Probing the electronic demands of transmetalation in the palladium-catalyzed cross-coupling of arylsilanolates

Article abstract of DOI:10.1016/j.tet.2011.03.066

The electronic characteristics of coupling partners in the transmetalation step for the cross-coupling reaction of arylsilanolates have been investigated. The ability to interrogate the transmetalation event by in situ preparation of the arylpalladium(II) silanolate intermediate has enabled a Hammett analysis for both the aryl electrophile and arylsilanolate to be conducted. These studies reveal that electron-donating groups on the silicon nucleophile and electron-withdrawing groups on the electrophile accelerate the transmetalation process.

Full text of DOI:10.1016/j.tet.2011.03.066

Tetrahedron 67 (2011) 4391e4396
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Tetrahedron
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Probing the electronic demands of transmetalation in the palladium-catalyzed
cross-coupling of arylsilanolates
*
Scott E. Denmark , Russell C. Smith, Wen-Tau T. Chang
Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, IL 61801, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
The electronic characteristics of coupling partners in the transmetalation step for the cross-coupling
reaction of arylsilanolates have been investigated. The ability to interrogate the transmetalation event by
in situ preparation of the arylpalladium(II) silanolate intermediate has enabled a Hammett analysis for
both the aryl electrophile and arylsilanolate to be conducted. These studies reveal that electron-donating
groups on the silicon nucleophile and electron-withdrawing groups on the electrophile accelerate the
transmetalation process.
Received 5 February 2011
Received in revised form 16 March 2011
Accepted 21 March 2011
Available online 26 March 2011
Keywords:
Cross-coupling
Mechanism
Ó 2011 Elsevier Ltd. All rights reserved.
Hammett relationship
Transmetalation
Organosilicon
1. Introduction and background
organoboranes (Suzuki cross-coupling) are highly base dependent
and a pre-coordination of the transferring agent with the transition
Transition-metal cross-coupling reactions have ascended to
premier status in the panoply of strategy level carbonecarbon and
carboneheteroatom bond-forming reactions. The great diversity of
organometallic donors and organic electrophiles that participate in
this process accounts, in large measure, for the widespread adop-
tion of this technology.1 Despite the myriad permutations of donor
and acceptor that engage in successful cross-coupling reactions, the
basic catalytic cycle under palladium (or nickel) catalysis is re-
markably uniform across various families and involves: (1) oxida-
tive addition of an electrophilic halide or pseudo-halide to the M(0)
catalyst, (2) transmetalation of the transferable group from an or-
ganometallic donor, and (3) reductive elimination of the R1MLnR2
to generate a new CeC (or CeX) bond. Although the oxidative ad-
dition of an organic halide to a Pd(0) complex is common among
most coupling reactions, the transmetalation step is distinctive to
the organometallic donor employed. The transmetalation of orga-
nostannanes (Stille cross-coupling) has been extensively studied
but is still a matter of considerable debate.2 These transfers have
been suggested to follow an intermolecular SE2 mechanism by
means of stereochemical models. Cross-coupling reactions of
metal followed by delivery has been proposed for the trans-
metalation step but no concrete conclusions have been drawn to
date.3,4 Similarly, organosilane transmetalations can proceed via
a four-centered, closed transition structure (retentive), an acyclic,
open process (invertive),5 and a six-centered closed transition
structure (synfacial).6 Moreover, transmetalation via both neutral
8-Si-4 and anionic 10-Si-5 intermediates have been demon-
strated.7,8 Most of the evidence available to support these pathways
comes from kinetic analysis of the catalytic and, in some cases,
stoichiometric reactions.
A more detailed understanding of the critical transmetalation
step has been sought through the use of Hammett substituent effect
analyses for a variety of organometallic donors.9 By establishing
the influence of electronic perturbations in a catalytic reaction,
the transition state structures can be further refined. The effects
of substituents on arylstannanes,10 -boranes,11 -silanes,12 and -zin-
cates13 have been studied for cross-coupling reactions, however the
electronic influence by the organic acceptor for the transmetalation
step is not well established. In a cleverly designed competition
study, Hatanaka and co-workers established that electron-rich
arenes undergo transmetalation from silicon faster than electron-
deficient arenes (
DeShong, however reaches a contradictory conclusion that elec-
r
¼ꢀ1.5).12a A more recent study from Shukla and
* Corresponding author. 245 Roger Adams Laboratory, Box 18, Department of
Chemistry, University of Illinois, 600 S. Mathews Ave., Urbana, IL 61801, United
States. Tel.: þ1 217 333 0066; fax: þ1 217 333 3984; e-mail address: sdenmark@
illinois.edu (S.E. Denmark).
tron-deficient arenes transfer faster in intermolecular coupling re-
actions of aryltriethoxysilanes (
will shed light on the origin of this disparity and provide the
r
¼1.4).12b The results described here
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.066

4392
S.E. Denmark et al. / Tetrahedron 67 (2011) 4391e4396
first unified insights into the electronic requirements of both the
organic donor and acceptor in a palladium-catalyzed cross-coupling
reaction.
2.2. Preliminary investigation on the electronic influence
of substituents R1 and R2 on the activated transmetalation
The general trends for various palladium-catalyzed cross-cou-
pling reactions suggest that the transmetalation step is accelerated
by more electron-rich nucleophiles (organic donors) and by elec-
tron-poor electrophiles (organic acceptors). However, these trends
cannot be unambiguously ascribed to influences on the trans-
metalation step because the studies were conducted on fully op-
erating catalytic systems wherein substituent effects are manifest
in each of the stages of the catalytic cycle.14 Recent studies from
these laboratories on the mechanism of the cross-coupling reaction
of arylsilanolates with aryl halides in the presence of (t-Bu3P)2Pd
documented the intermediacy of a three-coordinate arylpalladiu-
m(II) arylsilanolate complex as the pretransmetalation species.7
These studies included the isolation and spectroscopic, crystallo-
graphic, and kinetic analysis of this intermediate.15 The ability to
prepare the pretransmetalation intermediate enables a direct in-
terrogation of the electronic characteristics of the critical step in the
catalytic cycle. By systematic variation of the substituents on both
the aryl halide and the arylsilanolate, the specific electronic de-
mands can be elucidated. Herein, we describe the results of
a Hammett substituent analysis for the transmetalation step in the
cross-coupling of arylsilanolates through use of stoichiometrically
generated arylpalladium(II) arylsilanolate complexes.
With a number of electronically disparate, three-coordinate,
arylpalladium(II) bromide complexes in hand, the rate constants
(kobs) for the cross-coupling were obtained. The influence of the
electronic properties of R1 in the electrophilic partner (i.e., the
arylpalladium(II) species derived from the aryl halide) was
investigated for the activated transmetalation with potassium
(4-methoxyphenyl)dimethylsilanolate Kþ3aꢀ. Formation of the
arylpalladium(II) silanolate complexes was accomplished in situ by
treating the arylpalladium(II) bromides 2 with 0.95 equiv of a so-
lution of Kþ3ꢀ in toluene at room temperature, which resulted in
the rapid formation of the desired T-shaped complexes 4. Addition
of a second quantity of Kþ3ꢀ (1.05 equiv) initiated the trans-
metalation step and the rate constants were determined from a plot
of the first-order decay of 4(aee)a.18 Each reaction was repeated in
duplicate and the averaged first-order rate constants for each
reaction and their relative rates are collected in Table 2. The aryl-
palladium(II) arylsilanolate complexes bearing electron-with-
drawing substituents on the aryl electrophile (4(cee)a) underwent
transmetalation faster than those bearing either no substituent
(4ba) or an electron-donating substituent (4aa) but the effect was
small. For example the 4-CF3 and the 4-OCF3 substituted arylpal-
ladium silanolate complexes 4ea and 4da reacted only 2.6 and 1.9
fold faster, respectively, than complex 4aa.
Given the matrix of data in Table 2, the electronic effect of
substituents on the nucleophile (R2) in the transmetalation step
could be secured by simply comparing the rate constants for a given
electrophile (e. g. Table 2, R1¼H). This analysis reveals that the more
electron-rich nucleophile (Kþ3aꢀ) reacts at a faster rate compared
to the other organosilicon donor groups (Kþ3bꢀ (H) or Kþ3eꢀ
(4-CF3)). For example, the transmetalation of the 4-MeO-
substituted arylsilanolate Kþ3aꢀ was roughly 2.5e4 times faster
compared to the 4-CF3-substituted arylsilanolate Kþ3eꢀ in-
dependent of the substitution of the electrophilic partner (R1).
When the relative rates for the arylsilanolate transmetalation
2. Results and discussion
2.1. Preparation of tert-butylphosphine arylpalladium(II)
bromide complexes
To facilitate the determination of the electronic influences of
substituents on both components in the transmetalation step,
a number of T-shaped arylpalladium(II) bromide complexes are
needed. Fortunately, a number of methods are available to access
a variety of electronically differentiated complexes, and the results
of the preparation are compiled in Table 1.16 However, methods for
the preparation and isolation of highly electron-deficient com-
plexes are noticeably absent. Attempts to prepare the 4-tri-
fluoromethylphenylpalladium bromide complex using neat aryl
halide led to rapid decomposition after >1 h of heating at 70 ꢁC.16a
To avoid decomposition of the arylpalladium(II) bromide complex,
a lower temperature (23 ꢁC) was employed, but less than 20% of
(t-Bu3P)(4-CF3C6H4)PdBr (2e) was obtained. Ultimately, the prep-
aration of 2e was accomplished by employing t-Bu3P$HBr as a cat-
alyst, entry 5.17
employing 4bx are plotted against the
s values for the substituents
on the nucleophile, a negative Hammett constant is obtained (Fig. 1,
r
¼ꢀ0.50).19 In addition, the Hammett value for the arylsilanolate
seems to be independent of the substituent on the arylpalladium
electrophile. Similar
r values were determined for each arylpalla-
dium electrophile investigated, suggesting that any synergistic
effect between the two components for transmetalation was
probably negligible.20
To probe the contribution of the electronic properties of sub-
stituents on the electrophilic partner on the rate of cross-coupling of
arylsilanolates, the relative rate constants for the coupling of both
potassium (phenyl)dimethylsilanolate Kþ3bꢀ and potassium (4-tri-
fluoromethylphenyl)dimethylsilanolate Kþ3eꢀ were investigated
with each electrophilic partner, 4aee (Table 2). Unsurprisingly, both
of these nucleophiles displayed similar trends in the rate cons-
tants with the various T-shaped complexes. For each arylsila-
nolate employed, the more electron-rich electrophile (t-
Bu3P)(4-MeOC6H4)PdX (4ax) provided the smaller rate constant (i.e.,
slower transmetalation) whereas the electron-deficient complexes
(t-Bu3P)(4-CF3OC6H4)PdX and (t-Bu3P)(4-CF3C6H4)PdBr (4dx and
4ex, respectively) provided the larger rate constants (i.e., faster
transmetalation).
Table 1
Preparation of T-shaped oxidative addition intermediates of palladium
Br
Br
conditions
Pd
(t-Bu3P)2Pd
+
R1
Pt-Bu3
R1
1
2
Entry
R1
Time, min
Solvent
Product
Yield, %
1a
2b
3c
4c
5c
MeO
H
F
CF3O
CF3
45
120
45
50
45
Neat
Neat
2-Butanone
2-Butanone
2-Butanone
2a
2b
2c
2d
2e
22
50
54
45
64
The Hammett analysis for the cross-coupling reaction of differ-
ent electrophilic partners employing Kþ3aꢀ provided a linear re-
lationship (using simple
s r value (Fig. 2,
values9) with a small
a
Conditions: Pd(dba)2 (1.0 equiv), t-Bu3P (1.1 equiv) aryl bromide (45.0 equiv),
r
¼0.49). The Hammett correlation for the effects of substituents on
22 ꢁC.
the arylpalladium electrophile on the rates of cross-coupling with
b
c
Conditions: (t-Bu3P)2Pd (1.0 equiv), aryl bromide (45.0 equiv), 70 ꢁC.
Conditions: (t-Bu3P)2Pd (1.0 equiv), aryl bromide (40e45.0 equiv), t-Bu3P$HBr
arylsilanolate nucleophiles (Kþ3bꢀ and Kþ3eꢀ) also provided linear
¼0.40, respectively.20
(0.03 equiv), 2-butanone, 70 ꢁC (Ref. 16).
free-energy relationships with
r¼0.35 and
r

S.E. Denmark et al. / Tetrahedron 67 (2011) 4391e4396
4393
Table 2
Activated transmetalation for a number of arylpalladium(II) arylsilanolate complexesa,b
R2
Me
Me
O- K+
Me
Si
R2
Br
R2
Me Si
R2
-
K+3
Pd
toluene, rt
O
Me
Me
+
Si
Pt-Bu3
Pd
R1
O– K+
R1
Pt-Bu3
R1
–
–
–
K+3a , K+3b , K+3e
4
5
2a-e
Arylsilanolate Kþ3ꢀ, R2
Arylpalladium bromide 2, R1
OMe (2a)
H (2b)
F (2c)
OCF3 (2d)
CF3 (2e)
OMe (3a)
H (3b)
CF3 (3e)
2.80
1.53
1.00d
3.27
1.82
1.28
4.64
2.39
1.34
5.56c
2.28
1.35
7.20
3.18
2.40
a
Reactions conditions: ca. 25 mM in 2aee, ca. 50 mM in Kþ3ꢀ in toluene (0.8 mL).
b
c
The relative rate constants were calculated from the smallest rate constant, which was for the transmetalation of 4ae with Kþ3eꢀ
Employed potassium (4-n-butoxyphenyl)dimethyl silanolate (see Discussion).
.
d
kobs for reaction of 2a with 3e¼7.48ꢂ10ꢀ5 sꢀ1
.
2.3. Preequilibrium considerations
Previous studies on the mechanism of activated cross-coupling
of arylsilanolates,7 revealed an interesting insight that potentially
complicates the interpretation of the studies herein. Specifically,
the rate of cross-coupling of stoichiometrically formed complexes 4
shows a first-order dependence on the concentration of added
silanolate, whereas under catalytic conditions, a zeroth-order de-
pendence on the silanolate is seen. This behavior is interpreted to
reflect a preequilibrium formation of the reactive 10-Si-5 silanolate
complex i shown in Scheme 1. This preequilibrium complicates the
determination of the electronic influence of substituents on the
silanolate (R2) because these electronic perturbations can be
manifested in two separate stages of the activated transmetalation
step: (1) the association of the silanolate with the silicon atom in
the 8-Si-4 arylpalladium silanolate to form the 10-Si-5 species and
(2) the formation of the new carbonepalladium bond in the
transmetalation step.22 From all of the foregoing studies, the rate of
displacement of bromide in the initial formation of the 8-Si-4
species is extremely fast independent of the substituents on the
silanolate or the arylpalladium bromide.7 However, the electronic
properties of the silanolate will influence the activation of the sil-
icon atom from the 8-Si-4 species to the 10-Si-5 siliconate and thus
the rate of the transmetalation (Scheme 1). First, the electrophi-
licity of the silicon atom in complex 4, and the nucleophilicity of the
oxygen atom in silanolate Kþ3ꢀ will affect the equilibrium con-
centration of complex i (step 1).23 Second, aryl substituents on both
partners will influence the accumulation of negative charge on the
10-Si-5 moiety, and thus affect the intrinsic rate of transmetalation
(step 2). To eliminate the contribution of the unknown and clearly
substituent dependent preequilibrium (factor 1), the activated
cross-coupling must be run under conditions where the rate con-
stant for the transmetalation has reached a saturation point. If this
kinetic regime could be attained, then the relative rate constants
obtained from the transmetalation studies should reflect solely the
formation of the palladiumecarbon bond (factor 2).
Fig. 1. Hammett plot for the transmetalation of various arylsilanolates in the phe-
nylpalladium complexes 4bx.
Fig. 2. Hammett plot for electronic effect for the electrophilic partner employing
K
þ3aꢀ
.
The fact that different arylsilanolates generate plots with similar
r
values suggests that the influence that the substituent on the
arylpalladium electrophile manifests in the transmetalation step is
independent of the arylsilanolate nucleophile used. In addition, the
2.4. Determination of saturation concentration
small magnitude of the
r values implies that the rate of cross-
coupling of different bromoarenes should not vary widely. In fact,
this trend was observed in the preparative cross-coupling of aryl-
silanolates using (t-Bu3P)2Pd wherein the reaction times for both
electron-rich and electron-deficient bromoarenes were compara-
ble within a given arylsilanolate set (3e4 h).21
Experimentally, the rate constant at the saturation point can be
established by increasing the concentration of the silanolate salts
Kþ3aꢀ, Kþ3bꢀ, and Kþ3eꢀ relative to silanolate complex 4 until no
further rate enhancement is observed. Unfortunately, the solubility
of Kþ3aꢀ in toluene precluded the saturation point from being

4394
S.E. Denmark et al. / Tetrahedron 67 (2011) 4391e4396
Scheme 1.
determined. Thus, a more soluble, electron-rich silanolate needed
to be investigated.
4-CF3) 4be with 2.0 and 4.0 equiv of Kþ3eꢀ results in only a minor
variation in the rate constant. Therefore, even at a 1:1 ratio of 4be/
Kþ3eꢀ the preequilibrium was nearly saturated.25,26
Appending a more lipophilic alkoxy group at C(4) of the arene
should improve organic solubility, but should not substantially alter
the sigma value for the Hammett analysis.24 Thus, potassium (4-n-
butoxyphenyl)dimethylsilanolate Kþ3fꢀ was prepared. This reagent
proved to be significantly more soluble and allowed the saturation
point to be attained. When 2.0 equiv of Kþ3fꢀ was added to the
three-coordinate palladium silanolate complex 4bf to promote the
transmetalation event, an increase in the rate constant was
obtained (kobs¼3.88ꢂ10ꢀ4 sꢀ1 vs kobs¼2.25ꢂ10ꢀ4 sꢀ1 for 1.0 equiv).
At this stage, additional quantities of silanolate were added until
either a solubility threshold was reached or leveling of the rate
constant was obtained. Gratifyingly, as the number of equivalents
of Kþ3fꢀ increased, the rate constant began to level-off (Table 3,
entries 2e4). Finally, a ratio of 8:1 for Kþ3fꢀ/4bf produced a maxi-
2.5. Implications of a Hammett correlation in the saturated
regime
The Hammett correlation for the electronic properties associ-
ated with the organosilanolate 3 yielded a negative r value thereby
indicating that the more electron-rich substituents improve the
reactivity. Using the saturated rate constants for each nucleophile,
the Hammett correlation provides a value for only the palla-
diumecarbon bond-forming event (Scheme 1, step 2). Although
a modest change was observed (
obtained employing only 1.0 equiv of arylsilanolate (
the slope remained negative, confirming that the transmetalation
step is accelerated by electron-rich arylsilanolates (Fig. 3). The in-
crease in the slope arises from the greater equilibrium concentra-
tion of i(bf) compared to i(be) (see Scheme 1).
r
¼ꢀ0.80) compared to the values
r
¼ꢀ0.50),19
mum rate constant of 5.15ꢂ10ꢀ4 sꢀ1
.
Table 3
Saturation points for the transmetalation of arylpalladium(II) arylsilanolate
complexes.a,b
Entry
R2
Silanolate
Equivalents of Kþ3ꢀ
kobs (sꢀ1
)
1
2
3
4
5
6
7
8
9
10
OMe
On-Bu
On-Bu
On-Bu
H
H
H
CF3
CF3
Kþ3aꢀ
Kþ3fꢀ
Kþ3fꢀ
Kþ3fꢀ
Kþ3bꢀ
Kþ3bꢀ
Kþ3bꢀ
Kþ3eꢀ
Kþ3eꢀ
Kþ3eꢀ
1.0
2.0
4.0
8.0
1.0
2.0
4.0
1.0
2.0
4.0
2.25ꢂ10ꢀ4
3.88ꢂ10ꢀ4
5.00ꢂ10ꢀ4
5.15ꢂ10ꢀ4
1.25ꢂ10ꢀ4
1.67ꢂ10ꢀ4
1.98ꢂ10ꢀ4
9.20ꢂ10ꢀ5
9.00ꢂ10ꢀ5
9.92ꢂ10ꢀ5
CF3
Reactions conditions: ca. 25 mM in 2aee, ca. 50 mM in Kþ3ꢀ in toluene (0.8 mL).
Rate constants were determined by the first-order decay of the arylpalladium
a
b
Fig. 3. Hammett plot employing kobs at the saturation point for the activated trans-
metalation step.
silanolate complex 4 using Ph3P(O) as an internal standard.
This same procedure was performed for both Kþ3bꢀ and Kþ3eꢀ
and different saturation points were reached for each nucleophile
(Table 3, entries 5e10). For example, the cross-coupling reaction of
(t-Bu3P)(C6H5)Pd(OSiMe2C6H5) 4bb with 2.0 and 4.0 equiv of
Kþ3bꢀ resulted in an increase in rate constants by factors of 1.33
and 1.58, respectively, clearly indicating a leveling off. Moreover,
carrying out the cross-coupling of (t-Bu3P)(C6H5)Pd(OSiMe2C6H4-
The negative Hammett value for the electronic effect of sub-
stituents on the arylsilanolate implies that, when saturated as the
10-Si-5 species, the greater electron density on the hypervalent
siliconate moiety (in particular on the migrating aryl group) leads
to a more facile transmetalation process. Nevertheless, the silicon
atom in the 8-Si-4 species 2 plays an important role in establishing
the preequilibrium, namely, the electrophilicity of this silicon atom

S.E. Denmark et al. / Tetrahedron 67 (2011) 4391e4396
4395
t
3
3
t
t
t
(t
2
i
4
t
5
t
t
ii
iii
iv
Scheme 2.
impacted the saturation point of the activation step of the various
arylsilanolate nucleophiles. As the concentration of Kþ3fꢀ in-
creased, the rate constant increased until the concentration de-
pendence for Kþ3fꢀ leveled off with an eightfold excess of
silanolate per complex 4. On the other hand, as the concentration of
Kþ3eꢀ increased, only minor variations in the rate constant were
seen. If the nucleophilicity of the silanolate were the dominant
factor, then the more nucleophilic silanolate is expected to reach
saturation more quickly. Therefore, the observation that the least
nucleophilic arylsilanolate reached a saturation point so readily
(fewest equivalents) leads to the conclusion that the electrophilicity
of the silicon atom is the major contributor to the activation
preequilibrium.
cross-coupling reactions and indicate a common feature among the
various cross-coupling reactions. The ability to isolate the pre-
transmetalation precursor provides a unique opportunity to in-
terrogate other aspects of this critical step, the subject of these
studies will be reported in due course.
Acknowledgements
We are grateful to the National Institutes of Health (GM-63167)
for financial support and to Johnson Matthey and Strem for gifts of
palladium catalysts. R.C.S. thanks the Aldrich Chemical Company
for a Graduate Student Innovation Award and Amgen for a Graduate
Fellowship. W.-T.T.C acknowledges the University of Illinois for
a graduate fellowship.
The results presented herein are consistent with an (intra-
molecular)27 electrophilic aromatic substitution on an activated
arylsilanolate moiety by an arylpalladium complex. The mechanism
of the activated transmetalation proceeds by generation of an 8-Si-
4 arylpalladium(II) silanolate complex (4, Scheme 2) from the first
formed oxidative addition product of a bromoarene to (t-Bu3P)2Pd,
compound 2 in combination with Mþ3ꢀ. In the presence of addi-
tional silanolate, a hypervalent 10-Si-5 siliconate i is formed from 4
in a preequilibrium, which renders the aryl group highly electron-
rich. Because the palladium center is coordinatively unsaturated,7
the migrating aryl group can initiate the transmetalation by do-
nation of electron density to the empty coordination site in the
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2011.03.066. These data
include MOL files and InChIKeys of the most important compounds
described in this article.
References and notes
1. (a) Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de Meijere, A., Diederich,
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M. Angew. Chem., Int. Ed. 2004, 43, 4704e4734.
formation of a p
-complex such as structure iii.28 The arene is then
transferred in a rate-limiting electrophilic aromatic substitution
process with concerted loss of a polysiloxane unit. This process may
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H.; Woerpel, K. A. J. Org. Chem. 1998, 63, 458e460; (c) Braga, A. A. C.; Morgon,
N. H.; Ujaque, G.; Lledos, A.; Maseras, F. J. Organomet. Chem. 2006, 691,
4459e4466; (d) Braga, A. A. C.; Ujaque, G.; Maseras, F. Organometallics 2006, 25,
3647e3654.
proceed via an intermediate
positive charge on the arene ring.28,29 The negative
arylsilanolates are consistent with an asynchronous generation of
the -complex in which the formation of the palladiumecarbon
bond precedes the breaking of the carbonesilicon bond. Following
reductive elimination, the monoligated palladium catalyst is
regenerated to complete the catalytic cycle.30
s
-complex iv, which places a partial
r
values for the
ꢀ
s
4. Hartwig has demonstrated the intermediacy of a RheOeB bond in
b-aryl
eliminations to form Rhearyl bonds. See Zhao, P.; Incarvito, C. D.; Hartwig, J. F. J.
Am. Chem. Soc. 2007, 129, 1876e1877.
5. Hatanaka, Y.; Hiyama, T. J. Am. Chem. Soc. 1990, 112, 7793e7794.
6. Denmark, S. E.; Werner, N. S. J. Am. Chem. Soc. 2010, 132, 3612e3620.
7. Denmark, S. E.; Smith, R. C. J. Am. Chem. Soc. 2010, 132, 1243e1245.
8. The NeXeL descriptors were introduced by Martin and co-workers to desig-
nate the bonding about any atom (X) in a resonance structure in terms of the
number of valence shell electrons (N) formally associated directly with that
atom and the number of ligands (L) directly bonded to it. See Perkins, C. W.;
Martin, J. C.; Arduengo, A. J.; Lau, W.; Alegria, A.; Kochi, J. K. J. Am. Chem. Soc.
1980, 102, 7753e7759.
3. Conclusion
The ability to prepare a pretransmetalation precursor has pro-
vided a refined insight into the electronic requirements for the
critical transmetalation step in the cross-coupling reaction of
organosilanolates. These results parallel other mechanistic studies
on the transmetalation of, inter alia, organoboranes in the Suzuki
9. Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165e195.
10. (a) Labadie, J.; Stille, J. K. J. Am. Chem. Soc. 1983, 105, 6129e6137; (b) Farina, V.;
Krishnan, B.; Marshall, D. R.; Roth, G. J. Org. Chem. 1993, 58, 5434e5444.

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11. (a) Zim, D.; Lando, V. R.; Dupont, J.; Monteiro, A. L. Org. Lett. 2001, 3,
3049e3051; (b) Nunes, C. M.; Monteiro, A. L. J. Braz. Chem. Soc. 2007, 18,
1443e1447; (c) Zim, D.; Nobre, S.; Monteiro, A. L. J. Mol. Catal. A: Chem. 2008,
287, 16e23; (d) Liang, L,; Chien, P.; Huang, M. Organometallics 2005, 24,
353e357; (e) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Organometallics 2004, 23,
4317e4324; (f) Lando, V. R.; Monteiro, A. L. Org. Lett. 2003, 5, 2891e2894.
12. (a) Hatanaka, Y.; Goda, K.; Okahara, Y.; Hiyama, T. Tetrahedron 1994, 50,
8301e8316; (b) Shukla, K. H.; DeShong, P. J. Org. Chem. 2008, 73, 6283e6291.
13. Dong, Z.-B.; Manolikakes, G.; Shi, L.; Knochel, P.; Mayr, H. Chem.dEur. J. 2010,
16, 248e253.
directly attached to a palladium atom to generate a tetracoordinate palladium
species, a significant change in the 31P chemical shift is expected.
27. (a) The results reported herein cannot be interpreted unambiguously in terms
of an intramolecular transmetalation, but the zeroth-order dependence on the
concentration of silanolate under catalytic conditions supports this conclusion,
see Ref. 7. (b) A cross-over experiment has been conducted to establish if the
transmetalation is intra- or intermolecular. Treatment of 1.0 equiv of the pre-
formed silanolate complex bearing a 4-methoxy group on the arylsilane (4ba)
with 1.0 equiv of (4-n-butoxyphenyl)dimethylsilanolate Kþ3fꢀ, the biaryl
product distribution was 45/55 for 5ba/5bf. Upon increasing the quantity of
external silanolate Kþ3fꢀ to 3.0 equiv per palladium complex, the product
distribution favored 5bf (79%) but still produced biaryl 5ba (21%). The product
distribution obtained in these experiments suggests that the silanolate complex
4ba participated in a silanolate exchange prior to transmetalation. As larger
quantities of the external silanolate were added, an equilibrium distribution of
the two complexes is generated that are equally activated towards trans-
metalation. These results confirm that the arylpalladium(II) silanolate complex
can undergo a rapid exchange with exogenous silanolate in solution. However,
under catalytic or stoichiometric conditions, the exchange is degenerate and
should not impact the analysis of the transmetalation step.
14. The study by Mayr and co-workers13 addressed this problem by circumventing
the oxidative addition step. These authors provided convincing evidence that
electron-donating groups on the arylzinc halide accelerate the transmetalation
step but did not perform a detailed Hammett analysis for the organic elec-
trophile in this step. They did clearly demonstrate the electronic demands of
the organic halide in the oxidative addition step.
15. The conclusions from the preceding study (Ref. 7) are as follows: (1) under cat-
alytic conditions, the turnover limiting step is ligand dissociation from
(t-Bu3P)2Pd so all subsequent steps are kinetically invisible, (2) arylpalladium(II)
arylsilanolate complex 4ca could be fully characterized by solution NMR and
X-ray crystallography, (3) 4ca undergoes thermal transmetalation to form biaryl
5ca, (4) the rate of transmetalation of 4ca is 10 fold faster in the presence of Kþ3aꢀ
(1.0 equiv), (5) the activated transmetalation of 4ca is first-order in Kþ3aꢀ but
saturation could not be reached because of limited solubility, and (6) the rate of
activated transmetalation of 4ca is 4.5 fold faster for Csþ3aꢀ than for Kþ3aꢀ.
28. (a) Ingold, C. K. Structure and Mechanism in Organic Chemistry; Cornell Uni-
versity Press: Ithaca, NY, 1953, pp 221e305; (b) Pfeiffer, P.; Wizinger, R. Justus
Liebigs Ann. Chem. 1928, 461, 132e154; (c) Wheland, G. W. J. Am. Chem. Soc.
1942, 64, 900e908.
29. The depicted cis configuration of the diarylpalladium complex ii is not in-
tended to imply that this is the immediate product of transmetalation, but
rather the necessary configuration for reductive elimination.
€
16. (a) Stambuli, J. P.; Incarvito, C. D.; Buhl, M.; Hartwig, J. F. J. Am. Chem. Soc. 2004,
126, 1184e1194; (b) Yamashita, M.; Hartwig, J. F. J. Am. Chem. Soc. 2004, 126,
5344e5345.
30. This complete picture of the electronic demands of the two coupling partners
together with the recognition that preequilibrium activation of the ar-
ylpalladium(II) arylsilanolate must be taken into consideration, provides the
necessary backdrop for a discussion of the contradictory conclusions reached
by Shukla and DeShong.12b In that study, the authors concluded, on the basis of
17. Barrios-Landeros, F.; Carrow, B. P.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130,
5842e5843.
18. The numbering scheme used throughout the paper is #xx where # is the
compound number and the first letter refers to the residue from the aryl
bromide and the second letter refers to the residue from the silanolate.
19. We recognize that the LFERs with three points and a modest R2 are not ideal,
but they are sufficient for the purpose of qualitative analysis at this stage.
20. See Supplementary data for the remaining graphs.
a positive
r value, that more electron-deficient arylsiliconates undergo trans-
metalation faster. Although the authors noted that their conclusions contra-
dicted those of Hiyama and co-workers12a and Farina and co-workers,10b they
made no attempt to reconcile the disparity. Shukla and DeShong explain their
observations by asserting that “Electron-withdrawing groups are better at
stabilizing the developing negative charge on the ipso-carbon in (the) transi-
tion state through inductive effects.” This argument is clearly wrong because
the negative charge at the ipso-carbon in the transition state is less than in the
ground state. Thus, the stabilizing effect of the substituent will be greater in the
ground state of the fluorosilicate complex than in the transition state, which
will lead to a decrease in rate. An argument that reconciles their observations
with all previous Hammett studies and with our own observations, focuses on
the effect of the para substituent of the arylsiliconate on the activation pre-
equilibrium with TBAF. Our studies have revealed a strong effect of the para
substituent of an arylsilanolate on the activation preequilibrium by a second
silanolate such that the more electron-deficient arylsilanolates reach the ac-
tivated pentacoordinate state more readily (compare the saturation points for
Kþ3eꢀ vs Kþ3fꢀ (Table 3)). Shukla and DeShong used only 1.0 equiv of TBAF for
all of their competition studies and therefore likely had higher concentrations
of the activated complexes from the electron-deficient arylsiliconates leading
to an erroneously higher rate of reaction that they interpreted as a faster
transmetalation. However, it must be noted that the reaction studied by Shukla
21. Denmark, S. E.; Smith, R. C.; Chang, W.-T. T.; Muhuhi, J. M. J. Am. Chem. Soc.
2009, 131, 3104e3118.
22. The substituent R2 also influences the displacement step on 2 in the catalytic
reactions, but that step need not be considered here because the formation of 4
is quantitative and irreversible (KBr precipitation) in the stoichiometric re-
actions herein.
23. Obviously, because the silanolate involved in these two aspects carries the
same substituent, these two effects are at odds. Only experimentation can
reveal, which will dominate the preequilibrium.
24.
s
(OMe)¼ꢀ0.27, (On-Bu)¼ꢀ0.32.
s
25. It should be mentioned in passing that our ability to reach a threshold value for
the rate of these cross-coupling reactions provides strong support for the in-
termediacy of species i.
26. We have tried to confirm the establishment of a saturated equilibrium spec-
troscopically. In the saturation experiment employing 8 equiv of 4-n-butoxy-
aryldimethylsilanolate, the chemical shift change observed at the first data
point compared to the unactivated silanolate-palladium complex is 0.206 ppm.
This change is not significant enough to be interpreted as the 5-coordinate
silicon. However, the perturbation of electron density on silicon from a tetra-
valent to a pentavalent silicate three bonds away from phosphorus is not likely
to effect the 31P chemical shift. On the contrary, if the second silanolate is
and DeShong involves a different electrophile (p-allylpalladium cation), which
could behave differently than the neutral palladium silanolate complexes
studies herein.