC using nC14H30 as an internal standard.
carboxylic acid employed with dimethyl dicarbonate added as
the activator to form a mixed anhydride of the carboxylic acid
and mono methyl ester of carbonic acid; ii) oxidative addition
of the mixed anhydride to zerovalent palladium species A to
give an (acyl)(methyl carbonato)palladium species B; iii) de-
carboxylation of the methyl carbonato ligand to give
(acyl)(methoxo)palladium species C;32 iv) transmetallation of
C with an arylboronic acid to give an (acyl)(aryl)palladium
species D; and v) reductive elimination of D to liberate the
coupling product of the acyl and aryl ligands with regeneration
of the Pd(0) species, which further carries the catalytic cycle.
For gaining further information on the mechanism of the
present process, we carried out competition reactions using
equimolar mixtures of phenylboronic acid and various para-
substituted phenylboronic acids in the catalytic reactions with
benzoic acid in the presence of dimethyl dicarbonate and
[Pd(PPh3)4]. In Table 7 are compared relative product yields,
P(Y)/P(H) of the ketones having the Y substituents at the para
position versus benzophenone, produced after heating the sys-
tems for 6 h in dioxane at 80 °C. The results indicate that the
para-substituted phenylboronic acids having the more electron-
withdrawing substituents react faster than the phenylboronic
acid derivatives having more electron-releasing substituents.33
Figure 2 demonstrates the results of the competition experi-
ments using the four pairs of para-substituted phenylboronic
acids and phenylboronic acid in the cross-coupling reactions
with benzoic acid carried out at 80 °C in the presence of dime-
thyl dicarbonate and [Pd(PPh3)4] as the catalyst. The plot of
logarithms of the relative yields of the ketones against Ham-
mett σp constants showed a reasonably good linear relationship
(r2 = 0.904) with a ρ value of 0.72. The positive ρ value sug-
gests that the cross-coupling reaction is favored when the aryl-
boronic acid has a higher Lewis acid character in the transmet-
allation process.
90
90
90
a) Typical conditions: a mixture containing benzoic acid (1
mmol), phenylboronic acid (1.2 mmol), dimethyl dicarbon-
ate (3.0 mmol), [Pd/BaSO4] (0.05 mmol), ligand, and diox-
ane (5 cm3) was stirred in a Schlenk tube under argon at 80
°C for 6 h.
b) Determined by GC using nC14H30 as an internal standard.
c) In toluene.
Scheme 3. Proposed mechanism for catalytic conversion of
carboxylic acids into unsymmetrical ketones in the pre-
sense of dimethyl dicarbonatate.
In the previous report dealing with palladium-catalyzed ke-
tone synthesis from carboxylic anhydrides and arylboronic ac-
ids,7 we observed that carboxylic anhydrides having electron-
withdrawing para substituents in the benzoic anhydride reacted
faster than the substrates having electron-donating substituents
when phenylboronic acid was used as the arylation reagent in
giving the aryl phenyl ketones. The result suggested the im-
we propose a catalytic cycle that consists of elementary pro-
cesses as shown in Scheme 3 to account for the catalytic for-
mation of aryl ketones from carboxylic acids and arylboronic
acids in the presence of dimethyl dicarbonate.
The catalytic system includes: i) exchange reaction of the

1340 Bull. Chem. Soc. Jpn., 75, No. 6 (2002)
Novel Pd-Catalyzed Ketone Synthesis
acylpalladium complex B further undergoes decarboxylation,
deprotonation of phenylacetylene by the methoxide, and cou-
pling of the acyl entity with the phenylethynyl entity, produc-
ing the product and the catalyst. Applicability of the present
methodology for synthesis of alkynyl ketones will be the sub-
ject of further studies.
(11)
While we were preparing this paper, Gooβen et al. have re-
ported a similar synthetic method of ketones from carboxylic
acids with organoboronic acids in the presence of pivalic anhy-
dride.37 They used a concept similar to ours reported in our
previous study on the aldehyde synthesis.9 However, as we de-
scribed in the present paper, the cross-coupling process using
pivalic anhydride as an activator is less satisfactory than the
present method with dimethyl dicarbonate in view of the
somewhat lower yields in giving ketones and in view of the
higher cost of pivalic anhydride than of dimethyl dicarbonate.
More recently, they reported also on the Pd-catalyzed cross-
coupling reaction of carboxylic acids with arylboronic acids in
the presence of disuccinimido carbonate as the activator.38
However, in the coupling reaction using disuccinimido carbon-
ate as the activator, addition of a base such as sodium carbon-
ate is necessary to drive the reaction. In addition, disuccinimi-
do carbonate is more expensive than dimethyl dicarbonate.
Fig. 2. Hammett plot for the relative reactivities of various
para-substituted phenylboronic acids to phenylboronic acid
in the cross-coupling reaction
portance of the oxidative addition of carboxylic anhydride in
the catalytic cycle. Now that factors controlling the oxidative
addition process (ii) in Scheme 3 and the transmetallation pro-
cess (iv) in Scheme 3 have been clarified to some extent, exam-
ination of the factors involved in each of the elementary pro-
cesses in Scheme 3 merits further studies in elucidating the re-
action mechanism.
In the Suzuki–Miyaura coupling of organic halides or or-
ganic triflates with aryl-, alkenyl-, and alkylboronic acids or
esters, addition of a base such as NaOEt, KOAc, and NaOH is
required to drive the reactions.17 The effect of addition of the
base was accounted for as replacement of the halide ligand in
the catalyst intermediate with the alkoxide, carboxylate, or hy-
droxide ligand that is more susceptible to transmetallation with
the oxophilic organoboron compounds than a halide ligand.34
In the present case, on the other hand, no base is required in
performing the cross-coupling process to yield ketones.35 The
reason may be found in the reaction mechanism as represented
by Scheme 3. If the mechanism shown in Scheme 3 is valid,
the acyl(methoxo)palladium intermediate C produced by de-
carboxylation of B possesses the oxygen-containing methox-
ide ligand amenable to the attack of the oxophilic arylboronic
acid to give D in step (iv) in Scheme 3.
Catalytic Synthesis of Alkynyl Ketone. On the basis of
the present study that supports involvement of the acyl(meth-
oxo)palladium complexes generated in the reaction mixture of
carboxylic acids with dimethyl dicarbonate on reaction with
Pd(0) complex, we further examined the possibility of devel-
oping a catalytic process to cause the coupling of the acyl enti-
ty in the carboxylic acid with terminal alkynes. It was found
that the benzoic acid was converted into 1,3-diphenyl-2-pro-
pyn-1-one36 when it was treated with dimethyl dicarbonate and
phenylacetylene in the presence of Pd(OAc)2 and PPh3 as
shown in Eq. 11.
Conclusion
We demonstrated here a new type of catalytic process to
convert carboxylic acids and organoboron compounds into un-
symmetrical ketones in one-pot under mild and neutral condi-
tions. The present process is applicable to various carboxylic
acids and organoboron compounds and is tolerant of a variety
of functional groups, such as cyano, nitro, and carbonyl
groups, and does not cause the C–Cl bond cleavage. Many
kinds of heterocyclic carboxylic acids can be readily coupled
with arylboronic acids under mild experimental conditions.
The present method allows the use of an α, β-unsaturated car-
boxylic acid such as trans-cinnamic acid. Dibasic carboxylic
acids could be also used to give diketones. Our studies of
competition reactions showed that arylboronic acids having
electron-withdrawing para substituents reacted faster, the re-
sult suggesting the importance of the electrophilicity of the
arylboronic acid in transmetallation process.
In view of the paucity of atom-efficient and environmentally
benign processes to synthesize unsymmetrical ketones under
mild conditions, the present method provides a convenient new
route to selective production of ketones under mild conditions.
We also found that a direct catalytic conversion of benzoic acid
with phenylacetylene into 1,3-diphenyl-2-propyn-1-one can be
achieved under similar conditions.
The catalytic coupling reaction is considered to proceed
through oxidative addition of the mixed anhydride produced
from benzoic acid and dimethyl dicarbonate to give the
acylpalladium intermediate B, as shown in Scheme 3. The
Experimental
General Procedures. All manipulations were carried out un-
der argon atmosphere using Schlenk tube techniques. Solvents

R. Kakino et al.
Bull. Chem. Soc. Jpn., 75, No. 6 (2002) 1341
were purified by the usual methods under argon. NMR spectra
were recorded on a JEOL Lambda 500 or a JEOL AL-400 spec-
trometer for 1H (referenced via residual solvent protons), 13C{1H}
(referenced to the solvent resonance), and 19F (referenced to triflu-
oroacetic acid in CDCl3 as an external standard) NMR. Coupling
constants (J values) are given in hertz (Hz), and spin multiplicities
are indicated as follows: s (singlet), d (doublet), t (triplet), m (mul-
tiplet), vt (virtual triplet), and br (broad). Gas chromatographic
analyses (GC) were carried out on a GC-353 equipped with TC1
column (0.25 mm i. d. × 30 m), using N2 as carrier gas. Low-res-
olution mass spectra were obtained with a JEOL JMS-Automass
150 that is coupled with a gas chromatograph. FAB analysis was
performed by the Materials Characterization Central Laboratory
of Waseda University.
Reagents. All carboxylic acids, carboxylic anhydrides, orga-
noboron compounds, and di-t-butyl dicarbonate were commercial
products and were used without further purification. Dimethyl di-
carbonate purchased from Aldrich was distilled before use. Phe-
nylacetylene was a commercial product, and was used directly.
[Pd(PPh3)4]39 and [Pd(PCy3)2]40 were prepared by the reported
procedures. [Pd2(dba)3] was prepared following a synthesis
report41 and was used without recrystallization of the crude pre-
cipitate obtained at the end of the synthesis. Pd(OAc)2 (Aldrich)
and Pd/BaSO4/(unreduced) (Aldrich) were used as received from
commercial suppliers. All tertiary phosphines were commercial
products and were used without further purification.
1). A procedure for obtaining the time-yield curve in synthesis
of heptanophenone is as follows. A dioxane solution (5 cm3) con-
taining [Pd(PPh3)4] (23.1 mg, 0.0200 mmol), heptanoic acid (129
mg, 0.991 mmol), phenylboronic acid (147 mg, 1.21 mmol), and
dimethyl dicarbonate (200 mg, 1.49 mmol) in a 25 cm3 Schlenk
tube was heated under argon at 80 °C. At each interval, the tube
was removed from the oil bath and cooled in a water bath immedi-
ately. The yields of heptanophenone were determined by GC us-
ing nC14H30 as an internal standard.
Synthesis of Unsymmetrical Ketones (Table 5).
A
typical
procedure is as follows (Run 5). A dioxane solution (5 cm3) con-
taining [Pd(PPh3)4] (11.9 mg, 0.0103 mmol), 4-trifluoromethyl-
benzoic acid (191 mg, 1.00 mmol), phenylboronic acid (147 mg,
1.21 mmol), and dimethyl dicarbonate (164 mg, 1.22 mmol) in a
25 cm3 Schlenk tube was heated under argon at 80 °C for six
hours. On cooling the reaction mixture, diethyl ether and H2O
were added and the aqueous layer was extracted with diethyl
ether. The combined ether solution was dried (MgSO4) and the
solvent was evaporated in vacuo. Purification of the residue by
column chromatography (hexane/ethyl acetate = 9:1) gave the
corresponding product (249 mg; yield 99%).
The following ketones were synthesized by the above general
procedure. GC yields based on carboxylic acids are in the paren-
thesis. The isolated yields are indicated by the square brackets.
Benzophenone (Run 1): [119-61-9] (97%); Benzophenone
was characterized by GC-MS by comparison with an authentic
sample (Tokyo Kasei Kogyo Co.). GC-MS m/z (rel intensity) 182
(100), 105 (54), 77 (66).
Effect of Homogeneous Catalysts (Table 1). A typical pro-
cedure is as follows (Run 2). A dioxane solution (5 cm3) contain-
ing [Pd(PCy3)2] (33.4 mg, 0.0501 mmol), p-toluic acid (136 mg,
0.999 mmol), phenylboronic acid (147 mg, 1.21 mmol), and pival-
ic anhydride (560 mg, 3.01 mmol) in a 25 cm3 Schlenk tube was
heated under argon at 80 °C for 24 h. The yields of 4-methylben-
zophenone were determined by GC using n-tetradecane (nC14H30)
as an internal standard.
4-Methoxybenzophenone (Run 2):
[611-64-9] (96%)
[86%]; 4-Methoxybenzophene was characterized by H, 13C{1H}
NMR, and GC-MS by comparison with an authentic sample (Ald-
rich). 1H NMR (acetone-d6, r. t., 400 MHz) δ 7.67 (m, 2H, aro-
matic H), 7.61 (m, 2H, aromatic H), 7.49 (m, 1H, aromatic H),
7.41 (m, 2H, aromatic H), 6.95 (m, 2H, aromatic H), 3.79 (s,
OCH3); 13C{1H} NMR (acetone-d6, r. t., 100 MHz) δ 195.0 (s, car-
bonyl C), 164.1 (s, aromatic C), 139.1 (s, aromatic C), 132.9 (s,
aromatic C), 132.5 (s, aromatic C), 130.8 (s, aromatic C), 130.1(s,
aromatic C), 129.0 (s, aromatic C), 114.4 (s, aromatic C), 55.9 (s,
OCH3). GC–MS m/z (rel intensity) 212 (42), 135 (98), 105 (13),
92 (14), 77 (46).
1
Effects of Solvent and Temperature (Table 2).
A
typical
procedure is as follows (Run 4). Dioxane solutions (5 cm3) con-
taining [Pd(PPh3)4] (58.0 mg, 0.0502 mmol), p-toluic acid (139
mg, 1.02 mmol), phenylboronic acid (147 mg, 1.21 mmol), and
pivalic anhydride (560 mg, 3.01 mmol) in a 25 cm3 Schlenk tube
were stirred under argon at room temperature at 60 °C, 80 °C, and
100 °C, respectively, for 24 hours. The effects of solvents were
examined in THF, acetone, toluene, 1-methyl-2-pyrrolidinone
(NMP), hexane, and dioxane by carrying out the syntheses at 80
°C. The yields of 4-methylbenzophenone were determined by GC
using nC14H30 as an internal standard.
4-Methylbenzophenone (Run 3): [634-65-2] (97%); 4-Me-
thylbenzophene was characterized by GC-MS by comparison with
an authentic sample (Kanto Chemical Co.). GC-MS m/z (rel in-
tensity) 196 (99), 181 (21), 165 (9), 152 (8), 119 (95), 105 (50), 91
(68), 77 (74).
Effect of Activator (Table 3). A typical procedure is as fol-
lows (Run 4). A dioxane solution (5 cm3) containing [Pd(PPh3)4]
(23.1 mg, 0.0200 mmol), heptanoic acid (129 mg, 0.991 mmol),
phenylboronic acid (148 mg, 1.21 mmol), and dimethyl dicarbon-
ate (400 mg, 2.98 mmol) in a 25 cm3 Schlenk tube was heated un-
der argon at 80 °C for 24 h. The yields of heptanophenone were
determined by GC using nC14H30 as an internal standard.
4-Chlorobenzophenone (Run 4): [134-85-0] [88%]; 4-
1
Chlorobenzophenone was characterized by H, 13C{1H} NMR,
and GC-MS by comparison with an authentic sample (Tokyo
Kasei Kogyo Co.). 1H NMR (acetone-d6, r. t., 400 MHz) δ 7.69–
7.65 (m, 4H, aromatic H), 7.57–7.53 (m, 1H, aromatic H), 7.49–
7.42 (m, 4H, aromatic H); 13C{1H} NMR (acetone-d6, r. t., 100
MHz) δ 195.2 (s, carbonyl C), 138.8 (s, aromatic C), 138.0 (s, aro-
matic C), 137.0 (s, aromatic C), 133.3 (s, aromatic C), 132.2 (s.
aromatic C), 130.4 (s, aromatic C), 129.3 (s, aromatic C), 129.2 (s,
aromatic C). GC-MS m/z (rel intensity) 216 (9), 181 (3), 152 (2),
139 (29), 111 (42), 105 (73), 77 (100).
Influence of the Amount of Catalyst (Table 4).
A
typical
procedure is as follows (Run 2). A dioxane solution (5 cm3) con-
taining [Pd(PPh3)4] (11.6 mg, 0.0100 mmol), heptanoic acid (129
mg, 0.991 mmol), phenylboronic acid (146 mg, 1.20 mmol), and
dimethyl dicarbonate (200 mg, 1.49 mmol) in a 25 cm3 Schlenk
tube was heated under argon at 80 °C for 24 h. The yields of hep-
tanophenone were determined by GC using nC14H30 as an internal
standard.
4-Trifluoromethylbenzophenone (Run 5): [728-86-9] [98%];
1
4-Trifluoromethybenzophenone was characterized by H, 13C{1H}
NMR, and GC-MS by comparison with an authentic sample
1
(ACROS). H NMR (acetone-d6, r. t., 400 MHz) δ 7.84 (m, 2H, ar-
Time-Yield Curve in Formation of Heptanophenone (Fig.
omatic H), 7.79 (m, 2H, aromatic H), 7.71–7.69 (m, 2H, aromatic

1342 Bull. Chem. Soc. Jpn., 75, No. 6 (2002)
Novel Pd-Catalyzed Ketone Synthesis
H), 7.58–7.56 (m, 1H, aromatic H), 7.47–7.44 (m, 2H, aromatic
H); 13C{1H} NMR (CDCl3, r. t., 100 MHz) δ 195.3 (s, carbonyl C),
146.6 (s, aromatic C), 136.6 (s, aromatic C), 133.6 (q, 2JCF = 32.3
Hz aromatic C), 133.0 (s, aromatic C), 130.0 (s, aromatic C), 130.0
(s, aromatic C), 128.4 (s, aromatic C), 125.3 (q, 3JCF = 3.32 Hz ar-
omatic C), 123.6 (q, 1JCF = 272.0 Hz, CF3); 19F NMR (acetone-d6,
r. t., 471 MHz) δ −62.2 (s, CF3). GC–MS m/z (rel intensity) 250
(52), 231 (7), 173 (47), 145 (52), 125 (9), 105 (96), 77 (99).
aromatic H), 7.86 (m, 1H, aromatic H), 7.71 (m, 1H, aromatic H),
7.66 (m, 1H, aromatic H), 7.55 (m, 2H, aromatic H), 7.26 (m, 1H
aromatic H); 13C{1H} NMR (acetone-d6, r. t., 100 MHz) δ 187.9
(s, carbonyl C), 144.2 (s, aromatic C), 138.9 (s, aromatic C), 135.6
(s, aromatic C), 135.2 (s, aromatic C), 132.9 (s, aromatic C), 129.6
(s, aromatic C), 129.2 (s, aromatic C), 129.0 (s, aromatic C). GC–
MS m/z (rel intensity) 188 (99), 171 (13), 160 (12), 111 (97), 105
(72), 77 (98).
3-Benzoylpyridine (Run 14): [5424-19-1] (85%); 3-Ben-
zoylpryridine was characterized by GC–MS by comparison with
an authentic sample (Tokyo Kasei Kogyo Co.). GC–MS m/z (rel
intensity) 183 (80), 154 (6), 105 (89), 77 (99).
Chalcone (Run 15): [614-47-1] (56%); Chalcone was char-
acterized by GC–MS by comparison with an authentic sample
(Tokyo Kasei Kogyo Co.). GC–MS m/z (rel intensity) 208 (47),
179 (15), 165 (9), 131 (29), 105 (23), 77 (100).
Chalcone (Run 16): [614-47-1] (43%); Chalcone was char-
acterized by GC–MS by comparison with an authentic sample
(Tokyo Kasei Kogyo Co.). GC–MS m/z (rel intensity) 208 (50),
179 (16), 165 (9), 131 (30), 105 (23), 77 (100).
4-Formyl-4ꢀ-methylbenzophenone (Run 6):
[88%]; 1H
NMR (CDCl3, r. t., 400 MHz) δ 10.13 (s, 1H, formyl H), 8.00 (m,
2H, aromatic H), 7.90 (m, 2H, aromatic H), 7.72 (m, 2H, aromatic
H), 7.31 (m, 2H, aromatic H), 2.46 (s, 3H, CH3); 13C{1H} NMR
(CDCl3, r. t., 100 MHz) δ 195.4 (carbonyl C), 191.5 (formyl C),
144.1 (s, aromatic C), 142.9 (s, aromatic C), 138.2 (s, aromatic C),
134.0 (s, aromatic C), 130.3 (s, aromatic C), 130.1 (s, aromatic C),
129.4 (s, aromatic C), 129.2 (s, aromatic C), 21.8 (s, CH3). GC–
MS m/z (rel intensity) 224 (26), 195 (5), 165 (6), 152 (5), 133
(11), 119 (98), 104 (10), 91 (43), 77 (23). FAB-MS: Found m/z
225.0902 (M + H), Calcd for C15H12O2: 224.0837 (M).
4-Cyanobenzophenone (Run 7): [1503-49-7] (98%); 4-Cy-
anobenzophenone was characterized by GC–MS by comparison
with an authentic sample (Aldrich). GC–MS m/z (rel intensity)
207 (42), 130 (26), 105 (99), 77 (55).
4-Nitrobenzophenone (Run 8): [1144-74-4] (96%); 4-Ni-
trobenzophene was characterized by GC–MS by comparison with
an authentic sample (Aldrich). GC–MS m/z (rel intensity) 227
(32), 207 (6), 150 (12), 105 (100), 77 (55).
Heptanophenone (Run 17): [1671-75-6]
(96%);
Hep-
tanophenone was characterized by GC–MS by comparison with
an authentic sample (Tokyo Kasei Kogyo Co.). GC–MS m/z (rel
intensity) 190 (44), 133 (40), 120 (82), 105 (72), 91 (11), 77
(100).
Isobutyrophenone (Run 18): [611-70-1] (52%); Isobuty-
rophenone was characterized by GC–MS by comparison with an
authentic sample (Tokyo Kasei Kogyo Co.). GC–MS m/z (rel in-
tensity) 148 (17), 105 (99), 77 (49).
2, 2-Dimethylpropiophenone (Run 19): [938-16-9] (20%);
2,2-Dimethylpropiophenone was characterized by GC–MS by
comparison with an authentic sample (Aldrich). GC–MS m/z (rel
intensity) 162 (23), 119 (6), 105 (97), 91 (7), 77 (100).
Cross-Coupling Reaction of Dibasic Carboxylic Acids (Eqs.
7 and 8). A typical procedure is as follows (Eq. 8). A dioxane
solution (5 cm3) containing [Pd(PPh3)4] (12.1 mg, 0.0105 mmol),
azelaic acid (188 mg, 0.999 mmol), phenylboronic acid (293 mg,
2.40 mmol), and dimethyl dicarbonate (325 mg, 2.42 mmol) in a
25 cm3 Schlenk tube was heated under argon at 80 °C for six
hours. After the reaction mixture was cooled, diethyl ether and
H2O were added and the aqueous layer was extracted with diethyl
ether. The combined ether solution was dried (MgSO4) and the
solvent was evaporated in vacuo. Purification of the residue by
column chromatography (hexane/ethyl acetate = 9:1) gave the
corresponding product (245 mg; yield 79%).
4-Methoxybenzophenone (Run 9): [611-64-9] (97%); 4-
Methoxybenzophene was characterized by GC–MS by compari-
son with an authentic sample (Aldrich). GC–MS m/z (rel intensi-
ty) 212 (42), 135 (98), 105 (13), 92 (14), 77 (46).
4-Trifluoromethylbenzophenone (Run 10):
[728-86-9]
(98%); 4-Trifluoromethybenzophenone was characterized by GC–
MS by comparison with an authentic sample (ACROS) . GC–MS
m/z (rel intensity) 250 (87), 231 (7), 173 (52), 145 (73), 125 (13),
105 (98), 77 (99).
3, 3ꢀ-Dimethylbenzophenone (Run 11): [2852-68-8] [85%];
3, 3ꢀ-Dimethylbenzophenone was characterized by 1H and
13C{1H} NMR by comparison with the literature.42 1H NMR
(CDCl3, r. t., 400 MHz) δ 7.62 (s, 2H, aromatic H), 7.56 (m, 2H,
aromatic H), 7.40–7.35 (m, 4H, aromatic H), 2.41 (s, 6H, CH3);
13C{1H} NMR (CDCl3, r. t., 100 MHz) δ 197.0 (s, carbonyl C),
138.0 (s, aromatic C), 137.7 (s, aromatic C), 133.0 (s, aromatic C),
130.3 (s, aromatic C), 127.9 (s, aromatic C), 127.2 (s, aromatic C),
21.4 (s, CH3). GC–MS m/z (rel intensity) 210 (23), 195 (14), 165
(6), 119 (99), 91 (50).
1, 9-Diphenyl-1, 9-nonanedione (Eq. 8):
[28861-21-4]
1
3-Benzoylfuran (Run 12): [6453-98-1] [85%]; 3-Benzoylfu-
(79%); 1,9-Diphenyl-1,9-nonanedione was characterized by H
NMR by comparison with the literature.44 1H NMR (CDCl3, r. t.,
400 MHz) δ 7.88 (m, 4H, aromatic H), 7.48 (m, 2H, aromatic H),
7.38 (m, 4H, aromatic H), 2.90 (t, 4H, 3JHH = 7.45 Hz, COCH2),
1.69–1.65 (m, 4H, alkyl H), 1.35–1.28 (m, 6H, alkyl H); 13C{1H}
NMR (CDCl3, r. t., 100 MHz) δ 200.3 (s, carbonyl C), 137.0 (s, ar-
omatic C), 132.8 (s, aromatic C), 128.5 (s, aromatic C), 127.9 (s,
aromatic C), 38.6 (s, COCH2), 29.4 (s, alkyl C), 29.2 (s, alkyl C),
24.3 (s, alkyl C).
1
ran was characterized by H and 13C{1H} NMR by comparison
with the literature.43 1H NMR (acetone-d6, r. t., 400 MHz) δ 8.19
(s, 1H, aromatic H), 7.88 (m, 2H, aromatic H), 7.73 (s, 1H, aro-
matic H), 7.64 (m, 1H, aromatic H), 7.53 (m, 2H, aromatic H),
6.90 (s, 1H, aromatic H); 13C{1H} NMR (CDCl3, r. t., 100 MHz) δ
189.2 (s, carbonyl C), 148.4 (s, aromatic C), 143.8 (s, aromatic C),
138.7 (s, aromatic C), 132.4 (s, aromatic C), 128.7 (s, aromatic C),
128.4 (s, aromatic C), 126.4 (s, aromatic C), 110.1 (s, aromatic C).
GC–MS m/z (rel intensity) 172 (78), 144 (9), 115 (20), 105 (24),
95 (99), 77 (63).
1, 4-Dibenzoylbenzene (Eq. 7): [3016-97-5] (91%); 1, 4-
Dibenzoylbenzene was characterized by GC–MS by comparison
with an authentic sample (Aldrich). GC–MS m/z (rel intensity)
286 (30), 209 (38), 181 (12), 152 (19), 105 (100), 77 (87).
Cross-Coupling Reaction of Benzoylformic Acid (Eq. 9).
A dioxane solution (5 cm3) containing [Pd(PPh3)4] (11.9 mg,
2-Benzoylthiophene (Run 13): [135-00-2] (99%) [88%]; 2-
1
Benzoylthiophene was characterized by H, 13C{1H} NMR, and
GC–MS by comparison with an authentic sample (Tokyo Kasei
Kogyo Co.). 1H NMR (acetone-d6, r. t., 400 MHz) δ 7.98 (m, 2H,

R. Kakino et al.
Bull. Chem. Soc. Jpn., 75, No. 6 (2002) 1343
intensity) 206 (49), 178 (79), 129 (100), 77 (20).
0.0103 mmol), benzoylformic Acid (149 mg, 0.992 mmol), p-
tolylboronic acid (165 mg, 1.21 mmol), and dimethyl dicarbonate
(163 mg, 1.22 mmol) in a 25 cm3 Schlenk tube was heated under
argon at 80 °C for 6 h. The yield of 4-methylbenzophenone was
determined by GC using nC14H30 as an internal standard. 4-Meth-
ylbenzophenone was characterized by GC–MS by comparison
with an authentic sample (Kanto Chemical Co.). GC–MS m/z (rel
intensity) 196 (42), 181 (13), 165 (5), 152 (5), 119 (96), 105 (25),
91 (39), 77 (45).
This study was supported by grants from the Ministry of Ed-
ucation, Science, Sports and Culture and Nippon Zeon Co.,
Ltd. We are grateful for their support.
References
1
a) J. Tsuji, “Palladium Reagents and Catalysts: Innovations
in Organic Synthesis,” John Wiley & Sons, Chichester (1995). b)
J. Tsuji, “Transition Metal Reagents and Catalysts: Innovations in
Organic Synthesis,” John Wiley & Sons, Chichester (2000).
Cross-Coupling Reaction of Benzoic Acid with Other Orga-
noboron Compounds in the Presence of Dimethyl Dicarbonate
(Eq. 10). A typical procedure using NaBPh4 is given below. A
dioxane solution (5 cm3) containing [Pd(PPh3)4] (23.2 mg, 0.0201
mmol), benzoic acid (122 mg, 0.999 mmol), sodium tetraphenylb-
orate (410 mg, 1.20 mmol), and dimethyl dicarbonate (200 mg,
1.49 mmol) in a 25 cm3 Schlenk tube was heated under argon at
80 °C for 24 h. The yields of benzophenone were determined by
2
“Metal-catalyzed Cross-coupling Reactions,” ed by F.
Diederich and P. J. Stang, Wiley-VCH, Weinheim (1998).
S. Bräse and A. de Meijere, “Metal-catalyzed Cross-cou-
3
pling Reactions,” ed by F. Diederich and P. J. Stang, Wiley-VCH,
Weinheim (1998), pp. 99–166, and references cited therein.
n
4
For reviews see: a) A. Yamamoto, Adv. Organomet. Chem.,
GC using C14H30 as an internal standard. Benzophenone was
34, 111 (1992). b) Y.-S. Lin and A. Yamamoto, “Topics in Orga-
nometallic Chemistry,” ed by S. Murai, Springer, Berlin (1999),
Vol. 3, pp. 161–192. c) A. Yamamoto, R. Kakino, and I. Shimizu,
Helv. Chim. Acta, 84, 2996 (2001).
characterized by GC–MS by comparison with an authentic sample
(Tokyo Kasei Kogyo Co.). GC–MS m/z (rel intensity) 182 (81),
105 (98), 77 (97).
Effect of Heterogeneous Catalysts (Table 6). A typical pro-
cedure is as follows (Run 10). A dioxane solution (5 cm3) con-
taining Pd/BaSO4 (5 wt%) (106 mg, 0.0498 mmol), triphe-
nylphosphine (54.0 mg, 0.206 mmol), benzoic acid (123 mg, 1.01
mmol), phenylboronic acid (146 mg, 1.20 mmol), and dimethyl
dicarbonate (400 mg, 2.98 mmol) in a 25 cm3 Schlenk tube was
heated under argon at 90 °C for 6 h. The yield of benzophenone
5
K. Nagayama, I. Shimizu, and A. Yamamoto, Bull. Chem.
Soc. Jpn., 72, 799 (1999).
6
a) K. Nagayama, F. Kawataka, M. Sakamoto, I. Shimizu,
and A. Yamamoto, Bull. Chem. Soc. Jpn., 72, 573 (1999). b) K.
Nagayama, F. Kawataka, M. Sakamoto, I. Shimizu, and A.
Yamamoto, Chem. Lett., 1995, 367.
n
7
R. Kakino, S. Yasumi, I. Shimizu, and A. Yamamoto, Bull.
Chem. Soc. Jpn., 75, 137 (2002).
R. Kakino, I. Shimizu, and A. Yamamoto, Bull. Chem. Soc.
Jpn., 74, 371 (2001).
was determined by GC using C14H30 as an internal standard.
Benzophenone was characterized by GC–MS by comparison with
an authentic sample (Tokyo Kasei Kogyo Co.). GC–MS m/z (rel
intensity) 182 (100), 105 (97), 77 (98).
8
9
a) K. Nagayama, I. Shimizu, and A. Yamamoto, Bull.
Competitive Reactions of Various Para-Substituted Phenyl-
Chem. Soc. Jpn., 74, 1803 (2001). b) K. Nagayama, I. Shimizu,
and A. Yamamoto, Chem. Lett., 1998, 1143.
10 For reviews see: J. Tsuji, “Comprehensive Organic Synthe-
sis,” ed by B. M. Trost and I. Fleming, Pergamon, Oxford (1991),
Vol. 7, pp. 449–468.
11 a) T. V. Lee, “Comprehensive Organic Synthesis,” ed by B.
M. Trost and I. Fleming, Pergamon, Oxford (1991), Vol. 7, pp.
296–29. b) K. Omura and D. Swern, Tetrahedron, 34, 1651
(1978). c) A. J. Mancuso, S.-L. Huang, and D. Swern, J. Org.
Chem., 43, 2480 (1978).
12 a) S. V. Ley and A. Madin, “Comprehensive Organic Syn-
thesis,” ed by B. M. Trost and I. Fleming, Pergamon, Oxford
(1991), Vol. 7, pp. 260–267. b) E. J. Corey and J. W. Suggs, Tetra-
hedron Lett., 1975, 2647.
13 G. Procter, “Comprehensive Organic Synthesis,” ed by B.
M. Trost and I. Fleming, Pergamon, Oxford (1991), Vol. 7, pp.
318–325.
14 a) G. A. Olah, “Friedel-Crafts and Related Reactions,”
Wiley-Interscience, New York (1964), Vol. 1. b) S. B. Mahato, J.
Indian Chem. Soc., 77, 175 (2000).
15 For reviews see: a) B. T. O’Neill, “Comprehensive Organic
Synthesis,” ed by B. M. Trost and I. Fleming, Pergamon, Oxford
(1991), Vol. 1, pp. 397–458. b) R. K. Dieter, Tetrahedron, 55,
4177 (1999).
16 Friedel Crafts acylation: a) S. Kobayashi and N.
Hashizume, Jpn. Patent 10-87549 (1998); Chem. Abstr., 128,
257234 (1998). b) M. Morimoto, A. Miyata, and A. Okamoto,
Jpn. Patent 9-151155 (1997); Chem. Abstr., 127, 95087 (1997). c)
boronic Acids and Phenylboronic Acid (Table 7, Fig. 2).
A
typical procedure is as follows. A dioxane solution (5 cm3) con-
taining [Pd(PPh3)4] (11.6 mg, 0.0100 mmol), benzoic acid (121
mg, 0.991 mmol), 4-methoxyphenylboronic acid (456 mg, 3.00
mmol), phenylboronic acid (367 mg, 3.01 mmol), and dimethyl
dicarbonate (163 mg, 1.22 mmol) in a 25 cm3 Schlenk tube was
heated under argon at 80 °C for 6 h. The GC analysis revealed
that 52% of benzophenone and 32% of 4-methoxybenzophenone
were generated in the reaction mixture. On the basis of the
amounts of the two ketones, the relative reactivity of phenylboron-
ic acids was determined as 0.62.
Cross-Coupling Reaction of Benzoic Acid with Phenylacety-
lene (Eq. 11). A toluene solution (5 cm3) containing Pd(OAc)2
(11.7 mg, 0.0521 mmol), triphenylphosphine (53.1 mg, 0.202
mmol), benzoic acid (123 mg, 1.01 mmol), phenylacetylene (121
mg, 1.18 mmol), and dimethyl dicarbonate (400 mg, 2.98 mmol)
in a 25 cm3 Schlenk tube was heated under argon at 100 °C for 24
h. The yield of 1,3-diphenyl-2-propyn-1-one was determined by
n
GC using C14H30 as an internal standard. 1, 3-Diphenyl-2-pro-
pyn-1-one [7338-94-5] was characterized by 1H and 13C{1H}
NMR by comparison with the literature.36k 1H NMR (CDCl3, r. t.,
400 MHz) δ 8.22 (m, 2H, aromatic H), 7.69 (m, 2H, aromatic H),
7.62 (m, 1H, aromatic H), 7.52 (m, 2H, aromatic H), 7.48 (m, 1H,
aromatic H), 7.42 (m, 2H, aromatic H); 13C{1H} NMR (CDCl3, r.
t., 100 MHz) δ 177.8 (s, carbonyl C), 136.8 (s, aromatic C), 134.0
(s, aromatic C), 132.9 (s, aromatic C), 130.6 (s, aromatic C), 129.4
(s, aromatic C), 128.5 (s, aromatic C), 128.5 (s, aromatic C), 120.0
(s, aromatic C), 93.1 (s, alkyne), 86.8 (s, alkyne). GC–MS m/z (rel

1344 Bull. Chem. Soc. Jpn., 75, No. 6 (2002)
Novel Pd-Catalyzed Ketone Synthesis
W. S. Johnson, Org. React., ꢁ, 114 (1944). d) H. R. Snyder and F.
X. Werber, Org. Synth., ꢂ, 798 (1955). e) J. M. Gruber and R.
Seemayer, U. S. Patent 5962743 (1999); Chem. Abstr., 131,
243065 (1999). f) K. Suzuki and M. Mukaiyama, Jpn. Patent 6-
145092 (1994); Chem. Abstr., 121, 255400 (1994). Bimolecular
condensation with decarboxylation and dehydration: g) J. F.
Thorpe and G. A. R. Kon, Org. Synth., ꢃ, 187 (1932). h) W. E.
Bachmann and N. C. Deno, J. Am. Chem. Soc., 71, 3540 (1949).
i) L. Ruzicka, M. Stoll, and H. Schinz, Helv. Chim. Acta, 9, 249
(1926). j) G. Blanc, Bull. Soc. Chim. Fr., 3, 778 (1908). k) R. L.
Burwell, Jr., Chemtracts, 11, 75 (1998). l) R. Pestman, R. M.
Koster, A. V. Duijne, J. A. Z. Pieterse, and V. Ponec, J. Catal.,
168, 265 (1997). m) N. Saito, Jpn. Patent 8-198796 (1996);
Chem. Abstr., 125, 246890 (1996); n) K. Matsuoka and K.
Tagawa, Jpn. Patent 61-207354 (1986); Chem. Abstr., 106, 52127
(1987). o) H. Yokoyama, R. Setoyama, and T. Maki, Jpn. Patent
3-261739 (1991); Chem. Abstr., 116, 173566 (1992). p) M.
Gliński, J. Kijeński, and A. Jakubowski, Appl. Catal., A, 128, 209
(1995), and references cited therein. Acylation with organometal-
lic reagents of electropositive metals such as lithium and magne-
sium: q) M. J. Jorgenson, Org. React., 18, 1 (1970). r) B. T.
O’Neill, “Comprehensive Organic Synthesis,” ed by B. M. Trost
and I. Fleming, Pergamon, Oxford (1991), Vol. 1, pp. 410–413. s)
V. Fiandanese, G. Marchese, and L. Ronzini, Tetrahedron Lett.,
24, 3677 (1983). t) G. M. Rubottom and C. Kim, J. Org. Chem.,
48, 1550 (1983). u) Y. Ahn and T. Cohen, Tetrahedron Lett., 35,
203 (1994). v) T. Fujisawa, T. Mori, and T. Sato, Tetrahedron
Lett., 23, 5059 (1982). w) T. Fujisawa, S. Iida, H. Uehara, and T.
Sato, Chem. Lett., 1983, 1267. x) T. Fujisawa, T. Mori, K.
Higuchi, and T. Sato, Chem. Lett., 1983, 1791. y) M. Araki and T.
Mukaiyama, Chem. Lett., 1974, 663. z) F. Alonso, E. Lorenzo,
and M. Yus, J. Org. Chem., 61, 6058 (1996), and references cited
therein.
Org. Lett., 2, 1843 (2000).
22 Cross-coupling reaction of thioesters with organozinc com-
pounds in the presence of palladium catalysts has also been re-
ported. H. Tokuyama, S. Yokoshima, T. Yamashita, and T.
Fukuyama, Tetrahedron Lett., 39, 3189 (1998).
23 R. Kakino, H. Narahashi, I. Shimizu, and A. Yamamoto,
Chem. Lett., 2001, 1242.
24 In reaction of carboxylic acids with acetic anhydride in the
presence of rhodium and palladium complexes, Miller et al. found
conversion of carboxylic acids to olefins of one less carbon atom.
J. A. Miller, J. A. Nelson, and M. P. Byrne, J. Org. Chem., 58, 18
(1993).
25 Palladium(Ⅱ) acetate is smoothly reduced to Pd(0) in the
presence of tertiary phosphines. a) F. Ozawa, A. Kubo, and T.
Hayashi, Chem. Lett., 1992, 2177. b) T. Hayashi, A. Kubo, and F.
Ozawa, Pure Appl. Chem., 64, 421 (1992). c) C. Amatore, A.
Jutand, and M. A. M'Barki, Organometallics, 11, 3009 (1992); d)
T. Mandai, T. Matsumoto, J. Tsuji, and S. Saito, Tetrahedron Lett.,
34, 2513 (1993).
26 Reactions of chloroarenes with arylboronic acids in the
presence of homogeneous palladium catalysts to give biaryls have
been reported. a) A. F. Littke, C. Dai, and G. C. Fu, J. Am. Chem.
Soc., 122, 4020 (2000). b) A. F. Littke and G. C. Fu, Angew.
Chem., Int. Ed., 37, 3387 (1998). c) D. W. Old, J. P. Wolfe, and S.
L. Buchwald, J. Am. Chem. Soc., 120, 9722 (1998). d) J. P. Wolfe
and S. L. Buchwald, Angew. Chem., Int. Ed., 39, 2413 (1999). e)
J. P. Wolfe, R. A. Singer, B. H. Yang, and S. L. Buchwald, J. Am.
Chem. Soc., 121, 9550 (1999). f) X. Bei, H. W. Turner, W. H.
Weinberg, and A. S. Guram, J. Org. Chem., 64, 6797 (1999). g)
C. Zhang, J. Huang, M. L. Trudell, and S. P. Nolan, J. Org. Chem.,
64, 3804 (1999). h) A. Zapf, A. Ehrentraut, and M. Beller, Angew.
Chem., Int. Ed., 39, 4153 (2000).
27 Cross-coupling reaction of sterically hindered carboxylic
anhydrides such as pivalic anhydride with organoboronic acids is
known to proceed ineffectively, Ref. 7.
28 The decarbonylation of the (phenylglyoxyloyl)palladium
complex takes place readily in organic solvents under mild condi-
tion, giving the (benzoyl)palladium complex. F. Ozawa, T.
Sugimoto, T. Yamamoto, and A. Yamamoto, Organometallics, 3,
692 (1984).
17 For a recent review on palladium-catalyzed cross-coupling
reaction of organoboron compounds. a) N. Miyaura and A.
Suzuki, Chem. Rev., 95, 2457 (1995). b) A. Suzuki, J. Organomet.
Chem., 576, 147 (1999). c) A. Suzuki, “Metal-catalyzed Cross-
coupling Reactions,” ed by F. Diederich and P. J. Stang, Wiley-
VCH, Weinheim, (1998), pp. 49–97.
18 a) T. Ishiyama, N. Miyaura, and A. Suzuki, Bull. Chem.
Soc. Jpn., 64, 1999 (1991). b) T. Ishiyama, H. Kizaki, N.
Miyaura, and A. Suzuki, Tetrahedron Lett., 34, 7595 (1993). c)
M. Ishikura and M. Terashima, J. Org. Chem., 59, 2634 (1994). d)
T. Ishiyama, N. Miyaura, and A. Suzuki, Tetrahedron Lett., 32,
6923 (1991). e) T. Ishiyama, M. Murata, A. Suzuki, and N.
Miyaura, J. Chem. Soc., Chem. Commun., 1995, 295. f) Y.
Wakita, T. Yasunaga, M. Akita, and M. Kojima, J. Organomet.
Chem., 301, C17 (1986). g) T. Kondo, Y. Tsuji, and Y. Watanabe,
J. Organomet. Chem., 345, 397 (1988). h) R. Grigg, J. Redpath,
V. Sridharan, and D. Wilson, Tetrahedron Lett., 35, 7661 (1994).
19 a) M. Haddach and J. R. McCarthy, Tetrahedron Lett., 40,
3109 (1999). b) N. A. Bumagin and D. N. Korolev, Tetrahedron
Lett., 40, 3057, (1999). c) C. S. Cho, K. Itotani, and S. Uemura, J.
Organomet. Chem., 443, 253, (1993). d) G. W. Kabalka, R. R.
Malladi, D. Tejedor, and S. Kelley, Tetrahedron Lett., 41, 999
(2000). e) H. Chen and M.-Z. Deng, Org. Lett., 2, 1649 (2000).
20 L. S. Liebeskind and J. Srogl, J. Am. Chem. Soc., 122,
11260 (2000).
29 Palladium-catalyzed cross-coupling reactions with sodium
arylborates have been reported. a) P. G. Ciattini, E. Morera, and
G. Ortar, Tetrahedron Lett., 33, 4815 (1992). b) J.-Y. Legros and
J.-C. Fiaud, Tetrahedron Lett., 31, 7453 (1990). c) Ref. 19 c).
30 Palladium catalyzed cross-coupling reactions with organic
electrophiles with 2-aryl-1,3,2-dioxaborinane derivatives is known
to proceed effectively. a) T. Watanabe, N. Miyaura, and A.
Suzuki, Synlett., 1992, 207. b) T. Moriya, N. Miyaura, and A.
Suzuki, Synlett., 1994, 149.
31 a) B. H. Lipshutz, J. A. Sclafani, and P. A. Blomgren, Tet-
rahedron, 56, 2139 (2000). b) G. Marck, A. Villiger, and R.
Buchecker, Tetrahedron Lett., 35, 3277 (1994). c) B. H. Lipshutz
and P. A. Blomgren, J. Am. Chem. Soc., 121, 5819 (1999). d) B.
H. Lipshutz, T. Tomioka, P. A. Blomgren, and J. A. Sclafani, In-
org. Chim. Acta, 296, 164 (1999). e) R. Rossi, F. Bellina, A.
Carpita, and R. Gori, Synlett, 1995, 344. f) L. Bleicher and N. D.
P. Cosford, Synlett, 1995, 1115. g) G. P. Roth and V. Farina, Tet-
rahedron Lett., 36, 2191 (1995).
21 Cross-coupling reaction of thioesters with organoboronic
acid anhydrides in the presence of [Pd(PPh3)4] and a base such as
K3PO4 has been reported. B. Zeysing, C. Gosch, and A. Terfort,
32 Decarboxylation of methyl carbonato ligand in (methyl
carbonato)palladium complex to give (methoxo)palladium com-
plex was reported. For reviews see: a) J. Tsuji and I. Minami, Acc.

R. Kakino et al.
Bull. Chem. Soc. Jpn., 75, No. 6 (2002) 1345
Chem. Res., 20, 140 (1987). b) J. Tsuji, Tetrahedron, 42, 4361
(1985). Fundamental study: F. Ozawa, T.-il Son, S. Ebina, K.
Osakada, and A. Yamamoto, Organometallics, 11, 171 (1992).
33 A similar phenomenon has been reported for the cross-cou-
pling reaction of 2-propynyl carbonates with para-substituted
phenylborates in the presence of [Pd(PPh3)4]. Ref. 30 b).
34 a) T. Ishiyama, M. Murata, and N. Miyaura, J. Org. Chem.,
60, 7508 (1995). b) N. Miyaura, K. Yamada, H. Suginome, and A.
Suzuki, J. Am. Chem. Soc., 107, 972 (1985). c) Ref. 17.
Chem., 60, 7612 (1995). g) G. Bartoli, C. Cimarelli, and G.
Palmieri, Tetrahedron Lett., 32, 7091 (1991). h) M. Yamaguchi,
K. Shibato, S. Fujiwara, and I. Hirao, Synthesis, 1986, 421. i) S.
Fukuoka, H. Nanri, T. Katsuki, and M. Yamaguchi, Tetrahedron
Lett., 28, 6205 (1987). j) P. G. Ciattini, E. Morera, and G. Ortar,
Tetrahedron Lett., 32, 6449 (1991). k) L. Delaude, A. M. Masdeu,
and H. Alper, Synthesis, 1994, 1149, and references cited therein.
37 L. J. Gooβen, and K. Ghosh, Angew. Chem., Int. Ed., 40,
3458 (2001).
35 Reports on palladium-catalyzed cross-coupling reaction of
organic compounds with organoboron reagents in the absence of a
base. a) F. Sasaya, N. Miyaura, and A. Suzuki, Bull. Korean
Chem. Soc., 8, 329 (1987). b) Ref. 7, 8, 20, 23, 30 b), 37, 38.
36 Representative preparative methods of α, β-alkynyl ketone.
a) Y. Tohda, K. Sonogashira, and N. Hagihara, Synthesis, 1977,
777. b) T. Kobayashi and M. Tanaka, J. Chem. Soc., Chem. Com-
mun., 1981, 333. c) P. Li, W. M. Fong, L. C. F. Chao, S. H. C.
Fung, and I. D. Williams, J. Org. Chem., 66, 4087 (2001). d)
S.-K. Kang, K.-H. Lim, P.-S. Ho, and W.-Y. Kim, Synthesis, 1997,
874. e) V. B. Hegde, J. M. Renga, and J. M. Owen, Tetrahedron
Lett., 42, 1847 (2001). f) A. R. Katritzky and H. Lang, J. Org.
38 L. J. Gooβen, and K. Ghosh, Chem. Commun., 2001, 2084.
39 D. R. Coulson, Inorg. Synth., 13, 121 (1972).
40 V. V. Grushin, C. Bensimon, and H. Alper, Inorg. Chem.,
33, 4804 (1994).
41 T. Ukai, H. Kawazura, Y. Ishii, J. J. Bonnet, and J. A. Ibers,
J. Organomet. Chem., 65, 253 (1974).
42 C. S. Cho, Y. Yoshimori, and S. Uemura, Bull. Chem. Soc.
Jpn., 68, 950 (1995).
43 T. Satoh, T. Itaya, K. Okuro, M. Miura, and M. Nomura, J.
Org. Chem., 60, 7267 (1995).
44 Y. D. Gong, H. Tanaka, N. Iwasawa, and K. Narasaka, Bull.
Chem. Soc. Jpn., 71, 2181 (1998).