A R T I C L E S
Johns et al.
Cl]262 were prepared using the reported procedures. (COD)Pd(CH2Ph)-
Cl63 was prepared via an alternate procedure to that found in the
literature.
palladium chloride complexes than on the allyl palladium
complexes with a tetrafluoroborate counterion, reactions of
dienes catalyzed by the combination of Xantphos and [Pd(η3-
allyl)Cl]2 occurred in higher yields than reactions catalyzed by
the combination of Xantphos and [Pd(CH3CN)4](BF4)2.
General Procedure for the Preparation of [(Bisphosphine)Pd-
(η3-allyl)]Cl. Into a 50 mL round-bottom flask equipped with a
magnetic stirbar was placed [Pd(η3-allyl)Cl]2 (200 mg, 0.547 mmol).
Into a second 50 mL round-bottom flask equipped with a magnetic
stirbar was placed 2 equiv of bisphosphine (1.09 mmol). Benzene (15
mL) was added to each flask, and the resulting solutions stirred for 10
min at 50 °C to ensure complete dissolution. The solutions were
subsequently combined. After stirring for 30 min at 50 °C, the resulting
solution/suspension was allowed to cool to room temperature. Com-
plexes that precipitated were isolated by filtration in air and were
washed 2 times with 50 mL of Et2O and dried in vacuo. Complexes
that were soluble in benzene were isolated by removing all volatiles
and recystallizing the residue from dichloromethane and Et2O or
pentane. The resulting crystals were isolated from the supernatant,
washed with 2 × 10 mL of Et2O or pentane, and dried in vacuo.
General Procedure for the Preparation of [(Bisphosphine)Pd-
(η3-allyl)]X (X ) BF4 or OTF). Into a 20 mL scintillation vial equipped
with a magnetic stirbar was placed [Pd(η3-allyl)Cl]2 (29.4 mg, 0.0804
mmol) and 2 equiv of bisphosphine (0.161 mmol). Dichloromethane
(4 mL) was added, and the solution was stirred for 10 min. The
appropriate silver salt (2 equiv, 0.161 mmol) was added to the stirring
solution, and the resulting suspension was stirred for 30 min. Filtration
through Celite yielded a clear solution, which was concentrated to 1
mL under reduced pressure, layered with Et2O or pentane, and cooled
at -35 °C for 12 h. The resulting crystals were washed 2 times with
3 mL of Et2O or pentane and dried in vacuo.
General Procedure for the Preparation of [(Bisphosphine)Pd-
(benzyl)Cl]. Into a 20 mL scintillation vial equipped with a magnetic
stirbar was placed (COD)Pd(CH2Ph)Cl (50.0 mg, 0.147 mmol) and 1
equiv of bisphosphine (0.147 mmol). Dichloromethane (4 mL) was
added, and the solution was stirred for 10 min. Filtration through Celite
yielded a clear solution, which was concentrated to 1 mL under reduced
pressure, layered with pentane, and cooled at -35 °C. The resulting
crystals were isolated from the supernatant, washed with 2 × 5 mL of
pentane, and dried in vacuo.
General Procedure for the Preparation of [(Bisphosphine)Pd-
(η3-benzyl)]X (X ) BF4 or OTF). Into a 20 mL scintillation vial
equipped with a magnetic stirbar was placed (COD)Pd(CH2Ph)Cl (50.0
mg, 0.147 mmol) and 1 equiv of bisphosphine (0.147 mmol). Dichlo-
romethane (5 mL) was added, and the solution was stirred for 10 min.
The appropriate silver salt (1 equiv, 0.147 mmol) was added to the
stirring solution, and the resulting suspension was stirred for 10 min.
Filtration through Celite yielded a clear solution, which was concen-
trated to 1 mL under reduced pressure, layered with Et2O or pentane,
and cooled to -35 °C. The resulting crystals were isolated from the
supernatant, washed with 2 × 5 mL of Et2O or pentane, and dried in
vacuo.
Conclusions
Highly active late transition metal catalysts for hydroamina-
tions are needed to accomplish olefin hydroamination in a
synthetically valuable fashion. Although much progress must
be made to develop transition metal-catalyzed hydroamination,
we have demonstrated that improved catalysts for additions of
arylamines to vinylarenes and dienes can be developed and that
these improved catalysts can tolerate the types of functionality
commonly found in natural products and pharmaceutically active
materials. This work has shown that palladium complexes of
Xantphos are much more reactive catalysts for the hydroami-
nation of dienes and vinylarenes than catalysts reported previ-
ously for this reaction. These reactions occur selectively to add
the amine N-H bond of arylamines to vinylarenes in the
presence of nitrile, nitro, ester, amide, carboxylic acid, phenolic
hydroxyl, hydroxyalkyl, and enolizable keto groups.
In addition to demonstrating increased activity and high
functional group tolerance from catalysts with Xantphos as
ligand, we have revealed some of the factors that control the
rates of the catalytic reactions and the rate of the C-N bond-
forming step. By monitoring the reactions of isolated bisphos-
phine-ligated allyl- and benzylpalladium complexes with amines,
we demonstrated a correlation between bite angle and rate of
nucleophilic attack on η3-benzyl complexes and unsymmetrical
η3-allyl complexes. We also showed that the population of active
catalyst in the hydroaminations of dienes depends on the bite
angle of the ligand and that the concentration of the allylpal-
ladium complex may be the major factor that influences the
rate of the catalytic hydroamination of symmetrical dienes.
Finally, while the origin of the differences in the rate of attack
as a function of counterion remain to be delineated, we have
shown that the rate of attack is affected significantly by the
counterion, even when it is not directly coordinated to the metal.
Experimental Procedures
General Experimental Procedure and Reagent Availability. All
manipulations were carried out under an inert atmosphere using a
nitrogen-filled glovebox or standard Schlenk techniques. All glassware
was oven or flame dried immediately prior to use. THF and diethyl
ether were obtained as HPLC grade without inhibitors; benzene, toluene,
dichloromethane, and pentane were obtained as ACS reagent grade.
THF, diethyl ether, benzene, toluene, dichloromethane, and pentane
were degassed by purging with nitrogen for 45 min and dried with a
solvent purification system containing a 1 m column containing
activated alumina. All reagents were obtained from commercial sources
General Procedure for the Preparation of [(Bisphosphine)Pd-
(η3-1,1-dimethylallyl)]OTf. Into a 20 mL scintillation vial equipped
with a magnetic stirbar was placed [Pd(η3-1,1-dimethylallyl)Cl]2 (40.0
mg, 0.0948 mmol) and 2 equiv of bisphosphine (0.190 mmol).
Dichloromethane (5 mL) was added, and the solution was stirred for
10 min. Silver trifluoromethanesulfonate (2 equiv, 48.7 mg, 0.190
mmol) was added to the stirring solution, and the resulting suspension
was stirred for 30 min. Filtration through Celite yielded a clear solution,
which was concentrated to 1 mL under reduced pressure, layered with
Et2O or pentane, and cooled at -35 °C for 12 h. The resulting
precipitate was washed 2 times with 3 mL of Et2O or pentane and
dried in vacuo.
1
and used without further purification. H NMR spectra were obtained
at 400 or 500 MHz and recorded relative to residual protio-solvent.
13C NMR spectra were obtained at 101 or 126 MHz, and chemical
shifts were recorded relative to the solvent resonance. 31P NMR spectra
were obtained at 122, 162, or 202 MHz, and chemical shifts are reported
relative to 85% H3PO4. [Pd(η3-allyl)Cl]261 and [Pd(η3-1,1-dimethylallyl)-
(60) Malaise, G.; Barloy, L.; Osborn, J. A.; Kyritsakas, N. C. R. Chim. 2002, 5,
(62) Auburn, P. R.; Mackenzie, P. B.; Bosnich, B. J. Am. Chem. Soc. 1985,
107, 2033-46.
(63) Stockland, R.; Anderson, G.; Rath, N.; Braddock-Wilking, J.; Ellegood, J.
Can. J. Chem. 1996, 74, 1990-1997.
289-296.
(61) Palenik, R. C.; Palenik, G. J. Synth. Inorg. Met. Org. Chem. 1992, 22,
1395-1399.
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1838 J. AM. CHEM. SOC. VOL. 128, NO. 6, 2006