Palladium-catalyzed reactions of arylboron compounds with carboxylic acid chlorides

Article abstract of DOI:10.1023/B:RUCB.0000030812.95602.0a

Reactions of sodium tetraarylborates and arylboronic acids with acyl chlorides in the presence of palladium salts afford non-symmetrical ketones in high yields under mild conditions.

Full text of DOI:10.1023/B:RUCB.0000030812.95602.0a

364
Russian Chemical Bulletin, International Edition, Vol. 53, No. 2, pp. 364—369, February, 2004
Palladiumꢀcatalyzed reactions of arylboron compounds
with carboxylic acid chlorides
D. N. Korolev and N. A. Bumaginꢀ
Department of Chemistry, M. V. Lomonosov Moscow State University,
Leninskie Gory, 119992 Moscow, Russian Federation.
Fax: +7 (095) 939 0126. Eꢀmail: bumagin@org.chem.msu.su
Reactions of sodium tetraarylborates and arylboronic acids with acyl chlorides in the
presence of palladium salts afford nonꢀsymmetrical ketones in high yields under mild conꢀ
ditions.
Key words: crossꢀcoupling, organoboron compounds, palladium, synthesis of ketones, acyl
chlorides.
Crossꢀcoupling of organoboron compounds with orꢀ
none from Ph4BNa and PhCOCl using various catalysts,
ganic electrophiles catalyzed by palladium and nickel
complexes (the Suzuki reaction) is currently one of the
most attractive methods for the formation of new carꢀ
bon—carbon bonds, which is widely used in organic synꢀ
thesis.1 In water or waterꢀorganic solvent mixtures, the
Suzuki reaction is very effectively catalyzed by palladium
salts PdX2 containing no phosphine ligands.2 "Ligandꢀ
free" palladium was successfully used as a catalyst for
reactions of sterically hindered tris(1ꢀnaphthyl)borane
with aryl halides and diaryliodonium salts.3 It was interꢀ
esting to apply this approach to the synthesis of nonꢀ
symmetrical ketones by reactions of organoboron comꢀ
pounds with acyl chlorides as electrophilic reagents. This
approach has been employed4 for acyldeboration of soꢀ
dium tetraphenylborate with various RCOCl in THF in
the presence of Pd(PPh3)4 at 25 °C. However, under these
conditions, only one phenyl group of Ph4BNa is involved
in the reaction. Later, it was shown that arylboronic acids5
and triorganoboranes6 can also be used in crossꢀcoupling
with acyl chlorides under similar conditions. Earlier, we
found that in the presence of ligandꢀfree palladium, soꢀ
dium tetraarylborates and arylboronic acids react with
acyl chlorides under very mild conditions to give nonꢀ
symmetrical ketones in high yields.7 According to the
published data,8 the Suzuki reaction catalyzed by phosꢀ
phine complexes of palladium requires more drastic conꢀ
ditions and proceeds more slowly. In the present work,
the synthetic aspects of this reaction and some of its speꢀ
cific features are described in detail.
bases, and solvents (Scheme 1, Table 1). In the presence
of 1 mol. % Pd(OAc)2 and Na2CO3 (1.5 equiv.), the
reaction smoothly proceeded at room temperature in acꢀ
etone, 1,4ꢀdioxane, DMF, and THF to give benzopheꢀ
none in 79—96% yield over 4 to 6 h (see Table 1, enꢀ
tries 1—4). With PdCl2 as the catalyst, the reaction time
was 8 h and the yield decreased to 74% (entry 5). It should
be emphasized that in the presence of Na2CO3, all the
four Ph groups of Ph4BNa are involved in the reaction (as
distinct from the previous data4).
Scheme 1
i. [Pd], Na2CO3, 20 °C.
In dichloromethane, chloroform, benzene, and toluꢀ
ene, even in the presence of a base and a phaseꢀtransfer
catalyst (5 mol. % Bu4NBr), the yield of benzophenone
does not exceed 24%, which suggests that acyldeboration
involves only one Ph group of Ph4BNa. A possible reason
is that these solvents poorly solvate Na2CO3, which imꢀ
pedes its reaction with organoboron compounds (see
Table 1, entries 6—9). Coordination of the base to the
boron atom is the key factor that determines the effiꢀ
ciency of the crossꢀcoupling of organoboron compounds
with electrophilic agents.9
Other bases (K2CO3, K3PO4, Ba(OH)2, and Ag2CO3)
can also be used (entries 10—13); in the presence of
Ba(OH)2, the reaction is completed in 4 h to give benꢀ
zophenone in quantitative yield (entry 13). In all cases,
all of the four Ph groups of sodium tetraphenylborate are
transferred. In the absence of a base, the yield of the
ketone is 23%, which suggests the transfer of only one Ph
Results and Discussion
1. Acyldeboration of sodium tetraarylborates
In a search for the optimum reaction conditions in
anhydrous organic solvents, we synthesized benzopheꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 350—355, February, 2004.
1066ꢀ5285/04/5302ꢀ0364 © 2004 Plenum Publishing Corporation

Synthesis of nonꢀsymmetrical ketones
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 2, February, 2004
365
Table 1. Effects of the solvent, base, and catalyst on the reaction of benzoyl chloride with sodium
tetraphenylboratea
Entry
Solvent
Base
Catalyst
τ/h
Yieldb (%)
1
2
3
4
5
6
7
8
Acetone
THF
DMF
1,4ꢀDioxane
Acetone
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
K2CO3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
6
5
4
6
8
40
40
40
40
6
5
5
4
5
40
40
40
40
96
79
86
85
74
19
22
20
24
94
93
84
96
23
21
18
15
—
Dichloromethanec
Chloroformc
Benzenec
Toluenec
Acetone
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2(PPh3)2
PdCl2(dppf)
Pd(dba)2
9
10
11
12
13
14
15
16
17
18
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
K3PO4
Ba(OH)2
Ag2CO3
—
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Pd blackd
a PhCOCl (1 mmol), a base (1.5 mmol), Ph4BNa (0.25 mmol), a solvent (5 mL), and a catalyst
(1 mol. %), 20 °C, argon.
b Preparative yield.
c In the presence of Bu4NBr (0.05 mmol, 5 mol. %).
d Powder (particle size 0.1—0.5 mm).
group (entry 14). Nearly the same yield of benzophenone
was attained4 in THF with Pd(PPh3)4 as the catalyst, but
the reaction time was 20 h.
Unsatisfactory results were obtained in the presence
of Pd(dba)2 (dba is dibenzylideneacetone) and Pd black
(entries 17, 18), although Pd black is known2b to effecꢀ
tively catalyze the crossꢀcoupling of 3ꢀiodobenzoic acid
with PhB(OH)2 (20 °C, 3 h, 80%).
Phosphine complexes of palladium, PdCl2(PPh3)2 and
PdCl2(dppf), which are widely used in various versions of
the Suzuki reaction,1 proved to be significantly less effiꢀ
cient as precursors of a catalyst than ligandꢀfree pallaꢀ
dium (entries 15, 16). The reaction products are benꢀ
zophenone (yield 18—21%, corresponding to the transfer
of only one Ph group of sodium tetraphenylborate) and
benzoic anhydride, which undergoes no further conꢀ
versions.
In the presence of water, the reaction rate and the
yield are only slightly sensitive to the nature of an organic
solvent. For instance, in homogeneous water—THF and
water—DMF mixtures (see Table 2, entries 6, 7), the
reaction occurs as in aqueous acetone, and benzopheꢀ
none is obtained in quantitative yield in 1 h. In contrast,
in the twoꢀphase toluene—water system (see Table 2, enꢀ
try 8) even in the presence of a phaseꢀtransfer catalyst, the
yield of the ketone is substantially lower, probably beꢀ
cause of hydrolysis as a side reaction.
The use of other bases (K3PO4 and Ba(OH)2) does not
change the reaction pattern significantly (see Table 2,
entries 12, 13). The reaction occurs also without any base
(entry 14).
Note that benzoic anhydride is also formed in all reacꢀ
tions carried out in aqueous media, probably as a result of
the partial hydrolysis of PhCOCl (see Table 2).
We found that acyldeboration can be substantially acꢀ
celerated by adding water in the case of slowly hydrolyzꢀ
able acyl chlorides (Table 2). For instance, the reaction of
PhCOCl with Ph4BNa in anhydrous acetone is comꢀ
pleted in 6 h (see Table 2, entry 1), while its duration in
80—90% aqueous acetone is 1 to 1.5 h (see Table 2,
entries 2—4). At a water content of 50 vol. %, the reaction
is completed in 15 min. Surprisingly, even in water, in
which benzoyl chloride is virtually insoluble, the reaction
proceeds more rapidly than in dry acetone (see Table 2,
entry 5).
The amount and subsequent transformations of benꢀ
zoic anhydride depend on the type of the Pd catalyst. In
the presence of PdCl2(PPh3)2, Pd(dba)2, and Pd black,
benzoyl chloride forms benzoic anhydride very rapidly
(in 15—20 min) and quantitatively, while benzophenone
is detected in trace amounts. Then, benzoic anhydride
reacts with organoboron compounds "Ph—B" over 4—5 h
(entries 9—11) to give benzophenone in 48—56% yield
(with respect to the starting benzoyl chloride; Scheme 2,
pathway a); this is a virtually quantitative yield with reꢀ
spect to one acyl group of benzoic anhydride.

366
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 2, February, 2004
Korolev and Bumagin
Table 2. Reaction of benzoyl chloride with Ph4BNa in aqueous organic mediaa
Entry
Solvent
Base
Catalyst
τ/h
Yieldb (%)
1
2
3
4
5
6
7
8
Acetone
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
K3PO4
Pd(OAc)2
PdCl2
PdCl2
PdCl2
PdCl2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2(PPh3)2
Pd(dba)2
Pd blackd
PdCl2
6
1
1.5
0.25
5
1
1
1
5
4
5
1
1
96
95
93
98
98
96
96
67c
56
55
48
97
96
29
Acetone—water (4 : 1)
Acetone—water (10 : 1)
Acetone—water (1 : 1)
Water
THF—water (4 : 1)
DMF—water (4 : 1)
Toluene—water (2 : 1)
Acetone—water (4 : 1)
Acetone—water (4 : 1)
Acetone—water (4 : 1)
Acetone—water (4 : 1)
Acetone—water (4 : 1)
Acetone—water (4 : 1)
9
10
11
12
13
14
Ba(OH)2
—
PdCl2
PdCl2
5
a PhCOCl (1 mmol), Ph4BNa (0.25 mmol), a base (1.5 mmol), a catalyst (1 mol. %), a solvent (5 mL),
20 °C, argon.
b Preparative yield.
c In the presence of Bu4NBr (0.05 mmol, 5 mol. %).
d Powder (particle size 0.1—0.5 mm).
Scheme 2
Table 3. Synthesis of aryl ketones from RCOCl and Ar4BNa*
Entry
Ar
RCOCl
τ/h
Yield**
(%)
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
С6H5COCl
4ꢀCH3C6H4COCl
2ꢀBrC6H4COCl
6
5.5
5
5
2.5
3
1
1
1
5 min
20 min
2.5
6
96
84
92
86
64
96
66
88
95
98
84
61
86
59
4ꢀBrC6H4COCl
Acidification of the reaction mixture with HCl results
3ꢀNO2C6H4COCl
(E)ꢀPhCH=CHCOCl
CH2=C(CH3)COCl
2ꢀFuroyl chloride
2ꢀThenoyl chloride
nꢀC7H15COCl
C6H5OCH2COCl
3ꢀNO2C6H4COCl
4ꢀCH3C6H4COCl
3ꢀNO2C6H4COCl
in the formation of benzoic acid in 40—45% yield.
In the presence of ligandꢀfree palladium, benzoyl chloꢀ
ride is completely converted into benzophenone (90%)
and benzoic anhydride (∼10%) in 5 min. After 1 h, the
yield of benzophenone becomes nearly quantitative, and
benzoic acid is detected in trace amounts (<1%) (entry 2).
These data suggest that the reaction of benzoic anhydride
with the phenylboron compound "Ph—B" catalyzed by
ligandꢀfree palladium proceeds in a nonꢀtrivial manner
with involvement of both benzoyl groups (Scheme 2,
pathway b).
Under the optimum conditions found (acetone,
Na2CO3, 1 mol. % Pd(OAc)2, 20 °C), Ar4BNa easily
reacts with acid chlorides of alkanoic, α,βꢀunsaturated,
and substituted benzoic and heterocyclic acids (Table 3).
Alkanoic acid chlorides react most rapidly (Scheme 3) to
9
10
11
12
13
Ph
Ph
4ꢀMeC6H4
4ꢀMeC6H4
14 4ꢀEtOC6H4
1.5
* PhCOCl (1 mmol), Ar4BNa (0.25 mmol), Na2CO3 (1.5 mmol),
Pd(OAc)2 (1 mol. %), acetone (5 mL), 20 °C, argon.
** Preparative yield.
give alkyl phenyl ketones in high yields in 5 to 20 min (see
Table 3, entries 10, 11).
Reactions with α,βꢀunsaturated acid chlorides are
completed in 1 to 3 h affording the corresponding ketones
in quantitative yields (Scheme 4).
Scheme 3
2ꢀFuroyl and 2ꢀthenoyl chlorides also easily react with
Ph4BNa (Scheme 5).
Aroyl chlorides containing electronꢀdonating and weak
electronꢀwithdrawing substituents react with Ph4BNa
without difficulty (see Table 3). However, the yields of
aryl 3ꢀnitrophenyl ketones from 3ꢀnitrobenzoyl chloride
i. [Pd], 5—20 min, 84—100%.
R = nꢀC6H13, PhO

Synthesis of nonꢀsymmetrical ketones
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 2, February, 2004
367
Scheme 4
Table 4. Synthesis of nonꢀsymmetrical ketones from benzoyl
chloride and arylboronic acids ArB(OH)2
a
Entry
Ar
τ/h
Preparative
yield (%)
1
2
3b
4c
5d
6
7
8
9
2ꢀMeC6H4
3ꢀMeC6H4
3ꢀMeC6H4
3ꢀMeC6H4
3ꢀMeC6H4
2
1.5
72
28
80
2
1
1
1.5
80
95
59
79
79
79
96
85
76
i. [Pd], 1—3 h, 92—96%.
R1 = Ph, R2 = H; R1 = H, R2 = Me
4ꢀMeC6H4
Scheme 5
3ꢀNO2ꢀ4ꢀMeC6H4
5ꢀBromoꢀ2ꢀthienyl
5ꢀFormylꢀ3ꢀthienyl
a
PhCOCl (1 mmol), ArB(OH)2 (1.05 mmol), Na2CO3
(1.5 mmol), PdCl2 (1 mol. %), acetone—water (3 : 1, 5 mL),
i. [Pd], 1 h, 88—95%.
20 °C, argon.
b PdCl2(PPh3)2 (1 mol. %).
c In dry acetone.
d In dry THF.
X = O, S
are somewhat lower (59—64%), and 3ꢀnitrobenzoic acid
is detected in the reaction mixture upon its workup.
In the reactions of 2ꢀ and 4ꢀbromobenzoyl chlorides,
the bromine atoms remain unaffected, and the correꢀ
sponding bromobenzophenones were obtained in high
yields (see Table 3, entries 3, 4).
Scheme 7
It is noteworthy that all possible intermediates of the
acyldeboration of Ph4BNa, namely, Ph3B, Ph2B(OH),
and PhB(OH)2, were detected as transient species in the
reaction mixtures by TLC (Scheme 6). Obviously, they
also serve, once formed, as sources of the phenyl group
for acyldeboration.
i. [Pd], 20 °C, up to 96%.
It was demonstrated with the reaction of benzoyl chloꢀ
ride with 4ꢀmethylꢀ3ꢀnitrophenylboronic acid as an exꢀ
ample that the NO2 group remains intact during the reacꢀ
tion (see Table 4, entry 7).
Because of very mild conditions of acyldeboration,
thenoylboronic acids with such substituents as bromine
and a formyl group can be successfully used in crossꢀ
coupling (entries 8, 9).
Scheme 6
As in the reactions of sodium tetraphenylborate, the
reaction rate and yield significantly decrease when phosꢀ
phine complexes of palladium are used as catalysts.
Unlike Ph4BNa, arylboronic acids in anhydrous meꢀ
dia react much more slowly than in aqueous solvents
(cf. entries 2, 4, 5). It should be noted that the reaction of
PhCOCl with PhB(OH)2 in toluene in the presence of
5 mol. % Pd(PPh3)4 at 100 °C for 16 h affords benzopheꢀ
none in 80% yield.5a
To involve arylboronic acids in reactions with reacꢀ
tive, easily hydrolyzable acyl chlorides, optimum reaction
conditions in anhydrous media should be found. For this
purpose, we studied model reactions of benzoyl chloride
with 4ꢀtolylboronic and 4ꢀfluorophenylboronic acids in
the presence of 1 mol. % Pd(OAc)2 and various bases
(Table 5). Sodium carbonate, which acts well in reactions
with Ph4BNa, does not provide high yields (entry 1).
Trialkylamines or pyridine (i.e., the bases forming soluble
adducts with boric acid under these conditions) increase
the reaction rate and the yield of the ketone. As in aqueꢀ
2. Acyldeboration of arylboronic acids
Arylboronic acids are the most stable and most accesꢀ
sible organoboron compounds. For this reason, we studꢀ
ied their reactions with carboxylic acid chlorides.
The acyldeboration of arylboronic acids with benzoyl
chloride was carried out in aqueous 75% acetone in the
presence of 1 mol. % PdCl2 and Na2CO3 in an inert atmoꢀ
sphere at 20 °C. Under these conditions, arylꢀ and hetꢀ
arylboronic acids easily react with benzoyl chloride to give
substituted benzophenones and aryl hetaryl ketones in high
yields (Scheme 7, Table 4). For instance, the reactions of
PhCOCl with isomeric tolylboronic acids are completed
in 1.5 to 2 h and afford 2ꢀ, 3ꢀ, and 4ꢀmethylbenzophenones
in 79—95% yields (entries 1, 2, 6).

368
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 2, February, 2004
Korolev and Bumagin
Table 5. Reactions of arylboronic acids with benzoyl chloride in
organomagnesium or ꢀlithium compounds and B(OMe)3. Carꢀ
boxylic acid chlorides were prepared from carboxylic acids and
SOCl2.11 Solvents were purified using standard procedures.
Reactions of acyl chlorides with sodium tetraarylborates in
anhydrous media. Benzoyl chloride (0.12 mL, 1 mmol), NaBPh4
(0.09 g, 0.26 mmol), dry Na2CO3 (0.159 g, 1.5 mmol),
dry acetone (5 mL), and PdCl2 (or Pd(OAc)2) (0.0022 g,
1•10–5 mol L–1, 1 mol. %) were placed in a Schlenk vessel in an
argon atmosphere. The reaction mixture was stirred at ≈20 °C
for 6 h. The course of the reaction was monitored by TLC
(Silufol UVꢀ254; hexane—ether, 4 : 1). After the reaction was
over, the mixture was diluted with water (20—25 mL) and the
products were extracted with ether (3×15 mL). The combined
organic extracts were dried with CaCl2 and the solvent was
removed to give benzophenone (0.174 g, 96%).
The above procedure was used to study the effects of the
solvent, base, and catalyst on the reaction of Ph4BNa with
PhCOCl (see Table 1) and to carry out the reactions of Ar4BNa
with RCOCl (see Table 3).
Reaction of benzoyl chloride with Ph4BNa in aqueous organic
media. Benzoyl chloride (0.12 mL, 1 mmol), NaBPh4 (0.09 g,
0.26 mmol), aqueous 0.15 M Na2CO3 (1 mL), acetone (4 mL),
and aqueous 0.1 M PdCl2 (0.1 mL) were placed in a Schlenk
vessel in an argon atmosphere. The reaction mixture was stirred
at ≈20 °C for 1 h. The reaction mixture was worked up as deꢀ
scribed above to give benzophenone (0.172 g, 95%).
anhydrous mediaa
Entry Arylboronic acid
Base
τ/h
Yieldb
(%)
1
4ꢀMeC6H4B(OH)2
4ꢀMeC6H4B(OH)2
4ꢀFꢀC6H4B(OH)2
4ꢀFꢀC6H4B(OH)2
Na2CO3
Na2CO3
CH3COONa
NaF
48
24
150
150
48
48
5 min
16
32
74
67
57
81
72
64
24
5
2c
3
4
5
6
7d
8
9e
10e
11e
4ꢀMeC6H4B(OH)2 CH3COONa
4ꢀMeC6H4B(OH)2
4ꢀMeC6H4B(OH)2
4ꢀMeC6H4B(OH)2
4ꢀMeC6H4B(OH)2 Triethylamine
4ꢀMeC6H4B(OH)2 Tributylamine
NaF
NaF
Ag2O
1
12
4
74
14
4ꢀMeC6H4B(OH)2
Pyridine
a PhCOCl (1 mmol), ArB(OH)2 (1.05 mmol), a base (1.5 mmol),
Pd(OAc)2 (1 mol. %), dry acetone (5 mL), 20 °C, argon.
b Preparative yield.
c In dry DMF.
d Without a solvent in a microwave oven (radiation power 300 W).
e In the presence of 3 mmol of the base.
ous organic media, the reaction in anhydrous solvents is
mainly impeded by the formation of benzoic anhydride,
even with thoroughly dried reagents. Under these condiꢀ
tions, the resulting anhydride seems to be inert in oxidaꢀ
tive addition and is isolated as a byꢀproduct.
Reactions of PhCOCl with Ph4BNa in other aqueous orꢀ
ganic media were carried out analogously (see Table 2).
A similar procedure was used to synthesize nonꢀsymmetrical
phenyl ketones from benzoyl chloride and arylboronic acids,
with the exception that NaBPh4 is replaced by an arylboronic
acid (1.05 mmol) (see Table 4).
The most convenient system for acyldeboration in anꢀ
hydrous media is dry acetone and tributylamine as a base
(see Table 5, entry 10). More basic but less bulky triethylꢀ
amine and pyridine are less suitable under these condiꢀ
tions since they rapidly react with PhCOCl to give acꢀ
etoneꢀinsoluble adducts PhCOCl•Et3N and PhCOCl•Py,
respectively. In this case, the yield of the ketone is low
(see Table 5, entries 9, 11). The use of sodium fluoride or
acetate increases the yield of the ketone. However, the
reaction time is noticeably larger and the degree of hydroꢀ
lytic cleavage of the acid chloride changes considerably
and is irreproducible, and the yield of the product is also
irreproducible.
Thus, nonꢀsymmetrical aromatic ketones were syntheꢀ
sized in high yields from easily accessible starting reagents,
namely, arylboron compounds and carboxylic acid chloꢀ
rides. The high catalytic activity of palladium salts in aqueꢀ
ous organic media makes the method economically atꢀ
tractive. The optimum conditions are mild, which allows
functionalized substrates to be employed in this reaction.
Syntheses of nonꢀsymmetrical phenyl ketones by the reacꢀ
tions of benzoyl chloride with arylboronic acids in an anhydrous
medium. Benzoyl chloride (0.12 mL, 1 mmol), 4ꢀtolylboronic
acid (0.1426 g, 1.05 mmol), dry acetone (5 mL), tributylamine
(0.36 mL, 1.5 mmol), and Pd(OAc)2 (0.0022 g) were placed in a
Schlenk vessel in an argon atmosphere. The reaction mixture
was stirred at ≈20 °C for 12 h. The course of the reaction was
monitored by TLC (Silufol UVꢀ254; hexane—ether, 4 : 1). After
the reaction was over, the mixture was diluted with water
(20—25 mL) and the products were extracted with ether
(3×15 mL). The combined organic extracts were washed with
dilute HCl (1 : 4) (3×15 mL) and dried with CaCl2. The solvent
was removed to give 4ꢀmethylbenzophenone (0.145 g, 74%).
An analogous procedure was used to study the effects of the
solvent and the base on the reactions of PhCOCl with arylboronic
acids (see Table 5).
All the compounds obtained were characterized by 1H NMR
spectra, melting points, and elemental analysis data. Analytical
samples of solid compounds were prepared by recrystallization
from hexane or a hexane—acetone mixture. Analytical samples
of liquid compounds (at room temperature) were prepared by
passing their ethereal solutions through a layer of silica gel (2 cm)
with subsequent removal of the solvent. 2,4ꢀDinitrophenylꢀ
hydrazones of the ketones were prepared as follows.12 Conc.
H2SO4 (0.5 mL) was slowly added to a suspension of 2,4ꢀdiꢀ
nitrophenylhydrazine (0.4 g) in 10 mL of ethanol. The mixture
was heated until the solution became transparent, and a ketone
(∼0.2 g) was added to the hot solution. After 2 to 10 min, 2,4ꢀdiꢀ
nitrophenylhydrazone precipitated on cooling.
Experimental
1
H NMR spectra were recorded on a Bruker AMꢀ400 specꢀ
trometer (400 MHz) in CDCl3 and DMSOꢀd6. Chemical shifts
were measured with reference to residual protons of the solꢀ
vents. Arylboronic acids and sodium tetraarylborates were preꢀ
pared according to known procedures10 from the corresponding

Synthesis of nonꢀsymmetrical ketones
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 2, February, 2004
369
Benzophenone, m.p. 47—48 °C (Ref. 13: m.p. 48—49 °C).
2,4ꢀDinitrophenylhydrazone, m.p. 237—238 °C (Ref. 13:
m.p. 238 °C).
2ꢀMethylbenzophenone, oil. 2,4ꢀDinitrophenylhydrazone,
m.p. 184—189 °C (Ref. 14: m.p. 184—190 °C).
3ꢀMethylbenzophenone, oil. 2,4ꢀDinitrophenylhydrazone,
m.p. 221—222 °C (Ref. 14: m.p. 221 °C).
(c) S. Kotha, K. Lahiri, and D. Kashinath, Tetrahedron,
2002, 58, 9633.
2. V. V. Bykov and N. A. Bumagin, Izv. Akad. Nauk, Ser.
Khim., 1997, 1399 [Russ. Chem. Bull., 1997, 46, 1344 (Engl.
Transl.)].
3. N. A. Bumagin and D. A. Tsarev, Tetrahedron Lett., 1998,
39, 8155.
4ꢀMethylbenzophenone, m.p. 59—60 °C (Ref. 14: m.p.
59—60 °C). 2,4ꢀDinitrophenylhydrazone, m.p. 204—205 °C
(Ref. 13: m.p. 202 °C).
4. C. S. Cho, K. Itotani, and S. Uemura, J. Organomet. Chem.,
1993, 443, 253.
5. (a) M. Haddach and J. R. McCarthy, Tetrahedron Lett.,
1999, 40, 3109; (b) Y. Urawa and K. Ogura, Tetrahedron
Lett., 2003, 44, 271; (c) H. Chen and M. Z. Deng, Org. Lett.,
2000, 2(12), 1649.
6. G. W. Kabalka, R. R. Malladi, D. Tejedor, and S. Kelley,
Tetrahedron Lett., 2000, 41, 999.
7. N. A. Bumagin and D. N. Korolev, Tetrahedron Lett., 1999,
40, 3057.
4ꢀFluorobenzophenone, m.p. 46—48 °C (Ref. 14: m.p.
48.2—48.7 °C). 2,4ꢀDinitrophenylhydrazone, m.p. 230—231 °C
(Ref. 15: m.p. 230—233 °C).
1
2ꢀBromobenzophenone, oil (Ref. 14: m.p. 42 °C). H NMR
(DMSOꢀd6), δ: 7.45—7.80 (m, 6 H, C6H4Br, mꢀH (Ph));
7.85—7.95 (m, 3 H, oꢀ and pꢀH (Ph)).
4ꢀBromobenzophenone, m.p. 80—82 °C (Ref. 14: m.p. 82 °C).
3ꢀNitrobenzophenone, m.p.. 92—94 °C (Ref. 14: m.p. 92 °C).
Chalcone (benzylideneacetophenone), m.p. 57—58 °C
(Ref. 14: m.p. 58 °C). 2,4ꢀDinitrophenylhydrazone, m.p.
242—245 °C (Ref. 13: m.p. 244 °C).
2ꢀMethylꢀ1ꢀphenylpropꢀ2ꢀenꢀ1ꢀone, oil (Ref. 16: oil).
1H NMR (DMSOꢀd6), δ: 2.05 (s, 3 H, Me); 6.01 (s, 1 H,
=CH2); 6.19 (s, 1 H, =CH2); 7.33—7.42 (m, 5 H, Ph).
2ꢀBenzoylfuran, oil (Ref. 14: oil; Ref. 17: m.p. 42—44 °C).
1H NMR (DMSOꢀd6), δ: 6.79 (br.s, 1 H, 4ꢀH (Fur)); 7.40—7.55
(m, 4 H, 3ꢀH (Fur), mꢀ and pꢀH (Ph)); 8.01—8.07 (m, 3 H,
5ꢀH (Fur), oꢀH (Ph)).
8. J. P. Genet and M. Savignac, J. Organomet. Chem., 1999,
576, 305.
9. N. Miyaura and A. Suzuki, J. Org. Chem., 1998, 63, 4726.
10. K. A. Kocheshkov and A. N. Nesmeyanov, Sinteticheskie
metody v oblasti metalloorganicheskikh soedinenii elementov
3 gruppy [Synthetic Techniques for Organometallic Comꢀ
pounds of the Group III Elements], Izdꢀvo AN SSSR, Mosꢀ
cow, 1945.
11. Organikum. Organischꢀchemisches Grundpraktikum, VEB
Deutscher Verlag der Wissenschaften, Berlin, 1990, p. 57.
12. W. Kemp, Qualitative Organic Analysis. Spectrochemical Techꢀ
niques (2nd ed.), McGrawꢀHill, London, 1982, p. 57.
13. F. L. Schneider, Qualitative Organic Microanalysis. Cognition
and Recognition of Carbon Compounds, SpringerꢀVerlag, Wien,
1964, p. 353.
2ꢀBenzoylthiophene, m.p. 54—56 °C (Ref. 18: m.p.
55—56 °C). 1H NMR (DMSOꢀd6), δ: 7.21 (br.s, 1 H,
4ꢀH (thienyl), J = 1.2 Hz); 7.50—7.70 (m, 7 H, 3ꢀ and 5ꢀH
(thienyl, Ph)).
1ꢀPhenyloctanꢀ1ꢀone, oil. 1H NMR (DMSOꢀd6), δ: 0.88 (t,
3 H, Me, J = 7.1 Hz); 1.25—1.30 (m, 10 H, 3,4,5,6,7ꢀCH2);
2.90 (t, 2 H, 2ꢀCH2, J = 7.0 Hz); 7.50 (m, 3 H, mꢀ and pꢀH (Ph));
7.95 (d, 2 H, oꢀH (Ph), J = 7.8 Hz). 2,4ꢀDinitrophenylꢀ
hydrazone, m.p. 120—122 °C (Ref. 19: m.p. 122 °C).
2ꢀPhenoxyꢀ1ꢀphenylethanꢀ1ꢀone, oil (Ref. 20: m.p.
71—72 °C). 1H NMR (DMSOꢀd6), δ: 5.32 (s, 2 H, CH2O);
6.85—6.95 (m, 3 H, oꢀ and pꢀH (PhO)); 7.40—7.60 (m, 5 H,
mꢀH (PhO), mꢀ and pꢀH (PhCO)); 8.00 (d, 2 H, oꢀH (PhCO),
J = 7.7 Hz).
4ꢀMethylꢀ3ꢀnitrobenzophenone, m.p. 129—130 °C (Ref. 14:
m.p. 130—132 °C).
2ꢀBenzoylꢀ5ꢀbromothiophene, m.p. 35—38 °C (Ref. 21: m.p.
38—39 °C).
4ꢀBenzoylthiopheneꢀ2ꢀcarbaldehyde, m.p. 75—77 °C
(Ref. 22: m.p. 74—75 °C).
14. Dictionary of Organic Compounds (5th ed.), Chapman and
Hall, New York, 1982.
15. S. S. Kulp and M. J. McGee, J. Org. Chem., 1983, 48, 4097.
16. J. Cousseau and P. Albert, J. Org. Chem., 1989, 54, 5380.
17. L. Strekowski, R. L. Wydra, M. T. Cegla, A. Czarny, and
S. Patterson, J. Org. Chem., 1989, 54, 6120.
18. G. Stadnikoff and L. Kaschtanoff, Ber., 1928, 61, 1389.
19. J. Attenburrow, J. Elks, B. A. Hems, and K. N. Speyer,
J. Chem. Soc., 1949, 510.
20. P. H. Kandanarachchi, T. Autrey, and J. A. Franz, J. Org.
Chem., 2002, 67, 7937.
21. J. K. Stille, Heng Su, P. Brechot, G. Parrinello, and L. S.
Hegedus, Organometallics, 1991, 10, 1183.
22. L. I. Belen´kii, G. P. Gromova, A. V. Kolotaev, and M. M.
Krayushkin, Khim. Geterotsikl. Soedin., 2000, 393, 315 [Chem.
Heterocycl. Compd., 2000, 393 (Engl. Transl.)].
References
1. (a) A. Suzuki, J. Organomet. Chem., 1999, 576, 147;
(b) N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457;
Received September 12, 2003;
in revised form December 17, 2003