Rationale behind the resistance of dialkylbiaryl phosphines toward oxidation by molecular oxygen

Article abstract of DOI:10.1021/ja0683180

Electron-rich dialkylbiaryl phosphines, which comprise a common class of supporting ligands for Pd-catalyzed cross-coupling reactions, are highly resistant toward oxidation by molecular oxygen. Presented herein are possible reasons why this class of phosphine ligands manifests this property. Experimental and theoretical data suggest that the two alkyl substituents on the phosphorus center and the 2′ and 6′ positions of the biaryl backbone play an important role in inhibiting oxidation of this class of ligands.

Full text of DOI:10.1021/ja0683180

Published on Web 03/28/2007
Rationale Behind the Resistance of Dialkylbiaryl Phosphines
toward Oxidation by Molecular Oxygen
Timothy E. Barder and Stephen L. Buchwald*
Contribution from the Department of Chemistry, Massachusetts Institute of Technology,
77 Massachusetts AVenue, Cambridge, Massachusetts 02139
Received November 28, 2006; E-mail: sbuchwal@mit.edu
Abstract: Electron-rich dialkylbiaryl phosphines, which comprise a common class of supporting ligands
for Pd-catalyzed cross-coupling reactions, are highly resistant toward oxidation by molecular oxygen.
Presented herein are possible reasons why this class of phosphine ligands manifests this property.
Experimental and theoretical data suggest that the two alkyl substituents on the phosphorus center and
the 2′ and 6′ positions of the biaryl backbone play an important role in inhibiting oxidation of this class of
ligands.
Introduction
The use of dialkylbiaryl phosphines as supporting ligands for
Pd-catalyzed cross-coupling reactions has seen enormous growth
since their introduction in 1998.1 Dialkylbiaryl ligands can be
prepared in a simple one-pot procedure,2 and over 10 are now
commercially available.3 Although these phosphine ligands are
electron-rich, due to the two alkyl substituents on phosphorus
(most often cyclohexyl or tert-butyl), oxidation to the phosphine
oxide does not readily occur. It has been determined that 2-(di-
tert-butylphosphino)biphenyl can be stored on the benchtop for
up to 4 years without any detection of phosphine oxide as
evidenced by 31P NMR. The inertness of these phosphines
toward oxidation is often taken for granted, and as such, the
reason(s) behind this property still remains largely unclear.
Herein, we describe what we believe as plausible hypotheses
as to this robustness, followed by experimental and theoretical
experiments on various phosphines and their oxidation by O2.
Postulations on the Resistance of Dialkylbiaryl Phosphines
toward Oxidation. Our initial two hypotheses on the lack of
reactivity of dialkylbiaryl phosphines toward oxidation by O2
were the following: (1) there exists an electronic interaction
between the lone pair of electrons on phosphorus and the non-
phosphine-containing ring of the ligands which prevents the
phosphorus from being oxidized (Figure 1a) and/or (2) a
prereaction complex between O2 and the phosphine ligand is
Figure 1. Two hypotheses as to the robustness of biaryl phosphines toward
oxidation by molecular oxygen.
Figure 2. Possible consequence of either of the two hypotheses on the
oxidation of biaryl phosphines.
highly unfavored as the O2 molecule needs to navigate between
the two in close contact with the phosphorus center (Figure 1b).
In either case, we suggest that, for oxidation to occur by O2,
the phosphine center needs to invert or rotate such that the lone
pair of electrons is facing away from the non-phosphine
containing ring of the ligand prior to oxidation (A-away, Figure
2). However, little is known about the possibility of rotation/
inversion of the phosphorus center in these ligands since only
one species is observed via 31P NMR for any given biaryl
phosphine. Solid state analyses on various biaryl phosphines
(via X-ray crystallography) and theoretical studies reveal that
the lone pair of electrons on the phosphorus center is positioned
above the non-phosphine-containing ring of the ligand in all
examples examined to date (i.e., in a geometry such as A).4
We therefore sought to conduct studies using NMR and DFT
calculations on various biaryl-based as well as triaryl and trialkyl
(1) Selected recent papers using biaryl phosphines in cross-coupling reac-
tions: (a) Huang, X.; Anderson, K. W.; Zim, D.; Jiang, L.; Klapars, A.;
Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 6653-6655. (b) Walker,
S. D.; Barder, T. E.; Martinelli, J. R.; Buchwald, S. L. Angew. Chem., Int.
Ed. 2004, 43, 1871-1876. (c) Milne, J. E.; Buchwald, S. L. J. Am. Chem.
Soc. 2004, 126, 13028-13032. (d) Barder, T. E.; Walker, S. D.; Martinelli,
J. R.; Buchwald, S. L. J. Am. Chem. Soc. 2005, 127, 4685-4696. (e)
Billingsley, K. L.; Anderson, K. W.; Buchwald, S. L. Angew. Chem., Int.
Ed. 2006, 45, 3483-3488. (f) Burgos, C. H.; Barder, T. E.; Huang, X.;
Buchwald, S. L. Angew. Chem., Int. Ed. 2006, 45, 4321-4326. (g)
Anderson, K. W.; Tundel, R. E.; Altman, R. A.; Buchwald, S. L. Angew.
Chem., Int. Ed. 2006, 45, 6523-6527.
(4) Biaryl phosphines analyzed via X-crystallography include the following:
2-(2′,4′,6′-triisopropylbiphenyl)diphenylphosphine, 2-(2′,4′,6′-triisopropy-
lbiphenyl)-3,4,5,6-tetramethyl-di-tert-butylphosphine, and 2-(2′,4′,6′-triiso-
propylbiphenyl)-tert-butyl-N-(1-phenethyl)phosphine. ORTEP diagrams of
these structures are included in the Supporting Information.
(2) Tomori, H.; Fox, J. M.; Buchwald, S. L. J. Org. Chem. 2000, 65, 5334-
5341.
(3) A number of biaryl phosphines are available from Strem Chemicals, Inc.
and Sigma-Aldrich Co.
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Dialkylbiaryl Phosphine Resistance toward Oxidation
A R T I C L E S
Figure 3. Bar graph illustrating the percentage of oxidized phosphine present (determined by 31P NMR) after 65 h in PhMe under the given reaction
conditions depicted for each ligand.7
phosphines, and transition state structures involving the oxida-
tion of these ligands.
electrons on phosphorus is not perturbed by the non-phosphine-
containing ring of the ligand. Identical calculations were
conducted on 2-(2′,6′-dimethoxybiphenyl)-dicyclohexylphos-
phine, 2, and the HOMO energy levels for each isomer were
found to be nearly identical as well (-0.196 eV vs -0.197 eV).
We believe that if a P-arene interaction was present, noticeable
differences would exist in the energy level of the HOMO in
these calculations; however, as no such deviations are present,
we rule out the possibility of a P-arene interaction in biaryl
phosphine complexes.
We first used DFT to analyze if a phosphine-arene interac-
tion exists in biaryl phosphine ligands. The simplest dicyclo-
hexylbiaryl phosphine, which possesses two cyclohexyl groups
on phosphorus, 1, was optimized using an all-atom DFT
approach (B3LYP/6-31G(d))5 using Gaussian 036 without any
approximations (e.g., P(biphenyl)H2 instead of the entire ligand
structure). Although the optimization without any approxima-
tions requires more computational time, it is necessary to
accurately analyze both the steric and electronic nature of the
phosphorus center. Two distinct local minima were located: the
first with the lone pair of electrons on phosphorus pointing
toward the non-phosphine-containing ring (1, cf. A in Figure
2) and the second with the lone pair of electrons on phosphorus
pointing away from the non-phosphine-containing ring of the
ligand (1-away, cf. A-away in Figure 2). The energies of the
MO containing the lone pair of electrons on phosphorus
(HOMO) of each structure were compared and found to be
identical (-0.207 eV). This suggests that the lone pair of
In order to test the second hypothesis above, molecular oxy-
gen was positioned above the non-phosphine-containing phenyl
ring of the ligand in 1 and 2. Although ground state optimiza-
tions determined that there was an interaction between the non-
phosphine-containing ring of the ligands and 1O2, no such inter-
actions (favorable or unfavorable) were found while using 3O2.
Hence, we conclude that the unfavorable interaction between 3O2
and the non-phosphine-containing ring of the ligand is present
in a ligand-O2 prereaction complex and the second hypothesis
is ruled out. We next turned to experimental studies with various
ligands and oxidizing conditions in attempts to observe a trend
for oxidation of the various phosphine ligands employed.
(5) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648-5652. (b) Lee, C.; Yang,
W.; Parr, R. G. Phys. ReV. B 1988, 37, 785.
(6) Frisch, M. J., et. al. Gaussian 03, revision B.05; Gaussian, Inc.: Wallingford,
CT, 2004.
(7) For compounds 1-10, a small amount of phosphinate ester was observed
via 31P NMR. Phosphinate esters are expected side products from phosphine
oxidation: see ref 11.
Oxidation of Various Phosphines under Air and O2.
Several phosphines, ranging from triphenylphosphine to exceed-
ingly bulky dialkylbiaryl phosphines, were subjected to various
oxidizing conditions. In these experiments, 0.05 mmol of
phosphine in 1 mL of toluene was vigorously stirred under either
an air or O2 atmosphere at 25 or 100 °C for 65 h (Figure 3). It
is important to note that the mole fraction of 1.08 atm of O2 in
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Barder and Buchwald
toluene is known to be 0.001 01 at 298.41 K.8 This value
decreases slightly to 0.000 90 at 348.29 K (under 1.12 atm of
O2)8 and likely decreases further as the temperature of toluene
approaches 373 K (100 °C). Hence, a slightly greater amount
of oxygen is present in the solution of reactions run under O2
at 25 °C than 100 °C. Regardless of this fact, only a minimal
amount of oxidation occurred here for any of the ligands
examined (except PCy3) when stirred under an atmosphere of
O2 at 25 °C for 65 h.
ligand with two tert-butyl groups on phosphorus, 11, was
extremely resistant to oxidation and only 19% of the phosphine
oxide was found to be present after subjecting this phosphine
to an atmosphere of O2 at 100 °C for 65 h. This is an interesting
observation since oxidation of the analogous ligand with
isopropyl groups (8) instead of tert-butyl groups at 100 °C in
an atmosphere of O2 was facile (99% phosphine oxide,
respectively, after 65 h). This illustrates that the addition of only
one methyl group on each of the alkyl substituents on the
phosphorus center in 8 is responsible for such a dramatic
decrease in oxidation of the phosphine! Furthermore, increasing
the size of the non-phosphine-containing ring of the ligand also
decreased the amount of oxidation observed. The addition of
three isopropyl groups on the 2′, 4′, and 6′ positions of the non-
phosphine-containing ring of the ligand (13) reduced the amount
of phosphine oxide observed under an atmosphere of O2 at 100
°C to only 13%. It was also determined that removal of the 4′
isopropyl group in 13, to yield 12, did not affect the amount of
phosphine oxide formed under the three conditions employed.
Finally, two diarylbiaryl phosphines (14 and 15) with two
phenyl groups on the phosphorus center were subjected to the
three oxidizing conditions. As expected, very little phosphine
oxide was observed in both cases as the electron density on the
phosphorus center is substantially decreased relative to dialky-
lbiaryl phosphines.
It was not surprising to find that, in the reaction of
tricyclohexylphosphine (3), no free phosphine remained under
any of the reaction conditions after 65 h. However, tri-
phenylphosphine (4) did not completely oxidize even under an
atmosphere of O2 at 100 °C for 65 h. The comparison of
triphenylphosphine and tricyclohexylphosphine confirms the
well-known fact that electron density residing on the phosphorus
center is a major factor that influences the rate of oxidation of
phosphine ligands. Oxidation of dicyclohexylphenylphosphine
(5), a less electron-rich phosphine relative to PCy3, was quite
slow at 25 °C in an atmosphere of O2 for 65 h (only 7%
phosphine oxide was detected by 31P NMR). It is important to
note here that the minimum value (Vmin) of the molecular
electrostatic potential (MESP), which corresponds to the
electron-donating (more negative value) or -withdrawing ability
(more positive value)9 of the phosphorus center, differs only
slightly between dicyclohexylphenylphosphine (5) and the
dialkylbiaryl phosphines used in this study (Vmin ) -41.2 kcal/
mol for 5 and Vmin ) -43.9 kcal/mol for 8 to -49.0 kcal/mol
for 9).9b This suggests that any differences between the
oxidations of dicyclohexylphenylphosphine and dialkylbiaryl
phosphines are due to steric, not electronic, factors as dialkyl-
biaryl phosphines are more electron-rich than dicyclohexyl-
phenylphosphine according to the MESP minimum values.
Oxidation of 6, a phosphine similar to 1 with a cyclohexyl group
instead of phenyl as the non-phosphine containing ring of the
ligand, still readily occurred at 100 °C in air or under O2 after
65 h. It was found that 72% of the oxidized phosphine was
present after 65 h in an air atmosphere at 100 °C and 95% of
the oxidized phosphine when the oxidation was conducted
under O2.
Clearly, increasing the size of the two alkyl substituents on
the phosphorus center has a dramatic influence on the rate of
oxidation of biaryl phosphine ligands, as best illustrated by the
oxidation of 8 and 11. Additionally, it appears that inclusion of
bulky substituents on the 2′ and 6′ positions of the non-
phosphine-containing ring of the ligand (when alkyl substituents
are present on the phosphorus center) also has a dramatic effect
on the rate of ligand oxidation.
Theoretical Data on the Rotation/Inversion of the Phos-
phorus Center. It would be unusual if Pd (and Pd bound to
other ligands beside the phosphine, e.g., Pd(Ph)Br) can ef-
ficiently bind to all of the phosphines in Figure 3 (all of the
biaryl ligands depicted are efficient for cross-coupling reactions),
but it is difficult for O2 to bind and therefore oxidize the
phosphorus center. Although our original two hypotheses were
flawed, we postulated that certain aspects of these hypotheses
may hold true (e.g., that the phosphorus center needs to rotate
such that the lone pair of electrons is distal to the non-phosphine-
containing ring of the ligand rather than above it) and help shed
light on the fact that Pd-binding and subsequent reactions at
the Pd center are rapid while oxidation is difficult. In order for
the phosphine to arrive at a geometry that is depicted in A-away,
either inversion of the phosphorus center or rotation of the
phosphorus center must occur. However, the calculated activa-
tion energy for inversion of the phosphorus center in 2 is 31.9
kcal/mol. This value agrees well with a report from Baechler
and Mislow10 documenting experimental activation energies of
inversion of various phosphines. Reaction temperatures of at
least 130 °C were required to observe phosphine inversion in
this report, and similar, if not more severe conditions, are likely
required for inversion of the phosphorus center in the phosphines
analyzed here. Hence we rule out inversion of the phosphorus
center to arrive at a geometry such as A-away. We next returned
to DFT to determine the thermodynamic and kinetic param-
We next examined the oxidation of dialkylbiaryl phosphines
under the three conditions listed in Figure 3. Ligands 1 and 2
demonstrate similar behaviors under these conditions (e.g.,
>95% phosphine oxide formed under O2 at 100 °C). However,
the inclusion of larger substituents at the 2′ and 6′ positions of
the non-phosphine-containing ring of the biaryl backbone (e.g.,
-Oi-Pr) significantly slowed the rate of oxidation, as demon-
strated with 9 (69% phosphine oxide was observed under O2 at
100 °C). Furthermore, as the bulk of the substituents at the 2′
and 6′ positions is increased (to isopropyl), as in 10, oxidation
becomes even more difficult. Under an atmosphere of O2 at
100 °C only 28% of phosphine oxide was present after 65 h.
Replacing the two dicyclohexyl groups on phosphorus with
tert-butyl groups had a pronounced effect on the rate of
oxidation for the biaryl class of phosphines. The simplest biaryl
(8) Fischer, K.; Wilken, M. J. Chem. Thermodyn. 2001, 33, 1285-1308.
(9) (a) Politzer, P., Truhlar, D. G., Eds. Chemical Applications of Atomic and
Molecular Electrostatic Potentials; Plenum Press: New York, 1981. (b)
Vmin from an MESP plot was recently proposed as a quantitative measure
of the electron effect of phosphine ligands: Suresh, C. H.; Koga, N. Inorg.
Chem. 2002, 41, 1573-1578.
(10) Baechler, R. D.; Mislow, K. J. Am. Chem. Soc. 1970, 92, 3090-3093.
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A R T I C L E S
Table 1. Thermodynamic and Kinetic Parameters for Rotation
around the C1-P Bond in Various Ligands
the phosphorus center and (2) a second phosphine abstracting
the second oxygen from compound C in Figure 5 for ligands
possessing two cyclohexyl or isopropyl groups on the phos-
phorus center.
Discussion
Possible Reasons Behind the Lack of Oxidation of Di-
alkylbiaryl Phosphines. The basis for the mechanisms shown
in Figure 4 has been previously proposed for the oxidation of
phosphines by O2;11 however, these mechanism have not taken
into consideration phosphines as large as dialkylbiaryl phos-
phines. The intermediate formed in the reaction between the
phosphine and O2 is not likely to undergo a reaction with a
second phosphine in conformation C due to the difficulty in a
bimolecular reaction with extremely large dialkylbiaryl phos-
phines. However, if the phosphorus center rotates prior to
reaction with O2, the subsequent reaction with a second
phosphine is likely much more facile due to the temporary lack
of bulk from the non-phosphine ring of the ligand. Additionally,
it is possible that the product from the reaction of phosphine
with O2, C, may rotate to C-away; however, this rotation likely
follows the same kinetic trend as illustrated in Table 1.
Regardless of which pathway is active (phosphorus rotation first,
phosphorus reacting with O2 first, or a combination of both),
the size of the alkyl substituents on the phosphine center and
the size of the substituents on the 2′ and 6′ positions of the
non-phosphine-containing ring of the ligand influence the rate
of oxidation.
eters involved in the rotation of the phosphorus center to point
away from the non-phosphine-containing ring of the ligand.
Transition state structures for the rotation of the phosphorus
center were determined for 1, 2, and 8-13. Table 1 lists these
ligands in order of increasing ligand size. Based upon the
activation energies, it appears that rotation of the phosphorus
center is relatively facile for ligands bearing two isopropyl or
two cyclohexyl groups on the phosphorus center (1, 2, and
8-10). However, for ligands possessing two tert-butyl groups
(11-13), rotation is much more difficult. As discussed above,
the difference between the rate of oxidation of 8 and 11 may
stem, in part, from this as ∆G‡ ) 12.1 kcal/mol for the rotation
of the phosphorus center in 8 and ∆G‡ ) 26.3 kcal/mol for
rotation of the phosphorus center in 11. Additionally, as the
size of the ligand is increased, ∆G for the rotation is also
increased (2.7 kcal/mol for 8 to 13.1 kcal/mol for 12). Hence,
not only is phosphorus rotation more difficult as the size of the
alkyl substituents on the phosphorus center are increased (from
isopropyl f cyclohexyl f tert-butyl), but the ratio of products
due to this rotation favors the A conformation over the A-away
conformation. Somewhat surprisingly, it does not appear that
the interaction between the alkyl groups on the phosphorus
center and the substituents on the 2′ and 6′ positions of the non-
phosphine-containing ring of the ligand influences the activation
energy for rotation. Instead, the difficulty in rotation arises from
the alkyl groups on phosphorus passing over the top ring of the
ligand (highlighted in red in the transition state structure in Table
1). However, as the size of the alkyl groups on phosphorus as
well as the groups on the 2′ and 6′ positions are increased,
oxidation is clearly retarded. We do not believe this is due to a
difficulty in molecular oxygen coming in close proximity to
phosphorus but a difficulty in the following: (1) the ligand
accessing a geometry with the lone pair of electrons on
phosphorus being distal to the non-phosphine-containing ring
of the ligand for ligands possessing two tert-butyl groups on
The fact that a nearly identical amount of phosphine oxide
is observed for ligands 11-13 under an atmosphere of either
air (∼20% O2) or O2 at 100 °C for 65 h suggests that the
concentration of O2 in toluene minimally influences the rate at
which the phosphine oxide is formed. It is possible that, with
these ligands, rotation of the phosphorus center such that the
lone pair of electrons is distal to the non-phosphine-containing
ring of the ligand is rate limiting, as no dependence on O2
concentration is observed. This is consistent with the finding
that the activation energy for phosphorus rotation in ligands
11-13 is high (∆G‡ > 25 kcal/mol) and the fact that the
equilibrium for phosphorus rotation lies heavily on the side of
the conformation in which the lone pair of electrons on
phosphorus is above the non-phosphine-containing ring (con-
formation A) of the ligand. For ligands 2, 9, and 10, substantially
more phosphine oxide is observed when these ligands are
subjected to an atmosphere of O2 at 100 °C for 65 h rather than
an atmosphere of air at 100 °C for 65 h. In these cases, rotation
of the phosphorus center is facile (∆G‡ < 15 kcal/mol in all
cases), which allows for a greater amount of the R3P-O-O
species to be formed. This intermediate can then react with a
second phosphine to form 2 equiv of the phosphine oxide. It
seems plausible that the rate-limiting step for the oxidation of
these ligands is the bimolecular process involving an R3P-O-O
species with R3P.
(11) General mechanism: Kosolapoff, G. M.; Maier, L. Organic Phosphorus
Compounds; Wiley-Interscience: New York, 1972; Vol. 3, p 346. For
3O2: (a) Rauhut, M. M.; Currier, H. A. J. Org. Chem. 1961, 26, 4626-
4628. (b) Burkett, H. D.; Hill, W. E.; Worley, S. D. Phosphorus and Sulfur
1984, 20, 169-172. For 1O2: (a) Nahm, K.; Li, Y.; Evanseck, J. D.; Houk,
K. N.; Foote, C. S. J. Am. Chem. Soc. 1993, 115, 4879-4884. (b) Tsuji,
S.; Kondo, M.; Ishiguro, K.; Sawaki, Y. J. Org. Chem. 1993, 58, 5055-
5059. (c) Ho, D. G.; Gao, R.; Celaje, J.; Chung, H.-Y.; Selke, M. Science
2003, 302, 259-262.
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Figure 4. Possible mechanism to explain the resistance of biaryl phosphines toward oxidation by O2.
Figure 5. Comparison of a possible transition state structure of a second phosphine abstracting an oxygen from an R3P-O-O species with the X-ray crystal
structure of [2]2PdCl2.1d
Figure 6. Comparison of a possible transition state structure of a second phosphine abstracting an oxygen from an R3P-O-O species with the X-ray crystal
structure of [2]2Pd.1d
It is worth noting that the amount of phosphine oxide
observed with ligand 10 is more similar to the amount observed
with ligands composed of (biaryl)P(t-Bu)2 than with ligands
composed of (biaryl)PCy2. This is not due to the difficulty in
rotation of the phosphorus center to an orientation such as that
depicted in A-away, as the activation energy for this rotation
with 10 is only 12.5 kcal/mol, but instead due to a difficulty in
the R3P-O-O species reacting with another molecule of 10.
Since the non-phosphine-containing ring of 10 is much larger
than 8 or 9, the biomolecular process is much more difficult;
hence, the smaller amount of phosphine oxide is observed.
Further support for the mechanism depicted in Figure 4 is
provided by examining various complexes composed of two
biaryl phosphine ligands bound to a metal center. Several L2-
PdCl2 complexes (where L ) 2, 9, 10, and 2-(2′-isopropylbi-
phenyl)dicyclohexylphosphine) have been prepared and struc-
turally characterized.1d,12 All of these complexes contain two
biaryl phosphines that are in close proximity to one another
(related to a bimolecular process depicted in Figure 4), and both
phosphine ligands are in the A-away orientation. These data
suggest that it is difficult for the phosphorus centers of two
biaryl phosphines to come into close proximity when they exist
in a geometry such as A. Rotation of the phosphorus to a
geometry such as A-away allows for the phosphorus center in
(12) See the Supporting Information for X-ray crystal structures of L2PdCl2
complexes.
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Dialkylbiaryl Phosphine Resistance toward Oxidation
A R T I C L E S
biaryl phosphines to more readily exist in close contact (Figure
5). Additionally, a bis-phosphine complex ([2]2Pd),1d which
possesses a smaller metal center (Pd vs PdCl2 above), positions
one of the biaryl phosphines with the non-phosphine-containing
ring of the ligand distal to the Pd (cf. A-away) while the other
ligand has the non-phosphine-containing ring of the ligand
directly below the Pd center (cf. A) (Figure 6). This structure
suggests that two dialkylbiaryl phosphines can exist in close
proximity with one of the non-phosphine-containing rings of
the ligand in the A conformation; however, the other non-
phosphine-containing ring of the ligand is required to exist in
a geometry such as A-away. Finally, the fact that we have been
unable to isolate larger L2Pd(0) complexes (e.g., [9]2Pd, [10]2Pd)
or even successfully synthesize larger L2Pd(0) complexes (e.g.,
[11]2Pd, [12]2Pd) lends credence to the difficulty in two of these
phosphine ligands existing in close proximity to one another
(resembling the bimolecular process in Figure 4).
oxygen. It is likely that abstraction of the second oxygen from
an R3P-O-O species by a second phosphine is difficult when
the lone pair of electrons on the phosphorus center is above the
non-phosphine-containing ring of the ligand. Rotation of the
phosphorus center to a less hindered environment likely has to
occur prior to abstraction of the second oxygen from an R3P-
O-O species. This rotation may even be rate limiting for ligands
possessing two tert-butyl groups on the phosphorus center.
Acknowledgment. We are grateful to the NIH for funding
(GM-46059). We thank Merck, Amgen, and Boehringer Ingel-
heim for additional unrestricted support. T.E.B. was supported,
in part, by an American Chemical Society Organic Division
Fellowship (supported by Novartis), which he gratefully ac-
knowledges.
Supporting Information Available: Experimental procedures
for the oxidation of ligands, coordinates of all optimized
structures, and the full citation for ref 6 (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
Conclusion
In conclusion, we have presented experimental and theoretical
data that help elucidate possible reasons why dialkylbiaryl
phosphine ligands are resistant toward oxidation by molecular
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