Simple, highly active palladium catalysts for ketone and malonate arylation: Dissecting the importance of chelation and steric hindrance

Article abstract of DOI:10.1021/ja983378u

A remarkably active catalyst system for α-arylation of ketones and malonates was developed by proposing that sterically hindered alkylphosphines would accelerate the catalytic reaction rates. We initially tested the bisphosphine ligand D'BPF (1,1'-bis-(di-tert-butylphosphino)ferrocene) for this palladium-catalyzed chemistry. This catalyst system led to fast reaction rates for reactions of aryl bromides with ketones, including room temperature chemistry in many cases. In some cases turnover numbers were 20 000. The catalyst also gave mild reactions with aryl chlorides with yields that were similar to the chemistry with aryl bromides. Independent synthesis of the arylpalladium enolate complexes with isobutyrophenone enolate showed that only one phosphorus of the bisphosphine ligand D'BPF was coordinated in the enolate complex. Thus, we tested sterically hindered alkylphosphine ligands for the ketone and malonate arylation process and found that P(t-Bu)₃ gave exceptionally fast rates and high turnover numbers for these reactions. These results demonstrate several principles for the catalytic chemistry that we did not anticipate: palladium complexes of monophosphine ligands can activate aryl chlorides under mild conditions, and palladium enolates coordinated by certain monophosphines can undergo C-C bond-forming reductive elimination much faster than β-hydrogen elimination.

Full text of DOI:10.1021/ja983378u

J. Am. Chem. Soc. 1999, 121, 1473-1478
1473
Simple, Highly Active Palladium Catalysts for Ketone and Malonate
Arylation: Dissecting the Importance of Chelation and Steric
Hindrance
Motoi Kawatsura and John F. Hartwig*
Contribution from the Department of Chemistry, Yale UniVersity, P.O. Box 208107,
New HaVen, Connecticut 06520-8107
ReceiVed September 22, 1998
Abstract: A remarkably active catalyst system for R-arylation of ketones and malonates was developed by
proposing that sterically hindered alkylphosphines would accelerate the catalytic reaction rates. We initially
t
tested the bisphosphine ligand D BPF (1,1′-bis-(di-tert-butylphosphino)ferrocene) for this palladium-catalyzed
chemistry. This catalyst system led to fast reaction rates for reactions of aryl bromides with ketones, including
room temperature chemistry in many cases. In some cases turnover numbers were 20 000. The catalyst also
gave mild reactions with aryl chlorides with yields that were similar to the chemistry with aryl bromides.
Independent synthesis of the arylpalladium enolate complexes with isobutyrophenone enolate showed that
t
only one phosphorus of the bisphosphine ligand D BPF was coordinated in the enolate complex. Thus, we
tested sterically hindered alkylphosphine ligands for the ketone and malonate arylation process and found that
P(t-Bu)3 gave exceptionally fast rates and high turnover numbers for these reactions. These results demonstrate
several principles for the catalytic chemistry that we did not anticipate: palladium complexes of monophosphine
ligands can activate aryl chlorides under mild conditions, and palladium enolates coordinated by certain
monophosphines can undergo C-C bond-forming reductive elimination much faster than â-hydrogen elimination.
Introduction
onate arylations require aryl iodides. Similarly, palladium-
14
catalyzed reactions of malononitriles occur in lower yields with
bromoarenes and require harsher conditions for hydrolysis than
malonic esters.
The coupling of enolates with aryl halides, a transformation
as fundamental as enolate alkylation, has historically been
difficult to conduct.
1-3
Previously, this reaction was reported
Recently our group, Buchwald and Palucki,16 and Satoh et
al.17 showed that palladium complexes catalyzed a simple ketone
arylation process. The use of resolved rather than racemic
BINAP and substrates that form quaternary carbons allowed
15
with use of tin enolates of methyl ketones in modest yields and
1,4
in low yields with higher homologs. In addition this reaction
was conducted with use of silyl enol ethers in the presence of
2
tin fluoride, which also uses a stoichiometric amount of tin
18
this reaction to be conducted asymmetrically. We have sought
an understanding of the catalyst properties that are important
to develop more active systems for the arylation of carbonyl
compounds. We began this effort with several hypotheses that
were untested for the ketone arylation. First, oxidative addition
of the aryl halides and reductive elimination of product both
involve a low-coordinate Pd(0) reactive intermediate. Therefore,
steric effects should increase the energy of the more stable high
coordinate species, decreasing the relative energy of the reactive
and presumably generates the same tin enolate. Direct intramo-
lecular reactions of ketones with aryl halides in modest yields
was reported many years ago with stoichiometric or high catalyst
loadings of Ni(COD)2.3 Intramolecular ketone arylation has
been recently conducted more successfully with palladium
,5
6
complexes. Other methods involve the use of electrophilic and
often toxic main group aryl reagents.7,8 The coupling of
malonates with aryl halides is even less common. In some cases
these reactions can be conducted with stoichiometric amounts
1
9,20
intermediate and increasing reaction rates.
Second, alkyl-
9
,10
11
of copper
or with catalytic amounts of copper most
12,13
commonly with o-halobenzoic acids.
However, these mal-
(11) Okuro, K.; Furuune, M.; Miura, M.; Nomura, M. J. Org. Chem.
993, 58, 7606-7607.
(12) Bruggink, A.; McKillop, A. Tetrahedron 1975, 31, 2607-2619.
(13) McKillop, A.; Rao, D. P. Synthesis 1977, 759.
1
(1) Kosugi, M.; Hagiwara, I.; Sumiya, T.; Migita, T. Bull. Chem. Soc.
Jpn. 1984, 57, 242-246.
(
(
2) Kuwajima, I.; Urabe, H. J. Am. Chem. Soc. 1982, 104, 6831-6833.
(14) Malononitrile has been shown to react with aryl iodides with
3) Semmelhack, M. F.; Chong, B. P.; Stauffer, R. D.; Rogerson, T. D.;
palladium catalysts to form the less readily hydrolyzed aryl malononi-
triles: Uno, M.; Seto, K.; Takahashi, S. J. Chem. Soc., Chem. Commun.
1984, 932-933.
(15) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119, 12382-
12383.
(16) Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 11108-
11109.
Chong, A.; Jones, L. D. J. Am. Chem. Soc. 1975, 97, 2507-2516.
(4) Kosugi, M.; Suzuki, M.; Hagiwara, I.; Goto, K.; Saitoh, K.; Migita,
T. Chem. Lett. 1982, 939-940.
(5) Millard, A. A.; Rathke, M. W. J. Org. Chem. 1977, 99, 4833-4835.
(6) Muratake, H.; Natsume, M. Tetrahedron Lett. 1997, 38, 7581-7582.
(7) Barton, D. H. R.; Finet, J. P.; Khamsi, J.; Pichon, C. Tetrahedron
Lett. 1986, 27, 3619-3522.
(17) Satoh, T.; Kawamura, Y.; Miura, M.; Nomura, M. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 1740-1742.
(18) Åhman, J.; Wolfe, J. P.; Troutman, M. V.; Palucki, M.; Buchwald,
S. L. J. Am. Chem. Soc. 1998, 120, 1918-1919.
(19) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 7369-
7370.
(
8) Barton, D. H. R.; Donnelly, D. M. X.; Finet, J.-P.; Guiry, P. J. J.
Chem. Soc., Perkin Trans. 1 1992, 1365-1375.
(
9) Osuka, A.; Kobayashi, S.; Suzuki, H. SYNTHESIS 1983, 67-68.
(10) Setsune, J.-i.; Matsukawa, K.; Wakemoto, H.; Kitao, T. Chem. Lett.
1
981, 367-370.
1
0.1021/ja983378u CCC: $18.00 © 1999 American Chemical Society
Published on Web 02/03/1999

1474 J. Am. Chem. Soc., Vol. 121, No. 7, 1999
Kawatsura and Hartwig
phosphines should be more resistant toward P-C cleavage
Table 1. Reaction of Ketones and Malonates with ArBr, ArCl, and
ArOTs
processes than arylphosphines, and should provide higher
2
1,22
turnover numbers.
Third, chelation would prevent the
enolate intermediates from undergoing â-hydrogen elimina-
tion,2
3,24
which would prevent formation of R-aryl ketone
products. Consistent with this third hypothesis, our pervious
catalysts containing either DPPF or a more sterically hindered
o-tolyl version of this ligand and the catalyst systems reported
by Buchwald involved either bisphosphine ligands or ligands
with both phosphorus and nitrogen donor atoms that can chelate
to the metal and/or act as hemilabile ligands.1
6,18,25
For these reasons, we initiated our studies by using palladium
complexes of the sterically hindered bisphosphine ligand 1,1′-
t
19,26
bis(di-tert-butylphosphino)ferrocene (D BPF, 1).
The high
activity of these catalysts confirmed some of our hypotheses,
but preliminary mechanistic data disproved the importance of
chelation and led us to select simple, sterically hindered alkyl
monophosphines as remarkably active catalysts for arylation of
both ketones and malonates. These synthetic studies and
preliminary mechanistic results are reported here.
Results and Discussion
t
Synthetic Studies with D BPF. The overall ketone arylation
reaction is shown in eq 1. As shown in Table 1, reactions
a
; B ) Pd(OAc)
2
. b 1:1.25 ratio of Pd/L for reactions
A ) Pd(dba)
2
of aryl bromides or for aryl chlorides using monophosphines; 1:0.5
ratio of Pd/L for reactions of aryl chlorides using ligand 1; 1.5 equiv
of NaO-t-Bu for all reactions except those for acetophenone that used
c
2
.2 equiv of base, 1.1 equiv of ketone, THF solvent. Yields are an
d
average of two runs on 1 or 2 mmol scale. 89:11 ratio of isomers in
t
employing D BPF as ligand provided mild arylation of ketones
crude reaction. e 74:26 ratio of isomers in crude reaction. f 87:13 ratio
g
with bromoarenes. Turnover numbers of 20 000 were observed
in some cases. Monoarylation of acetophenone was accom-
plished with 2 equiv of base. Heterocyclic bromides that might
displace a hindered phosphine were also suitable substrates.
Reactions employing D BPF as ligand coupled dialkyl ketones
with bromoarenes (Entries 11 and 13). Reactions with cyclo-
hexanone selectively gave the monoarylation product. 4-Methyl-
of isomers in crude reaction. 76:24 ratio of isomers in crude reaction.
Reaction conducted in dioxane solvent using 1.1 equiv of NaO-t-Bu.
h
complete reaction, and 1 mol % ligand was optimal.27 Reactions
of chloroarenes with acyclic dialkyl ketones showed similar
selectivity to those with bromoarenes. Typical palladium
chemistry of aryl chlorides occurs at high temperatures or with
electron-poor chloroarenes. These results and others reported
t
3-pentanone reacted with 3-bromoanisole to provide the products
2
5
from a single R-arylation in 84% yield, with the product formed
from arylation of the less hindered alkyl group dominating. The
ratio of R-arylation products was 89:11 in the crude reaction
mixture (GC analysis).
recently demonstrate that lower temperatures are possible for
many coupling processes with palladium complexes.
t
Ketones did not react with aryl tosylates when using D BPF
as ligand, but a related chelating phosphine with tert-butyl
substituents 1-diphenylphosphino-2-(di-tert-butylphosphino)-
t
The catalyst containing D BPF provided clean chemistry with
28-30
chloroarenes at only 70 °C. Electron neutral and even electron
rich chloroarenes gave the coupled product in high yield, and
sterically hindered aryl chlorides were suitable substrates despite
the size of the ligand. The use of 2 mol % of Pd(dba)2 led to
ethylferrocene (PPF-t-Bu , 2)
gave good yields when using
2
5 mol % catalyst at 70 °C. Little palladium-catalyzed chemistry
with aryl tosylates has been reported previously and only one
19
example of cross-coupling. Although 2 is a homochiral ligand
in its commercially available form and the product contains a
new stereocenter, the basic conditions lead to the formation of
racemic product.
(
20) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 3694-
3
1
1
7
1
1
703.
(
21) Goodson, F. E.; Wallow, T. I.; Novak, B. M. J. Am. Chem. Soc.
997, 119, 12441-12453.
(
22) Morita, D. K.; Stille, J. K.; Norton, J. R. J. Am. Chem. Soc. 1995,
(27) Pd(dba)2 did not catalyze the ketone arylation and slowly gave biaryl
product. One can understand the activity of this Pd/bisphosphine ratio in
terms of the mechanistic data and results with the 1:1 Pd/monophosphine
ratio described below.
(28) This ligand is commercially available from Strem.
(29) Togni, A.; Breutel, C.; Schnyder, A.; Spindler, F.; Landert, H.;
Tijani, A. J. Am. Chem. Soc. 1994, 116, 4062-4066.
(30) Togni, A.; Breutel, C.; Soares, M. C.; Zanetti, N.; Gerfin, T.;
Gramlich, V.; Spindler, F.; Rihs, G. Inorg. Chim. Acta 1994, 222, 213-
24.
17, 8576-8581.
23) Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1996, 118, 7217-
218.
(
(24) Hayashi, T.; Knoishi, M.; Kumada, M. Tetrahedron Lett. 1979, 21,
871-1874.
(25) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998,
20, 9722-9723.
26) Butler, I. R.; Cullen, W. R.; Kim, T. J.; Rettig, S. J.; Trotter, J.
Organometallics 1985, 4, 972-80.
(

Catalysts for Ketone and Malonate Arylation
J. Am. Chem. Soc., Vol. 121, No. 7, 1999 1475
Scheme 1
From these initial studies, we concluded that sterically hindered
monophosphines may be appropriate for this type of cross
coupling.
Synthetic Studies Involving Sterically Hindered Alkyl-
monophosphines. Considering our mechanistic conclusions
t
concerning the coordination number of D BPF in the arylpal-
ladium enolate intermediate, we evaluated PhP(t-Bu)2 as a model
t
for monodentate D BPF in the ketone arylation. We also
evaluated the simple, commercially available monophosphines
3
3,34
P(t-Bu)3
and PCy3. The reactions of aryl bromides with
Qualitative Mechanistic Studies. Scheme 1 shows a general
mechanism for the ketone arylation. Considering the success
of chelating phosphine ligands in previous palladium-catalyzed
arylation of ketone enolates that could undergo â-hydrogen
elimination, it seemed likely that this ligand property was
important to favor reductive elimination over â-hydrogen
elimination.2
ketones occurred in high yields with these ligands. Reactions
with P(t-Bu)3 were faster than those with PhP(t-Bu)2, and further
chemistry with PhP(t-Bu)2 was not pursued. Cyclohexanone,
3-methyl-2-propanone, acetophenone, propiophenone, and isobu-
tyrophenone reacted with electron rich, electron neutral, electron
poor, sterically hindered, or sterically unhindered aryl bromides
and aryl chlorides in high yield when using P(t-Bu)3 as ligand
3,24,31
t
Preliminary mechanistic data with D BPF as ligand cast doubt
(Table 1) Turnover numbers for reaction of propiophenone with
upon the requirements for chelation. Arylpalladium enolate
phenyl bromide were as high as 20 000. Reaction of propiophe-
none with aryl chlorides also occurred in high yield when using
PCy3 as ligand.
t
complexes were generated with both DPPF and D BPF ligands
to evaluate structure/reactivity relationships. Reaction of (DP-
PF)Pd(p-Tol)(Br) (3)15 with the enolate of isobutyrophenone
gave a single set of doublets (δ 29.83, 10.37, J ) 34.2 Hz)
corresponding to an arylpalladium enolate complex 4 (eq 2).
We were able to find conditions that led to monoarylation of
all ketones except methyl alkyl ketones. These conditions were
developed by considering the acid/base equilibria that result from
a more acidic and less nucleophilic reaction product. Reactions
of methyl aryl ketones occurred with high selectivity for
monoarylation by using 2 equiv of base. If 1 equiv of base is
used, the enolate ion of the product is formed in preference to
the enolate of the starting ketone and the enolate of the product
ketone is an active reagent for the arylation process. Two
equivalents of alkoxide base ensures that all ketones exist in
their enolate form. The reaction of dialkyl ketones occurred with
high selectivity for monoarylation when using 1 equiv of base.
In this case, we propose that neither product nor starting ketone
is quantitatively deprotonated by the alkoxide base. Further, the
enolate of the product is deprotonated at the more acidic tertiary
benzylic position, which is sterically hindered and less reactive
than the more nucleophilic and less hindered enolate of the
starting ketone. Qualitative studies showed that methyl alkyl
ketones do undergo formation of diarylation products in good
yield, but these reactions were not pursued in detail.
This enolate was identified as an O-bound enolate due to the
1
two different enolate methyl groups observed in the H NMR
spectrum near 2 ppm. This species reacted at room temperature
in the presence or absence of added PPh3 to trap the Pd(0)
product, but gave <10% yield of R-aryl ketone. Biaryls,
presumably from disproportionation of the arylpalladium enolate
and from P-C cleavage, were the major products.
t
In contrast, addition of isobutyrophenone enolate to (D BPF)-
3
2
Pd(Ph)(Br) (5) at -78 °C (eq 3) generated a single arylpal-
The selectivity for arylation of dialkyl ketones with two
enolizable positions is perplexing at this point. Overall, it appears
that bisphosphine ligands provide better selectivity than do the
ligands in this work that are either monophosphines or bind in
a monodentate fashion when the enolate is coordinated. The
higher selectivity may, in fact, indicate that the bisphosphines
with the smaller aryl substituents generate more sterically
demanding enolate complexes. More detailed mechanistic
analysis concerning the structures, exchanges, and reductive
elimination rates of different enolate complexes are necessary
to provide an unambiguous reason for the observed selectivity
and a means to combine the high selectivity with high activity
in a simple ligand system.
ladium enolate product 6 that underwent reductive elimination
1
in quantitative yield at room temperature ( H NMR spectroscopy
with internal standard). Moreover, the 31P{1H} NMR spectrum
of the enolate complex displayed two singlets at 24.8 and 57.2
ppm in a 1:1 ratio. One singlet lay in the region of coordinated
ligand and the other in the region near, but not identical with
t
that of free D BPF (24.6 ppm). We have not yet rigorously
determined the geometry and hapticity of the enolate ligand,
due to its reactivity at room temperature, its temperature-
1
dependent H NMR spectra, and the overlap of enolate methyl
resonances with the tert-butyl groups of the ligand. However,
the absence of resonances near 2 ppm suggest a different binding
mode than for the DPPF complex 4. Further studies on complex
Arylation of Malonates. The alkylation of malonates is one
of the fundamental reactions of organic chemistry and allows
the synthesis of various carboxylic acids. Arylation of malonates
is synthetically challenging as discussed in the introduction.
6
and related palladium enolates will be conducted in the future.
For now, it is important to realize that this complex clearly
t
t
However, the use of either D BPF or P(t-Bu)3 in combination
contains a D BPF ligand that is bound to the metal by only one
phosphorus atom as determined by 31P{ H} NMR spectroscopy.
1
with palladium catalyst precursors led to mild arylation of simple
malonates. Reaction of phenyl chloride with di-tert-butylma-
(
31) Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119, 8232-
245.
32) This complex was prepared by addition of DB PF to {Pd[P(o-tolyl)3]-
Ph)Br}2 in toluene and precipitation by addition of pentane. Mann, G.;
Hartwig, J.F. To be submitted for publication.
8
(33) Nishiyama, M.; Yamamoto, T.; Koie, Y. Tetrahedron Lett. 1998,
t
(
39, 617-620.
(
(34) Yamamoto, T.; Nishiyama, M.; Koie, Y. Tetrahedron Lett. 1998,
39, 2367-2370.

1476 J. Am. Chem. Soc., Vol. 121, No. 7, 1999
Kawatsura and Hartwig
lonate in the presence of NaO-t-Bu and a combination of Dt-
BPF and Pd(dba)2 as catalyst led to the formation of aryl
malonate product in high yield at 100 °C. Reactions with this
catalyst system did not form useful yields of aryl malonates
from diethylmalonate in dioxane solvent. However, reactions
between the inexpensive diethyl malonate and phenyl bromide
with Pd(OAc)2 and P(t-Bu)3 as catalyst did cleanly produce the
desired aryl malonate product.
recrystallizing the crude precipitate.40 The potassium enolate of
isobutyrophenone was prepared by addition of isobutyrophenone to a
toluene/pentane solution of potassium hexamethyldisilazide and was
recrystallized from THF/ether after isolation by filtration. All other
solvents and compounds were used as received.
General Procedure for the Reaction of Ketone with Arylbromide.
The reaction conditions and results are shown in Table 1. A typical
procedure is given for the reaction in Entry 1.
1
,2-Diphenyl-1-propanone:41 Pd(dba)
2
(23.0 mg, 0.040 mmol), Dt-
Intermolecular reactions of malonates with aryl halides using
t
BPF (23.7 mg, 0.050 mmol), and NaO Bu (288 mg, 3.00 mmol) were
suspended in 2 mL of THF in a screw-capped vial. The vial was sealed
with a cap containing a PTFE septum and removed from the drybox.
Bromobenzene (314 mg, 2.00 mmol) and propiophenone (289 mg, 2.20
mmol) were added to the reaction mixture by syringe. The reaction
mixture was stirred at 25 °C and monitored by GC analysis. The crude
reaction was diluted with ether and washed with water and brine. The
1
4
transition metal catalysts are rare if not unprecedented, and
have been conducted intramolecularly only at high tempera-
3
5
tures. These malonate arylations did not occur in reasonable
rates when using DPPF, BINAP, PPh3, or P(o-tolyl)3 as ligand.
In most cases, it is likely that the anions of â-dicarbonyl
compounds will form complexes that are stable to reductive
elimination. Of course, acetylacetonate complexes are common
and are often remarkably stable. In the case of the complexes
containing tert-butylphosphine ligands, these â-dicarbonylate
complexes are more reactive than expected and lead to the
formation of aryl malonates. This chemistry is certainly valuable
synthetically as a route to R-aryl carboxylic acid derivatives
that are a common building block for pharmaceutical materials.
organic layer was dried over Na
2 4
SO , filtered, and concentrated in
Vacuo. The residue was chromatographed on silica gel (hexane/EtOAc
1
)
95/5) to give 396 mg (94%) of 1,2-Diphenyl-1-propanone:
NMR: (CDCl ) δ 7.95 (d, J ) 7.3 Hz, 2H), 7.48 (t, J ) 7.3 Hz, 1H),
.40-7.37 (m, 2H), 7.30-7.29 (m, 4H), 7.23-7.17 (m, 1H), 4.70 (q,
H
3
7
13
1
J ) 6.8 Hz, 1H), 1.54 (d, J ) 6.8 Hz, 3H); C{ H} NMR (CDCl ) δ
3
200.32, 141.55, 136.53, 132.83, 129.04, 128.82, 128.53, 127.82, 126.95,
47.91, 19.57.
2
-Methyl-1,2-diphenyl-1-propanone:42 Bromobenzene (157 mg,
Conclusions
2
1.00 mmol), isobutyrophenone (163 mg, 1.10 mmol), Pd(dba) (11.5
t
t
mg, 0.020 mmol), D BPF (11.8 mg, 0.025 mmol), and NaO Bu (144
The results presented here suggest several important principles
for the palladium-catalyzed arylation of ketones. First, the
selectivity for reductive elimination from the enolate intermedi-
ate, rather than â-hydrogen elimination, does not require
chelation or arylphosphine ligands and is driven toward reduc-
tive elimination by steric hindrance. Second, high selectivity
for reaction with the less hindered side of a dialkyl ketone may
benefit from chelation, and palladium complexes of the simple
monophosphines here and complexes of bidentate phos-
mg, 1.50 mmol) were used. Reaction at 50 °C for 6 h gave 196 mg
(
9
5
87%) of product after silica gel chromatography (hexane/EtOAc )
1
3
5/5). H NMR (CDCl ) δ 7.48 (d, J ) 7.2 Hz, 2H), 7.38-7.33 (m,
13
H), 7.29-7.26 (m, 1H), 7.21 (t, J ) 7.9 Hz, 2H), 1.62 (s, 6H); C-
1
{ H} NMR (CDCl ) δ 203.67, 145.29, 136.25, 131.67, 129.72, 129.02,
3
127.95, 126.79, 125.72, 51.41, 27.87.
1-Phenyl-2-(3-pyridyl)-1-propanone:43 3-Bromopyridine (158 mg,
1.00 mmol), propiophenone (148 mg, 1.10 mmol), Pd(dba)
2
(11.5 mg,
t
t
0
.020 mmol), D BPF (11.9 mg, 0.025 mmol), and NaO Bu (144 mg,
15,16,18
1.50 mmol) were used. Reaction at 55 °C for 12 h gave 183 mg (87%)
of 1-phenyl-2-(3-pyridyl)-1-propanone after silica gel chromatography
phines
serve as complementary catalysts. Third, activation
of chloroarenes under mild conditions does not require chelation,
1
(
)
7
7
{
hexane/EtOAc ) 80/20). H NMR (CDCl
3
) δ 8.61 (s, 1H), 8.47 (d, J
as one might expect from previous palladium chemistry with
4.8 Hz, 1H), 7.94 (d, J ) 7.5 Hz, 2H), 7.61 (d, J ) 7.9 Hz, 1H),
chloroarenes.3
6-38
Finally, arylation of simple malonates occurs
.52 (t, J ) 7.5 Hz, 1H), 7.42 (t, J ) 7.5 Hz, 2H), 7.23 (dd, J ) 4.8,
with catalyst systems containing sterically hindered alkylphos-
phines, providing a convenient route to R-aryl carboxylic acids.
A detailed mechanistic basis for these conclusions will be one
subject of future studies in our lab.
13
.9 Hz, 1H), 4.75 (q, J ) 6.9 Hz, 1H), 1.56 (d, J ) 6.9 Hz, 3H); C-
1
3
H} NMR (CDCl ) δ 199.46, 149.32, 148.13, 136.85, 135.81, 135.04,
133.09, 128.57, 128.54, 123.69, 44.68, 19.20.
2-(3-Methoxyphenyl)-4-methyl-3-pentanone: 3-Bromoanisole (187
mg, 1.00 mmol), 2-methyl-3-pentanone (100 mg, 1.10 mmol), Pd(dba)
2
t
t
Experimental Section
(11.5 mg, 0.020 mmol), D BPF (11.8 mg, 0.025 mmol), and NaO Bu
288 mg, 3.00 mmol) were used. Reaction at 50 °C for 12 h gave 189
(
General Methods. Reactions were conducted with standard Schlenk
mg (92%) of a mixture of 2-(3-methoxyphenyl)-4-methyl-3-pentanone
and 2-(3-methoxyphenyl)-2-methyl-3-pentanone after silica gel chro-
1
13
1
and drybox techniques. H and C{ H} NMR spectra were recorded
1
on a Bruker AM 500 MHz spectrometer with TMS ( H) or residual
matography (hexane/ether ) 95/5). The ratio of isomers was determined
1
3
31
1
protiated ( C) solvent used as a reference. P{ H} NMR spectra were
1
by GC analysis in the crude reaction mixture. H NMR: (CDCl
3
) δ
recorded on an Omega 300 MHz spectrometer with shifts reported
relative to an external 85% H PO standard; resonances downfield of
3 4
7
)
.24 (t, J ) 7.9 Hz, 1H), 6.84-6.78 (m, 2H), 6.76 (s, 1H), 3.89 (q, J
6.9 Hz, 1H), 3.80 (s, 3H), 2.70 (sept, 6.9 Hz, 1H), 1.37 (d, J ) 6.9
the standard are reported as positive. Low resolution mass spectra were
obtained on a Hewlett Packard 5890 series II gas chromatograph
interfaced with a Hewlett Packard 5989 A mass spectrometer. Tet-
rahydrofuran was distilled from sodium and benzophenone and was
stored in the drybox. 1,1′-Bis(di-tert-butylphosphino)ferrocene39 was
prepared by literature procedures and was recrystallized under nitrogen.
13 1
Hz, 3H), 1.08 (d, J ) 6.9 Hz, 3H), 0.93 (d, J ) 6.9 Hz, 3H); C{ H}
NMR (CDCl
3
) δ 214.42, 159.93, 142.33, 129.76, 120.35, 113.61,
12.34, 55.16, 39.10, 25.17, 19.23, 18.28, 18.02. MS m/e (rel intensity)
06 (42), 135 (100), 120 (12), 105 (34), 91 (38), 77 (24), 71 (55), 51
: C, 75.69; H, 8.80. Found: C, 75.75:
H, 8.71. Selected H NMR of minor isomer: 0.97 (t, J ) 7.3 Hz, 3H),
1
2
18 2
(6). Anal. Calcd for C13H O
1
“
2
[Pd(DBA) ]” is predominantly a mixture of Pd(dba)
3
and Pd
2 3
(dba)
1
.48 (s, 6H), 2.24 (q, J ) 7.3 Hz, 2H), 3.81 (s, 3H), aromatic region
and was obtained by the synthesis reported for [Pd
2
(DBA)
3
] without
overlaps with major isomer. MS m/e (rel intensity) 206 (41), 149 (100),
(
35) Ciufolini, M. A.; Qi, H. B.; Browne, M. E. J. Org. Chem. 1988,
3, 4149-4151.
36) Ben-David, Y.; Portnoy, M.; Milstein, D. J. Am. Chem. Soc. 1989,
11, 8742-8743.
37) Ben-David, Y.; Portnoy, M.; Milstein, D. J. Chem. Soc., Chem.
Commun. 1989, 1816-1817.
38) Ben-David, Y.; Portnoy, M.; Gozin, M.; Milstein, D. Organome-
tallics 1992, 11, 1995-1996.
39) Cullen, W. R.; Kim, T. J.; Einstein, F. W. B.; Jones, T. Organo-
metallics 1983, 2, 714-719.
135 (9), 121 (56), 109 (31), 91 (28), 77 (12), 65 (6), 57 (6).
5
1
(
(40) Ukai, T.; Kawazura, H.; Ishii, Y.; Bounet, J. J.; Ibers, J. A. J.
Organomet. Chem. 1974, 65, 253.
(
(41) Yoshida, T.; Matsuda, T.; Okano, T.; Kitani, T.; Otsuka, S. J. Am.
Chem. Soc. 1979, 101, 2027-2038.
(
(42) Baumstark, A. L.; Vasquez, P. C.; Chen, Y.-X. J. Org. Chem. 1994,
59, 6692-6696.
(
(43) Rathke, M. W.; Vogiazoglou, D. J. Org. Chem. 1987, 52, 3697-
3968.

Catalysts for Ketone and Malonate Arylation
-Phenyl-1-cyclohexanone:44 Bromobenzene (157 mg, 1.00 mmol),
J. Am. Chem. Soc., Vol. 121, No. 7, 1999 1477
2
(99%) of 2-(4-methylphenyl)-1-phenyl-1-propanone after silica gel
1
cyclohexanone (108 mg, 1.10 mmol), Pd(dba) (11.5 mg, 0.020 mmol),
2
chromatography (hexane/EtOAc ) 95/5). H NMR (CDCl
3
) δ 7.96 (d,
t
t
D BPF (11.8 mg, 0.025 mmol), and NaO Bu (144 mg, 1.50 mmol) were
J ) 8.1 Hz, 2H), 7.47 (t, J ) 8.1 Hz, 1H), 7.38 (t, J ) 8.1 Hz, 2H),
used. Reaction at 55 °C for 3 h gave 122 mg (70%) of 2-phenyl-1-
7.18 (d, J ) 8.0 Hz, 2H), 7.11 (d, J ) 8.0 Hz, 2H), 4.66 (q, J ) 6.7
Hz, 1H), 2.29 (s, 3H), 1.52 (d, J ) 6.7 Hz, 3H); 13C{ H} NMR (CDCl
1
cyclohexanone after silica gel chromatography (hexane/ether ) 90/
3
)
1
1
1
2
2
1
0). H NMR (CDCl
3
) δ 7.35 (t, J ) 7.2 Hz, 2H), 7.27 (t, J ) 7.2 Hz,
δ 200.46, 138.55, 136.82, 136.51, 132.75, 129.74, 128.82, 128.50,
H), 7.16 (d, J ) 7.2 Hz, 2H), 3.62 (dd, J ) 12.3, 5.4 Hz, 1H), 2.57-
.44 (m, 2H), 2.31-2.27 (m, 1H), 2.18-2.15 (m, 1H), 2.09-1.99 (m,
H), 1.87-1.59 (m, 2H); C{ H} NMR (CDCl
28.557, 128.34, 126.86, 57.34, 42.22, 42.18, 35.13, 27.83, 25.31.
127.68, 47.52, 21.03, 19.58.
2-(2-Methylphenyl)-1-phenyl-1-propanone:47 2-Chlorotoluene (127
1
3
1
3
) δ 210.14, 138.88,
mg, 1.00 mmol), propiophenone (148 mg, 1.10 mmol), Pd(dba) (18.3
2
t
t
mg, 0.032 mmol), D BPF (11.9 mg, 0.025 mmol), and NaO Bu (144
General Procedure for the Reaction of Ketone with Arylchloride.
mg, 1.50 mmol) were used. Reaction at 70 °C for 12 h gave 189 mg
The reaction conditions and results are shown in Table 1. A typical
procedure is given for the reaction of Entry 15.
(84%) of 2-(2-methylphenyl)-1-phenyl-1-propanone after silica gel
1
chromatography (hexane/EtOAc ) 95/5). H NMR (CDCl
3
) δ 7.38 (d,
41
(36.6 mg, 0.064 mmol), Dt-
1
,2-Diphenyl-1-propanone: Pd(dba)
2
J ) 7.3 Hz, 2H), 7.46 (t, J ) 7.3 Hz, 1H), 7.36 (t, J ) 7.3 Hz, 2H),
7.21 (d, J ) 7.3 Hz, 1H), 7.12 (t, J ) 7.3 Hz, 1H), 7.09 (t, J ) 7.3 Hz,
t
BPF (23.8 mg, 0.050 mmol), and NaO Bu (288 mg, 3.00 mmol) were
suspended in 2 mL of THF in a screw-capped vial. The vial was sealed
with a cap containing a PTFE septum and removed from the drybox.
Chlorobenzene (225 mg, 2.00 mmol) and propiophenone (295 mg, 2.20
mmol) were added to the reaction mixture by syringe. The vial was
heated at 70 °C and monitored by GC analysis. The crude reaction
was diluted with ether and washed with water and brine. The organic
1H), 7.04 (t, J ) 7.3 Hz, 1H), 4.77 (q, J ) 6.8 Hz, 1H), 2.51 (s, 3H),
1.48 (d, J ) 6.8 Hz, 3H); 13C{ H} NMR (CDCl
1
3
) δ 200.97, 140.19,
136.61, 134.57, 132.82, 132.69, 131.02, 128.52, 126.99, 126.90, 126.80,
44.61, 19.63, 18.06.
2-(2-Methylphenyl)-1-phenyl-1-ethanone:48 2-Chlorotoluene (127
2
mg, 1.00 mmol), acetophenone (132 mg, 1.10 mmol), Pd(dba) (18.3
t
t
layer was dried over Na
residue was chromatographed on silica gel (hexane/EtOAc ) 95/5) to
give 365 mg (87%) of 1,2-diphenyl-1-propanone.
2
SO
4
, filtered, and concentrated in Vacuo. The
mg, 0.032 mmol), D BPF (11.9 mg, 0.025 mmol), and NaO Bu (144
mg, 1.50 mmol) were used. Reaction at 70 °C for 12 h gave 175 mg
(83%) of 2-(2-methylphenyl)-1-phenyl-1-ethanone after recrystalization
1
2-(3-Methoxyphenyl)-1-phenyl-1-propanone: 3-Chloroanisole (285
from n-hexane. H NMR (CDCl
3
) δ 8.04 (d, J ) 7.3 Hz, 2H), 7.59 (t,
mg, 2.00 mmol), propiophenone (295 mg, 2.20 mmol), Pd(dba) (36.6
2
J ) 7.3 Hz, 1H), 7.50 (t, J ) 7.3 Hz, 2H), 7.22-7.14 (m, 4H), 4.33 (s,
2H), 2.29 (s, 3H); C{ H} NMR (CDCl ) δ 197.51, 136.95, 133.57,
3
t
t
13 1
mg, 0.064 mmol), D BPF (23.8 mg, 0.050 mmol), and NaO Bu (288
mg, 3.00 mmol) were used. Reaction at 70 °C for 2 h gave 477 mg
133.23, 130.42, 133.15, 130.37, 128.73, 128.39. 127.29, 126.18, 43.53,
19.86.
(
99%) of 2-(3-methoxyphenyl)-1-phenyl-1-propanone after silica gel
1
chromatography (hexane/EtOAc ) 95/5). H NMR (CDCl
J ) 7.5 Hz, 2H), 7.48 (t, J ) 7.5 Hz, 1H), 7.38 (t, J ) 7.5 Hz, 2H),
.21 (t, J ) 7.8 Hz, 1H), 6.88 (d, J ) 7.8 Hz, 1H), 6.83 (s, 1H), 6.74
d, J ) 7.8 Hz, 1H), 4.65 (q, J ) 7.0 Hz, 1H), 3.77 (s, 3H), 1.53 (d,
3
) δ 7.96 (d,
Reactions with Tri-tert-butylphosphine as Ligand. The reaction
conditions and results are shown in Table 1. A typical procedure is
given for the reaction in Entry 8.
7
(
1,2-Diphenyl-1-ethanone:49 Pd(OAc) (2.3 mg, 0.010 mmol), tri-
2
1
3
1
t
J ) 7.0 Hz, 3H); C{ H} NMR (CDCl
1
4
3
) δ 200.13, 160.02, 143.05,
36.50, 132.80, 129.99, 128.76, 128.49, 120.20, 113.53, 112.15, 55.15,
7.91, 19.45. MS m/e (rel intensity) 240(11), 135 (14), 105 (100), 91
: C, 79.97; H, 6.71.
tert-butylphosphine (2.1 mg, 0.010 mmol), and NaO Bu (211 mg, 2.20
mmol) were suspended in 1 mL of THF in a screw-capped vial. The
vial was sealed with a cap containing a PTFE septum and removed
from the drybox. Bromobenzene (157 mg, 1.00 mmol) and acetophe-
none (132 mg, 1.10 mmol) were added to the reaction mixture by
syringe. The reaction mixture was stirred at 25 °C and monitored by
GC analysis. The crude reaction was diluted with ether and washed
with 1 N HCl, water, and brine. The organic layer was dried over Na2-
(11), 77 (40), 51 (9). Anal. Calcd for C16
H O
16 2
Found: C, 79.74: H, 6.65.
2
-(3-Methoxyphenyl)-2-methyl-1-phenyl-1-propanone: 3-Chlo-
roanisole (143 mg, 1.00 mmol), isobutyrophenone (163 mg, 1.10 mmol),
t
2
Pd(dba) (18.3 mg, 0.032 mmol), D BPF (12.0 mg, 0.025 mmol), and
t
NaO Bu (144 mg, 1.50 mmol) were used. Reaction at 70 °C for 12 h
SO , filtered, and concentrated in Vacuo. The residue was chromato-
4
gave 201 mg (79%) of 2-(3-methoxyphenyl)-1-phenyl-1-propanone after
graphed on silica gel (hexane/EtOAc ) 95/5) to give 188 mg (96%)
1
1
silica gel chromatography (hexane/EtOAc ) 95/5). H NMR (CDCl
3
)
of 1,2-diphenyl-1-ethanone: H NMR (CDCl ) δ 8.02 (d, J ) 7.1 Hz,
3
2H), 7.58-7.26 (m, 8H), 4.31 (s, 2H); 13C{ H} NMR (CDCl ) δ 197.52,
136.79, 134.67, 133.09, 129.54, 129.50, 128.64, 128.62, 126.88, 45.50.
1
δ 7.51 (d, J ) 8.3 Hz, 2H), 7.37 (t, J ) 7.4 Hz, 1H), 7.29-7.22 (m,
3
3
8
2
1
1
H), 6.91 (d, J ) 7.4 Hz, 1H), 6.88 (t, J ) 2.3 Hz, 1H), 6.81 (dd, J )
1
3
1
.3, 2.3 Hz, 1H), 3.79 (s, 3H), 1.58 (s, 6H); C{ H} NMR (CDCl
3
) δ
2-(4-Benzoylphenyl)-1-phenyl-1-propanone: Pd(OAc) (4.5 mg,
2
03.51, 160.06, 146.95, 136.24, 131.70, 130.00, 129.66, 127.96, 118.24,
11.90, 111.67, 55.17, 51.38, 27.79. MS m/e (rel intensity) 254 (14),
49 (100), 121 (48), 105 (99), 91 (27), 77 (67), 65 (7), 51 (18). Anal.
0.020 mmol), tri-t-butylphosphine (4.1 mg, 0.020 mmol), NaO Bu (144
t
mg, 1.50 mmol), 4-bromobenzophenone (261 mg, 1.00 mmol), and
propiophenone (148 mg, 1.10 mmol) were used. Reaction at 70 °C for
12 h gave 304 mg (97%) of 2-(4-benzoylphenyl)-1-phenyl-1-propanone
Calcd for C17
-(4-Methoxyphenyl)-1-phenyl-1-propanone: 4-Chloroanisole (284
mg, 2.00 mmol), propiophenone (295 mg, 2.20 mmol), Pd(dba) (36.6
18 2
H O : C, 80.29; H, 7.13. Found: C, 80.50: H, 7.14.
45
1
2
after silica gel chromatography (hexane/EtOAc ) 85/15). H NMR
2
(CDCl ) δ 7.96 (d, J ) 7.7 Hz, 2H), 7.76-7.75 (m, 4H), 7.58 (t, J )
3
t
t
mg, 0.064 mmol), D BPF (23.8 mg, 0.050 mmol), and NaO Bu (288
7.2 Hz, 1H), 7.52 (t, J ) 7.1 Hz, 1H), 7.47 (t, J ) 7.7 Hz, 2H), 7.43-
7.40 (m, 4H), 4.79 (q, J ) 6.9 Hz, 1H), 1.59 (d, J ) 6.9 Hz, 3H);
mg, 3.00 mmol) were used. Reaction at 70 °C for 12 h gave 192 mg
13
1
(
92%) of 2-(4-methoxyphenyl)-1-phenyl-1-propanone after silica gel
C{ H} NMR (CDCl ) δ 199.66, 196.14, 146.16, 137.51, 136.23,
3
1
chromatography (hexane/EtOAc ) 95/5). H NMR (CDCl
J ) 8.0 Hz, 2H), 7.48 (t, J ) 8.0 Hz, 1H), 7.39 (t, J ) 8.0 Hz, 2H),
.20 (d, J ) 8.7 Hz, 2H), 6.85 (d, J ) 8.7 Hz, 2H), 4.65 (q, J ) 6.8
3
) δ 7.95 (d,
133.10, 132.40, 130.82, 129.94, 129.80, 128.75, 128.63, 128.26, 127.79,
47.72, 19.37. MS m/e (rel intensity) 314 (10), 105 (100), 77 (38), 51
(13). Anal. Calcd for C H O : C, 84.05; H, 5.77. Found: C, 83.91:
7
22
18
2
13
1
Hz, 1H), 3.76 (s, 3H), 1.51 (d, J ) 6.8 Hz, 3H); C{ H} NMR (CDCl
δ 200.55, 158.51, 136.53, 133.50, 132.73, 128.80, 128.76, 128.49,
14.40, 55.15, 46.95, 19.55.
-(4-Methylphenyl)-1-phenyl-1-propanone:46 4-Chlorotoluene (253
mg, 2.00 mmol), propiophenone (295 mg, 2.20 mmol), Pd(dba) (36.6
3
)
H, 5.88.
Reaction with 0.005 mol% catalyst: Pd(OAc)
2
(0.5 mg, 0.0023
1
t
mmol), tri-tert-butylphosphine (0.4 mg, 0.0020 mmol), and NaO Bu
(5.80 g, 60.3 mmol) were suspended in 5 mL of THF in a screw-capped
test tube. Bromobenzene (6.28 g, 40.0 mmol) and propiophenone (5.90
g, 44.0 mmol) were added to the reaction mixture in the drybox. The
2
2
t
t
mg, 0.064 mmol), D BPF (23.8 mg, 0.050 mmol), and NaO Bu (288
mg, 3.00 mmol) were used. Reaction at 70 °C for 1 h gave 440 mg
(47) Wagner, P. J.; Zhou, B.; Hasegawa, T.; Ward, D. L. J. Am. Chem.
(
44) Baradarani, M. M.; Joule, J. A. J. Chem. Soc., Perkin Trans. 1 1980,
Chem. 1991, 113, 9640-9654.
7
2-77.
(48) Wagner, P. J.; Meador, M. A.; Zhou, B.; Park, B.-S. J. Am. Chem.
Soc. 1991, 113, 9630-9639.
(45) Morgan, J.; Pinhey, J. T.; Rowe, B. A. J. Chem. Soc., Perkin Trans.
1
1997, 1005-1008.
(49) Gurudutt, K. N.; Pasha, M. A.; Ravindranath, B.; Srinivas, P.
Tetrahedron 1984, 40, 1629-1632.
(46) Curtin, D. Y.; Pollak, P. I. J. Am. Chem. Soc. 1951, 73, 992-994.

1
478 J. Am. Chem. Soc., Vol. 121, No. 7, 1999
Kawatsura and Hartwig
(4.5 mg, 0.020 mmol),
reaction tube was sealed with a cap and the mixture was stirred for 24
h at 60 °C. The reaction was diluted with ether and washed with water
Phenyl diethylmalonate:51 Pd(OAc)
2
t
t
P( Bu)
3
(4.1 mg, 0.020 mmol), and NaO Bu (100 mg, 1.04 mmol) were
and brine. The organic layer was dried over Na
concentrated in Vacuo. The residue was chromatographed on silica gel
2
SO
4
, filtered, and
suspended in 2 mL of dioxane in a screw-capped vial. The vial was
sealed with a cap containing a PTFE septum and removed from the
drybox. Bromobenzene (157 mg, 1.00 mmol) and diethyl malonate (176
mg, 1.10 mmol) were added to the reaction mixture by syringe. The
reaction was heated at 70 °C and monitored by GC analysis. The
reaction mixture was diluted with ether and washed with water and
(
hexane/EtOAc ) 95/5) to give 8.2 g (98%) of 1,2-diphenyl-1-
propanone.
Reaction of propiophenone with p-tolyltosylate: Pd(OAc)
mg, 0.040 mmol), ligand 2 (27.1 mg, 0.050 mmol), NaO Bu (144 mg,
2
(9.0
t
1
.50 mmol), and 4-methylphenyl-p-toluene sulfonate (262 mg, 1.00
2 4
brine. The organic layer was dried over Na SO , filtered, and
mmol) were suspended in 1 mL of dioxane in a screw-capped vial.
The vial was sealed with a cap containing a PTFE septum and removed
from the drybox. Propiophenone (132 mg, 1.10 mmol) was added to
the reaction mixture by syringe. The reaction mixture was stirred at
concentrated in Vacuo. The residue was chromatographed on silica gel
(hexane/EtOAc ) 80/20) to give 205 mg (86%) of phenyl diethylbu-
1
tylmalonate: H NMR (CDCl
3
) δ 7.42-7.33 (m, 5H), 4.62 (s, 1H),
13
1
4.23 (q, J ) 7.3 Hz, 4H), 1.27 (t, J ) 7.3 Hz, 6H); C{ H} NMR
(CDCl ) δ 168.13, 132.84, 129.25, 128.56, 128.16, 61.75, 57.98, 13.98.
Generation of {Pd(DPPF)(p-Tol)[OC(dCMe )Ph]}. Into a vial
was weighed 8.3 mg (0.01 mmol) of {Pd(DPPF)(p-Tol)(Br)}, and
into a second vial was weighed 2.6 mg (0.01 mmol) of KOC(dCMe )-
Ph‚THF. The palladium complex was suspended in 0.6 mL of benzene-
and the suspension was added to the vial of enolate. The sample
1
00 °C and monitored by GC analysis. The crude reaction was diluted
with ether and washed with 1 N HCl, water, and brine. The organic
layer was dried over Na SO , filtered, and concentrated in Vacuo. The
3
2
3
1
2
4
residue was chromatographed on silica gel (hexane/EtOAc ) 95/5) to
give 135 mg (60%) of 2-(4-methoxyphenyl)-1-phenyl-1-propanone.
Reactions with Tricyclohexylphosphine as ligand. The reaction
conditions and results are shown in Table 1. A typical procedure is
given for the reaction of Entry 17.
2
d
6
was transferred to an NMR sample tube and was shaken for 1-2 min
until the palladium complex reacted with the enolate to make an orange
solution with a white precipitate (KBr). The sample was then placed
48
1
2
,2-Diphenyl-1-propanone: Pd(OAc) (4.5 mg, 0.020 mmol), Tri-
1
31
1
t
into the NMR probe and H and P{ H} NMR spectra were recorded
cyclohexyphosphine (5.6 mg, 0.020 mmol), and NaO Bu (144 mg, 1.50
mmol) were suspended in 1 mL of THF in a screw-capped vial. The
vial was sealed with a cap containing a PTFE septum and removed
from the drybox. Chlorobenzene (113 mg, 1.00 mmol) and propiophe-
none (144 mg, 1.10 mmol) were added to the reaction mixture by
syringe. The reaction mixture was stirred at 50 °C and monitored by
GC analysis. The crude reaction was diluted with ether and washed
1
at room temperature. H NMR (C
6 6
D ) δ 8.39 (t, 8.0 Hz, 4 H), 7.41 (t,
9
Hz, 4H), 7.2-7.0 (m, 11H), 6.89 (m, 4H), 6.80 (d, 6.6 Hz, 4H), 6.51
(
3
3
m, 2H), 4.43 (s, 2H), 3.90 (s, 2H), 3.87 (s, 2H), 3.72 (s, 2H), 2.29 (s,
H), 2.11 (s, 3H), 1.85 (s, 3H); 31P{ H} (C
1
D
6 6
) δ 29.83, 10.37 (J )
4.2 Hz).
t
Generation of {Pd(D BPF)(Ph)[OC(dCMe
2
)Ph]}. Into a vial was
t
32
weighed 7.4 mg (0.01 mmol) of {Pd(D BPF)(Ph)(Br)}, and into a
second vial was weighed 2.6 mg (0.01 mmol) of KOC(dCMe )Ph‚
THF. The palladium complex was suspended in 0.6 mL of benzene-d
2 4
with water and brine. The organic layer was dried over Na SO , filtered,
2
and concentrated in Vacuo. The residue was chromatographed on silica
gel (hexane/EtOAc ) 95/5) to give 204 mg (97%) of 1,2-diphenyl-1-
propanone
6
2
and the suspension was added to the vial of enolate. The sample was
transferred to an NMR sample tube and was shaken for 1-2 min until
the palladium complex reacted with the enolate to make an orange
solution with a white precipitate (KBr). The sample was then placed
Reaction of Malonates with Aryl Halides: Phenyl Di-tert-
5
0
t
butylmalonate: Pd(OAc)
2
(9.0 mg, 0.040 mmol), D BPF (23.8 mg,
t
0
.050 mmol), and NaO Bu (288 mg, 3.00 mmol) were suspended in 2
1
31
1
into the NMR probe and H and P{ H} NMR spectra were recorded
mL of dioxane in a screw-capped vial. The vial was sealed with a cap
containing a PTFE septum and removed from the drybox. Chloroben-
zene (225 mg, 2.00 mmol) and di-tert-butyl malonate (480 mg, 2.20
mmol) were added to the reaction mixture by a syringe. The reaction
was heated at 100 °C and monitored by GC analysis. The reaction
mixture was diluted with ether and was washed with water and brine.
1
at room temperature. H NMR (toluene-d
8
, 0 °C) δ 1.18 (d, 10.8 Hz,
8H), 1.23 (s, 3H), 1.24 (s, 3H), 1.32 (d, 14 Hz, 18H), 4.12 (s, 2H),
.27 (s, 2H), 4.29 (s, 2H), 4.44 (m, 2H), 6.8-7.3 (m, 6H), 7.56 (d, 7.1
1
4
31
1
6 6
Hz, 2H), 7.86 (d, 6.8 Hz); P{ H} NMR (C D ) δ 24.8 (s), 57.2 (s).
Acknowledgment. We thank Boehringer Ingelheim for
2 4
The organic layer was dried over Na SO , filtered, and concentrated
t
support of this work and Grace Mann for a sample of (D BPF)-
in Vacuo. The residue was chromatographed on silica gel (hexane/
Pd(Ph)(Br). JFH is a recepient of a Camille Dreyfus Teacher
Scholar Award and an NSF Yound Investigator Award and is
an Alfred P. Sloan Fellow.
EtOAc ) 80/20) to give 465 mg (80%) of phenyl di-tert-butylma-
1
lonate: H NMR (CDCl
3
) δ 7.40-7.33 (m, 5H), 4.44 (s, 1H), 1.47 (s,
3
13
1
18H); C{ H} NMR (CDCl ) δ 167.44, 133.51, 129.30, 128.38, 127.83,
8
1.92, 60.10, 27.87.
JA983378U
(
50) Semmelhack, M. F.; Chorg, B. P.; Stauffer, R. D.; Rogerson, T.
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