Towards a facile synthesis of triarylethanones: Palladium-catalyzed arylation of ketone enolates under homogeneous and heterogeneous conditions

Article abstract of DOI:10.1016/j.tet.2003.12.065

The palladium-catalyzed regioselective α-monoarylation of deoxybenzoins and α,α-diarylation of acetophenones provides general, efficient access to 1,2,2-triarylethanones. After a comprehensive search for suitable experimental conditions to optimize such transformations, both reactions are alternatively conducted by means of either commercially available polymer-anchored catalysts or a very simple homogeneous catalytic system, thus avoiding the use of complex ligands. In addition, the synthesis of deoxybenzoins employing polymer-supported fibrous palladium catalysts is reported for the first time, and the excellent catalyst recycling properties suggest applicability to industrial purposes.

Full text of DOI:10.1016/j.tet.2003.12.065

Tetrahedron 60 (2004) 2393–2408
Towards a facile synthesis of triarylethanones: palladium-
catalyzed arylation of ketone enolates under homogeneous and
heterogeneous conditions
*
Fatima Churruca, Raul SanMartin, Monica Carril, Imanol Tellitu and Esther Domınguez
*
´
´
´
Kimika Organikoa II Saila, Zientzi Fakultatea, Euskal Herriko Unibertsitatea, PO Box 644, 48080 Bilbao, Spain
Received 8 October 2003; revised 17 November 2003; accepted 23 December 2003
Abstract—The palladium-catalyzed regioselective a-monoarylation of deoxybenzoins and a,a-diarylation of acetophenones provides
general, efficient access to 1,2,2-triarylethanones. After a comprehensive search for suitable experimental conditions to optimize such
transformations, both reactions are alternatively conducted by means of either commercially available polymer-anchored catalysts or a very
simple homogeneous catalytic system, thus avoiding the use of complex ligands. In addition, the synthesis of deoxybenzoins employing
polymer-supported fibrous palladium catalysts is reported for the first time, and the excellent catalyst recycling properties suggest
applicability to industrial purposes.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
work on developing heterogeneous catalytic systems made
in the last years, essentially in order to reduce the cost and
technical problems associated with removal of the catalyst
and also to increase its lifetime.5,6
Among the plethora of new methodologies provided by
palladium based catalysts, the direct insertion of an aryl
moiety next to a carbonyl group must be outlined, since such
protocol has solved a long-standing problem in synthetic
organic chemistry.1 Indeed, palladium-catalyzed a-aryla-
tion of such soft, non-organometallic nucleophiles as ketone
enolates with aryl halides avoids the need of preliminary
transformation steps or the use of stoichiometric amounts of
tin, lead or bismuth reagents.2,3
The heterogenization of homogeneous catalysts using a
suitable modification of ligands by anchoring of P- or
N-containing groups onto a polymer support has received
much attention among the catalyst-product separation
strategies developed so far, and elegant applications of
such polymer-anchored palladium catalysts to Heck, Suzuki
and Sonogashira coupling reactions have been described,
showing in some cases high overall turning-numbers by
efficient catalyst recycle.7 Nevertheless, the catalyst prepa-
ration often involves high cost/specialized techniques, and
the leaching of the catalyst due to its relative instability
under reaction conditions is also a matter of concern in a
world immersed in a race towards waste effluent mini-
mization.7a,b,e–g,8
However, depending on the substrate, complex ligand
systems are sometimes required, and several competitive
processes have been described, i.e., ortho-arylation and
uncontrolled mono/multiple arylations.4
Otherwise, despite its crucial role in synthetic organic
chemistry, arylation of ketone enolates, as well as other
modern palladium-catalyzed C–C bond-forming reactions
have not been transferred to an industrial scale, bar a few
examples.5 One of the problems that the extension of such
reactions to the large-scale synthesis of bulk chemicals must
bear is related to the fact that working with homogeneously
catalyzed systems involves costly removal of relatively
expensive palladium catalyst residues. Hence the research
Following our search for reliable synthetic protocols leading
to phenanthrofused heterocycles,9 we planned the construc-
tion of the appealing pentacyclic systems 1 and 2 from a
joint key precursor, 1,2,2-triarylethanones 3, interesting by
themselves not only for their close resemblance to
tamoxifen, the most widely used adjuvant drug therapy for
the treatment of estrogen receptor-positive breast cancer,10
but also because they have been reported as useful drugs for
the treatment of metabolic disorders.11
Keywords: Arylation; Ketones; Palladium and compounds.
*
Corresponding authors. Tel.: þ34-946015435; fax: þ34-944648500
(R.S.); tel.: þ34-946012577; fax: þ34-946012748 (E.D.);
In this paper we wish to present our advances towards the
e-mail address: qopsafar@lg.ehu.es; qopdopee@lg.ehu.es
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.12.065

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F. Churruca et al. / Tetrahedron 60 (2004) 2393–2408
mono/multiple arylations of alkyl aryl ketones 4 and 5
by means of both homogeneous and polymer-anchored
palladium catalysts, as well as a novel heterogeneously
conducted monoarylation of acetophenones featuring an
efficient catalyst-recycling.
2. Results and discussion
2.1. Selective a-monoarylation of deoxybenzoins
Taking into account that the final steps of our scheduled
approach to phenanthroderivatives 1 and 2 would probably
require mono- or polyalkoxylated substrates, we initially
envisaged that a selective a-monoarylation methodology
amenable to both electron rich deoxybenzoins 4,12 and aryl
halides 6 would constitute a convenient entry to intermedi-
ates 3. Accordingly, an array of experimental conditions
were assayed on 1,2-bis(3,4-dimethoxyphenyl)ethanone 4a
and bromobenzene 6a in order to obtain the corresponding
triarylethanone 3a.
Despite previous reports,1c,13 no target phenylated ketone
3a was obtained in the absence of ligand or by using bulky
bidentate phosphine ligands such us BINAP or DPPF.
Another catalyst (PdCl2) already used by Miura et al. to
perform the arylation of 1,2-diphenylethanone14 exhibited a
high dependence on the electronic nature of the ketone
precursor, as only poor results were obtained when applied
to model substrate 4a, even using iodobenzene 7 as the
Table 1. Selected a-arylation assays performed by homogenous palladium catalysts
Entry
Reaction conditions
Product (%)a
1
2
3
4
5
6
7
8
2 mol% Pd2dba3, NaOtBu, THF, 80 8C, 6 hb
2 mol% Pd(OAc)2, KOtBu, toluene, 90 8C, 3 hb
5 mol% Pd(OAc)2, K2CO3, toluene, 90 8C, 23 hb
4a (92)
4a (90)
4a (93)
2 mol% Pd2(dba)3, 5 mol% BINAP, KOtBu, THF, 70 8C, 6 hb
5 mol% Pd2(dba)3, 5 mol% DPPF, KOtBu, THF, 70 8C, 6 hb
5 mol% PdCl2, K2CO3, DMF, 100 8C, 6 hc
4a (98)
4a (97)
—
d
5 mol% PdCl2, Cs2CO3, DMF, 100 8C, 6 hc,e
4a (68) 3a (20)
4a (50) 3a (24)
—
5 mol% PdCl2, 20 mol% PPh3, K2CO3, DMF, 130 8C, 6 hc
5 mol% PdCl2, 20 mol% PPh3, K2CO3, DMF, 100 8C, 6 hc,e
2 mol% Pd(OAc)2, 5 mol% PPh3, K2CO3, o-xylene, 170 8C, 22 hb
5 mol% Pd(OAc)2, 5 mol% PPh3, Cs2CO3, o-xylene, 170 8C, 12 hb
2 mol% Pd(OAc)2, 5 mol% PPh3, Cs2CO3, DMF, 170 8C, 0.7 hb
2 mol% Pd(OAc)2, 8 mol% PPh3, K2CO3, o-xylene, 150 8C, 9 hf
2 mol% Pd(OAc)2, 8 mol% PPh3, Cs2CO3, DMF, 150 8C, 0.5 hf
5 mol% Pd(OAc)2, 6.25 mol% PEt3, Cs2CO3 DMF, 150 8C, 6 hb
5 mol% Pd(OAc)2, 6.25 mol% PnBu3, NaOtBu, THF, 80 8C, 6 hb
5 mol% Pd(OAc)2, 20 mol% PtBu3, Cs2CO3 DMF, 150 8C, 7 hb
5 mol% Pd(OAc)2, 6.25 mol% PtBu3, NaOtBu, THF, 80 8C, 6 hb
5 mol% Pd(OAc)2, 20 mol% P(o-tolyl)3, Cs2CO3, DMF, 150 8C, 1 hb
5 mol% Pd(OAc)2, 20 mol% P(o-tolyl)3, NaOtBu, THF, 80 8C, 6 hb
d
9
10
11
12
13
14
15
16
17
18
19
20
3a (58) 8 (31) 9 (6)
3a (23) 8 (32) 9 (25)
3a (56) 8 (38)
3a (86)
3a (89)
4a (41) 3a (32) 8 (29)
4a (96)
4a (56)-d
4a (74) 3a (12)-d
4a (67) 3a (16)
4a (91)
a
GC-MS yields of detected products measured on the basis of the starting amount of diarylketone 4a. Propiophenone was used as the internal standard.
1.3 equiv. of 6a and 2.5 equiv. of base were used.
1.2 equiv. of 6a and 1.2 equiv. of base were used.
Complex mixtures of products were obtained.
1.2 equiv. of iodobenzene 7 were used instead of 6a.
1 equiv. of 6a and 2.5 equiv. of base were used.
b
c
d
e
f

F. Churruca et al. / Tetrahedron 60 (2004) 2393–2408
Table 2. Palladium-catalyzed a-arylation of deoxybenzoins 4
2395
arylating agent. An increase of the yield of target 3a was
achieved by means of the catalytic system Pd(OAc)2/PPh3
but in this case significant amounts of ortho-arylated
product 8 were also isolated whatever the solvent employed.
This interesting15 but inconvenient side reaction was
predictable, as a similar behaviour had already been
reported by the latter authors when using Pd(OAc)2, leading
to uncontrolled multiple arylation processes.4d–f Little
amounts of a-diketone 9 were also isolated in some cases
when no degassed solvents were used.16 However, a careful
optimization of the reaction conditions (temperature,
reaction time and relative amounts of catalyst and
bromobenzene 6a) avoided both ortho-arylation and
oxidation reactions, thus providing triarylethanone 3a in
good yields (Table 1, entries 13 and 14). After choosing
DMF solvent for shorter reaction time, a range of
triarylethanones 3a–n were synthesized combining, under
such conditions, different deoxybenzoins 4 and aryl
bromides 6.
Entry
R1
R2
R3
R4
R5
3 (%)a
1
2
3
4
5
6
7
8
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
H
H
H
H
H
OMe
OMe
OMe
OMe
OMe
OMe
OMe
H
H
H
H
H
H
H
H
H
H
OMe
H
H
H
H
H
H
H
H
H
H
3a (85)
3b (51)
3c (46)
3d (47)
OMe
H
OMe
OCH2O
OMe
H
OMe
OMe
3e (55)
OMe
NO2
H
According to the moderate to good yields obtained in most
cases, we can conclude that the presented methodology
constitutes a convenient access to 1,2,2-triarylethanones,
even rivaling the elegant Heck-type triarylation approach
recently reported by Nilsson et al.17 Indeed, apart from the
mild conditions employed,18 neither complex ligand
systems4a–c,19 nor excess of the coupling partners are
required, unlike previous reports where up to 2.3 excess of
one of them is needed and reaction yields are measured with
regard of the starting amount of the haloarene.4d,13a,e,14,20
3f (12)
3g (44)
3h (74)
3i (80)
3j (73)
3k (71)
3l (57)
H
H
9
H
H
10
11
12
13
14
OMe
H
OMe
OCH2O
H
OMeH
OMeH
3m (70)
NO2
H
H
H
H
3n (54)
a
Isolated yield.
2.2. A search for structure/reactivity relationship.
Theoretical and practice-based insights
It is clear from the data shown in Table 2 that our method
provides a simple approach to triarylethanones 3. However,
in order to increase our knowledge about the dependence of
the already optimized procedure on the electronic nature
and steric volume of the coupling partners 4 and 6, a series
of computational calculations (Tables 3–5) was performed,
mainly focussed on the relative stability of intermediates
10–12 shown in Scheme 1, a mechanistic depict made in
concordance with the generally assumed reaction-steps.1c,21
Table 3. Calculated heats of formation of ketone enolates 11
a
a
Entry
Ar1
Ar2
E11a
E11b
1
2
3
4
5
6
7
8
9
10
Ph
Ph
Ph
Ph
Ph
Ph
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
3,4-(MeO)2C6H3
Ph
Ph
Ph
210.13
247.39
249.77
248.94
286.57
246.70
249.01
248.94
284.83
2160.44
6.55
223.23
232.97
232.39
268.03
24.19
28.23
27.38
242.01
2149.96
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
3,4-(MeO)2C6H3
3,4-(MeO)2C6H3
With regard to enolate intermediate 11, the calculation
performed by the semiempirical protocol AM1 revealed,
besides the already known higher stability of resonance
form 11a, that i) the presence of methoxy substituents
stabilizes, with a cumulative effect, both resonance forms
11a–b and ii) a complete delocalization of the negative
charge across the system in 11a, as can be deduced from the
almost equivalent formation heat values found in entries 2
and 6, or 3 and 7.
Ph
3,4-(MeO)2C6H3
a
Heat of formation expressed in kcal/mol.
Table 4. Calculated heats of formation of oxidative addition intermediates
10
PM3 semiempirirical method was used to evaluate the
relative stability of palladium(II) intermediate 10, showing
in this case that substituted aryl groups, and in particular the
methoxylated ones, stabilize more efficiently complex 10
than simple phenyl group. Finally, the calculated (PM3)
energy levels for intermediates formed by ligand substi-
tution 12a–c evidence the higher stability of O-bound
palladium complex 12b,22 along with the already mani-
fested cumulative stabilizing effect of methoxy substituents.
a
Entry
Ar3
E10
1
2
3
4
5
6
Ph
3-MeOC6H4
4-MeOC6H4
3,4-(MeO)2C6H3
4-NO2 C6H4
2,3,4-(MeO)3C6H2
72.79
33.89
35.14
0.10
60.24
237.65
a
Heat of formation expressed in kcal/mol.

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F. Churruca et al. / Tetrahedron 60 (2004) 2393–2408
Table 5. Calculated heats of formation of ketone enolates 12
Ar1
Ar2
Ar3
E12a
E12b
E12c
a
a
a
Entry
1
2
3
4
5
6
7
Ph
Ph
Ph
Ph
Ph
Ph
129.26
55.20
55.1
126.75
53.96
53.34
133.03
56.92
55.48
3,4-(MeO)2C6H3
Ph
Ph
3,4-(MeO)2C6H3
3,4-(MeO)2C6H3
3,4-(MeO)2C6H3
3,4-(MeO)2C6H3
Ph
2,3,4-(MeO)2C6H2
Ph
3,4-(MeO)2C6H3
3,4-(MeO)2C6H3
3,4-(MeO)2C6H3
3,4-(MeO)2C6H3
3,4-(MeO)2C6H3
57.73
52.71
58.36
213.05
214.43
289.13
219.08
219.45
293.50
212.81
215.69
289.10
a
Heat of formation expressed in Kcal/mol.
also isolated from every reaction mixture leading to ketones
3b–g and 3j–n, respectively. Such behaviour, provoked by
a palladium-mediated P–C bond cleavage in phosphanes, is
already known in other organic reactions where the catalytic
system comprises palladium and phosphine ligands,25 but
unreported so far in arylation of ketone enolates. In order to
illustrate the latter process in our arylation, a tentative
mechanistic proposal is shown in Scheme 2, including
phosphonium bromide 13, which has been suggested by
some authors as a necessary intermediate in this kind of
reactions.26
Scheme 1.
Turning back to experimental results, we can observe a
decrease in reaction yields the higher the number of alkoxy
groups is attached to both coupling reagents, especially to
ketone 4. If the calculated increasing stability of the
corresponding polymethoxylated intermediates 10–12 is
considered, such stability can be tentatively associated with
a relative lack of reactivity towards formation of palladium
enolate or reductive elimination key steps,23 thus allowing
competition with undesirable side-reactions. An additional
factor to be considered is steric hindrance at the ligand
exchange or at reductive elimination step from C-bound
palladium enolate,24 probably crucial to explain the low
yield obtained for heptamethoxylated ketone 3f (Table 2,
entry 6).
Scheme 2.
Taking into account that phenyl migration from phosphine
ligands occurs most likely when electron rich arenes or aryl
halides are employed,25a,j,26 it is not surprising in our case
the observed exchange with methoxylated haloarenes 6.
Unfortunately, all attempts to avoid phenyl migration by
using other phosphines (see entries 15–20 in Table 1)
provided negligible results.
Regarding concomitant side-processes, if ortho-arylation
had been effectively avoided, which one remained? A more
detailed examination of the crude mixtures from the
reaction leading to ketone 3d revealed the presence of
phenylated product 3a (20%). Although to a lower extent
(10–15%), undesired phenyl derivatives 3a and 3h were

F. Churruca et al. / Tetrahedron 60 (2004) 2393–2408
Table 6. Selected a,a-diarylation assays performed by homogeneous palladium catalysts
2397
Entry
Reaction conditions
Product (%)a
1
2
3
4
5
6
7
8
6a, 5 mol% Pd2dba3, NaOtBu, THF, 80 8C, 6 hb,c
5a (99)
3i (11) 5a (79)
3i (49) 5a (31)
3i (82) 5a (4) 4b (4)
3i (18) 5a (65) 4b (1)
3i (71) 5a (1) 4b (2)
3i (68) 5a (12) 4b (1)
3i (94) 5a (2) 4b (2)
3i (27) 5a (35)
3i (8) 5a (51) 4b (22)
5a (4) 4b (80)
3o (54) 5a (8) 4c (11) 3j (9)
3o (25) 5a (59) 3j (11)
3o (72) 5a (2) 4c (4) 3j (8)
3o (5) 5a (70)
6a, 3 mol% PdCl2, 12 mol% PPh3, K2CO3, DMF, 130 8C, 1.5 hb,c
7, 3 mol% PdCl2, Cs2CO3, DMF, 100 8C, 6 hd,e
6a, 5 mol% Pd(OCOCF3)2, 20 mol% PPh3, Cs2CO3, DMF, 150 8C, 1.5 hb,e
6a, 0.5 mol% Pd(PPh3)4, Cs2CO3, DMF, 150 8C, 3 hb,e
6a, 1 mol% Pd(PPh3)4, Cs2CO3, o-xylene, 150 8C, 5 hb,e
6a, 1 mol% Pd(OAc)2, 5 mol% PPh3, Cs2CO3, DMF, 150 8C, 2 hb,e
6a, 5 mol% Pd(OAc)2, 20 mol% PPh3, Cs2CO3, DMF, 150 8C, 1 hb,e
6a, 5 mol% Pd(OAc)2, 6.3 mol% PEt3, Cs2CO3, DMF, 150 8C, 6 hb,c
6a, 5 mol% Pd(OAc)2, 20 mol% P(o-tolyl)3, Cs2CO3, DMF, 153 8C, 1 hb,c
6a, 5 mol% Pd(OAc)2, 6.3 mol% P(o-tolyl)3, NaOtBu, THF, 80 8C, 6 hb,c
6b, 5 mol% Pd(OCOCF3)2, 20 mol% PPh3, Cs2CO3, DMF, 150 8C, 1.5 hb,e
6b, 1 mol% Pd(PPh3)4, Cs2CO3, o-xylene, 150 8C, 5 hb,e
9
10
11
12
13
14
15
6b, 5 mol% Pd(OAc)2, 20 mol% PPh3, Cs2CO3, DMF, 153 8C, 1.5 hb,e
6b, 5 mol% Pd(OAc)2, 20 mol% PtBu3, NaOtBu, THF, 80 8C, 6 hb,c
a
GC-MS yields of detected products measured on the basis of the starting amount of acetophenone 5a. Propiophenone was used as the internal standard.
3.4 equiv. of bromoarene 6 were used.
2.5 equiv. of base were used.
2.2 equiv. of iodobenzene 7 were used instead of 6a.
3.0 equiv. of base were used.
b
c
d
e
Table 7. Palladium-catalyzed a,a-diarylation of acetophenones 5
2.3. a,a-Diarylation of acetophenones
To the best of our knowledge, although diverse examples of
palladium-catalyzed multiple arylation of carbonyl com-
pounds have been reported in the last years,4d–e,13a,c–e,14,27
no examples of a general, regioselective methodology for
the a,a-diarylation of ketones have been presented so far.28
Interestingly, in our case, such transformation would
constitute a direct access to target triarylethanones 3 from
commercially available acetophenones 5, thus eluding a
preliminary preparation of deoxybenzoins 4.
With this aim in mind, and taking into account the above
disclosed results on the monoarylation of deoxybenzoins 4,
acetophenone 5a was submitted to an array of experimental
conditions employing bromobenzene 6a and 3-bromo-
anisole 6b as arylating agents (Table 6). In spite of the
good results provided by Pd(OCOCF3)2/PPh3, Pd(PPh3)4
and Pd(OAc)2/PPh3 when using 6a, diarylation of
methoxylated derivative 6b required the use of the latter
catalytic system, in a slightly different but reasonably
similar conditions to the already optimized protocol for the
monoarylation of deoxybenzoins (compare Table 6, entries
8 and 14 with Table 1, entry 14).
Entry
R1
R2
R3
R4
3 (%)a
1
2
3
4
5
6
7
8
OMe
OMe
OMe
OMe
OMe
H
H
H
H
Me
Me
Me
Me
OMe
OMe
OMe
OMe
OMe
H
H
H
H
H
H
H
H
OMe
NO2
F
H
H
OMe
F
H
3h (62)
3p (57)
3d (47)
3q (35)
3r (52)
3i (91)
3o (71)
3s (61)
3t (63)
3u (87)
3v (69)
3w (60)
3x (68)
OMe
OMe
H
H
H
OMe
OMe
H
9
10
11
12
13
H
H
H
H
OMe
OMe
H
H
OMe
F
In order to test the generality of the reported procedure, a
series of commercially available acetophenones 5 and
bromoarenes 6 were coupled under the latter conditions,
and save for the relatively low yield of nitro derivative 3q,
a
Isolated yields.

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F. Churruca et al. / Tetrahedron 60 (2004) 2393–2408
Figure 1. Example of FibreCate structure and different catalytic centers in FibreCate 1000 series.
the good results shown in Table 7 confirm that a reliable
entry to triarylethanones 3 had been achieved by means of a
simple, convenient protocol.
of other carbonyl compounds revealed an only report on
arylation of a diactivated methylene derivative, diethyl
malonate, by means of a Pd-loaded zeolite catalyst.30
The trend of nitro group to be reduced in the presence of
Pd/PPh3 catalytic systems is already known,25h and
certainly, according to the NMR signals corresponding to
free amino groups detected in the crude mixture, it is one of
the reasons of the low yield for ketone 3q. Although AsPh3
has been employed for the palladium-catalyzed arsination
of p-nitrophenyl triflate without observing any reducing
process,25i in our hands reduction to amino group was again
observed along with an even lower yield for 3q (7%) when
replacing PPh3 by AsPh3.
Considering the difference between substrates, and more
interested in polymer-supported catalysts, we sought for a
convenient polymer-anchored catalyst to perform diaryla-
tion of acetophenones 5, finally choosing commercially
available FibreCate 1001, FibreCate 1000-D7 and Fibre-
Cate 1026 to carry out a series of preliminary assays. Our
election was made considering not only the fibrous nature of
the latter catalysts (Fig. 1), a feature that involves several
advantages in terms of ease of handling, good mechanical
properties and high functional group accessibility but also
the excellent results displayed in other palladium-catalyzed
coupling processes like Suzuki or Heck reactions.31 In order
to extend our comparative search to other heterogeneous
systems, Pd/C catalyst32 was also assayed and the results
compared to those obtained from polymer-supported
catalysts.
The second factor that presumably decreased the yield of
ketone 3q and the rest of triarylethanones generated from
other bromoarenes than bromobenzene 6a was again
phenyl-aryl exchange between bromoarenes 6 and PPh3
ligand. Indeed, variable amounts of monophenylated
ketones like 3j (5–17%) were detected from the corre-
sponding reaction mixtures,29 and the similarity of such
products generated from ‘phenyl migration’ to target
ketones interfered with the purification works, thus even
reducing the so-isolated yields.
As summarized in Table 8, although all the heterogenized
catalysts assayed provided target diphenylated product 3i,
only by using FibreCate 1026 the latter ketone 3i was
obtained with good yield (entry 10), and this procedure
resulted also applicable to diarylation with methoxylated
bromoarene 6b (entry 13). Obviously palladium catalyzed
processes cannot be compared when so different conditions
as homogeneous and heterogeneous catalysis have been
employed, but it is somehow surprising that the polymer-
anchored catalyst FibreCate 1001, with a higher similarity
2.4. a,a-Diarylation conducted by heterogeneous
catalysis
A preliminary literature search for heterogeneous palladium
catalysis applied to arylation of ketones or even to arylation

F. Churruca et al. / Tetrahedron 60 (2004) 2393–2408
Table 8. Selected a,a-diarylation assays performed by heterogeneous catalysis
2399
Entry
Reaction conditions
Product (%)a
1
2
3
4
5
6
7
8
6a, 5% Pd/C, Na2CO3, MeOH, 80 8C, 6 hb
5a (98)
5a (94)
6a, 5% Pd/C, NaOH, NH4HCO2, 100 8C, H20, 2 hb
6a, 5% Pd/C, Na2CO3, DMF, 150 8C, 1.5 hb
6a, 1% FC 1001, K2CO3, toluene, 130 8C, 10 hc
6a, 5% FC 1001, K2CO3, toluene, 130 8C, 10 hc
6a, 1% FC 1000-D7, K2CO3, toluene, 130 8C, 10 hc
6a, 2% FC 1000-D7, K2CO3, o-xilene, 153 8C, 6 hc
6a, 2% FC 1000-D7, Cs2CO3, DMF, 153 8C, 1 hc
6a, 2% FC 1026, Cs2CO3, DMF, 153 8C, 3 hc
6a, 5% FC 1026, Cs2CO3, DMF, 153 8C, 1 hc
6b, 5% FC 1001, K2CO3, toluene, 130 8C, 10 hc
6b, 1% FC 1000-D7, K2CO3, toluene, 130 8C, 10 hc
6b, 5% FC 1026, Cs2CO3, DMF, 153 8C, 1 hc
3i (2) 5a (89) 4b (3)
3i (4) 5a (71) 4b (13)
3i (8) 5a (40) 4b (43)
3i (45) 5a (32) 4b (16)
3i (15) 5a (32) 4b (42)
5a (87) 4b (3)
9
3i (17) 5a (41)
10
11
12
13
3i (93) 5a (2) 4b (2)
3o (6) 5a (47) 4c (32)
3o (32) 5a (37) 4c (17)
3o (85) 4c (2) 3j (1)
a
GC-MS yields measured on the basis of the starting amount of ketone 2a. Propiophenone was used as the internal standard.
3.3 equiv. of aryl bromide 6, a 5% Pd/C mixture and 3 equiv. of base were used.
3.3 equiv. of aryl bromide 6, 3 equiv. of base and the indicated FibreCate catalyst (FC) were used. The disclosed proportion of FC (%) refers to the relative
b
c
amount of Pd metal from the FC catalyst. The average content of Pd in the employed FC samples is 3%.
Table 9. Polymer-anchored palladium-catalyzed a,a-diarylation of acetophenones 5
Entry
R1
R2
R3
R4
3 (%)a
1
2
3
4
5
6
7
8
OMe
OMe
OMe
OMe
OMe
H
H
H
H
Me
Me
Me
Me
OMe
OMe
OMe
OMe
OMe
H
H
H
H
H
H
H
H
OMe
NO2
F
H
H
OMe
F
H
3h (90)
3p (82)
3d (64)
3q (20)
3r (70)
3i (89)
3o (79)
3s (80)
3t (73)
3u (93)
3v (75)
3w (92)
3x (80)
OMe
OMe
H
H
H
OMe
OMe
H
9
10
11
12
13
H
H
H
H
OMe
OMe
H
H
OMe
F
a
Isolated yields.

2400
F. Churruca et al. / Tetrahedron 60 (2004) 2393–2408
to the optimized homogeneous system Pd(OAc)2/PPh3,
turned out to be the least efficient to perform target
diarylation. On the other hand, FibreCate 1026, with a
closer resemblance to the non-effective homogeneous
PdCl2/PPh3 system, featured excellent qualities for such
task and therefore was applied to the synthesis of triaryl
ethanones 3 disclosed in Table 9.33
shown in Table 8 were assayed in order to effect the
regioselective a-monoarylation of deoxybenzoins 4 using
polymer-supported catalysts.
Again FibreCate 1026 turn out to be the most efficient
catalyst for this task, but despite an easier purification, the
yields of target triarylethanones 3 prepared under such
conditions were in most cases, as shown in Table 10, clearly
inferior to the ones obtained from the previously mentioned
homogeneous Pd(OAc)2/PPh3 catalyst (Table 7). We
tentatively propose that, in comparison with acetophenone
derivatives 5, deoxybenzoins 4 could encounter a higher
steric hindrance to reach the catalytic centers attached to the
polymer-bone, thus preventing to some extent an effective
catalysis.
A brief comparative look at Tables 7 and 9 shows an evident
advantage in terms of yield when the heterogeneous system
was employed. Such improvement is mainly due to the
practical avoidance (,4%) of phenyl migration, which in
addition facilitates purification of target ketones 3. More-
over, catalyst separation carried out by simple filtration of
the reaction mixture. However, there is a weak spot in our
firstly reported diarylation under heterogeneous conditions,
clearly related to the relatively high temperatures required
(153 8C). The limit of the thermal stability of FibreCate
Series has been established at circa 120 8C,31 therefore it
was predictable that leaching of the catalyst could happen
under our harsher reaction conditions. Indeed, no catalytic
activity was found for already used FibreCate 1026
catalyst, and such leaching behaviour would also explain
the detected traces of phenyl exchange products.
In addition, the same relatively high temperature (153 8C)
was required, thus damaging the catalyst and making it
useless for further arylations.
It should be pointed out that, in spite of the lack of catalyst
recycling shown in the polymer-supported versions of
the described arylations, four different approaches to the
1,2,2-triarylethanone system 3 have been presented.
2.5. a-Monoarylation of deoxybenzoins under
heterogeneous conditions
Apart from the Heck-type synthesis reported by Nilsson
et al.17 the other existing methodologies to construct
such interesting framework,10,11,34 which involve (i) TiCl4/
Sm-promoted reductive coupling of benzophenones and
nitriles,35 (ii) oxidative nucleophilic addition of diphenyl
methyl anion to benzaldehyde,36 (iii) pinacolinic
rearrangement37 and (iv) nucleophilic substitution with
benzotriazole derived carbanions,38 generally present
serious limitations concerning tolerability of func-
tional groups and restricted substitution patterns at the
precursors.
Once observed the improvement made in diarylation
reaction by means of polymer anchored FibreCate 1026,
a range of experimental conditions similar to the ones
Table 10. Polymer-anchored palladium-catalyzed a-arylation of deoxy-
benzoins 4
In addition, the applicability of our four procedures to
mono/polymethoxylated substrates have been completely
proved, thus extending the scope of palladium-catalyzed
arylation of ketone enolates to electron-rich substrates. It
cannot be ignored that in previous reports on this subject,
neutral or electron-deficient coupling partners are normally
used,4a,c,13a,b,e and no account on the use of methoxylated
ketones has been found in the literature.
2.6. a-Monoarylation of acetophenones using polymer-
anchored catalysts
Taking profit of our experience in the synthesis of
triarylethanones 3 from acetophenones 5 and deoxyben-
zoins 4 by both homogeneous and heterogeneous catalysis,
and in order to complete the interconversion among the
three systems 3–5, we planned the heterogeneously
conducted monoarylation of acetophenones 5 as a new
general entry to such important intermediates as deoxy-
benzoins.39
Entry
R1
R2
R3
R4
3 (%)a,b
1
2
3
4
5
6
7
8
9
10
OMe
OMe
OMe
OMe
OMe
H
H
H
H
H
OMe
OMe
OMe
OMe
H
H
H
H
H
H
H
H
OMe
3a (40)c
3b (53)c
3d (53)
3e (38)
3h (51)c
3i (57)c
3j (54)
OMe
OMe
OCH2O
H
H
H
H
OMe
OMe
H
OMe
H
OMe
OCH2O
3k (60)
3l (37)
3m (45)
Although different procedures for the synthesis of deoxy-
benzoins by palladium-catalyzed arylation of aceto-
phenones have been reported,40 no heterogeneous
conditions have been used so far. As described above,
several assays to effect a,a-diarylation of acetophenones 5
H
a
Isolated yield.
b
c
Unless indicated, 3.3 equiv. of aryl bromide 6, 5% FibreCatTM 1026
catalyst and 3 equiv. of Cs2CO3 were used.
2.2 equiv. of aryl bromide 6 were used.

F. Churruca et al. / Tetrahedron 60 (2004) 2393–2408
Table 11. Selected a-monoarylation assays performed by heterogeneous catalysis
2401
Entry
Reaction conditions
Product (%)a
1
2
3
4
5
6
7
8
6a, 5% FC 1001, K2CO3, toluene, 100 8C, 10 hb
6a, 2% FC 1000-D7, K2CO3, o-xylene, 100 8C, 6 hb
6b, 5% FC 1001, K2CO3, toluene, 130 8C, 10 hb
6a, 2% FC 1000-D7, Cs2CO3, DMF, 100 8C, 1 hb
6a, 5% FC 1001, NaOtBu, THF, 85 8C, 6 hb
6b, 2% FC 1001, NaOtBu, THF, 85 8C, 6 hc
6a, 5% FC 1000-D7, NaOtBu, THF, 85 8C, 6 hb
6b, 5% FC 1000-D7, NaOtBu, THF, 85 8C, 6 hb
6b, 2% FC 1000-D7, NaOtBu, THF, 85 8C, 6 hc
6a, 2% FC 1026, NaOtBu, THF, 85 8C, 6 hb
6a, 5% FC 1026, NaOtBu, THF, 85 8C, 6 hb
5a (41) 4b (45)
5a (35) 4b (42)
5a (54) 4c (31)
5a (87) 4b (1)
4b (52) 15a (4)
4c (39) 15b (47)
4b (89) 15a (1)
4c (95)
9
10
11
4c (26) 15b (43)
5a (40) 4b (31)
5a (1) 4b (35)
a
GC-MS yields measured on the basis of the starting amount of ketone 2a. Propiophenone was used as the internal standard.
b
c
3.4 equiv. of aryl bromide 6, 3 equiv. of base and the indicated FibreCate catalyst (FC) were used. The disclosed proportion of FC (%) refers to the relative
amount of Pd metal from the FC catalyst. The average content of Pd in the employed FC samples is 3%.
2.4 equiv. of aryl bromide 6 were used.
Table 12. Polymer-anchored palladium-catalyzed a-monoarylation of
acetophenones 4
using FibreCate catalysts had afforded deoxybenzoins in
different proportions (see for example entries 5, 7 and 11 in
Table 8). Keeping in mind that the insertion of the second
aryl group required relatively high temperatures, a range of
milder conditions were assayed on acetophenone 5a and
aryl bromides 6a–b.
Indeed, lowering the reaction temperatures to 85 8C along
with suitable changes in the base/solvent system allowed us
to obtain target diaryl ketones 4b and 4c in good yields
(Table 11, entries 7 and 8), this time using FibreCate 1000-
D7 as the most adequate catalyst. Accordingly, a series of
deoxybenzoins 4 were easily prepared by the above-
optimized procedure combining commercially available
acetophenones 5 and aryl bromides 6 (Table 12). Apart from
the good results achieved in this firstly reported synthesis of
deoxybenzoins by heterogeneous catalysis, it is worth
mentioning that no aryl exchange-derived product was
detected. Moreover, ortho-arylation side-reaction leading to
derivatives 15 was efficiently avoided.
Entry
R1
R2
R3
R4
4 (%)a,b
1
2
3
4
5
6
7
8
OMe
OMe
OMe
OMe
H
H
H
H
Me
Me
Me
Me
OMe
OMe
OMe
OMe
H
H
H
H
H
OMe
H
OMe
H
OMe
H
H
F
H
H
OMe
F
H
H
4a (72)
4d (90)c
4e (88)d
4f (74)c
4b (87)
4c (92)
4g (91)c
4h (80)c
4i (86)c
4j (86)
H
OMe
OMe
H
With regard to catalyst recycle features, both recovery and
reusability must be outlined. Recovery of the polymer-
anchored catalyst was nearly quantitative (.97%) in all
cases by simple filtration from the reaction mixture, and the
so-recovered catalyst, after an easy treatment,41 was reused
up to 5 times without noticing any decrease in its catalytic
activity, since the same yields were obtained employing
equivalent amounts of the catalyst.
9
H
10
11
12
H
H
H
OMe
OMe
H
OMe
F
4k (82)c
4l (74)c
a
Isolated yield. The same value was obtained after five uses of the
recovered catalyst.
Unless indicated, 3.3 equiv. of aryl bromide 6, %5 FibreCatTM 1000-D7
catalyst and 3 equiv. of NaOtBu were used.
2.2 equiv. of aryl bromide 6 were used.
b
c
Finally, a comparative reflection on the use of the four
protocols to access the triarylethanone framework 3
d
1.5 equiv. of aryl bromide 6 were used.

2402
F. Churruca et al. / Tetrahedron 60 (2004) 2393–2408
presented in this paper should be made, considering as well
the significance of the above described synthesis of
deoxybenzoins. Although considered as alternative ways
to the same end, the term complementary is more accurate,
above all in the cases where the aryl group attached to C-2
position are different, as only monoarylation of deoxy-
benzoins 4 would provide such products.
4.2. General procedure for the a-monoarylation of
deoxybenzoins 4 under homogeneous conditions
Dry degassed DMF (20 mL) was added to an oven dried
reaction flask charged with Pd(OAc)2 (0.065 mmol),
Cs2CO3 (7.75 mmol), PPh3 (0.25 mmol), ketone 1
(3.1 mmol) and arylbromide 4 (3.1 mmol) under argon at
room temperature. The resultant stirred suspension was
heated to 150 8C for 0.5–1 h. After cooling, HCl (50 mL of
a 1.4 M solution in water) was added and the aqueous layer
was extracted with CH2Cl2 (3£30 mL). The combined
organic extracts were washed with saturated aqueous NH4Cl
(5£100 mL), dried over anhydrous sodium sulfate and
evaporated in vacuo to give a residue which was purified by
flash chromatography on silicagel using 10–50% EtOAc/
hexane as eluent.
In terms of number of steps required, a,a-diarylation of
acetophenones 5 is clearly more direct. According to the
slightly better yields obtained and the ease of purification,
the approach based on polymer-anchored FibreCate 1026
would be the most convenient, although the lack of catalyst
reuse cannot be obviated.
On the other hand, comparison between homogeneous
and polymer-support catalysts in the a-monoarylation of
deoxybenzoins features that the simple Pd(OAc)2/PPh3
system provides better results, probably due to the already
mentioned hindrance of the substrate to access the catalyst
site.
4.2.1. 1,2-Bis(3,4-dimethoxyphenyl)-2-phenylethanone
1
(3a).45 85%. Amber oil; Rf 0.51 (50% EtOAc/hexane); H
NMR (250 MHz, CDCl3) d 3.82 (3H, s), 3.84 (3H, s), 3.88
(3H, s), 3.90 (3H, s), 5.96 (1H, s), 6.81 (2H, s), 6.82 (1H, d,
J¼9.0 Hz), 7.23–7.29 (5H, m), 7.32 (1H, s), 7.59 (1H,
d, J¼1.9 Hz), 7.65 (1H, dd, J¼8.3, 1.9 Hz); 13C NMR
(63 MHz, CDCl3) d 55.7, 55.9, 58.3, 109.8, 110.8, 110.9,
111.9, 121.1, 123.5, 126.9, 128.5, 128.8, 129.7, 131.6,
139.5, 147.9, 148.7, 148.9, 153.0, 196.9; FTIR (neat film,
cm21): 1672, 1262, 1024; EIMS (m/z, %) 392 (Mþ, 3), 390
(17), 227 (27), 165 (100). Anal. calcd for C24H24O5: C,
73.45; H, 6.16. Found: C, 73.41; H, 6.22.
However, the best candidates of monoarylation (homo-
geneous) and diarylation (heterogeneous) approaches to
triarylethanones 3 match if the highly advantageous
preparation of deoxybenzoins 4 by means of recyclable
FibreCate 1000-D7 catalyst is considered.
3. Conclusion
4.2.2. 1,2-Bis(3,4-dimethoxyphenyl)-2-(3-methoxyphenyl)-
ethanone (3b). 51%. Reddish oil; Rf 0.42 (50% EtOAc/
hexane); H NMR (250 MHz, CDCl3) d 3.72 (3H, s), 3.81
To sum up, the synthesis of structurally appealing 1,2,2-
triarylethanones has been effected by four arylation
procedures mediated by palladium catalysts. Two of them
involve the a-monoarylation of deoxybenzoins performed
by both homogeneous and polymer-anchored catalysts.
Slight modifications in the corresponding experimental
conditions provide two alternative protocols based on the
regioselective a-diarylation of commercially available
acetophenones conducted again in both homogeneous and
hetereogeneous fashions. Altogether, the presented mono-
arylation and diarylation procedures comprise a general,
efficient entry to the 1,2,2-triarylethanone system, featuring
a high functional group tolerance, especially amenable
to mono/polymethoxylated substrates. This research is
elegantly complemented by the firstly reported a-mono-
arylation of acetophenones performed by polymer-
supported catalysts, a cleaner, more efficient (in terms of
chemical usage) protocol for the preparation of deoxy-
benzoins with obvious environmental and economic
benefits regarding catalyst recovery and reuse.
1
(6H, s), 3.86 (3H, s), 3.87 (3H, s), 5.93 (1H, s), 6.75–6.86
(7H, m), 7.20 (1H, d, J¼9.5 Hz), 7.57 (1H, s), 7.64 (1H, d,
J¼8.3 Hz); 13C NMR (63 MHz, CDCl3) d 54.9, 55.6, 55.8,
58.1, 109.7, 110.7, 110.9, 111.9, 114.7, 121.1, 123.4, 129.4,
129.6, 131.4, 141.0, 147.8, 148.7, 148.8, 152.9 159.5, 196.6;
FTIR (neat film, cm21): 1673, 1263, 1025; EIMS (m/z, %)
422 (Mþ, 3), 257 (34), 165 (100); HRMS calcd for
C25H26O6 422.1729, found 422.1722. Anal. calcd for
C25H26O6: C, 71.07; H, 6.20. Found: C, 70.96; H, 6.27.
4.2.3. 1,2-Bis(3,4-dimethoxyphenyl)-2-(4-methoxyphenyl)-
ethanone (3c). 46%. Orange oil; Rf 0.49 (50% EtOAc/
1
hexane); H NMR (250 MHz, CDCl3) d 3.73 (3H, s), 3.79
(3H, s), 3.81 (3H, s), 3.85 (3H, s), 3.86 (3H, s), 5.91 (1H, s),
6.78–6.85 (6H, m), 7.16 (2H, d, J¼8.3 Hz), 7.57 (1H, s),
7.63 (1H, d, J¼8.3 Hz); 13C NMR (63 MHz, CDCl3) d 54.9,
55.6, 55.8, 57.4, 109.7, 110.7, 110.9, 111.8, 113.8, 120.9,
123.4, 129.7, 129.6, 131.5, 131.9, 147.8, 148.6, 148.8,
152.9, 158.3, 197.1; FTIR (neat film, cm21): 1673, 1263,
1025; EIMS (m/z, %) 422 (Mþ, 3), 257 (100), 165 (34);
HRMS calcd for C25H26O6 422.1729, found 422.1725.
Anal. calcd for C25H26O6: C, 71.07; H, 6.20. Found: C,
71.13; H, 6.31.
4. Experimental
4.1. General methods
4.2.4. 1,2,2-Tris(3,4-dimethoxyphenyl)ethanone (3d).
1
47%. Reddish oil; Rf 0.30 (50% EtOAc/hexane); H NMR
(250 MHz, CDCl3) d 3.78 (6H, s), 3.79 (6H, s), 3.84 (3H, s),
3.85 (3H, s), 5.89 (1H, s), 6.77 (6H, s), 6.79 (1H, d, J¼
8.3 Hz), 7.56 (1H, s), 7.63 (1H, dd, J¼8.3, 1.6 Hz); 13C
NMR (63 MHz, CDCl3) d 55.6, 55.9, 57.8, 109.8, 110.8,
For general experimental details, see Ref. 12c. The semi-
empirical calculations were performed42 according to the
models Austin Method 1 (AM1)42 and Parametrization
Method 3 with extensions for most transition metals
(PM3)43,44

F. Churruca et al. / Tetrahedron 60 (2004) 2393–2408
2403
110.9, 111.8, 121.0, 123.5, 129.7, 131.8, 147.9, 148.7,
148.8, 153.0, 197.1; FTIR (neat film, cm21): 1676, 1260,
1025; EIMS (m/z, %) 452 (Mþ, 1), 287 (100), 165 (27);
HRMS calcd for C26H28O7 452.1835, found 452.1819.
Anal. calcd for C26H28O7: C, 69.01; H, 6.24. Found: C,
68.91; H, 6.26.
4.2.10. 2-(3-Methoxyphenyl)-1,2-diphenylethanone (3j).
1
73%. Yellow oil; Rf 0.62 (30% EtOAc/hexane); H NMR
(250 MHz, CDCl3) d 3.76 (3H, s), 6.26 (1H, s), 6.92 (1H, d,
J¼8.3 Hz), 7.09 (1H, d, J¼7.5 Hz), 7.11 (1H, s) 7.33–7.47
(9H, m), 8.21 (2H, d, J¼7.1 Hz); 13C NMR (63 MHz,
CDCl3) d 54.5, 58.8, 111.8, 114.8, 121.1, 126.7, 127.9,
128.0, 128.2, 128.3, 128.4, 128.5, 128.7, 129.3, 132.6,
136.3, 138.6, 140.1, 159.4, 197.5 (CO); FTIR (neat film,
cm21): 1686, 1261, 1049; EIMS (m/z, %) 302 (Mþ,15), 197
(57), 182 (15), 165 (20), 153 (12), 105 (100); HRMS calcd
for C21H18O2 302.1307, found 302.1303. Anal. calcd for
C21H18O2: C, 83.42; H, 6.00. Found: C, 83.38; H, 6.14.
4.2.5. 1,2-Bis(3,4-dimethoxyphenyl)-2-(3,4-methylene-
dioxyphenyl)ethanone (3e). 55%. Orange oil; Rf 0.49
1
(50% EtOAc/hexane); H NMR (250 MHz, CDCl3) d 3.82
(3H, s), 3.83 (3H, s), 3.87 (3H, s), 3.90 (3H, s), 5.86 (1H, s),
5.90 (2H, s), 6.70–6.83 (7H, m), 7.57 (1H, s), 7.62 (1H, d,
J¼8.3 Hz); 13C NMR (63 MHz, CDCl3) d 55.7, 57.8, 100.9,
108.1, 109.4, 109.8, 110.8, 111.0, 111.8, 121.0, 121.9, 123.4,
129.6, 131.7, 133.3, 146.4, 147.7, 148.0, 148.8, 148.9, 153.0,
196.9; FTIR (neat film, cm21): 1673, 1263, 1025; EIMS
(m/z, %) 436 (Mþ, 3), 271 (100), 165 (59); HRMS calcd
for C25H24O7 436.1522, found 436.1536. Anal. calcd for
C25H24O7: C, 68.80; H, 5.54. Found: C, 68.84; H, 5.47.
4.2.11. 2-(4-Methoxyphenyl)-1,2-diphenylethanone (3k).
71%. Yellow powder: mp 128–129 8C (MeOH)(Lit.14 128–
130 8C (MeOH))
4.2.12. 2-(3,4-Dimethoxyphenyl)-1,2-diphenylethanone
(3l).45 57%. Yellow powder: mp 98–99 8C; Rf 0.60 (50%
EtOAc/hexane); 1H NMR (250 MHz, CDCl3) d 3.76 (6H, s),
6.00 (1H, s), 6.78 (2H, s), 6.82 (1H, s), 7.26–7.44 (9H, m),
7.99 (2H, d, J¼7.1 Hz); 13C NMR (63 MHz, CDCl3) d 55.6,
58.7, 111.0, 112.0, 121.2, 126.9, 128.4, 128.5, 128.7, 131.2,
132.9, 136.6, 139.1, 147.9, 148.9, 198.2; FTIR (neat film,
cm21): 1684, 1263, 1027; EIMS (m/z, %) 332 (Mþ, 7), 227
(100), 196 (11), 105 (9), 77 (10). Anal. calcd for C22H20O3:
C, 79.50; H, 6.06. Found: C, 79.58; H, 5.97.
4.2.6. 1,2-Bis(3,4-dimethoxyphenyl)-2-(2,3,4-trimethoxy-
phenyl)ethanone (3f). 12%. Orange oil; Rf 0.41 (50%
EtOAc/hexane); 1H NMR (250 MHz, CDCl3) d 3.72 (3H, s),
3.80 (3H, s), 3.82 (3H, s), 3.85 (6H, s), 3.88 (3H, s), 3.89
(3H, s), 6.19 (1H, s), 6.55 (1H, d, J¼8.7 Hz), 6.63 (1H, d,
J¼8.7 Hz), 6.82–6.84 (4H, m), 7.58 (1H, s), 7.69 (1H, d,
J¼7.5 Hz); 13C NMR (63 MHz, CDCl3) d 51.9, 55.8, 55.9,
60.6, 106.6, 109. 9, 110.8, 111.0, 112.3, 121.6, 123.2, 123.7,
126.5, 129.7, 130.5, 141.8, 147.9, 148.6, 148.9, 150.6,
152.8, 197.5; FTIR (neat film, cm21): 1670, 1262, 1095;
EIMS (m/z, %) 482 (Mþ, 2), 317 (100), 165 (12), 151 (45);
HRMS calcd for C27H30O8 482.1941, found 482.1944.
Anal. calcd for C27H30O8: C, 67.21; H, 6.27. Found: C,
67.26; H, 6.20.
4.2.13. 2-(3,4-Methylendioxyphenyl)-1,2-diphenyletha-
none (3m). 70%. Yellow powder: mp 117–118 8C; Rf
1
0.60 (30% EtOAc/hexane); H NMR (250 MHz, CDCl3) d
5.83 (2H, s), 5.94 (1H, s), 6.70 (2H, s), 6.77 (1H, s), 7.19
(1H, d, J¼7.1 Hz), 7.23–7.28 (4H, m), 7.34 (2H, dd, J¼7.1,
7.1 Hz) 7.43 (1H, d, J¼7.5 Hz), 7.98 (2H, d, J¼7.1 Hz); 13C
NMR (63 MHz, CDCl3) d 58.7, 100.9, 108.1, 109.5, 122.1,
127.0, 128.4, 128.6, 132.9, 136.5, 139.0, 146.5, 147.8,
198.0; FTIR (neat film, cm21): 1684, 1249, 1038; EIMS
(m/z, %) 316 (Mþ, 7), 211 (100), 181 (15), 152 (20), 105
(21), 77 (16); HRMS calcd for C21H16O3 316.1099, found
316.1097. Anal. calcd for C21H16O3: C, 79.73; H, 5.10.
Found: C, 79.63; H, 5.17.
4.2.7. 1,2-Bis(3,4-dimethoxyphenyl)-2-(4-nitrophenyl)-
ethanone (3g). 44%. Orange oil; Rf 0.45 (50% EtOAc/
1
hexane); H NMR (250 MHz, CDCl3) d 3.77 (3H, s), 3.81
(3H, s), 3.84 (3H, s), 3.87 (3H, s), 6.04 (1H, s), 6.80–6.84
(4H, m), 7.34 (2H, d, J¼8.3 Hz), 7.51 (1H, s) 7.59 (1H, d,
J¼8.3 Hz), 8.06 (2H, d, J¼7.5 Hz); 13C NMR (63 MHz,
CDCl3) d 55.8, 55.9, 57.9, 109.9, 110.7, 111.3, 111.5, 121.0,
123.4, 126.7, 129.0, 129.8, 130.0, 146.6, 147.2, 148.4,
148.9, 149.3, 153.4, 195.5; FTIR (neat film, cm21): 1653,
1507, 1344, 1261, 1022; EIMS (m/z, %) 165 (100); HRMS
calcd for C24H23NO7 437.1475, found 437.1484. Anal.
calcd for C24H23NO7: C, 65.90; H, 5.30; N 3.20. Found: C,
65.95; H, 5.21; N 3.27.
4.2.14. 2-(4-Nitrophenyl)-1,2-diphenylethanone (3n).47
1
54%. Orange oil; Rf 0.58 (30% EtOAc/hexane); H NMR
(250 MHz, CDCl3) d 6.21 (1H, s), 7.32–7.46 (9H, m), 7.52
(1H, d, J¼7.1 Hz), 8.03 (2H, d, J¼8.2 Hz), 8.14 (2H, d,
J¼8.2 Hz); 13C NMR (63 MHz, CDCl3) d 58.9, 123.5,
127.7, 128.3, 128.6, 128.7, 128.8, 128.9, 129.2, 130.1,
130.2, 133.5, 135.9, 137.4, 146.6, 196.8; FTIR (neat film,
cm21): 1684, 1518, 1346; EIMS (m/z, %) 362 (Mþ, 3), 257
(100), 91 (54). Anal. calcd for C20H15NO3: C, 75.70; H,
4.76; N 4.41. Found: C, 75.60; H, 4.81; N 4.53.
4.2.8. 1-(3,4-Dimethoxyphenyl)-2,2-diphenylethanone
(3h).46 74%. White powder: mp 142–143 8C (MeOH); Rf
1
0.63 (50% EtOAc/hexane); H NMR (250 MHz, CDCl3) d
3.87 (3H, s), 3.90 (3H, s), 6.02 (1H, s), 6.82 (1H, d,
J¼8.3 Hz), 7.22–7.35 (10H, m), 7.58 (1H, s), 7.64 (1H, d,
J¼8.3 Hz); 13C NMR (63 MHz, CDCl3) d 55.4, 55.6, 58.6,
109.7, 110.6, 123.3, 126.7, 128.3, 128.7, 129.4, 139.1,
148.5, 152.8, 196.4; FTIR (neat film, cm21): 1673, 1260,
1023; EIMS (m/z, %) 165 (100), 137 (6), 122 (2), 77 (4).
Anal. calcd for C22H20O3: C, 79.50; H, 6.06. Found: C,
79.43; H, 6.17.
4.3. General procedure for the a,a-diarylation of
acetophenones 5 under homogeneous conditions
Dry degassed DMF (5 mL) was added to an oven-dried
reaction flask charged with Pd(OAc)2 (0.04 mmol), Cs2CO3
(2.46 mmol), PPh3 (0.16 mmol), acetophenone
(0.82 mmol), and aryl bromide 6 (2.79 mmol) under argon
at room temperature. The resultant stirred suspension was
heated to 153 8C for 0.8–7 h. After cooling, HCl (15 mL of
a 1.4 M solution in water) was added, and the aqueous layer
5
4.2.9. 1,2,2-Triphenylethanone (3i). 80%. White powder:
mp 137–138 8C (MeOH)(Lit.14 138–138.5 8C (MeOH)).

2404
F. Churruca et al. / Tetrahedron 60 (2004) 2393–2408
was extracted with CH2Cl2 (3£10 mL). The combined
organic extracts were washed with saturated aqueous NH4Cl
(5£40 mL), dried over anhydrous sodium sulfate, and
evaporated in vacuo to give a residue that was purified by
flash chromatography on silicagel using 10–50% EtOAc/
hexane as eluent. By use of this procedure the compounds
3i, 3o, 3s–t and 3w were prepared. However, the
preparation of triarylethanones 3d, 3h, 3p–r, 3u–v and
3x required the use of 1.80 mmol of arylbromide 6.
(Mþ, 2), 165 (100), 137 (10), 77 (10); HRMS calcd for
C22H18F2O3 368.1224, found 368.1227. Anal. calcd for
C22H18F2O3: C, 71.73; H, 4.93. Found: C, 71.69; H, 4.84.
4.3.5. 2,2-Bis(3,4-dimethoxyphenyl)-1-phenylethanone
1
3s.45 61%. Orange oil; Rf 0.66 (50% EtOAc/hexane); H
NMR (250 MHz, CDCl3) d 3.77 (6H, s), 3.78 (3H, s), 3.79
(3H, s), 5.92 (1H, s), 6.77 (5H, m), 7.32–7.40 (4H, m), 7.98
(2H, d, J¼8.3 Hz); 13C NMR (63 MHz, CDCl3) d 55.4,
55.6, 55.7, 58.0, 110.8, 111.8, 120.9, 128.3, 128.5, 131.3,
132.7, 136.5, 147.8, 148.7, 198.3; FTIR (neat film, cm21):
1684, 1265, 1026; EIMS (m/z, %) 392 (Mþ, 2), 287 (100),
105 (50). Anal. calcd for C24H24O5: C, 73.45; H, 6.16.
Found: C, 73.53; H, 6.11.
1,2,2-Tris(3,4-dimethoxyphenyl)ethanone (3d) (47%).
1-(3,4-Dimethoxyphenyl)-2,2-diphenylethanone (3h) (62%).
1,2,2-Triphenylethanone (3i) (91%).
4.3.6. 2,2-Bis(4-fluorophenyl)-1-phenylethanone (3t).
1
63%. Yellow oil; Rf 0.32 (20% EtOAc/hexane); H NMR
4.3.1. 2,2-Bis(3-methoxyphenyl)-1-phenylethanone
(3o).48 71%. Orange powder: mp 73–75 8C (MeOH); Rf
0.66 (30% EtOAc/hexane); H NMR (250 MHz, CDCl3) d
(250 MHz, CDCl3) d 6.00 (1H, s), 7.02 (4H, ddd, J¼8.7,
8.3, 1.9 Hz), 7.29 (4H, ddd, J¼8.7, 5.5, 2.4 Hz), 7.39–7.45
(2H, m), 7.53 (1H, dddd, J¼7.5, 7.1, 2.4, 1.6 Hz), 7.95–7.99
(2H, m); 13C NMR (63 MHz, CDCl3) d 57.6, 115.7, 128.7,
128.9, 129.6, 130.5, 133.3, 134.6, 161.9, 167.9; FTIR (neat
film, cm21): 1626; EIMS (m/z, %) 203 (10), 105 (100), 77
(28); HRMS calcd for C20H14F2O 308.1013, found
308.1010. Anal. calcd for C20H14F2O: C, 77.91; H, 4.58.
Found: C, 77.86; H, 4.64.
1
3.76 (6H, s), 6.10 (1H, s), 6.86 (2H, d, J¼8.3 Hz), 6.97–
6.99 (4H, m), 7.30 (2H, dd, J¼8.3, 7.9 Hz), 7.39–7.51 (3H,
m), 8.11 (2H, d, J¼7.1 Hz); 13C NMR (63 MHz, CDCl3) d
54.8, 59.0, 112.0, 114.9, 121.2, 128.3, 128.6, 129.4, 132.8,
136.4, 140.1, 159.5, 197.5; FTIR (neat film, cm21): 1684,
1260, 1049; EIMS (m/z, %) 322 (Mþ, 13), 227 (73), 105
(100); HRMS calcd for C22H20O3 332.1401, found
332.1405. Anal. calcd for C22H20O3: C, 79.50; H, 6.06.
Found: C, 79.58; H, 6.01.
4.3.7. 2,2-Diphenyl-1-(4-methylphenyl)ethanone (3u).
87%. White powder: mp 99–100 8C (MeOH)(Lit.49 100–
101 8C (MeOH)).
4.3.2. 2,2-Bis(3-methoxyphenyl)-1-(3,4-dimethoxyphenyl)-
ethanone (3p). 57%. Yellow oil; Rf 0.64 (50% EtOAc/
1
hexane); H NMR (250 MHz, CDCl3) d 3.75 (6H, s), 3.87
4.3.8. 2,2-Bis(3-methoxyphenyl)-1-(4-methylphenyl)-
ethanone (3v). 69%. Yellow oil; Rf 0.39 (30% EtOAc/
(3H, s), 3.89 (3H, s), 5.96 (1H, s), 6.76–6.89 (7H, m), 7.21
(2H, d, J¼7.9 Hz), 7.59 (1H, d, J¼1.9 Hz), 7.65 (1H, dd,
J¼8.3, 1.9 Hz); 13C NMR (63 MHz, CDCl3) d 55.0, 55.7,
55.8, 58.7, 109.8, 110.8, 112.1, 114.9, 121.3, 123.5, 129.4,
129.6, 140.5, 148.7, 153.0, 159.6, 196.3; FTIR (neat film,
cm21): 1675, 1261, 1048; EIMS (m/z, %) 165 (100); HRMS
calcd for C24H24O5 392.1624, found 392.1616. Anal. calcd
for C24H24O5: C, 73.45; H, 6.16. Found: C, 73.57; H, 6.07.
1
hexane); H NMR (250 MHz, CDCl3) d 2.38 (3H, s), 3.76
(6H, s), 5.97 (1H, s), 6.80 (2H, dd, J¼8.3, 2.3 Hz), 6.84 (2H,
d, J¼2.3 Hz), 6.88 (2H, d, J¼7.9 Hz), 7.21 (2 h, d, J¼
8.3 Hz), 7.25 (2H, dd, J¼8.3, 7.9 Hz), 7.93 (2H, d, J¼
8.3 Hz); 13C NMR (63 MHz, CDCl3) d 21.4, 54.9, 59.0,
112.1, 114.9, 121.3, 128.9, 129.1, 129.4, 134.0, 140.3,
143.7, 159.6, 197.2; FTIR (neat film, cm21): 1682, 1260,
1050; EIMS (m/z, %) 346 (Mþ, 4), 227 (6), 119 (100), 91
(7); HRMS calcd for C23H22O3 346.1569, found 346.1572.
Anal. calcd for C23H22O3: C, 79.74; H, 6.40. Found: C,
79.62; H, 6.47.
4.3.3. 2,2-Bis(4-nitrophenyl)-1-(3,4-dimethoxyphenyl)-
ethanone (3q). 35%. Orange oil; Rf 0.30 (20% Et2O/
1
hexane); H NMR (250 MHz, CDCl3) d 3.90 (3H, s), 3.93
(3H, s), 6.21 (1H, s), 6.84 (1H, d, J¼9.1 Hz), 7.44 (4H, d,
J¼8.7 Hz), 7.54–7.58 (2H, m), 8.21 (4H, d, J¼8.7 Hz);13C
NMR (63 MHz, CDCl3) d 55.9, 56.1, 57.7, 110.0, 110.8,
123.8, 124.1, 128.6, 129.9, 145.2, 147.3, 149.4, 154.1,
194.0; FTIR (neat film, cm21): 1682, 1516, 1345, 1262,
1022; EIMS (m/z, %) 422 (Mþ, 1), 227 (5), 207 (17), 165
(100), 137 (10), 77 (12); HRMS calcd for C22H18N2O7
422.1114, found 422.1111. Anal. calcd for C22H18N2O7: C,
62.56; H, 4.30; N 6.63. Found: C, 62.49; H, 4.25; N 6.71.
4.3.9. 2,2-Bis(3,4-dimethoxyphenyl)-1-(4-methylphenyl)-
ethanone (3w). 60%. Orange oil; Rf 0.64 (50% EtOAc/
hexane); H NMR (250 MHz, CDCl3) d 2.36 (3H, s), 3.81
1
(6H, s), 3.81 (6H, s), 5.91 (1H, s), 6.79 (6H, m), 7.20 (2H, d,
J¼8.3 Hz), 7.91 (2H, d, J¼8.3 Hz); 13C NMR (63 MHz,
CDCl3) d 21.5, 55.7, 58.1, 110.9, 112.0, 121.1, 128.9, 129.2,
131.7, 134.2, 143.7, 147.9, 148.8, 198.1; FTIR (neat film,
cm21): 1681, 1263, 1027; EIMS (m/z, %) 406 (Mþ, 4), 287
(100), 207 (48), 119 (10); HRMS calcd for C25H26O5
406.1780, found 406.1768. Anal. calcd for C25H26O5: C,
73.87; H, 6.45. Found: C, 73.93; H, 6.49.
4.3.4. 2,2-Bis(4-fluorophenyl)-1-(3,4-dimethoxyphenyl)-
ethanone (3r). 52%. Yellow oil; Rf 0.47 (40% EtOAc/
1
hexane); H NMR (250 MHz, CDCl3) d 3.88 (3H, s), 3.90
(3H, s), 5.98 (1H, s), 6.82 (1H, d, J¼8.7 Hz), 6.99 (4H, ddd,
J¼8.7, 8.3, 1.9 Hz), 7.22 (4H, ddd, J¼8.7, 5.1, 2.4 Hz), 7.56
(1H, d, J¼1.9 Hz) 7.61 (1H, dd, J¼8.7, 1.9 Hz); 13C NMR
(63 MHz, CDCl3) d 55.8, 55.9, 57.0, 109.9, 110.9, 115.5,
123.6, 129.6, 130.4, 135.0, 149.0, 153.3, 161.8, 196.4; FTIR
(neat film, cm21): 1678, 1265, 1026; EIMS (m/z, %) 366
4.3.10. 2,2-Bis(4-fluorophenyl)-1-(4-methylphenyl)ethan-
one (3x). 68%. Yellow oil; Rf 0.43 (20% EtOAc/hexane);
1H NMR (250 MHz, CDCl3) d 2.37 (3H, s), 3.76 (6H, s),
5.99 (1H, s), 7.02 (2H, d, J¼8.7 Hz), 7.19–7.31 (8H, m),
7.89 (2H, d, J¼8.3 Hz); 13C NMR (63 MHz, CDCl3) d 21.5,
57.3, 115.6, 128.3, 129.0, 129.3, 130.4, 134.8, 144.2, 161.9,

F. Churruca et al. / Tetrahedron 60 (2004) 2393–2408
2405
197.4; FTIR (neat film, cm21): 1620; EIMS (m/z, %) 320
(Mþ, 2), 119 (100), 91 (21); HRMS calcd for C21H16F2O
322.1169, found 322.1175. Anal. calcd for C21H16F2O: C,
78.25; H, 5.00. Found: C, 78.34; H, 4.96.
silicagel using 10–50% EtOAc/hexane as eluent. By use of
this procedure the compounds 3d–e and 3j–m were
prepared. However, the preparation of triarylethanones
3a–b and 3h–i required the use of 0.44 mmol of
arylbromide 6.
4.4. General procedure for the a,a-diarylation of
acetophenones 5 by means of polymer-anchored
palladium catalysts
1,2-Bis(3,4-dimethoxyphenyl)-2-phenylethanone (3a) (40%).
1,2-Bis(3,4-dimethoxyphenyl)-2-(3-methoxyphenyl)ethan-
one (3b) (53%).
Dry degassed DMF (1 mL) was added to an oven-dried
reaction flask charged with FibreCate 1026 (0.01 mmol of
Pd), Cs2CO3 (0.6 mmol), ketone 2 (0.2 mmol), and aryl
bromide 3 (0.68 mmol) under argon at room temperature.
The resultant stirred suspension was heated to 153 8C for
0.8–1 h. After cooling, the mixture was filtered, washed
with CH2Cl2 and the filtrate was evaporated in vacuo to give
a residue that was purified by flash chromatography on
silicagel using 10–50% EtOAc/hexane as eluent.
1,2,2-Tris(3,4-dimethoxyphenyl)ethanone (3d) (53%).
1,2-Bis(3,4-dimethoxyphenyl)-2-(3,4-methylenedioxy-
phenyl)ethanone (3e) (38%).
1-(3,4-dimethoxyphenyl)-2,2-diphenylethanone (3 h) (51%).
1,2,2-Triphenylethanone (3i) (57%).
1,2,2-Tris(3,4-dimethoxyphenyl)ethanone (3d) (64%).
1-(3,4-Dimethoxyphenyl)-2,2-diphenylethanone (3h) (90%).
1,2,2-Triphenylethanone (3i) (89%).
2-(3-Methoxyphenyl)-1,2-diphenylethanone (3j) (54%).
2-(4-Methoxyphenyl)-1,2-diphenylethanone (3k) (60%).
2-(3,4-Dimethoxyphenyl)-1,2-diphenylethanone (3l) (37%).
2,2-Bis(3-methoxyphenyl)-1-phenylethanone (3o) (79%).
2-(3,4-Methylendioxyphenyl)-1,2-diphenylethanone (3m)
(45%).
2,2-Bis(3-methoxyphenyl)-1-(3,4-dimethoxyphenyl)ethan-
one (3p) (82%).
4.6. General procedure for the a-monoarylation of
acetophenones 5 by means of polymer-anchored
palladium catalysts
2,2-Bis(4-nitrophenyl)-1-(3,4-dimethoxyphenyl)ethanone
(3q) (20%).
2,2-Bis(4-fluorophenyl)-1-(3,4-dimethoxyphenyl)ethanone
(3r) (70%).
Dry degassed THF (1 mL) was added to an oven-dried
reaction flask charged with FibreCate 1000-D7 (0.01 mmol
of Pd), NaOtBu (0.6 mmol), ketone 5 (0.2 mmol), and
arylbromide 6 (0.68 mmol) under argon at room tempera-
ture. The resultant stirred suspension was heated to 85 8C for
1 h. After cooling, the mixture was filtered, washed with
CH2Cl2 and the filtrate was evaporated in vacuo to give a
residue that was purified by flash chromatography on
silicagel using 10–50% EtOAc/hexane as eluent.
2,2-Bis(3,4-dimethoxyphenyl)-1-phenylethanone 3s (80%).
2,2-Bis(4-fluorophenyl)-1-phenylethanone (3t) (73%).
2,2-Diphenyl-1-(4-methylphenyl)ethanone (3u) (93%).
2,2-Bis(3-methoxyphenyl)-1-(4-methylphenyl)ethanone
(3v) (75%).
After each reaction, the the filtrand was washed succes-
sively with HCl (3 mL of a 5% solution in water), Na2CO3
(3 mL of a 10% solution in water), H2O (2 mL), THF
(2 mL) and NaCl (5 mL of a saturated solution in CH3CN).
After drying in vacuo, the so-recycled catalyst was ready to
be reused under the above described conditions. The same
experiment was carried out 5 times, providing the
corresponding deoxybenzoin 4 with the same yield.
2,2-Bis(3,4-dimethoxyphenyl)-1-(4-methylphenyl)etha-
none (3w) (92%).
2,2-Bis(4-fluorophenyl)-1-(4-methylphenyl)ethanone (3x)
(80%).
4.5. General procedure for the a-monoarylation of
deoxybenzoins 4 by means of polymer-anchored
palladium catalysts
By use of this procedure the compounds 4a, 4b–c and 4j
were prepared. However, the preparation of deoxybenzoins
4d, 4f, 4g–h and 4k–l required the use of 0.44 mmol of
arylbromide 6 and the preparation of deoxybenzoin 4e
required the use of 0.24 mmol of arylbromide 6.
Dry degassed DMF (1 mL) was added to an oven-dried
reaction flask charged with FibreCate 1026 (0.01 mmol of
Pd), Cs2CO3 (0.6 mmol), ketone 4 (0.2 mmol), and
arylbromide 6 (0.68 mmol) under argon at room tempera-
ture. The resultant stirred suspension was heated to 153 8C
for 1 h. After cooling, the mixture was filtered, washed with
CH2Cl2 and the filtrate was evaporated in vacuo to give a
residue that was purified by flash chromatography on
4.6.1. 1,2-Bis(3,4-dimethoxyphenyl)ethanone 4a. 72%.
White powder: mp 105–106 8C (MeOH)(Lit.50 105–107 8C
(EtOH/H20)).
4.6.2. 1-(3,4-Dimethoxyphenyl)-2-phenylethanone 4d.

2406
F. Churruca et al. / Tetrahedron 60 (2004) 2393–2408
90%. Yellow powder: mp 101–103 8C (MeOH)(Lit.51
105 8C (MeOH)).
(neat film, cm21): 1685; EIMS (m/z, %) 119 (100), 91
(36). Anal. calcd for C15H13FO: C, 78.93; H, 5.74. Found:
C, 78.99; H, 5.80.
4.6.3. 1-(3,4-Dimethoxyphenyl)-2-(3-methoxyphenyl)-
ethanone 4e. 88%. Yellow powder: mp 58–60 8C
(MeOH)(Lit.52 57–60 8C (MeOH)).
Acknowledgements
4.6.4. 1-(3,4-Dimethoxyphenyl)-2-(4-fluorophenyl)etha-
none 4f. 74%. Yellow powder: mp 102–103 8C (MeOH)
(Lit.53 102–104 8C (MeOH)).
This research was supported by the University of the Basque
Country (Project UPV 41.310-13656) and the Spanish
Ministry of Science and Technology (MCYT BQU2001-
0313). Both institutions are gratefully acknowledged. F. C.
also thanks the Ministry of Education, Culture and Sports
(MECD) for a predoctoral scholarship. Finally, Johnson-
Matthey Chemicals is acknowledged for a generous
donation of FibreCate catalysts.
4.6.5. 1,2-Diphenylethanone 4b. 87%. White powder: mp
55–56 8C (MeOH)(Lit.54 56 8C (MeOH)).
4.6.6. 1-Phenyl-2-(3-methoxyphenyl)ethanone 4c. 92%.55
Yellow oil. The spectroscopic data of 4c correspond to the
literature55 data.
4.6.7. 1-Phenyl-2-(3,4-dimethoxyphenyl)ethanone 4g.
91%. Yellow powder: mp 80–81 8C (MeOH)(Lit.56 87–
88 8C (EtOH)).
References and notes
1. (a) Prim, D.; Campagne, J.-M.; Joseph, D.; Andrioletti, B.
Tetrahedron 2002, 58, 2041–2075. (b) Miura, M.; Nomura,
M. Top. Curr. Chem. 2002, 219, 211–241. (c) Culkin, D. A.;
Hartwig, J. F. Acc. Chem. Res. 2003, 36, 234–245.
4.6.8. 1-Phenyl-2-(4-fluorophenyl)ethanone 4h. 80%.
White powder: mp 107–108 8C (MeOH)(Lit.54 108–
110 8C (MeOH)).
2. (a) Beugelmans, R.; Boudet, B.; Quintero, L. Tetrahedron
´ ´
Lett. 1980, 21, 1943–1944. (b) Durandetti, M.; Nedelec, J.-Y.;
4.6.9. 2-Phenyl-1-(4-methylphenyl)ethanone 4i. 86%.
White powder: mp 107–108 8C (MeOH)(Lit.56 108–
1098C (MeOH)).
´
Perichon, J. Org. Chem. 1996, 61, 1748–1755. (c) Kang,
S.-K.; Ryu, H.-C.; Hong, Y.-T. J. Chem. Soc., Perkin Trans. 1
2000, 3350–3351.
3. (a) Barton, D. H. R.; Donnelly, D. M. X.; Finet, J.-P.; Guiry,
J. Chem. Soc., Perkin. Trans. 1 1992, 1365–1375. (b) Pinhey,
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4.6.10. 2-(3-Methoxyphenyl)-1-(4-methylphenyl)ethan-
one 4j. 86%. Yellow oil; Rf 0.55 (20% EtOAc/hexane);
1H NMR (250 MHz, CDCl3) d 2.45 (3H, s), 3.83 (3H, s),
4.28 (2H, s), 6.82–6.93 (3H, m), 7.30 (2H, d, J¼7.5 Hz),
7.97 (2H, d, J¼8.3 Hz); 13C NMR (63 MHz, CDCl3) d 21.6,
45.4, 55.0, 112.2, 114.9, 121.7, 128.8, 129.2, 129.5, 133.9,
136.1, 143.9, 159.6, 197.1; FTIR (neat film, cm21): 1684,
1257, 1045; EIMS (m/z, %) 240 (Mþ, 10), 119 (100), 91
(25); HRMS calcd for C16H16O2 240.1150, found 240.1155.
Anal. calcd for C16H16O2: C, 79.97; H, 6.71. Found: C,
79.89; H, 6.60.
4. The use of relatively complex ligand systems is described:
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2002, 344, 209–217. (b) Rutherford, J. L.; Rainka, M. P.;
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4.6.11. 2-(3,4-Dimethoxyphenyl)-1-(4-methylphenyl)-
ethanone 4k.57 82%. Orange powder: mp 92–93 8C
(MeOH); Rf 0.51 (30% EtOAc/hexane); 1H NMR
(250 MHz, CDCl3) d 2.39 (3H, s), 3.84 (3H, s), 3.85 (3H,
s), 4.19 (2H, s), 6.77–6.80 (3H, m), 7.24 (2H, d, J¼7.9 Hz),
7.91 (2H, d, J¼8.3 Hz); 13C NMR (63 MHz, CDCl3) d 21.6,
44.9, 55.8, 111.1, 112.3, 121.5, 127.0, 128.7, 129.2, 133.9,
143.9, 147.8, 148.9, 197.5; FTIR (neat film, cm21): 1682,
1268, 1028; EIMS (m/z, %) 270 (Mþ, 23), 151 (33), 119
(100), 91 (19). Anal. calcd for C17H18O3: C, 75.53; H, 6.71.
Found: C, 75.61; H, 6.65.
5. (a) Alper, H.; Arya, P.; Bourque, S. C.; Jefferson, G. R.;
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4.6.12. 2-(4-Fluorophenyl)-1-(4-methylphenyl)ethanone
4l.58 74%. Orange powder: mp 103–104 8C (MeOH);
Rf 0.41 (20% EtOAc/hexane); 1H NMR (250 MHz,
CDCl3) d 2.41 (3H, s), 4.23 (2H, s), 7.01 (2H, dd, J¼8.7,
8.3 Hz), 7.21 (2H, dd, J¼8.7, 5.5 Hz), 7.26 (2H, d,
J¼8.3 Hz), 7.80 (2H, d, J¼8.3 Hz); 13C NMR (63 MHz,
CDCl3) d 21.6, 44.3, 115.4 (d, JC–F¼21.5 Hz), 128.6,
129.3, 130.3 (d, JC–F¼3.6 Hz), 130.9 (d, JC–F¼9.0),
133.9, 144.1, 161.8 (d, JC–F¼244.1 Hz), 197.0; FTIR
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I.; Olivera, R.; Pascual, S.; Domınguez, E. Recent Res. Devel.
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19. Most firmly established methodologies for the arylation of
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ligands. See: (a) Hamada, T.; Chieffi, A.; Ahman, J.;
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´
See: (a) SanMartin, R.; Martınez de Marigorta, E.;
22. It has been experimentally demonstrated that the predominant
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Domınguez, E. Tetrahedron 1994, 50, 2255–2264. See also
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23. Interestingly, it has been suggested that the reductive
elimination rate is insensitive to enolate electronic properties
and therefore, the progress of the reaction mainly depends on
the formation of the corresponding enolate. Otherwise, it has
also been proposed that a higher difference in relative
stabilities between C- and O-bound palladium enolates
involves a more impeded reductive elimination, since this
step must happen through the C-palladium enolate. Such
criterion can be applied if the differences between total energy
values obtained from the most stable of C-palladium enolates
(normally 12a) and the O-bound one 12b (Table 5) are
compared to their corresponding reaction yields (Table 2). For
example, 129.262126.75¼2.51 kcal/mol and 213.052
(219.08)¼6.03 kcal/mol values are obtained from Table 5,
entries 1 and 5, respectively. The corresponding reaction
yields are 80 and 12%, as shown in Table 2, entries 9 and 6,
respectively. See Ref. 1c.
´
(c) Olivera, R.; SanMartin, R.; Domınguez, E.; Solans, X.;
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25. Phenyl-aryl exchange has been reported using both

2408
F. Churruca et al. / Tetrahedron 60 (2004) 2393–2408
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