PCP-Bis(phosphinite) pincer complexes: new homogeneous catalysts for α-arylation of ketones

Article abstract of DOI:10.1016/j.tetlet.2006.03.040

Two new p-alkoxycarbonylated palladium bis(phosphinite) PCP pincer complexes are easily prepared and for the first time evaluated as homogeneous catalysts in α-arylation of ketone enolates. Apart from the total absence of phenyl-aryl exchange by-products and significantly low catalyst loadings, the general α-arylation protocols described in this letter feature not only a broad applicability to a range of ketones and aryl bromides with marked electronic and steric differences but also the possibility to generate mono-diarylated products.

Full text of DOI:10.1016/j.tetlet.2006.03.040

Tetrahedron Letters 47 (2006) 3233–3237
PCP-Bis(phosphinite) pincer complexes: new homogeneous
catalysts for a-arylation of ketones
*
*
F a´ tima Churruca, Raul SanMartin, Imanol Tellitu and Esther Dom ´ı nguez
Kimika Organikoa II Saila, Zientzia eta Teknologia Fakultatea, Euskal Herriko Unibertsitatea,
PO Box 644, 48080 Bilbao, Spain
Received 14 February 2006; revised 7 March 2006; accepted 8 March 2006
Available online 23 March 2006
Abstract—Two new p-alkoxycarbonylated palladium bis(phosphinite) PCP pincer complexes are easily prepared and for the first
time evaluated as homogeneous catalysts in a-arylation of ketone enolates. Apart from the total absence of phenyl–aryl exchange
by-products and significantly low catalyst loadings, the general a-arylation protocols described in this letter feature not only a broad
applicability to a range of ketones and aryl bromides with marked electronic and steric differences but also the possibility to generate
mono-diarylated products.
ꢀ
2006 Elsevier Ltd. All rights reserved.
Metal complexes based on pincer framework are an
appealing target because of their unique balance of sta-
bility versus reactivity, which can provide enhanced
erties by phosphinite ligands, have been proved to be
highly active in a number of C–C bond-forming reac-
5
,7
tions.
No ketone a-arylation has been described
1
reactivity and catalytic performances. In particular
employing the latter phosphinite complexes, and, to
the best of our knowledge, the use of pincer-type pallada-
cycles in a-arylation of ketone enolates has not been
there has been an increased interest in the use of PCP
pincer complexes in homogeneous catalysis due to their
2
8
excellent moisture-, air- and temperature-stability. In
investigated so far. In this context, considering our
9
the last years, the demand for a cleaner, environmentally
friendlier chemistry has led to the development of new
experience in palladium-catalyzed arylations of ketones
it seemed likely to us that phosphinite pincer complexes
could act as homogeneous catalysts for such an impor-
3
heterogeneous catalytic systems and, in our opinion,
1
0
PCP pincer-type complexes would constitute excellent
candidates for such task.
tant transformation.
The successful application of bis(phosphinite) PCP-pin-
cer palladacycles 1 in the firstly reported a-arylation of
ketones performed by pincer-type catalysts is disclosed
in this letter.
Consequently, and as part of our ongoing research on
the development of pincer-type heterogeneous cata-
4
lysts, we planned to transform homogeneous bis(phos-
5
phinite) PCP-pincer palladacycles into heterogeneous
catalysts by anchoring conveniently modified complexes
to an insoluble support. For that purpose, we devised
New alkoxycarbonylated complexes 1a and 1b were
easily prepared from commercially available ethyl 3,5-
dihydroxybenzoate 2 by a one-pot phosphorylation/
palladation sequence, according to procedures similar
to those described in the literature (Scheme 1). Thus,
reaction of the resorcinol derivative 2 with the appropri-
6
the preparation of suitable functionalized para-ethoxy-
carbonylated palladacycles 1, which would be subse-
quently submitted to several coupling reactions in
order to ensure their catalytic activity before the hetero-
genization step. Phosphinite PCP pincer complexes,
which appear to combine in one molecule the advanta-
ges of palladacycles and a modulation of catalyst prop-
5
ate chlorophosphine afforded the corresponding air- and
1
1
moisture-sensitive diphosphinite ligands, which were
subsequently treated with the suitable palladium source
[
PdCl (COD) or Pd(OCOCF ) ] to yield target palla-
2 3 2
1
2
dium complexes 1a and 1b.
Keywords: Palladacycles; Catalysis; Pincer complexes; a-Arylation.
*
Corresponding authors. Tel.: +34 9460 15435; fax: +34 9460 12748
R.S.); e-mail: raul.sanmartin@ehu.es
As mentioned above, the catalytic activity of 1a–b in
several C–C bond-forming reactions was initially tested
(
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.03.040

3234
F. Churruca et al. / Tetrahedron Letters 47 (2006) 3233–3237
OH
O
PR2
1
. PClR , Et N, toluene, reflux, 20h
2 3
EtOOC
EtOOC
Pd
X
2
. PdCl COD, toluene, reflux, 20h
2
OH
or
O
PR2
Pd(OCOCF ) , THF, rt, 4h
3
2
i
2
1a R= Pr, X=Cl
(92%)
1
b R=Ph, X=OCOCF3 (56%)
Scheme 1.
by a series of preliminary studies,13 showing excellent
catalytic properties in Heck, Suzuki and Sonogashira
cross-coupling reactions, as shown in Scheme 2.
9). Once the effectiveness of phosphinite palladacycles
1a–b to arylate sterically hindered aryl alkyl ketones
had been established (Table 1, entries 1–6), their ability
to catalyze selective mono- or/and diarylation reactions
1
7
Encouraged by these results, we then focussed our
attention to the application of so promising catalysts
to the a-arylation of ketone enolates, the main issue of
the present research.
of less hindered substrates was explored. Accordingly,
a careful search and development of experimental reac-
tion conditions was performed with acetophenone and
bromobenzene as substrates. The most remarkable
results are shown in Table 1. Regioselective quantitative
a-monoarylation of acetophenone was successfully
accomplished with 1a in the presence of either Cs CO
On the basis of our experience in ketone a-arylation
reactions, we considered that deoxybenzoins could be
challenging substrates to accomplish initial arylation
assays due to their steric hindrance at the a-position of
the carbonyl group. Our reported conditions for the ary-
lation of deoxybenzoins with Pd(OAc) (Cs CO as base
2
3
or K PO in toluene at 130 ꢁC (entries 10–11). Neverthe-
3
4
less, when using 1b, a slightly better outcome was
achieved with K PO as base. Considering the shorter
3
4
reaction times required by the latter procedure, it was
elected to expand its scope by application to different
substrates. A series of deoxybenzoins 5a–f were thus
prepared from the corresponding acetophenones and
aryl bromides in good yields (entries 12–16), thus
confirming the efficacy of pincer complexes 1 in such a
controlled a-monoarylation. Moreover, selective diaryl-
ation of acetophenone was also attained under the latter
reaction conditions after a reasonable increase of the
amount of aryl bromide, base and reaction temperature
2
2
3
9
a
in DMF) were initially applied to the a-phenylation of
phenyl benzyl ketone replacing Pd(OAc) with catalysts
2
1
a–b. The corresponding triarylethanone 3a was
obtained in good yields employing relatively low load-
ings (0.1 mol %) of both catalysts 1a and 1b (Table 1,
entry 1). Moreover, the latter procedure was extended
to a series of deoxybenzoins and bromoarenes affording
target triarylethanones 3a–f in high yields (entries 1–6).
It is noteworthy that not only the coupling of electron-
poor or neutral but also of electron-rich ketones and
1
8
(entry 17). The application of the so-optimized diaryl-
ation procedure to different acetophenones and to 1-
indanone afforded successfully target triarylethanones
3g–i and 6 (entries 18–21).
1
5
bromoarenes was effectively achieved. In addition to
the generality of the latest procedure regardless the elec-
tronic nature of the coupling partners, the excellent
yields obtained with substituted aryl bromides relied
on the total absence of by-products derived from
In view of the results summarized in Table 1, phosphi-
nite pincer-type complexes 1a–b have shown to be highly
effective catalysts for the a-arylation of aryl and alkyl
ketones. Despite the higher efficacy of the complex 1a
in a-monoarylation of acetophenones, in general there
is no clear trend regarding catalytic activity between
both phosphinite catalysts, providing target aryl ketones
in similar yields.
1
6
phenyl–aryl exchange side reaction.
In a similar fashion the selective monoarylation of sym-
metrical dialkyl ketone, cyclohexanone, with several aryl
bromides was performed as shown in Table 1 (entries 7–
PhB(OH) , 1
Ph-Ph >99%
Cl
2
If these results are compared with our previous works
using the homogeneous Pd(OAc) /PPh system or hetero-
K CO H O
2
3,
2
2
9a–c
3
100 ºC
TM
geneous FibreCat catalysts,
the procedures now
introduced have led to higher overall yields for both
activated and deactivated aryl bromides even decreasing
the catalyst amounts from 2–5% to 0.1% (turnover num-
bers of 800–1000). It should be pointed out that,
although some authors have reported higher TON val-
ues, it has been only for particular cases of monoaryl-
ation reactions, where in addition considerably longer
H
Ph, 1
>99%
Ar-Br/I
pyrrolidine, 100 ºC
Ph
CO Me, 1
Ph
99%
2
1
7,19
CO Me
reaction times were needed.
Therefore, we consider
Na CO , DMF
2
2
3
>
that the protocol presented in this letter constitutes a
reliable methodology of general applicability for the
a-arylation of ketone enolates.
1
40 ºC
Scheme 2.

F. Churruca et al. / Tetrahedron Letters 47 (2006) 3233–3237
3235
Table 1. Ketone a-arylation catalyzed by PCP palladium pincer
complexes 1a–b
Table 1 (continued)
a,14
Entry Product
Method
Yield
b
(
%)
O
O
Ar
1
a-b (0.1 mol%)
+
ArBr
1
a
1b
R1
R2
R1
R2
1
0
1
O
O
B
C
>99 94
>99 88
Entry Product
Method
Yield
b
(
%)
1
1
a
1b
5a
O
O
1
A
A
78 84
1
2
B
B
>99 94
F
3
a
5
b
O
OMe
Me
2
95 96
1
1
3
4
OMe
>99 93
3
b
5c
O
O
Me
Me
3
A
88 96
B
B
>99 90
3
c
5d
MeO
O
O
O
MeO
c
4
A
92 95
15
16
F
>99 91
5
e
3
d
MeO
O
MeO
Me
c
OMe
B
>99 90
5
A
93 92
MeO
MeO
5f
3e
O
O
MeO
1
1
1
7
8
9
D
87
84
86
88
85
88
O
MeO
OMe
c
3a
6
A
95 91
MeO
MeO
3f
F
O
D
c
d
d
d
7
8
9
A
88 83
85 86
80 78
3g
4
a
F
O
c
A
F
4
O
b
OMe
D
O
c
A
3h
OMe
4
MeO
c
(
continued on next page)

3
236
F. Churruca et al. / Tetrahedron Letters 47 (2006) 3233–3237
3. Recent advances in heterogeneous catalysts are reported
Table 1 (continued)
in: (a) Astruc, D.; Heuze, K.; Gatard, S.; Mery, D.; Nlate,
S.; Plault, L. Adv. Synth. Catal. 2005, 347, 329–338; (b)
Guibal, E. Prog. Polym. Sci. 2005, 30, 71–109.
Entry
Product
Method
Yield
b
(
%)
1
a
1b
4
. Churruca, F.; SanMartin, R.; Tellitu, I.; Dom ´ı nguez, E.
O
Synlett 2005, 3116–3120.
i
Me
5. PdCl{C H -2,6-(OP Pr )}: (a) Morales-Morales, D.; Gra-
6
3
2
use, C.; Kasaoka, K.; Red o´ n, R.; Cramer, R. E.; Jensen,
C. M. Inorg. Chim. Acta 2000, 300–302, 958–963; PdO-
COCF {C H -2,6-(OPPh )}: (b) Bedford, R. B.; Draper,
2
0
1
D
84
86
3
i
3
6
3
2
S. M.; Scully, P. N.; Welch, S. L. New J. Chem. 2000, 24,
45–747.
7
O
6
. Immobilization of tridentate palladium complexes onto
heterogeneous and/or polymer support are described in:
2
D
89
89
(
a) Bergbreiter, D. E.; Osburn, P. L.; Frels, J. D. J. Am.
6
Chem. Soc. 2001, 123, 11105–11106; (b) Chan-
thateyanonth, R.; Alper, H. Adv. Synth. Catal. 2004,
a
Method A: ketone (0.5 mmol), aryl bromide (0.5 mmol), Cs
1.2 mmol), 1 (0.1 mol %), DMF (1 mL), 153 ꢁC, 60 min. Method B:
ketone (0.5 mmol), aryl bromide (0.5 mmol), K PO (1.2 mmol), 1
0.1 mol %), toluene (1 mL), 130 ꢁC, 75 min. Method C: ketone
0.5 mmol), aryl bromide (0.5 mmol), Cs CO (1.2 mmol),
0.1 mol %), toluene (1 mL), 130 ꢁC, 2 h. Method D: ketone
0.5 mmol), aryl bromide (1.05 mmol),
0.1 mol %), o-xylene (1 mL), 153 ꢁC, 22 h.
Determined by NMR on the basis of the amount of starting ketone.
Bis(ethylene glycol) dimethyl ether was used as the internal standard.
5 min.
2 3
CO
3
46, 1375–1384.
(
7
. (a) Morales-Morales, D.; Red o´ n, R.; Yung, C. N.; Jensen,
C. M. Chem. Commun. 2000, 1619–1620; (b) Eberhard, M.
R.; Wang, Z.; Jensen, C. M. Chem. Commun. 2002, 818–
3
4
(
(
(
(
(
2
3
1
8
2
19; (c) Solin, N.; Wallner, O. A.; Szab o´ , K. J. Org. Lett.
005, 7, 689–691.
3 4
K PO (1.35 mmol), 1
8
. The use of other palladacycles, to be precise CN chelate or
half-pincer complexes, as catalysts in arylations of ketones
is barely known. For the two examples reported so far see:
b
(
a) Schnyder, A.; Indolese, A. F.; Studer, M.; Blaser,
c
7
H.-U. Angew. Chem., Int. Ed. 2002, 41, 3668–3671; (b)
Viciu, M. S.; Kelly, R. A., III; Stevens, E. D.; Naud, F.;
Studer, M.; Nolan, S. P. Org. Lett. 2003, 5, 1479–1482.
. (a) Churruca, F.; SanMartin, R.; Tellitu, I.; Dom ´ı nguez,
E. Org. Lett. 2002, 4, 1591–1594; (b) Churruca, F.;
SanMartin, R.; Tellitu, I.; Dom ´ı nguez, E. Tetrahedron
Lett. 2003, 44, 5925–5929; (c) Churruca, F.; SanMartin,
R.; Carril, M.; Tellitu, I.; Dom ´ı nguez, E. Tetrahedron
d
Phenyl benzyl ketone was used as the internal standard.
9
In conclusion, PCP-bis(phosphinite) pincer complexes
have proved to be not only highly active Heck, Suzuki
and Sonogashira catalysts but also effective catalytic sys-
tems in ketone a-arylation reactions. The different pro-
cedures developed have allowed both regioselective
monoarylation and diarylation of hindered and unhin-
dered ketone enolates with a wide range of aryl bro-
mides of dissimilar electronic activation. Future
research is directed towards the immobilization of such
powerful catalysts onto an insoluble support in order to
get an easy recovery and reuse.
2
004, 60, 2393–2408; (d) Carril, M.; SanMartin, R.;
Churruca, F.; Tellitu, I.; Dominguez, E. Org. Lett. 2005,
, 4787–4789.
7
1
0. The last years have witnessed an increased interest in
palladium-catalyzed arylation of enolates as the key for
the access to a number of relevant compounds. See for
example: (a) Sole, D.; Vallverdu, L.; Solans, X.; Font-
Bardia, M.; Bonjoch, J. J. Am. Chem. Soc. 2003, 125,
1
587–1594; (b) Willis, M. C.; Taylor, D.; Gillmore, A. T.
Org. Lett. 2004, 6, 4755–4757; (c) MacKay, J. A.; Bishop,
R. L.; Rawal, V. H. Org. Lett. 2005, 7, 3421–3424; (d)
Honda, T.; Sakamaki, Y. Tetrahedron Lett. 2005, 46,
Acknowledgements
6
823–6825.
1
1. NMR spectroscopy showed the products to be greater
This research was supported by the University of the
Basque Country (Project UPV 41.310-13656) and the
Spanish Ministry of Education and Science (MEC
CTQ2004-03706/BQU). Petronor S. A. (Muskiz, Biz-
kaia) is gratefully acknowledged for the generous dona-
tion of hexane.
than 90% pure. 1,3-Bis(diisopropylphosphinito)-5-ethyl-
1
benzoate. Colourless oil. H NMR (500 MHz, CDCl ) d
3
1
(
.12–1.25 (27H, m, CH
2H, q, J 7.1 Hz, CH ), 6.65 (1H, s, H2), 6.98 (2H, s,
H4, H6). C NMR (63 MHz, CDCl ) d 14.23 (CH CH ),
4.85, 16.05 (CH CH), 25.33 (m, CH), 60.63 (CH ), 107.71
3
), 1.91–2.01 (4H, m, CH), 4.22
2
13
3
3
2
1
3
2
(
m, C2), 108.14 (m, C4, C6), 131.86 (C5), 158.26 (m, C1,
31
C3), 166.88 (CO). P NMR (202 MHz, CDCl
3
) d 149.56.
1
,3-Bis(diphenylphosphinito)-5-ethylbenzoate. Colourless
1
References and notes
oil. H NMR (500 MHz, CDCl ) d 1.36 (3H, t, J 7.1 Hz,
3
CH
3 2
), 4.34 (2H, q, J 7.1 Hz, CH ), 7.22 (1H, s, H2), 7.25
0
0
1
2
. For a review on this subject, see: (a) Albrecht, M.; van
Koten, G. Angew. Chem., Int. Ed. 2001, 40, 3750–3781; (b)
Singleton, J. T. Tetrahedron 2003, 59, 1837–1857; (c) Peris,
E.; Crabtree, R. H. Coord. Chem. Rev. 2004, 248, 2239–
(2H, s, H4, H6), 7.36–7.41 (12H, m, H3 , H4 ), 7.81–7.88
(8H, m, H2 ). C NMR (63 MHz, CDCl ) d 13.88 (CH ),
0
13
3
3
60.30 (CH ), 107.59 (m, C2), 107.94 (m, C4, C6), 128.55
2
0
0
0
0
(m, C3 ), 130.31 (m, C2 ), 132.49 (C4 ), 133.40 (C1 ),
3
1
2246.
133.68 (C5), 158.15 (m, C1, C3), 166.54 (CO). P NMR
. (a) Ohff, M.; Ohff, A.; van der Boom, M. E.; Milstein, D.
J. Am. Chem. Soc. 1997, 119, 11687–11688; (b) van der
Boom, M. E.; Milstein, D. Chem. Rev. 2003, 103, 1759–
(202 MHz, CDCl ) d 112.62.
3
12. Compound 2a: white solid, mp 130–130.5 ꢁC (EtOAc).
ꢀ
1
1
FTIR (neat film): 1713 cm
.
H NMR (500 MHz,
1792.
CDCl ) d 1.25–1.42 (27H, m, CH ), 2.48 (4H, hep, J
3
3

F. Churruca et al. / Tetrahedron Letters 47 (2006) 3233–3237
3237
7
.2 Hz, CH), 4.32 (2H, q, J 7.1 Hz, CH
2
), 7.22 (2H, s, H4,
) d 14.25 (CH CH ),
6.57, 17.11 (CH CH), 28.76 (m, CH), 60.90 (CH ), 107.08
7.45 (2H, m), 7.53 (1H, dddd, J 7.5, 7.1, 2.4, 1.6 Hz), 7.95–
7.99 (2H, m). 1,2-Bis(3,4-dimethoxyphenyl)-2-(4-methoxy-
1
3
H6). C NMR (63 MHz, CDCl
1
3
3
2
9
c 1
phenyl)ethanone 3f: H NMR (250 MHz, CDCl ) d 3.73
3
2
3
(
m, C4, C6), 130.74 (C5), 136.22 (m, C2), 165.88 (m, C1,
(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, J
8.3 Hz), 7.57 (1H, s), 7.63 (1H, d, J 8.3 Hz). 1-(3,4-
3
1
C3), 166.11 (CO). P NMR (202 MHz, CDCl
Anal. Calcd for C21 35ClO Pd: C, 45.42; H, 6.35.
Found: C, 45.46; H, 6.33. Compound 2b. white solid: mp
3
) d 188.52.
H
4 2
P
2
0a
1
Dimethoxyphenyl)-2,2-diphenylethanone 3d:
H NMR
ꢀ
1 1
2
45.5–246 ꢁC (EtOAc). FTIR (neat film): 1715 cm . H
(250 MHz, CDCl ) d 3.87 (3H, s), 3.90 (3H, s), 6.02 (1H,
3
NMR (500 MHz, CDCl
3
) d 1.36 (3H, t, J 7.1 Hz, CH
3
),
s), 6.82 (1H, d, J 8.3 Hz), 7.22–7.35 (10H, m), 7.58 (1H, s),
4
7
.33 (2H, q, J 7.1 Hz, CH ), 7.38 (2H, s, H4, H6), 7.47–
7.64 (1H, d, J 8.3 Hz). 2-(4-Fluorophenyl)-1-(4-methyl-
2
0
0
0
13
20b 1
.60 (12H, m, H3 , H4 ), 7.81–7.88 (8H, m, H2 ).
C
phenyl)ethanone 5e:
3
H NMR (250 MHz, CDCl ) d 2.41
NMR (63 MHz, CDCl
3
) d 14.23 (CH
3
), 61.12 (CH
2
),
(3H, s), 4.23 (2H, s), 7.01 (2H, dd, J 8,7, 8,3 Hz), 7.21 (2H,
dd, J 8.7, 5.5 Hz), 7.26 (2H, d, J 8.3 Hz), 7.80 (2H, d, J
8.3 Hz).
1
08.34 (m, C4, C6), 116.2 (q, J 290.8 Hz, CF
3
), 128.92 (m,
0
0
0
0
C3 ), 131.80 (m, C2 ), 132.31 (C4 ), 132.69 (C1 ), 133.11
(
1
C5), 133.52 (m, C2), 161.3 (q, J 35.9 Hz, COCF
3
),
64.43 (m, C1, C3), 165.77 (COO). P NMR (202 MHz,
) d 145.57. Anal. Calcd for C35 Pd: C,
4.67; H, 3.54. Found: C, 54.65; H, 3.58.
15. The yields of a-arylation of ketone enolates are generally
lower for electron-rich coupling partners than for neutral
or electron-deficient ones. (a) Palucki, M.; Buchwald, S. L.
J. Am. Soc. Chem. 1997, 119, 11108–11109; (b) Viciu, M.
S.; Germaneau, R. F.; Nolan, S. P. Org. Lett. 2002, 4,
4053–4056.
3
1
CDCl
5
3
27 3 6 2
H F O P
1
3. For these preliminary assays with phosphinite PCP
catalysts, the reaction conditions were those employed in
our previous work on NCN pincer catalysts. Accordingly,
the amount of catalysts 1 employed in the three cases
16. Phenyl migration or the phenyl/aryl exchange between an
aryl halide/triflate and the phenyl group of PPh is well
3
(
1
Suzuki, Sonogashira and Heck couplings) was
documented and becomes a deleterious side-process in
palladium-catalyzed arylation reactions. See Ref. 9b.
17. Several authors have reported arylations of such sub-
strates, but in most cases featuring a lack of control of the
reaction towards selective mono- or diarylation processes.
See Ref. 15a. See also: Ehrentraut, A.; Zapf, A.; Beller, M.
Adv. Synth. Catal. 2002, 344, 209–217.
ꢀ1
0
mol % Pd. See Ref. 4 for more details. For a
significant application of a related palladacycle to Heck
reaction, see: Miyazaki, F.; Yamaguchi, K.; Shibasaki, M.
Tetrahedron Lett. 1999, 40, 7379–7383.
1
4. General procedure (Method A): A dry 5-mL round
bottom flask was charged with the aryl bromide
(
0.5 mmol), ketone (0.5 mmol), catalyst 2 (0.0005 mmol
18. It should be taken into account that in addition to the
higher amounts of bromobenzene (2.1 equiv) and base
(2.7 equiv) needed for the diarylation reaction, the inser-
tion of the second aryl group implies the arylation of a
hindered ketone as deoxybenzoin requiring relatively
higher temperatures.
19. (a) Kawatsura, M.; Hartwig, J. F. J. Am. Soc. Chem. 1999,
121, 1473–1478; (b) Fox, J. M.; Huang, X.; Chieffi, A.;
Buchwald, S. L. J. Am. Soc. Chem. 2000, 122, 1360–1370.
20. (a) Alesso, E. N.; Tombari, D. G.; Ibanez, A. F.;
Bonafede, J. D.; Moltrasio, G. Y.; Aguirre, J. M. An.
Asoc. Quim. Argent. 1987, 75, 393–401; (b) Kim, C. K.;
Lee, I. Bull. Korean Chem. Soc. 1997, 18, 395–401.
Pd), Cs CO (1.2 mmol) and dry DMF (1 mL). The
2
3
mixture was stirred at 153 ꢁC under argon for 1 h. After
cooling, water (10 mL) was added, and the aqueous layer
was extracted with EtOAc (3 · 10 mL). The combined
organic extracts were dried over anhydrous sodium sulfate
and evaporated in vacuo. The residue was dissolved in
CDCl and analyzed by H NMR and C NMR (using
3
bis(ethylene glycol) dimethyl ether as an internal stan-
dard). For Methods B, C and D see Table 1. Selected
1
13
9
c
examples: 2,2-Bis(4-fluorophenyl)-1-phenylethanone 3g:
1
H NMR (250 MHz, CDCl
3
) d 6.00 (1H, s), 7.02 (4H, ddd,
J 8.7, 8.3, 1.9 Hz), 7.29 (4H, ddd, J 8.7, 5.5, 2.4 Hz), 7.39–