Bronsted base-modulated regioselectivity in the aerobic oxidative amination of styrene catalyzed by palladium

Article abstract of DOI:10.1021/ja0562806

Palladium(II)-catalyzed aerobic oxidative amination of styrene with oxazolidinone proceeds with catalyst-controlled regioselectivity: (CH ₃CN)₂PdCl₂ (1) and (Et₃N) ₂PdCl₂ (2) catalyze forma

Full text of DOI:10.1021/ja0562806

Published on Web 11/23/2005
Brønsted Base-Modulated Regioselectivity in the Aerobic
Oxidative Amination of Styrene Catalyzed by Palladium
Vitaliy I. Timokhin and Shannon S. Stahl*
Contribution from the Department of Chemistry, UniVersity of WisconsinsMadison,
1101 UniVersity AVenue, Madison, Wisconsin 53706
Received September 12, 2005; E-mail: stahl@chem.wisc.edu
Abstract: Palladium(II)-catalyzed aerobic oxidative amination of styrene with oxazolidinone proceeds with
catalyst-controlled regioselectivity: (CH3CN)2PdCl2 (1) and (Et3N)2PdCl2 (2) catalyze formation of the anti-
Markovnikov and Markovnikov enecarbamate products, 3 and 4, respectively. Kinetic studies and deuterium
kinetic isotope effects demonstrate that these two reactions possess different rate-limiting steps, and the
data indicate that the product regiochemistry arises from the presence or absence of an effective Brønsted
base in the reaction. In the presence of a Brønsted base such as triethylamine or acetate, the kinetically
preferred Markovnikov aminopalladation adduct of styrene is trapped via rapid deprotonation of a zwitterionic
intermediate and leads to formation of 4. In the absence of an effective Brønsted base, however, slow
deprotonation of this adduct enables aminopalladation to be reversible, and product formation proceeds
through the thermodynamically preferred anti-Markovnikov aminopalladation adduct to yield 3.
Introduction
in commercial organic molecules, ranging from commodity and
fine chemicals to pharmaceuticals and agrochemicals. Metal-
Aryl and alkyl olefins generally do not react with amines. In
recent years, however, a number of catalysts have been identified
that promote the intermolecular coupling of amines and
alkenes.1-10 The widespread interest in this chemistry arises
from the prominence of nitrogen-containing functional groups
catalyzed addition of amines to terminal alkenes can yield
several different products depending on the catalyst and reaction
conditions, including alkylamines via hydroamination (eq 1) and
imines or enamines via oxidative amination (eqs 2 and 3). These
reactions may proceed with Markovnikov or anti-Markovnikov
regioselectivity, and the desired isomer depends on the specific
application. The ability to achieve catalyst control over regio-
chemistry represents an important target of ongoing research
efforts.11
(1) For recent reviews and highlights, see: (a) Roundhill, D. M. Catal. Today
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675-703. (c) Nobis, M.; Driessen-Ho¨lscher, B. Angew. Chem., Int. Ed.
2001, 40, 3983-3985. (d) Brunet, J. J.; Neibecker, D. In Catalytic
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Hartung, C. G.; Seayad, J.; Thiel, O. R.; Tillack, A.; Trauthwein, H. Synlett
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Ed. 2003, 42, 2708-2710. (g) Hong, S.; Marks, T. J. Acc. Chem. Res.
2004, 37, 673-686.
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1268. (d) Brunet, J.-J.; Chu, N. C.; Diallo, O. Organometallics 2005, 24,
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Oxidative amination reactions are synthetically attractive
because they lead to a net increase in substrate functionality,
and we recently reported methods for the oxidative amination
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12640-12646.
(11) White and co-workers recently reported an example of Pd-catalyzed allylic
oxidation of terminal alkenes that preferentially forms the branched or linear
allylic acetate, depending on the reaction conditions: Chen, M. S.; White,
M. C. J. Am. Chem. Soc. 2004, 126, 1346-1347.
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9
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J. AM. CHEM. SOC. 2005, 127, 17888-17893
10.1021/ja0562806 CCC: $30.25 © 2005 American Chemical Society

Mechanism of Pd-Catalyzed Oxidative Amination
A R T I C L E S
of both aryl and alkyl olefins that use molecular oxygen as the
stoichiometric oxidant.12,13 The reaction of styrene with oxazo-
lidinone is noteworthy because an apparently subtle variation
of the catalyst leads to a complete switch in product regio-
chemistry. Specifically, the use of (CH3CN)2PdCl2 (1) and
(Et3N)2PdCl2 (2) as catalysts results in the formation of the anti-
Markovnikov and Markovnikov oxidative amination products,
respectively (eq 4). The synthetic implications of these observa-
tions prompted us to investigate the origin of this result, and
mechanistic studies described below implicate a novel, Brønsted
base-mediated mechanism for regiochemical modulation of
metal-catalyzed alkene amination reactions.
Figure 1. Molecular structure of 2 with 50%-probability thermal ellipsoids.
Bond lengths: Pd-N(1) ) Pd-N(1A) ) 2.1716(15) Å; Pd-Cl(1) ) Pd-
Cl(1A) ) 2.3179(6) Å.
ratio (Figure 2A). Addition of NEt3 decreases the yield of 3,
but formation of 4 is not observed until a NEt3:Pd ratio > 1 is
present in solution. The yield of 4 maximizes at a NEt3:Pd ratio
of ∼3, but at elevated NEt3 concentrations (NEt3:Pd > 3), both
the overall yield and initial rate of the catalytic reaction diminish
substantially (Figure 2A,B).16
Triethylamine is not unique in its ability to promote formation
of the Markovnikov oxidative amination product. If anionic
bases, such as acetate and bicarbonate, are used in combination
with 1, 4 is the only product obtained. For example, in the
presence of 100 mol % sodium acetate17 and 5 mol % 1 as the
catalyst, 4 is obtained in nearly quantitative yield (>95%).
Reactions conducted in the presence of NEt3 or NaOAc proceed
significantly faster (>5-fold) than those catalyzed by 1 in the
absence of base. Furthermore, use of the lithium salt of
deprotonated oxazolidinone in reactions catalyzed by 1 in the
absence of NEt3 also yields 4 as the exclusive amination product
(62%). These observations are inconsistent with a ligand steric-
effect model and suggest the change in reaction rate and
regioselectivity arise from a Brønsted base effect.
Kinetic Studies. Kinetic studies reveal distinct differences
between reactions catalyzed by 1 and 2. The dependence of the
initial reaction rate on styrene and oxazolidinone concentrations
was evaluated in each case by monitoring the product by gas
chromatography.18 With 1 as the catalyst (eq 4a), the rate
exhibits a linear dependence on [oxazolidinone] and a saturation
dependence on [styrene] (Figure 3). In contrast, with 2 as the
catalyst (eq 4b), the rate exhibits a saturation dependence on
[oxazolidinone] (Figure 4A) but retains a linear dependence on
[styrene] even to very high concentration (7.9 M, >90 vol %)
(Figures 4B and S1 (Supporting Information)).
Results and Discussion
Origin of Regiochemical Control: Evidence for a Brønsted
Base Effect. Our initial hypothesis to explain the regiochemical
outcome of the reactions in eq 4 focused on the coordination
chemistry of triethylamine. Addition of NEt3 to 1 results in
amine coordination to the palladium center, and catalyst 2 was
isolated from a 1:2 mixture of 1 and NEt3 and characterized by
X-ray crystallography (Figure 1). The trans stereochemistry,
together with the large NEt3 cone angle (158°),14 suggested that
ligand steric effects might alter the reaction regioselectivity.
Namely, a sterically congested metal center might favor
formation of aminopalladation intermediate, 5, which possesses
a primary alkyl ligand, over the other possible intermediate, 6,
which features a larger, secondary alkyl ligand. The steric effects
may be amplified by the fact that the Pd-N bond lengths of
2.17 Å are considerably shorter than Pd-P bond lengths
(∼2.33-2.35 Å) for structurally related trans-(R3P)2PdCl2
complexes.15
Deuterium kinetic isotope effects (KIEs) for both reactions
were evaluated by comparing the reaction rates with oxazoli-
dinone versus N-deuterooxazolidinone as the nucleophile.
Formation of the anti-Markovnikov product, 3, catalyzed by 1
exhibits a significant KIE, kH/kD ) 3.0(1) at 40 °C, whereas
formation of the Markovnikov product, 4, catalyzed by 2
exhibits essentially no isotope effect, kH/kD ) 1.1(1) at 40 °C.
Furthermore, no isotope effect is observed in the formation of
4 catalyzed by a mixture of 1 (5 mol %) and NaOAc (100 mol
%): kH/kD ) 0.98(5) at 40 °C. No statistically significant kinetic
isotope effects are evident when styrene is replaced with styrene-
d8 in any of the reactions.
This model is consistent with the regiochemical results;
however, several additional observations forced us to consider
an alternate explanation. Variation of the triethylamine con-
centration did not result in a systematic change in the 3/4 product
(12) (a) Timokhin, V. I.; Anastasi, N. R.; Stahl, S. S. J. Am. Chem. Soc. 2003,
125, 12996-12997. (b) Brice, J. L.; Harang, J. E.; Timokhin, V. I.; Anastasi,
N. R.; Stahl, S. S. J. Am. Chem. Soc. 2005, 127, 2868-2869.
(13) For intramolecular precedents of palladium-catalyzed aerobic oxidative
amination reactions, see: (a) van Benthem, R. A. T. M.; Hiemstra, H.;
Longarela, G. R.; Speckamp, W. N. Tetrahedron Lett. 1994, 35, 9281-
9284. (b) Ro¨nn, M.; Ba¨ckvall, J.-E.; Andersson, P. G. Tetrahedron Lett.
1995, 36, 7749-7752. (c) Larock, R. C.; Hightower, T. R.; Hasvold, L.
A.; Peterson, K. P. J. Org. Chem. 1996, 61, 3584-3585. (d) Fix, S. R.;
Brice, J. L.; Stahl, S. S. Angew. Chem., Int. Ed. 2002, 41, 164-166. (e)
Trend, R. M.; Ramtohul, Y. K.; Ferreira, E. M.; Stoltz, B. M. Angew. Chem.,
Int. Ed. 2003, 42, 2892-2895.
Thus far, attempts to characterize the catalyst resting state
by in situ NMR spectroscopic studies have been unrewarding.
(16) Triethylamine can coordinate to the CuCl2 cocatalyst; however, control
experiments demonstrate that the [NEt3] dependence correlates exclusively
with [Pd] and not [Cu].
(17) The poor solubility of NaOAc requires elevated loading. NBu4OAc, a
soluble source of acetate, achieves identical results at 10 mol % loading.
(18) See Supporting Information for additional details. The estimated uncertainty
for individual rate measurements is (10%.
(14) Seligson, A. L.; Trogler, W. C. J. Am. Chem. Soc. 1991, 113, 2520-2527.
(15) Based on analysis of trans-(R3P)2PdCl2 complexes in the Cambridge
Structural Database.
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A R T I C L E S
Timokhin and Stahl
Figure 2. Effect of [NEt3] on the product distribution (A) and the initial rate of Markovnikov product formation (B). Reaction conditions: (A) [styrene] )
1.26 M, [HNRZ] ) 0.21 M, [(CH3CN)2PdCl2] ) [CuCl2] ) 0.011 M, [NEt3] ) 0-0.042 M, p(O2) ) 1 atm, DME, 60 °C, 24 h; (B) [styrene] ) 1.30 M,
[HNRZ] ) 0.25 M, [(CH3CN)2PdCl2] ) [CuCl2] ) 0.013 M, [NEt3] ) 0-0.086 M, p(O2) ) 1 atm, DME, 60 °C.
Figure 3. Kinetic data for the anti-Markovnikov oxidative amination of styrene with oxazolidinone (HNRZ) catalyzed by (CH3CN)2PdCl2 (1). Reaction
conditions: (A) [HNRZ] ) 0.055-0.355 M, [styrene] ) 1.26 M, [1] ) [CuCl2] ) 0.011 M, p(O2) ) 1 atm, DME, 60 °C; (B) [HNRZ] ) 0.23 M, [styrene]
) 0.079-1.27 M, [1] ) [CuCl2] ) 0.011 M, p(O2) ) 1 atm, DME, 60 °C. The line in plot A reflects a linear least-squares fit of the data. The saturation
curve in plot B is obtained from a nonlinear least-squares fit to a generic hyperbolic function (y ) c1[St]/(c2[St] + c3), the specific form of which is described
in the Results and Discussion (eq 6).
Figure 4. Kinetic data for the Markovnikov oxidative amination of styrene with oxazolidinone (HNRZ) catalyzed by (Et3N)2PdCl2 (2). Reaction conditions:
(A) [HNRZ] ) 0.044-0.690 M, [styrene] ) 2.62 M, [1] ) [CuCl2] ) 0.013 M, [NEt3] ) 0.031, p(O2) ) 1 atm, DME, 60 °C; (B) [HNRZ] ) 0.23 M,
[styrene] ) 0.077-0.93 M, [1] ) [CuCl2] ) 0.011 M, [NEt3] ) 0.031 M, p(O2) ) 1 atm, DME, 60 °C. The line in plot B reflects a linear least-squares fit
of the data. The saturation curve in plot A is obtained from a nonlinear least-squares fit to a generic hyperbolic function (y ) c1[HNRZ]/(c2[HNRZ] + c3),
the specific form of which is described in the Results and Discussion (eq 8).
These efforts have been complicated by the presence of a
paramagnetic cocatalyst (CuCl2) the need to have very high
substrate:Pd ratios (g 50:1) to reach saturation substrate
concentrations, and the relative instability of the palladium
catalysts.
Proposed Mechanism and Analysis of Kinetic Data. The
data outlined above provide valuable clues into the origin of
regiochemical reversal in the oxidative amination of styrene.
These experimental results, together with insights from several
important studies of stoichiometric palladium-mediated alkene
amination reactions (see below), underlie the following mecha-
nistic proposal (Scheme 1).
Styrene enters the coordination sphere of Pd(II) via substitu-
tion of a neutral donor ligand, such as CH3CN or Et3N. Addition
of oxazolidinone to styrene may proceed with Markovnikov or
anti-Markovnikov regioselectivity, and we propose that forma-
tion of the Markovnikov aminopalladation intermediate C is
kinetically favored. In the presence of triethylamine or another
exogenous Brønsted base, such as acetate, this zwitterionic
intermediate undergoes rapid, irreversible deprotonation to form
D, and subsequent â-hydride elimination yields the Markovnikov
oxidative amination product 4. In the absence of triethylamine,
deprotonation of C will proceed more slowly. Under these
conditions, reversible aminopalladation of styrene enables
formation of the thermodynamically preferred anti-Markovnikov
intermediate, C′, which may be stabilized by formation of a
π-benzylic structure (i.e., C′′). Retention of this stabilizing effect
in the subsequent transition state results in preferential formation
of D′ over D and, ultimately, yields the anti-Markovnikov
product, 3.19,20
η3-Benzylic structures of palladium(II) have substantial
literature precedent,6b,21 and their intermediacy in the formation
of 3 will be favored by the presence of labile ligands in the
Pd(II) coordination sphere (i.e., CH3CN, DME). The recently
reported 1,2-diamination of conjugated dienes (e.g., eq 5)22
employs reaction conditions virtually identical with those in eq
(19) This mechanism is distinct from that of palladium-catalyzed hydroamination
reactions that proceed via η3-benzylic intermediates arising from insertion
of vinyl arenes into a Pd-H bond. Subsequent nucleophilic attack by an
external amine results in formation of MarkoVnikoV hydroamination
products (see ref 6b).
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Mechanism of Pd-Catalyzed Oxidative Amination
A R T I C L E S
Scheme 1. Proposed Mechanism of Palladium-Catalyzed Oxidative Amination of Styrene that Rationalizes the Observed Regioselectivity
4a, and the reaction is believed to proceed through an η3-allyl
intermediate analogous to C′′. Stereochemical evidence supports
backside attack of urea on a coordinated diene in these reactions.
aminopalladation of styrene is rate-limiting. In this case, the
product 4 arises from kinetically preferred formation of the
Markovnikov aminopalladation adduct, C (∆∆Gqbase). Overall,
this energetic profile explains both the reversal of product
regiochemistry and the enhanced rates observed when the
reaction is conducted in the presence of base.
According to this mechanism, a rate law for the production
of 3 reflects a three-step mechanism consisting of (1) preequi-
librium coordination of styrene, (2) steady-state addition of
oxazolidinone to the activated alkene, and (3) rate-limiting
deprotonation of the aminopalladation adduct C′ (eq 6).23 At
high [styrene], the preequilibrium will shift in favor of the Pd-
(II)-styrene adduct (B, Scheme 1), and further increases in the
styrene concentration will have no effect on the rate (Figure
A qualitative energy diagram corresponding to the proposed
catalytic mechanism illustrates the rate-limiting steps associated
with formation of the regioisomeric products, 3 and 4 (Figure
5). In the absence of added base, the presence of a substantial
kinetic isotope effect, kH/kD ) 3.0, suggests that formation of 3
(blue pathway) proceeds via rate-limiting proton transfer from
the aminopalladation adduct C′. The product regiochemistry
reflects the difference in transition states energies associated
with deprotonation of C and C′ (∆∆Gqno base). In the formation
of 4 (red pathway), no isotope effect is observed because the
presence of a Brønsted base significantly reduces the barrier to
proton-transfer (dashed curve), and under these conditions,
3B). Under these conditions, K
1[St] . 1, and the rate law
simplifies to an expression that is first order in [Pd]t
([Pd]t )
[A] + [B]) and [HNRZ] (eq 7).
K1k2k3[Pd]t[St][HNRZ]
(K1[St] + 1)(k-2 + k3)
d[3]
dt
)
(6)
(7)
k2k3[Pd]t[HNRZ]
k-2 + k3
d[3]
dt
)
(at high [St])
The rate law derived for (Et3N)2PdCl2-catalyzed production
of 4 (eq 8)23 is based on a two-step sequence consisting of (1)
(20) This mechanistic discussion focuses on the steps associated with palladium-
(II)-promoted oxidative coupling of styrene and oxazolidinone. Because
this portion of the catalytic cycle is turnover-limiting, we are unable to
gain direct insights into the mechanism of Cu(II)-mediated regeneration
of the oxidized catalyst with molecular oxygen. The proton equivalents
from [Et3NH]+ (or [BH]+) and the Pd(II)-hydride intermediate are utilized
in the reduction of dioxygen to water.
(21) (a) Gatti, G.; Lo´pez, J. A.; Mealli, C.; Musco, A. J. Organomet. Chem.
1994, 483, 77-89. (b) Rix, F. C.; Brookhart, M.; White, P. S. J. Am. Chem.
Soc. 1996, 118, 2436-2448. (c) LaPointe, A. M.; Rix, F. C.; Brookhart,
M. J. Am. Chem. Soc. 1997, 119, 906-917. (d) Lin, Y. S.; Yamamoto, A.
Organometallics 1998, 17, 3466-3478. (e) Nozaki, K.; Komaki, H.;
Kawashima, Y.; Hiyama, T.; Matsubara, T. J. Am. Chem. Soc. 2001, 123,
534-544. (f) Hii, K. K.; Claridge, T. D. W.; Giernoth, R.; Brown, J. M.
AdV. Synth. Catal. 2004, 346, 983-988.
Figure 5. Qualitative energy diagram associated with the mechanism in
Scheme 1. For clarity, the two-step aminopalladation of the styrene is
presented as a single process. The dashed curves reflect the effect of a
Brønsted base on the energy profile.
(22) Bar, G. L. J.; Lloyd-Jones, G. C.; Booker-Milburn, K. I. J. Am. Chem.
Soc. 2005, 127, 7308-7309.
(23) Rate law derivations are provided in the Supporting Information.
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A R T I C L E S
Timokhin and Stahl
Scheme 2. Reversible Aminopalladation Observed in the
Scheme 3. Mechanism of Stoichiometric Palladium(II)-Mediated
Amination of Ethylene Involving Three Independent Roles for
Alkylamine
Stoichiometric Addition of Me2NH to Pd(II)-Coordinated Styrene25
at NEt3:Pd ∼ 3 (i.e., 15 mol % NEt3, Figure 2B). The observed
inhibition at higher [NEt3] can be explained by the ability of
triethylamine to hinder styrene coordination.
steady-state displacement of NEt3 by styrene followed by (2)
rate-limiting addition of oxazolidinone on the coordinated
alkene. The rate saturates at high [oxazolidinone] (Figure 4A)
because, under these conditions, k2′[HNRZ] . k-1[NEt3] and
displacement of NEt3 by styrene is the rate-limiting step. The
rate law simplifies to an expression that is first order in [2] and
[St] (eq 9).24
This interpretation of the effect of triethylamine (Figure 2)
finds precedent in the stoichiometric amination of alkenes
mediated by (PhCN)2PdCl2, which requires 3 equiv of the
secondary alkylamine substrate.27 Mechanistic studies of this
reaction by Hegedus et al. revealed an independent role for each
of the 3 equiv of amine (Scheme 3): the first amine coordinates
to palladium as an ancillary ligand, the second equivalent
undergoes nucleophilic attack on the coordinated olefin, and
the third amine deprotonates the zwitterionic intermediate to
yield a (â-aminoalkyl)palladium(II) product.28,29 Furthermore,
they observed that aminopalladation of the olefin, the second
step in this mechanism, is reversible. The inability to achieve
catalytic amination of olefins in this system reflects, in part,
the strong coordinating ability of alkylamines, which inhibits
alkene activation when a large excess of amine is present relative
to palladium(II). In our catalytic system, the nitrogen nucleophile
is only weakly coordinating, and triethylamine, which serves
both as a ligand and as a base (cf. first and third steps of Scheme
3), is present in low, catalytic concentrations.
k1k2′[2][St][HNRZ]
d[4]
dt
)
(8)
(9)
k-1[NEt3] + k2′[HNRZ]
d[4]
dt
) k1[2][St] (at high [HNRZ])
This interpretation of the kinetic data finds support from
studies of the stoichiometric addition of amines to dicationic
Pd(II)-styrene complexes reported by Hahn and Vitagliano et
al. (Scheme 2).25 Addition of excess dimethylamine to the
styrene adduct, 7, in dichloromethane results in immediate
formation of the Markovnikov addition product, 9; however,
isomerization to the anti-Markovnikov aminopalladation product,
11, occurs within 1 h at room temperature.
Conclusion and Implications
Efficient metal-catalyzed reactions for the intermolecular
coupling of alkenes and nitrogen nucleophiles are still relatively
rare, and the ability to achieve selective formation of either
possible regioisomer is virtually unprecedented. On the basis
of the studies described herein, we postulate a unique Brønsted
base-modulated mechanism to achieve regiocontrol in the Pd-
(II)-catalyzed oxidative amination of styrene with oxazolidinone.
Regiochemical reversal is possible because the kinetic and
thermodynamic products of styrene aminopalladation exhibit
opposite regiochemistry. The thermodynamic preference for anti-
Markovnikov addition of oxazolidinone to styrene appears to
reflect the stability of η3-benzyl adducts, and therefore, applica-
tion of these mechanistic principles may be limited to substrates
that can achieve similar chelate-induced stabilization of the anti-
Markovnikov adduct. Recently, however, Atwood and co-
workers noted a similar regiochemical distinction between the
kinetic and thermodynamic products of stoichiometric amine
addition to Pt(II)-coordinated alkyl olefins (e.g., propene).30 In
this case, the anti-MarkoVnikoV aminoplatination adduct is
Role of Triethylamine. Triethylamine plays a complex role
in this chemistry, serving both as a ligand and as a Brønsted
base.26 The inverse relationship between the yield of the anti-
Markovnikov product, 3, and [NEt3] (filled triangles, Figure 2A)
appears to correlate with coordination of NEt3 to palladium,
which probably results in a less electrophilic metal center.
Formation of the Markovnikov product, 4, occurs only after
>1 equiv of NEt3 is added relative to palladium. This observa-
tion suggests that the first equivalent of NEt3 coordinates to
palladium and is unavailable to serve as a base. Between 1 and
2 equiv of NEt3 relative to palladium, free amine base can be
generated by displacement of the second NEt3 ligand from Pd
(step 1, Scheme 1), and the rate continues to rise to a maximum
(24) Our data cannot rigorously establish the aminopalladation mechanism. The
presence of base may facilitate formation of a Pd(II)-amido complex that
undergoes irreversible insertion of styrene with Markovnikov regioselec-
tivity. Our kinetic data in Figure 4 are consistent with this pathway if the
Pd(II)-amido complex is formed in a rapid preequilibrium (see rate law
and analysis in the Supporting Information). 1H NMR spectroscopic studies
to detect formation of such an intermediate have been inconclusive. The
specific pathway for aminopalladation, however, does not alter our principle
conclusion concerning the presence of a base-induced switch in regio-
selectivity.
(25) (a) Hahn, C.; Vitagliano, A.; Giordano, F.; Taube, R. Organometallics 1998,
17, 2060-2066. (b) Hahn, C.; Morvillo, P.; Vitagliano, A. Eur. J. Inorg.
Chem. 2001, 419-429. (c) Hahn, C.; Morvillo, P.; Herdtweck, E.;
Vitagliano, A. Organometallics 2002, 21, 1807-1818.
(26) For analysis of the complex kinetic influence of triethylamine on aerobic
alcohol oxidation catalyzed by Pd(OAc)2/NEt3, see: Schultz, M. J.; Adler,
R. S.; Zierkiewicz, W.; Privalov, T.; Sigman, M. S. J. Am. Chem. Soc.
2005, 127, 8499-8507.
(27) Åkermark, B.; Ba¨ckvall, J. E.; Hegedus, L. S.; Zetterberg, K.; Siirala-
Hanse´n, K.; Sjo¨berg, K. J. Organomet. Chem. 1974, 72, 127-138.
(28) Hegedus, L. S.; Åkermark, B.; Zetterberg, K.; Olsson, L. F. J. Am. Chem.
Soc. 1984, 106, 7122-7126.
(29) Recent mechanistic studies of platinum-catalyzed methods for the hy-
droamination of acrylonitrile and intramolecular hydroamination of alkenes
indicate that exogenous amine serves as a Brønsted base to deprotonate
the initially formed aminoplatination adduct: (a) Seul, J. M.; Park, S. J.
Chem. Soc., Dalton Trans. 2002, 1153-1158. (b) Bender, C. F.; Widen-
hoefer, R. A. J. Am. Chem. Soc. 2005, 127, 1070-1071.
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Mechanism of Pd-Catalyzed Oxidative Amination
A R T I C L E S
favored kinetically, presumably for steric reasons,31 and it
isomerizes to the Markovnikov adduct at elevated temperatures.
These results, together with the mechanistic principles outlined
in our study, suggest that the development of catalytic methods
for selective anti-Markovnikov addition of amines to alkylolefins
may be feasible.
discussions. We are grateful to Prof. M. Brookhart for suggesting
the possibility of an η3-benzyl intermediate to explain the
thermodynamic stability of the anti-Markovnikov aminopalla-
dation adduct. This work was supported by the Dreyfus
Foundation (Teacher-Scholar Award), the Sloan Foundation
(Research Fellowship), and the NIH (Grant RO1 GM67173).
Acknowledgment. We thank B. Popp, N. Anastasi, and I.
Guzei for experimental assistance and J. Brice for helpful
Supporting Information Available: Kinetic plot (Figure S1),
rate-law derivations, and experimental procedures. This material
is available free of charge via the Internet at http://pubs.acs.org.
(30) Pryadun, R.; Sukumaran, D.; Bogadi, R.; Atwood, J. D. J. Am. Chem. Soc.
2004, 126, 12414-12420.
(31) The complexes studied by Atwood and co-workers, PtCl2(Ph3P)(alkene),
possess a sterically encumbered triphenylphosphine ligand in the Pt(II)
coordination sphere that may result in kinetically favored attack at the
sterically less hindered alkene carbon.
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