Mechanistic significance of the Si-O-Pd bond in the palladium-catalyzed cross-coupling reactions of arylsilanolates

Article

pubs.acs.org/JACS

Mechanistic Signiﬁcance of the Si−O−Pd Bond in the Palladium-

Catalyzed Cross-Coupling Reactions of Arylsilanolates

Steven A. Tymonko, Russell C. Smith, Andrea Ambrosi, Michael H. Ober, Hao Wang,

and Scott E. Denmark*

Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801, United States

S

* Supporting Information

ABSTRACT: Through the combination of reaction kinetics (both stoichiometric

and catalytic), solution- and solid-state characterization of arylpalladium(II)

arylsilanolates, and computational analysis, the intermediacy of covalent adducts

containing Si−O−Pd linkages in the cross-coupling reactions of arylsilanolates has

been unambiguously established. Two mechanistically distinct pathways have been

demonstrated: (1) transmetalation via a neutral 8-Si-4 intermediate that dominates in

the absence of free silanolate (i.e., stoichiometric reactions of arylpalladium(II) arylsilanolate complexes), and (2)

transmetalation via an anionic 10-Si-5 intermediate that dominates in the cross-coupling under catalytic conditions (i.e., in

the presence of free silanolate). Arylpalladium(II) arylsilanolate complexes bearing various phosphine ligands have been isolated,

fully characterized, and evaluated for their kinetic competence under thermal (stoichiometric) and anionic (catalytic) conditions.

Comparison of the rates for thermal and anionic activation suggested, but did not prove, that intermediates containing the Si−

O−Pd linkage were involved in the cross-coupling process. The isolation of a coordinatively unsaturated, T-shaped

arylpalladium(II) arylsilanolate complex ligated with t-Bu₃P allowed the unambiguous demonstration of the operation of both

pathways involving 8-Si-4 and 10-Si-5 intermediates. Three kinetic regimes were identiﬁed: (1) with 0.5−1.0 equiv of added

silanolate (with respect to arylpalladium bromide), thermal transmetalation via a neutral 8-Si-4 intermediate; (2) with 1.0−5.0

equiv of added silanolate, activated transmetalation via an anionic 10-Si-5 intermediate; and (3) with >5.0 equiv of added

silanolate, concentration-independent (saturation) activated transmetalation via an anionic 10-Si-5 intermediate. Transition states

for the intramolecular transmetalation of neutral (8-Si-4) and anionic (10-Si-5) intermediates have been located computationally,

and the anionic pathway is favored by 1.8 kcal/mol. The energies of all intermediates and transition states are highly dependent

on the conﬁguration around the palladium atom.

by observing cross-coupling products from crystallographically

deﬁned arylpalladium(II) alkenylsilanolate complexes in the

absence of nucleophilic activators.

1. INTRODUCTION

In the preceding paper in this issue, the mechanism of

palladium-catalyzed cross-coupling of alkenylsilanolates with

aryl halides was investigated.¹From a combination of kinetic

analysis of catalytic reactions, X-ray structure determination of

stable complexes bearing phosphine ligands, and stoichiometric

reactions of those complexes, two distinct catalytic cycles were

revealed (Figure 1). Under “ligandless” conditions (dpppO₂),

the potassium alkenylsilanolate K⁺2⁻forms an 8-Si-4²

intermediate ii containing a discrete Si−O−Pd linkage, which

undergoes direct transmetalation to diorganopalladium species

iii, which suﬀers reductive elimination to form product 3. On

the other hand, the more nucleophilic cesium alkenylsilanolate

Cs⁺2⁻is able to access the 10-Si-5 intermediate iv, which

undergoes more rapid transmetalation via an activated pathway

to form species iii and ﬁnal product 3 therefrom.

The most compelling evidence for the simultaneous

operation of both pathways in the presence of Cs⁺2⁻is the

dependence of the reaction rate on the concentration of the

silanolate salt. The rate of the cross-coupling steadily increases

until ca. 90 equiv of Cs⁺2⁻(with respect to palladium) are used,

at which point the rate levels oﬀ, presumably at the saturation

point for intermediate iv. The kinetic competence of

intermediates containing the Si−O−Pd linkage is conﬁrmed

The lack of a rate dependence on the concentration of K⁺2⁻

reveals that the neutral transmetalation pathway is fully

operative for alkenylsilanolates. This remarkable conclusion

contradicts the long-held belief that the silicon must become

pentacoordinate for transmetalation to take place in successful

cross-coupling reactions.³In view of this revised mechanistic

picture, the question naturally arises if the same situation

obtains for the much more commonly employed arylsilanol-

ates⁴and if these, too, show a mechanistic dependence on

counterion or perhaps ligand.

2. GOALS OF THIS STUDY

The ability to independently prepare competent intermediates

along the catalytic cycle for the cross-coupling reaction of

organosilanolates creates a unique opportunity to systematically

study the features of the transmetalation step in detail.

Instructive experiments designed to probe the molecular detail

of this critical step can be devised, such as the following: (1)

Received: March 9, 2015

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Figure 1. Cross-coupling catalytic cycles for alkenylsilanolates.

Scheme 1

veriﬁcation of the mechanistic signiﬁcance of the putative Si−

O−Pd intermediate identiﬁed in foregoing studies, (2)

independent isolation and characterization of multiple aryl-

palladium(II) arylsilanolate complexes, (3) determination of

the kinetic competence of these isolable pre-transmetalation

intermediates, and (4) comparison of the kinetic behavior of

these complexes with the catalytic reactions. We report herein

the successful achievement of these goals through the

preparation of a number of arylpalladium(II) arylsilanolate

complexes stabilized by phosphine ligands. These species have

been thoroughly studied to elucidate the roles that ligands play

in the key transmetalation step. Furthermore, these isolable

intermediates and their kinetic behavior have further reﬁned the

controlling factors in the thermal and anionically activated

pathways that have been proposed for the cross-coupling of this

class of nucleophiles.

3. RESULTS

3.1. Preparation and Structural Analysis of Aryl-

palladium(II) Arylsilanolate Complexes. 3.1.1. Synthesis.

The synthesis of the 2-tolylpalladium(II) arylsilanolate

intermediates was accomplished by treating the preformed

TMEDA-arylsilanolate complexes with bis-chelating phosphine

ligands with more rigid backbones. Combination of the

(TMEDA)(2-tolyl)palladium iodide 4⁵with (4-

methoxyphenyl)dimethylsilanol 5 in the presence of silver

oxide (Ag₂O) aﬀorded (TMEDA)(2-tolyl)palladium 4-anisyl-

silanolate 6 in quantitative yield (Scheme 1). Treatment of 6

with a variety of chelating bisphosphines aﬀorded the (L₂)(2-

tolyl)palladium(II) silanolates 7e, 7f, 7p, and 7z in excellent

yields.⁶These complexes were quite stable at room temperature

1

when maintained under an inert atmosphere. The H NMR

spectra revealed the presence of single, discrete species, and the

³¹P NMR spectra for the cis-chelated phosphine complexes

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Table 1. X-ray Crystal Structures and Parameters of Arylpalladium(II) Silanolates 7e, 7z, 7p, 10, and 7t (Hydrogens Omitted for

Clarity)

parameter

Si−O, Å

Pd−O, Å

ipsoC−Pd, Å

P(1)−Pd, Å

7e (dppe)

1.584

7z (dppbz)

1.586

7p (dppp)

1.592

10 (dppf)

1.523

7t (Ph₃P)

1.564

2.067

1.995

2.313

2.319

169.3

178.6

22.6

2.044

2.052

2.085

2.035

2.050

2.057

2.021

2.216

2.199

2.214

2.234

P(2)−Pd, Å

2.343

2.316

2.367

2.343

Si−O−Pd, deg

P(1)−Pd−P(2), deg

³¹P NMR resonances

143.40

86.0

129.39

87.0

143.40

137.2

96.2

98.2

a

50.8, 26.0 (46.1)

52.2, 35.9 (30.5)

21.1, −10.5 (48.8)

33.4, 9.2 (33.8)

a

Reported in ppm. Number in parentheses refers to coupling constant, in Hz.

displayed two non-equivalent phosphorus nuclei in each

system. Gratifyingly, complexes 7e, 7p, and 7z all aﬀorded X-

ray-quality crystals, and their structures could be unambigu-

ously established. Unfortunately, all attempts to secure crystals

from 7f were unsuccessful. However, simply changing the aryl

residue on the palladium gave crystals suitable for X-ray

diﬀraction analysis. Thus, (dppf)(4-CF₃C₆H₄)Pd(OSi-

Me₂C₆H₄(4-OMe)) 10 was prepared following the same

procedure described above and aﬀorded X-ray-quality crystals.⁷

Arylpalladium(II) silanolate 7t, bearing two monodentate

triphenylphosphine ligands, was of interest because of the trans

conﬁguration of the phosphines on palladium, which is

unavailable to the bidentate ligands. The direct displacement

of the phosphine-ligated oxidative addition intermediate by an

arylsilanolate was ﬁrst attempted to determine the ability for a

direct replacement of the Pd−halogen bond. Unfortunately,

none of the desired arylpalladium silanolate complex could be

obtained, which suggested that the steric crowding around the

metal center was prohibitive.⁸Instead, the common TMEDA

intermediate 6 was treated with 2.0 equiv of triphenyl-

phosphine, which led to the clean displacement of the diamine

ligand and the formation of a new crystalline solid (Scheme 1).

Evidence for the trans relationship of the phosphine ligands was

available from ³¹P NMR, which shows a single resonance (³¹P

22.6 ppm); however, the complete structure of 7t was

eventually conﬁrmed by X-ray crystallography.

3.1.2. Structural Features. The key structural features of the

arylpalladium(II) arylsilanolate complexes from single-crystal

X-ray diﬀraction analysis are collected in Table 1.⁹For the

chelating bisphosphine complexes 7e, 7z, 7p, and 10, the

expected Pd−O−Si linkage with the cis orientation of the

ligands was conﬁrmed. The Pd(1)−O(1) bond length for each

complex was found to be ca. 2.044 Å, which is slightly shorter

than in other arylpalladium(II) silanolates. The only complex

that showed a slightly elongated Pd−O bond length is the dppf-

derived adduct 10 (2.085 Å), which may be a consequence of

the more electron-deﬁcient triﬂuoromethyl-substituted aryl

ring. The Si(1)−O(1) bond lengths of each arylpalladium(II)

arylsilanolate complex are all consistent with those of previously

reported metal silanolate complexes.¹⁰The trans inﬂuence of

the aryl group is signiﬁcant, as the P(2)−Pd(1) bond (2.343

and 2.316 Å) is much longer than the P(1)−Pd(1) bond (2.216

and 2.199 Å). One structural feature that is signiﬁcantly

diﬀerent among the various complexes is the P(1)−Pd−P(2)

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angle. Complexes 7e and 7z have a much more acute bonding

angle (86° and 87°, respectively) compared to 7p (96°) and 10

(98°). Furthermore, as the angle becomes more acute, the

respective bond distances between phosphorus and palladium

also decrease. This type of structural deformation may change

the rate of dissociation for these ligated complexes and

subsequently aﬀect the transmetalation step.

The structural features of complex 7t are, for the most part,

quite similar to those of the other arylsilanolate complexes. The

Pd(1)−O(1)−Si(1) angle of 169.3° is much greater in

comparison, placing the aryl group on silicon farther from

the metal center. The Pd(1)−C(ipso) bond length (1.995 Å) is

slightly shorter because of the presence of the silanolate moiety

(weaker trans inﬂuence) in the trans position in place of a

phosphine. Nearly ideal square-planar geometry is observed, as

seen in the O(1)−Pd(1)−P(1) and O(1)−Pd(1)−P(2) angles

of 91.9° and 88.8°.

test for this possibility, representative complexes 7p and 7t

were heated in the presence of free phosphine (Scheme 2). For

the bidentate complex 7p, the addition of only 10 mol % of

dppp was suﬃcient to completely suppress the cross-coupling

process, suggesting that ligand dissociation does occur prior to

transmetalation. This result also suggests that ligand dissocia-

tion is reversible prior to the irreversible transmetalation event.

For the more labile Ph₃P complex 7t, the thermal trans-

metalation proceeded in the presence of 50 mol % of added

Ph₃P, albeit at a greatly reduced rate.¹²From these data, the

inhibitory eﬀect of the ligand on the thermal transmetalation

rate appears to follow the trend dppbz ≫ dppf > dppp ∼ dppe

> PPh₃.

Scheme 2

3.2. Reactivity and Kinetic Analysis of Arylpalladium-

(II) Arylsilanolate Complexes. The following studies were

directed toward understanding how the respective ligands aﬀect

the transmetalation step. Moreover, these intermediates can

help establish which mode of transmetalation (8-Si-4 versus 10-

Si-5) occurs under various reaction conditions. With these

overarching goals in mind, each of the complexes prepared in

the foregoing section was evaluated for both its qualitative

reactivity and its quantitative comparisons to functioning

catalytic systems.

3.2.1. Four-Coordinate Arylpalladium(II) Arylsilanolate

Complexes. 3.2.1.1. Inﬂuence of Ligands on the Thermal

Transmetalation of Arylpalladium(II) Arylsilanolate Com-

plexes. To establish the eﬀects of ligands, in particular the

relationship between dissociation and transmetalation rate, the

isolated complexes 7e, 7z, 7p, 7f, and 7t were heated in

benzotriﬂuoride to establish the thermal transmetalation rates

(Table 2). A 12.5 mM solution of each complex in

benzotriﬂuoride was heated to 102 °C in the presence of 2-

bromotoluene (11).¹¹The cross-coupling product 12 was

formed in quantitative yield by GC analysis (except for 7z).

This result unambiguously establishes the viability of a direct

transmetalation of an 8-Si-4 arylpalladium(II) silanolate, as was

demonstrated for the alkenyl(dimethyl)silanolates.

3.2.1.2. Generation of a Ligandless Arylpalladium(II)

Arylsilanolate Species. Insofar as the preceding experiments

show that added ligand inhibits the transmetalation event, the

removal of ligand would be expected to provide increased

reaction rates. Liebeskind, Farina, and co-workers have

demonstrated the ability of copper(I) thiophenecarboxylate

(CuTC) to sequester phosphines in palladium-catalyzed cross-

coupling reactions.¹³CuTC was added as a phosphine

scavenger, as was done for the alkenylsilanolate complexes

previously. Thus, the reaction of these same complexes 7 (12.5

mM in benzotriﬂuoride) in the presence of 1.25 mM CuTC

could produce up to 1.25 mM ligandless arylpalladium(II)

silanolate (Table 3). Strikingly, the stoichiometric cross-

coupling of both dppp complex 7p and dppf complex 7f

proceeded at greatly increased rates in the presence of 10 mol

% of CuTC.¹⁴

The much higher reaction rate observed using the

monodentate ligand Ph₃P suggests that ligand dissociation

may play an important role in the transmetalation event. To

Table 2. Thermal Transmetalation Rates for 2-

a

Tolylpalladium(II) Silanolate Complexes

3.2.1.3. Catalytic Cross-Coupling of Arylsilanolate Com-

plexes. 3.2.1.3.1. Baseline “Ligandless” Kinetics. A full kinetic

analysis of the “ligandless” cross-coupling process was carried

out to establish the baseline for comparison of the eﬀects of the

ligands. Previous studies had established that the use of

allylpalladium chloride dimer (APC) aﬀords ligandless

palladium(0).¹⁵Moreover, it was discovered that phosphine

oxides serve very eﬀectively as weakly coordinating, stabilizing

ligands for the palladium nanoparticles formed and increase the

turnover number by preventing precipitation of palladium

black.¹⁶

entry

Pd complex

ligand

initial rate, 10⁻²mM/s

1

2

3

4

5

7t

Ph₃P

dppe

dppp

dppf

1.77

0.671

0.139

0.0941

0

7e

7p

7f

The initial rate kinetic analysis of the catalytic cross-coupling

of Cs⁺5⁻with 2-bromotoluene (11) using APC as the

palladium source in the presence of dppp(O)₂showed

zeroth-order behavior for both bromide and silanolate (Table

7z

dppbz

a

Average of triplicate runs.

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Cs⁺5⁻was determined using palladium complex 13p¹⁵(Table

5).

Table 3. CuTC-Assisted Transmetalation Rates for

Arylpalladium(II) Silanolate Complexes

a

Table 5. Initial Rates Using 13p as the Catalyst

entry Pd complex initial rate, 10⁻²mM/s rate factor increase vs thermal

1

2

3

4

5

7t

4.76

0.815

1.84

9.21

0

2.7

1.2

entry

Cs⁺5⁻, mM

11, mM

13p, mM

initial rate, 10⁻²mM/s

7e

7p

7f

1

2

3

4

5

6

7

125

250

500

250

125

83

7.5

2.14

4.24

7.23

3.96

4.41

1.12

3.22

13.3

97.9

0

83

7.5

7z

42

7.5

a

Average of triplicate runs.

167

83

7.5

3.75

11.25

a

Table 4. Initial Rates Using Phosphine Oxide as the Ligand

83

a

Average of triplicate runs.

The partial order in Cs⁺5⁻was obtained by comparison of

the initial rates of product formation versus diﬀerent

concentrations of Cs⁺5⁻(Table 5, entries 1−3). A slope of

0.876 establishes approximate ﬁrst-order behavior for this

component. A similar series of experiments established that the

rate of the reaction is clearly independent of the concentration

of 11 (entries 2, 4, and 5). Finally, the dependence of the rate

on the loading of the catalyst was determined at three loadings

of 13p at 83 mM in 11 (entries 6, 1, and 7, respectively). A

slope of 0.961 obtained from a log−log plot of the data is

consistent with a ﬁrst-order dependence of the observed rate

constant on the concentration of palladium. These data

establish the overall rate equation shown in eq 2.

Cs⁺5⁻,

11,

phosphine oxide

(concn, mM)

Pd,

initial rate,

10⁻²mM/s

entry

mM

1

62.5

125

250

125

62.5

125

250

125

83

dppp(O)₂(7.5)

dppp(O)₂(15.0)

Ph₃P(O) (15.0)

dppp(O)₂(7.5)

7.5

9.02

9.24

9.51

9.63

9.50

9.54

9.77

8.98

9.72

4.68

13.27

2

3

83

7.5

4

167

333

83

7.5

5

7.5

6

7.5

7

83

7.5

8

83

7.5

9

83

7.5

10

11

83

3.75

11.25

rate = k_obs[Cs⁺5⁻]^0.88[11]⁰with k_obs= k[13p]^0.96

83

(2)

a

Average of triplicate runs.

To determine the catalyst resting state, the coupling reaction

with complex 13p was monitored by ³¹P NMR spectroscopy.

The reaction was performed under normal catalytic conditions

(9.0 mol % 13p, 1.5 equiv of Cs⁺5⁻, 83 mM in 11) at 90 °C in

toluene-d₈(Scheme 3). After 30 min, GC analysis showed a

37% conversion to 12 (∼4 turnovers of Pd). ³¹P NMR analysis

of the reaction mixture showed that complex 7p was the

primary phosphine-containing species, along with dppp(O)₂

(lit.¹⁸+32.3 (CDCl₃)). Thus, 7p is the resting state of the

catalyst during the productive cross-coupling in the presence of

excess Cs⁺5⁻.

Arylpalladium(II) arylsilanolate complex 7p was next shown

to be a competent catalyst (or catalyst precursor) in the cross-

coupling of Cs⁺5⁻with 11. Under standard reaction conditions

using 7p as the catalyst, the reaction proceeded as expected.

Comparison of reactions using three loadings of 7p (Table 6)

showed approximately ﬁrst-order dependence (log/log plot

slope = 0.86) on the catalyst, with rates that were comparable

to those observed with 13p (cf. Table 5, entries 6 and 1, to

Table 6, entries 2 and 3, respectively).

4, entries 1−5) and ﬁrst-order behavior in palladium (entries 2,

10, and 11). To rule out any inﬂuence of dppp(O)₂, the

reaction was repeated with increased loading of phosphine

oxide (entries 2 vs 6) or with Ph₃PO in place of dppp(O)₂

(entries 7−9). No rate change was observed, ruling out any

contribution of the ligand.

These data establish the overall rate equation for the reaction

of Cs⁺5⁻with 11 catalyzed by [allylPdCl]₂as shown in eq 1.

This equation is consistent with either turnover-limiting direct

transmetalation from an arylpalladium(II) intermediate or

turnover-limiting activated transmetalation from the saturated

complex. These kinetic data were not suﬃcient to distinguish

these alternatives directly.¹⁷

rate = k_obs[Cs⁺5⁻]⁰[11]⁰[dppp(O)₂]⁰

with k_obs= k[Pd]

(1)

3.2.1.3.2. Inﬂuence of Ligands on Catalytic Cross-

Coupling Reactions with Ligated Complexes. The inﬂuence

of ligands on the rate of the catalytic cross-coupling of

arylsilanolates was assayed in two ways: (1) using ligated

precatalysts and (2) using the ligated arylpalladium(II)

arylsilanolate complex 7 as the catalyst. In the ﬁrst series of

experiments, the kinetic equation for the cross-coupling of

3.2.1.3.3. Source of Ligand Oxidation. The observation of

phosphine oxides in the cross-coupling reactions along with the

high rates observed in the absence of ligand (Scheme 3) made

it imperative that the oxidation source be identiﬁed. Because

the reactions are run in an inert atmosphere under anhydrous

conditions, the silanolate is the only obvious oxidant for the

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Scheme 3

Scheme 4

a

oxidation of phosphine ligand following aqueous aerobic

quench of the reaction.

Table 6. Partial Order in 7p

The incorporation of an ¹⁸O label from the silanolate into the

newly formed phosphine oxide provides some insight into how

the oxidation takes place. Transition-metal-mediated oxidations

of phosphines are known for both palladium and platinum. The

reduction of palladium(II) acetate to active palladium(0) with

Ph₃P produces acetic anhydride and Ph₃P(O) via an inner-

sphere electron-transfer process.¹⁹Likewise, bidentate phos-

phine monoxides such as dppp(O) can be prepared from dppp

and alkali metal hydroxide using a palladium catalyst and

dibromoethane.²⁰Of particular relevance to the system at hand

is the reduction of (dppe)Pt(OSiMe₃)₂in the presence of

excess trimethylphosphine to form (dppe)Pt(PMe₃)₂, Me₃P-

(O), and (Me₃Si)₂O, which is proposed to proceed via a

platinum oxo intermediate.²¹The presence of an analogous

palladium(II) bissilanolate intermediate could explain the

formation of phosphine oxides in the presence of silanolates

and arylpalladium(II) intermediates. Such intermediates could

be formed by disproportionation of intermediate v to produce

biarylpalladium complex vi and bissilanolatopalladium complex

vii (Scheme 5). The biarylpalladium complex vi could undergo

reductive elimination to form a homocoupling byproduct and

regenerate the active catalyst. Bissilanolate complex vii could

then undergo spontaneous or silanolate-catalyzed oxidation of

the phosphine.²²

entry

7p, mM

initial rate, 10⁻²mM/s

1

2

3

1.88

3.75

7.50

1.01

1.79

3.30

a

Average of triplicate runs.

phosphine. To test this possibility, ¹⁸O-labeled silanolate Cs⁺5⁻

was prepared by oxidative hydrolysis of silane 14 in the

presence of [¹⁸O]water (95% ¹⁸O), followed by silanolate

formation with cesium metal (Scheme 4). The incorporation of

¹⁸O was determined by mass spectrometry. Comparison of the

ratio of labeled (m/z = 184) to unlabeled (m/z = 182) silanol 5

in enriched and standard samples revealed a 94.4% ¹⁸O

incorporation.

The cross-coupling reaction was then carried out with the

labeled silanolate to aﬀord a 67% yield of 12 along with ∼30%

of dppp(O)₂. Analysis of the isolated dppp(O)₂by mass

spectroscopy showed 52% ¹⁸O enrichment (Scheme 4). The

enrichment was determined by comparison of the unlabeled

(m/z = 444), monolabeled (m/z = 446), and bislabeled (m/z =

448) dppp(O)₂in the isolated material relative to an unlabeled

standard. The mass spectrometric analysis of the labeled

dppp(O)₂showed a mixture of un-, mono-, and bislabeled

ligand. No appreciable quantity of dppp(O) was observed. This

experiment conﬁrms the ability of a silanolate to serve as the

stoichiometric oxidant in the formation of phosphine oxide.

The incomplete ¹⁸O incorporation is most likely due to

3.2.2. Three-Coordinate Arylpalladium Arylsilanolate

Complexes.²³Despite the accumulation of compelling evidence

Scheme 5

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that isolated arylpalladium(II) arylsilanolate complexes can

undergo transmetalation without anionic activation, the aryl-

silanolate salts undergo catalytic cross-coupling at greater rates,

thus rendering any conclusion ambiguous. Because of the

diﬀerence in reaction conditions, an irrefutable demonstration

that a pathway involving an 8-Si-4 species is operative under

catalytic conditions was still elusive. The problem rested squarely

in the choice of ligands; those ligands capable of forming

isolable, characterizable complexes deactivate the thermal cross-

coupling, whereas using those ligands under catalytic conditions

leads to destruction of the ligand and thus unknown

concentrations of active species. Fortunately, a solution to

this problem presented itself in the development of a

preparatively useful cross-coupling of arylsilanolates with aryl

halides using bis(tri-tert-butyl)phosphine palladium(0).^4aThe

isolation of stable, T-shaped complexes of arylpalladium halides

and alkoxides ligated with (t-Bu)₃P²⁴suggested that the

arylsilanolate complexes could also be suﬃciently stable for

isolation and kinetic study.

The following studies were conducted to address two major

mechanistic questions regarding the cross-coupling of aryl-

silanolates: (1) kinetic analysis of the cross-coupling reaction to

determine the rate-limiting step of the catalytic cycle for this

class of organosilanolates and (2) isolation of the putative 8-Si-

4 palladium(II) silanolate and identiﬁcation of a direct

transmetalation pathway. Once these goals were achieved, a

complete mechanistic picture can be formulated that shows

how organosilanol cross-coupling reactions proceed.

reported previously¹and suggests a turnover-limiting trans-

metalation from an arylpalladium(II) intermediate.

rate = k_obs[K⁺5⁻]⁰[15]⁰with k_obs= k[Pd]^0.98

(3)

Accordingly, if transmetalation is indeed the turnover-

limiting step, then either the 8-Si-4 or the 10-Si-5 aryl-

palladium(II) arylsilanolate complex should be detectable.

However, ³¹P NMR analysis of the reaction mixtures showed

that the predominant phosphine-containing species was (t-

Bu₃P)₂Pd (δ ³¹P, 85.4 ppm).²⁵A plausible explanation for this

behavior is that the signal for the palladium silanolate complex

is broadened at elevated temperatures and is not visible. Thus,

to gain insight into the individual steps in the catalytic cycle,

attention shifted to investigating these events stoichiometri-

cally.

3.2.2.2. Study of the Individual Steps in the Catalytic

Cycle. 3.2.2.2.1. Oxidative Addition. The independent syn-

thesis of the proposed transmetalation precursor began with the

preparation of the oxidative addition complex.²⁶The oxidative

addition of aryl halides employing t-Bu₃P has been studied

extensively by Hartwig and co-workers.²⁷Three-coordinate

arylpalladium(II) bromide 17 can be prepared by treating (t-

Bu₃P)₂Pd with an excess of 15 at elevated temperatures in the

presence of t-Bu₃P·HBr, which has been demonstrated to

catalyze the oxidative addition starting from 15.^27aThus,

combining 15 with (t-Bu₃P)₂Pd in 2-butanone at 70 °C in the

presence of 3 mol % of t-Bu₃P·HBr results in the formation of

17 in 82% yield (Scheme 7).

3.2.2.1. Kinetic Analysis of the Catalytic Reaction. To

vouchsafe that the arylsilanolate cross-coupling was proceeding

in a transmetalation-limiting regime, the rate equation for the

cross-coupling of K⁺5⁻with 4-ﬂuorobromobenzene (15)

catalyzed by (t-Bu₃P)₂Pd was determined. The partial order

in each component in the reaction was determined individually

at 95 °C in toluene (Scheme 6) using ¹⁹F NMR spectroscopic

analysis. Kinetic rates were determined from the slope of the

plot of the loss of aryl bromide over time, as determined

through >3 half-lives.

Scheme 7

3.2.2.2.2. Displacement of Palladium(II) Bromide Inter-

mediate by an Arylsilanolate. The critical displacement step

was eﬀected by adding an equimolar quantity of Cs⁺5⁻to a

solution of 17 in toluene. Inspection of both the ³¹P and ¹⁹F

NMR spectra of the mixture revealed no observable changes of

the diagnostic resonances. Even after 30 min, only a single

species was present that appeared to be the starting complex

17. To establish if, in fact, no reaction had taken place, or if the

resonance positions of the educt and product are isochronous, a

systematic titration study was undertaken (Scheme 8).²⁸

Accordingly, when complex 17 was treated with 0.2 equiv of

Cs⁺5⁻, a new ³¹P NMR signal was generated (77.0 ppm) in

addition to that for 17 (64.5 ppm) (Figure 2). An additional 0.3

equiv of Cs⁺5⁻was added to the reaction solution, and 17 was

consumed, leaving the species at 77.0 ppm as the major

constituent. The stoichiometry of these experiments revealed

Scheme 6

The partial order in silanolate obtained at three concen-

trations of K⁺5⁻showed no eﬀect of the concentration of K⁺5⁻

on the rate of the coupling and established zeroth-order

behavior for this component. Next, the rate dependence on the

concentration of 15 was similarly established to be zeroth order

using three concentrations for this component. Finally, the rate

dependence on the amount of the palladium catalyst was

determined by comparison of the rate constant (k_obs) versus

four diﬀerent loadings of Pd at 100 mM in 15. A positive slope

of 0.979, obtained from a log plot of k_obsversus [Pd], is

consistent with a ﬁrst-order dependence of the observed rate

constant on the concentration of palladium. Thus, the overall

rate equation for the reaction of K⁺5⁻with 15 catalyzed by (t-

Bu₃P)₂Pd is shown in eq 3 (with a rate of 1.06 × 10⁻²mM/s).

This rate equation matches that of the alkenylsilanolates

Scheme 8

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Figure 2. ³¹P NMR spectra of the displacement step for the cross-coupling of arylsilanolates.

that displacement occurs rapidly and the mutual coexistence of

the bromide complex 17 and silanolate product resulted in the

formation of a proposed dimer formulated as 19. Subsequent

addition of 0.5 equiv of Cs⁺5⁻caused the disappearance of the

signal at 77.0 ppm with concomitant formation of a new signal

at 65.4 ppm. This new species was spectroscopically identiﬁed

as the proposed arylpalladium(II) silanolate complex 18.²⁹

The structure of adduct 18 was conﬁrmed by isolation and

single-crystal X-ray analysis (Table 1 and Figure 3).^30,31As

expected, compound 18 contains the Pd−O−Si linkage that

was proposed for the transmetalation precursor. The bulk of

the tri(tert-butyl)phosphine allows for only one ligand to bind

to palladium, resulting in a three-coordinate complex with an

Figure 3. X-ray crystal structure of complex 18. Hydrogens omitted

empty coordination site. The phenyl ligand, which has the

largest trans inﬂuence,³²is located trans to the open

coordination site.²⁴The Pd(1)−O(1) bond length (2.02 Å)

remains consistent in the various isolated complexes in this

study. Furthermore, the Si(1)−O(1) bond length is typical for

silanolates, which suggests that the ligand eﬀect at the

palladium center is not as substantial compared to the eﬀect

in other bisphosphine arylpalladium(II) arylsilanolate com-

plexes (Table 1). A weak agostic interaction between one of the

H atoms of a t-Bu methyl group and the palladium is noted. In

addition, the Pd(1)−O(1)−Si(1) angle of 128.5° is consid-

erably more acute compared to the angles in other known

palladium(II)¹⁰and platinum(II)³³silanolates, and the non-

bonded distance between the silicon-bearing ipso carbon and

the palladium atom (3.70 Å) hints to a weak interaction that

anticipates the transmetalation event.

for clarity.

concomitant formation of PdL₂.³⁴The thermal transmetalation

process followed a ﬁrst-order decay at 2.45 × 10⁻³mM/s.

Because (t-Bu₃P)₂Pd has a 2:1 ligand/palladium ratio, the

stoichiometric transmetalation was performed in the presence

of t-Bu₃P to establish if a partial order in ligand could be

detected as well. Heating a solution of complex 18 (formed in

situ in toluene) in the presence of 2.0 and 5.0 equiv of t-Bu₃P

led to a clean reaction with rate constants of 2.66 × 10⁻³and

2.42 × 10⁻³mM/s, respectively. Thus, the similar rates of

thermal reaction at varying concentrations of free phosphine

clearly indicate a zeroth-order concentration dependence for

the ligand. These data suggest that, unlike for complexes 7 and

10, phosphine dissociation is not required for transmetalation

and the arene simply transfers directly to the open coordination

site on palladium. These experiments provide further evidence of

an unactivated, thermal transmetalation pathway for silicon-based

cross-coupling reactions.

3.2.2.2.3. Thermal Transmetalation of Arylpalladium

Arylsilanolate 18. With the desired arylpalladium(II) aryl-

silanolate complex in hand, we initiated a study of the

transmetalation process. Simply heating complex 18 in toluene

at 50 °C resulted in the formation of the biaryl product 16 with

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For the kinetic studies described above, the arylpalladium(II)

arylsilanolate complex 18 was generated in situ for ease of

manipulation. Consequently, 18 was formed together with

cesium or potassium bromide, and the ability for the inorganic

salt to serve an activating role could not be discounted. First, to

determine if any appreciable amount of the inorganic salt was

present in toluene, the solubilities of these inorganic salts were

determined.^35,36To ensure that similar rate constants could be

obtained in the absence of the alkali-metal bromide, the

reactions were repeated with careful separation of the inorganic

precipitate from the reaction solution. The rate constant for the

thermal transmetalation after removal of the inorganic salts was

similar to that previously determined; thus, the eﬀect of the

inorganic salt is negligible.

Table 7. Determination of Kinetic Regimes for

Transmetalation of 18 in the Presence of K⁺5⁻

3.2.2.2.4. Activated Transmetalation of Arylpalladium

Arylsilanolate 18. The ability to isolate and identify the

arylpalladium(II) arylsilanolate complex 18 ﬁnally enabled the

establishment of the kinetic regime operative under catalytic

conditions. This determination was accomplished by system-

atically varying the amount of potassium silanolate K⁺5⁻with

respect to the arylpalladium bromide 17. Since the rate of the

purely thermal conversion of 18 to 16 was established above,

any increase in the rate with superstoichiometric amounts of

K⁺5⁻would reveal the operation of the activated pathway.

Moreover, if the rate increased continuously, then a pre-

equilibrium activation step would be established, and if the rate

leveled oﬀ, then a turnover-limiting, intramolecular trans-

metalation would be established due to saturation. Thus,

treatment of 17 with 1 equiv of K⁺5⁻at room temperature

generated the arylpalladium(II) arylsilanolates complex 18 in

situ. The formation of 18 was conﬁrmed by the appearance of a

new ¹⁹F NMR resonance at −119.8 ppm. The transmetalation

and subsequent reductive elimination to the biaryl product 16

did not initiate until the reaction mixture was heated to 50 °C.

The formation of 16 was monitored by ¹⁹F NMR spectroscopy,

furnishing a rate of 2.45 × 10⁻³mM/s. The same experiment

was repeated with substoichiometric amounts of K⁺5⁻(relative

to 17), as well as superstoichiometric amounts (Table 7).

As the amount of K⁺5⁻was increased from 0.5 to 1 equiv, the

rate of formation of 16 increased, reﬂecting a higher

concentration of 18 in solution. Increasing the amount of

K⁺5⁻between 1.5 and 5 equiv caused a dramatic increase in the

rate of the reaction: 2.00 × 10⁻²and 2.91 × 10⁻²mM/s when

2.0 and 5.0 equiv of K⁺5⁻, respectively, were used,

corresponding to an 8-fold and a 12-fold increase compared

to the rate measured with 1.0 equiv. Further increasing the

amount of K⁺5⁻beyond 5.0 equiv did not change the rate of

the reaction.

entry

K⁺5⁻, equiv

rate, mM/s

1

2

3

4

5

6

7

8

9

0.5

0.6

0.75

1.0

1.5

2.0

3.0

5.0

7.5

7.72 × 10⁻⁴

9.17 × 10⁻⁴

1.48 × 10⁻³

2.45 × 10⁻³

1.72 × 10⁻²

2.00 × 10⁻²

2.56 × 10⁻²

2.91 × 10⁻²

3.02 × 10⁻²

Figure 4. Summary of kinetic regimes for the transmetalation of 18 in

the presence of K⁺5⁻.

silanolate Cs⁺5⁻. Importantly, the rate measured with 1 equiv of

Cs⁺5⁻was similar to that previously determined for K⁺5⁻.

However, when 17 was treated with more than 1 equiv of

Cs⁺5⁻at 50 °C, the formation of 16 was so fast that the rate

could not be measured. The reaction was instead performed at

25 °C.

The reaction rates measured with increasing amounts of

Cs⁺5⁻are shown in Table 8 and Figure 5. As was already

observed with K⁺5⁻, diﬀerent kinetic regimes could be

identiﬁed. Superstoichiometric amounts of Cs⁺5⁻ranging

from 1.5 to 5.0 equiv induced a much faster reaction than

with 1.0 equiv. For instance, the rates measured at 25 °C with 2

and 5 equiv of Cs⁺5⁻were 1.01 × 10⁻²and 1.98 × 10⁻²mM/s,

respectively, a 3.3-fold and a 6.5-fold increase compared to the

rate measured with 1.0 equiv at 50 °C. This regime corresponds

to an activated pathway via the 10-Si-5 intermediate Cs⁺20⁻

engaging in a pre-saturation equilibrium. At loadings of Cs⁺5⁻

greater than 5.0 equiv, a saturation regime was reached, and the

rate remained constant. Although a direct comparison of the

Overall, these data suggest the existence of three diﬀerent

kinetic regimes (Figure 4). With 1 equiv of K⁺5⁻and below, the

rate is determined by an unactivated, thermal transmetalation

process via the 8-Si-4 intermediate 18.³⁷Between 1.0 and 5.0

equiv of K⁺5⁻, the sudden increase in rate suggests an activated

pathway via the 10-Si-5 complex K⁺20⁻, where the excess

silanolate engages in a presaturation equilibrium with 18.

Beyond 5 equiv, the mechanism still follows an activated

pathway, but with complete saturation of 18 as K⁺20⁻, such

that no further increase in rate is observed. Because the catalytic

reaction is necessarily performed with a large excess of

silanolate with respect to palladium, it follows that the catalytic

reaction must fall into this activated, saturated regime.

Additional evidence for an activated transmetalation process

was obtained by employing the more nucleophilic cesium

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basicity of the silanolate in determining the reaction rate. In

other words, the position of the equilibrium between 18 and

M⁺20⁻is not dependent (or only moderately dependent) upon

which cation is used. It seems, rather, that diﬀerent cations

aﬀect the rate of the reaction as a consequence of their

association in the anionic intermediate M⁺20⁻. Under this

hypothesis, the reactive silanolate complex M⁺20⁻would carry

more negative charge when paired with the larger, less

coordinating cesium cation, which would promote a faster

transmetalation than when M⁺20⁻is paired with the more

strongly coordinating potassium cation.³⁸

Table 8. Determination of Kinetic Regimes for

Transmetalation of 18 in the Presence of Cs⁺5⁻

4. DISCUSSION

4.1. Reactivity of Arylpalladium Four-Coordinate

Arylpalladium(II) Arylsilanolate Complexes. The primary

goal of this study was to determine if the cross-coupling of

arylsilanolates could proceed via an unassisted transmetalation

from an 8-Si-4 arylpalladium(II) arylsilanolate intermediate or

via activation to form a 10-Si-5 siliconate. The initial

investigations focused on the thermal reactions of the isolated

complexes 7.

4.1.1. Stoichiometric Transmetalation of Arylpalladium(II)

Arylsilanolate Complexes. 4.1.1.1. Thermal Reaction of

Phosphine Complexes. The thermal cross-coupling reaction

of phosphine-ligated complexes 7 unambiguously established

that arylpalladium(II) arylsilanolate complexes are capable of

undergoing unactivated transmetalation via neutral, 8-Si-4

intermediates. Moreover, inhibition of the reaction of 7p by

free dppp requires that reversible ligand dissociation from viii

to ix occurs prior to transmetalation to x (Figure 6). Trapping

of x by the free ligand to form xi must be faster than

intramolecular capture by the pendant phosphine. The

observation of inverse order in Ph₃P in the cross-coupling of

7t requires that at least one phosphine ligand must dissociate

prior to transmetalation.³⁹Transmetalation then occurs from

subligated intermediate xiii to xiv.

entry

Cs⁺5⁻(equiv)

rate (mM/s)

a

1

3.06 × 10⁻³

6.46 × 10⁻³

1.01 × 10⁻²

1.45 × 10⁻²

1.98 × 10⁻²

1.99 × 10⁻²

2

3

4

5

6

1.5

2

3

5

7.5

a

Measured at 50 °C.

The observed reactivity trend of Ph₃P > dppe > dppp ∼ dppf

≫ dppbz can be interpreted in light of this mechanism.^40,41

Triphenylphosphine is expected to give the highest overall rates

because ligand reassociation (k₋₁) should be slowest for this

ligand. This enhanced rate can be further explained through

analysis of the X-ray crystal structure of 7p. The cis-chelating

dppp backbone in 7p places the phenyl groups on P(1) and

P(2) above and below the plane formed by the square-planar

coordination geometry. This arrangement places the silanolate

and arene substituents in staggered positions between the aryl

groups. As a result, the closest interaction between either

substituent and the ligand backbone is 3.24 Å between C(ipso)

and the phenyl group on P(2), leading to an unstrained

complex and thus a slow rate of ligand dissociation.

Continuing through the observed reactivity trend, the

equilibrium position for k₁/k₋₁should lie further to the right

for dppe complex 7e relative to other bidentate systems

because of the steric congestion introduced by the short tether

length. This congestion will both enhance dissociation and slow

intramolecular trapping. The low rates of cross-coupling

observed with dppp complex 7p and dppf complex 10 are

consistent with both equilibria K₁and K₂lying to the left due to

the high stability of the corresponding palladium(II) silanolate

complexes and the fast intramolecular trapping following the

ﬁrst dissociation.⁴⁰Finally, the complete lack of reactivity for

1,2-bis(diphenylphosphino)benzene complex 7z can be attrib-

Figure 5. Summary of kinetic regimes for the transmetalation of 18 in

the presence of Cs⁺5⁻.

rates obtained for K⁺5⁻at 50 °C and Cs⁺5⁻at 25 °C would be

meaningless, it is clear that the increased nucleophilicity of

Cs⁺5⁻facilitates the formation of the 10-Si-5 intermediate and

thus provides further evidence for an activated pathway.

It was initially hypothesized that the increased Lewis basicity

of Cs⁺5⁻would increase the equilibrium concentration of the

10-Si-5 intermediate Cs⁺20⁻and thus account for an increased

rate of transmetalation compared to K⁺5⁻. However, this

hypothesis was not supported by the experimental data. If the

Lewis basicity were a major factor, then saturation would take

place at a lower silanolate loading when Cs⁺5⁻is used.

Moreover, once saturation is reached, the rate of the reaction

should be the same, regardless of which counterion is involved,

as the reaction would proceed through the same, fully saturated

intermediate M⁺20⁻. However, the experimental reaction rates

show that saturation is reached roughly at the same silanolate

loading (5.0 equiv) for both K⁺and Cs⁺. In addition, when the

reaction was run with 7.5 equiv of K⁺5⁻at 25 °C, a rate of 2.71

× 10⁻³mM/s was measured, 7 times slower than that with

Cs⁺5⁻under the same conditions (1.99 × 10⁻²mM/s). These

observations rule out a substantial contribution of the Lewis

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Figure 6. Intermediates responsible for transmetalation of ligated complexes.

uted to the rigid ligand backbone preventing the ﬁrst

dissociation (k₁) from occurring.

4.1.1.2. Thermal Reaction of Phosphine Complexes in the

Presence of CuTC. The addition of a substoichiometric amount

of CuTC to arylpalladium(II) arylsilanolate complex 7p rapidly

resulted in the exclusive formation of biaryl product 12 (Figure

7). This reaction can proceed through the removal of the

should eliminate various rate-determining steps (Figure 8 and

Table 9). In the cross-coupling reaction of aryldimethylsilanol-

ates, all possible mechanisms are expected to begin with

precatalyst reduction to form palladium(0) and will be ﬁrst-

order in palladium catalyst. If oxidative addition (Figure 8, step

A) is turnover limiting, a ﬁrst-order behavior in aryl bromide

and zeroth-order behavior in silanolate will be observed.

Turnover-limiting displacement (step B) will be zeroth order in

bromide and ﬁrst order in silanolate. If displacement is slow,

arylpalladium(II) bromide xix should accumulate as the catalyst

resting state. Direct transmetalation from xx and reductive

elimination (steps C and F) cannot be distinguished by kinetic

analysis alone, as reactions which are turnover limiting at either

step will show no rate dependence on bromide or silanolate.

However, these two mechanistic possibilities will have

diﬀerent catalyst resting states: arylpalladium(II) arylsilanolate

xx will accumulate if transmetalation is turnover-limiting, and

biarylpalladium(II) xxi will accumulate if reductive elimination

is slow. Rate-limiting, irreversible activation of xx (step D) will

be ﬁrst order in silanolate and zeroth order in bromide. It

should be noted that, despite the presence of two molecules of

silanolate in intermediate xxii, only ﬁrst-order behavior is

predicted because the displacement to form xx is irreversible

and occurs prior to the rate-limiting step. This scenario requires

arylpalladium(II) arylsilanolate xx to be the catalyst resting

state. Finally, rate-limiting transmetalation from activated

complex xxii (step E) will show zeroth-order behavior in

bromide and either zeroth- or ﬁrst-order behavior in silanolate.

Zeroth-order behavior in silanolate will be observed if activation

to xxii is irreversible (which is chemically unreasonable) or the

pre-equilibrium is saturated as xxii. In either case, xxii will be

the catalyst resting state. A reversible, nonsaturated formation

of xxii will result in ﬁrst-order behavior in silanolate.

Figure 7. Catalytic cycle operative in the presence of CuTC.

phosphine ligand from the arylpalladium(II) arylsilanolate

complex viii by copper to form complex xv, which then

undergoes transmetalation (to xvi) and reductive elimination

forming biaryl product 12 and Pd(0). Oxidative addition to

bromide 11 present produces xvii. Ligand exchange with

another molecule of viii produces arylpalladium(II) bromide

xviii as the byproduct and generates more unligated xv. This

experiment provides unambiguous proof that arylpalladium(II)

arylsilanolate complexes are capable of undergoing unactivated

transmetalation via neutral, 8-Si-4 intermediates at rates

comparable to the rate of the catalytic reaction. Unfortunately,

because of the uncertainty in the actual amount of “ligandless”

palladium complex (xv) generated in the presence of CuTC, it

was not possible to make a quantitative comparison.⁴²Thus,

the species responsible for the key transmetalation step in the

catalytic reaction could not be established by the study of

stoichiometric reactions of isolated complexes.

The kinetic results from the “ligandless” reaction using APC

as the catalyst (Table 5) allow some of these scenarios to be

eliminated. The observation of zeroth-order behavior in

bromide rules out rate-limiting oxidative addition. Zeroth-

order behavior in silanolate is consistent with turnover-limiting

direct transmetalation via neutral complex xx (step C),

activated transmetalation from xxii with a saturated pre-

equilibrium (step E), or reductive elimination (step F). Of

these, only steps C and D are chemically viable. Reductive

elimination is known to be extremely rapid with palladium,^43a

4.1.2. Catalytic Reaction of Cs⁺5⁻under “Ligandless

Conditions”. The various steps of the catalytic cycle predict

diﬀerent concentration dependences on each component and

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Figure 8. Proposed cross-coupling pathways for four-coordinate arylpalladium(II) silanolates.

demonstrating that arylsilanolates were capable of unactivated

transmetalation via 8-Si-4 intermediates, the evidence was not

absolutely beyond reproach, because the structural and kinetic

characterization of intermediates did not give precisely those

involved in the actual preparative reactions. With the advent of

the aryl−aryl cross-coupling system that employed (t-Bu₃P)₂Pd,

such an opportunity was available and provided the long

sought-after unambiguous proof.

Table 9. Expected Kinetic Consequences

turnover-limiting step

order for silanolate

order for aryl halide

A

B

C

D

E

F

zeroth

ﬁrst

zeroth

ﬁrst

zeroth or ﬁrst

zeroth

4.2.1. Kinetic Analysis of the Cross-Coupling of Aryl-

silanolate Salts in the Presence of (t-Bu₃P)₂Pd. The analysis

for the cross-coupling catalyzed by (t-Bu₃P)₂Pd is identical to

that presented in Figure 8 and Table 9, but with diﬀerent

intermediate structures (Figure 9). The experimentally

determined rate equation for the cross-coupling of K⁺5⁻has

no order dependence for either aryl bromide or arylsilanolate

(−d[15]/dt = k_obs[K⁺5⁻]⁰[15]⁰with k_obs= k[Pd]^0.98). This rate

equation matches that of the alkenylsilanolates reported

previously,¹and either a turnover-limiting, transmetalation

from an arylpalladium(II) intermediate or rate-limiting

reductive elimination from the diarylpalladium species xxiii is

taking place.⁴⁴Turnover-limiting reductive elimination has

already been discounted.^1,43aHowever, this rate equation

cannot diﬀerentiate between direct transmetalation via 18 and

activated transmetalation via M⁺20⁻, as the ratio of silanolate/

Pd is high.

4.2.2. Isolation of the Transmetalation Step for the Cross-

Coupling of Arylsilanolates. 4.2.2.1. Direct, Thermal Trans-

metalation from an Arylpalladium(II) Silanolate Intermedi-

ate. The independent isolation and X-ray crystallographic

analysis of the palladium complex 18 has unambiguously

established the generation of the Pd−O−Si bond prior to

transmetalation. The transmetalation event most likely occurs

directly from complex 18 and not a ligand-free species, as no

dependence on the concentration of free phosphine was

determined. Moreover, the independence of the reaction rates

for 18 on the source of the silanolate (K⁺or Cs⁺) further

supports the conclusion that the transmetalation is a purely

thermal process.

such that only very specialized post-transmetalation inter-

mediates have ever been detected and isolated.^43bThus, the

species responsible for the key transmetalation step in the

catalytic reaction (xx or xxii, Figure 8) could not be established

by the kinetic analysis alone.

4.1.3. Catalytic Reaction of Cs⁺5⁻Promoted by Ligated

Complexes 7 and 13p. The ability of arypalladium(II)

arylsilanolate complexes 7e, 7p, 7t, and 7f to produce cross-

coupling products in the absence of silanolate conﬁrms the

existence of a direct transmetalation pathway. However, these

experiments as well as those with CuTC do not reﬂect the

circumstances operative under catalytic conditions, i.e., in the

presence of excess amounts of silanolate. Thus, whereas

thermal transmetalation is possible in the absence of silanolate,

that mechanism may not be relevant under the conditions used

for catalytic cross-coupling reactions. Therefore, to unify these

two families, catalytic cross-coupling reactions were carried out

with phosphine-ligated complexes 7 and 13p. However, these

reactions behaved very diﬀerently from both the thermal and

the catalytic reactions (in the absence of phosphines) in their

kinetic behavior (cf. Table 2, entry 3, and Table 3, entry 3, with

Tables 4, 5, and 6). Moreover, the observation of phosphine

oxides (Scheme 3) in the catalytic reactions of ligated

complexes, coupled with the requirement for ligand dissocia-

tion for transmetalation to occur, eﬀectively precludes any

possibility of interpreting these results in the context of the

stoichiometric or catalytic reactions.

4.2. Three-Coordinate Arylpalladium(II) Arylsilanolate

Complexes. As compelling as these results were in

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Figure 9. Proposed cross-coupling pathways for three-coordinate arylpalladium(II) silanolates.

Scheme 9

Thus, the three-coordinate arylpalladium(II) arylsilanolate is

suﬃciently poised to allow the arene to transfer onto palladium

without any ligand dissociation.⁴⁵The X-ray crystal structure of

18 provides some insight into the transmetalation process, as

the nucleophilic arene is proximal to the empty coordination

site of the palladium center. Therefore, the arene likely

coordinates to the palladium and subsequently suﬀers transfer

with formation of a polysiloxane subunit (Scheme 9). This

formulation can be viewed as an electrophilic aromatic

substitution at the ipso carbon bearing silicon with the Pd(II)

electrophile. Support for this depiction comes from the

Hammett study of the electronic demands of the aryl residues

in which increased transmetalation rates correlate with the

lesser electron density at palladium and greater electron density

at silicon.⁴⁶Alternatively this process can be viewed as a β-aryl

elimination.

4.2.2.2. Activated Transmetalation of an Arylpalladium(II)

Arylsilanolate Intermediate. The ability to isolate complex 18

enabled the unambiguous establishment of an activated

transmetalation pathway via a 10-Si-5 intermediate (M⁺20⁻,

Figure 9). The kinetic data in Figure 5 clearly show a signiﬁcant

increase in the rate of the cross-coupling with 18 as the amount

of K⁺5⁻increased. This rate increase is consistent with an

increasing concentration of a more reactive 10-Si-5 species

(K⁺20⁻) formed in rapid pre-equilibrium. At 5.0 equiv of K⁺5⁻

the rate leveled oﬀ, signaling that the concentration of K⁺20⁻

had reached a maximum and thus the turnover-limiting step

had reached saturation. Thus, a bimolecular transmetalation

step can be ruled out. The second molecule of arylsilanolate is

proposed to activate the silicon atom of the palladium complex,

generating a hypervalent siliconate (M⁺20⁻, Figure 8). This

pathway is similar to the Hiyama−Hatanaka proposal for

ﬂuoride-activated transmetalation of organosilicon reagents.³

Presumably, the activated silicon atom redistributes the electron

density onto its peripheral ligands, creating a greater partial

negative charge on the ipso-carbon of the arene. The more

nucleophilic organic moiety then transfers via a lower energy

pathway. Accordingly, given that the catalytic, aryl−aryl cross-

coupling reactions employ a 20-fold excess of silanolate compared to

the intermediate arylpalladium halide, it is safe to conclude that

these reactions (unlike the alkenylsilanolate cross-couplings) proceed

via the activated, 10-Si-5 pathway.

Further evidence for the activated transmetalation pathway

was established by employing the cesium arylsilanolate salt

(Cs⁺5⁻). This salt reacted so rapidly under activation (i.e.,

greater than 1.0 equiv of Cs⁺5⁻per substrate 17) that the

kinetic analysis had to be run at room temperature compared to

50 °C for K⁺5⁻. The greater rate of cross-coupling of the

cesium silanolate clearly implicates a kinetically signiﬁcant role

for the silanolate anion in the transmetalation step. The initial

hypothesis was that the increased rate arose from a greater

equilibrium concentration of the reactive complex Cs⁺20⁻as a

consequence of the greater nucleophilicity of the cesium vs the

potassium silanolate. Curiously, however, the saturation points

for the two are nearly identical.^47,48Thus, if the two silanolate

salts reach pre-equilibrium saturation at the same stoichiometry,

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Scheme 10

Scheme 11

Figure 10. Energy proﬁle for the transmetalation of 18 via the neutral (8-Si-4) pathway. Energies are in kcal/mol; energies given in parentheses have

been computed using the CPCM solvent model (UFF radii, toluene).

the diﬀerence in cross-coupling rates must be the intrinsic

reactivities of the two hypercoordinate complexes, K⁺and

Cs⁺20⁻! Given the fact that these species are most likely not

solvent-separated ion pairs in toluene, the diﬀerence may arise

from the greater negative charge localized on the 10-Si-5

species associated with the less coordinating cesium ion,

compared to the potassium ion.³⁸

4.2.2.3. Molecularity of the Transmetalation. An alter-

native view of the transmetalation step involves arene transfer

from the second silanolate molecule onto palladium through

either an intramolecular (four-membered ring transition state,

xxv) or a bimolecular (xxvi) process (Scheme 10). By

employing a diﬀerent silanolate as the “activator”, the resulting

product analysis could determine which arene participates in

the transfer. However, this experiment must employ silanolates

of identical electronic and steric properties so as to not

inﬂuence the migratory preference in the transmetalation step.

When 1.0 equiv of the preformed arylsilanolate complex 18

was treated with 1.02 equiv of (4-butoxyphenyl)dimethyl-

silanolate K⁺21⁻, the biaryl product distribution for 16:22 was

45/55 (Scheme 11). When the quantity of external silanolate

was increased to 3.02 equiv per palladium complex, the product

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distribution favored 22 (81%) but still produced biaryl 16

(19%). The product distribution obtained in these experiments

revealed that the silanolate complex participated in a silanolate

exchange prior to transmetalation, thus obviating any

conclusion about the molecularity of the transmetalation.

Additionally, since silanolate exchange has been established for

these pre-transmetalation intermediates, any attempt at a

bimolecular crossover experiment to establish inter- vs

intramolecular transmetalation would be not interpretable.

4.3. Computational Analysis of the Transmetalation

Step for Three-Coordinate Arylpalladium(II) Arylsilanol-

ate Complex 18.⁴⁹Although further details of the trans-

metalation event were not available experimentally, it was

possible to glean important insights into this step through

computational analysis of the transition states for trans-

metalation in both the thermal (8-Si-4) and anionically

activated (10-Si-5) processes. The availability of the X-ray

crystal structure coordinates for 18 greatly facilitated the

computational study and placed the calculated structures on

ﬁrm experimental grounds.

All crystallographically deﬁned T-shaped arylpalladium

phosphine complexes, including 18, take up the same

conﬁguration with the aryl group located opposite the empty

coordination site. This arrangement has been rationalized on

the basis of the greater trans inﬂuence of the aryl group

compared to the phosphorus or the oxygen or halogen ligand.³²

However, for completeness, both isomers of the ground-state

complexes and all of the intermediates and transition states for

both neutral and activated pathways were calculated. The

isomer found crystallographically is referred to throughout as

“iso1”, shown in black, and the other isomer, in which the

phosphine ligand is located opposite the empty coordination

site, is referred to as “iso2”, shown in red. Also, all of the

structures for the neutral (8-Si-4) pathway are labeled “N”, and

those for the anionic (10-Si-5) pathway are labeled “A”.

4.3.1. Thermal (8-Si-4) Transmetalation Process. The

energy surface identiﬁed for the neutral pathway is summarized

in Figure 10.⁵⁰The ﬁrst notable observation is that the ground-

state structures for the two isomers are nearly identical (after

correction for solvation). However, at the transition state and

for all intermediates thereafter, the structures in the iso2 family

are all of signiﬁcantly lower energy than those in the iso1 family

derived from the crystallographically identiﬁed complex! The

diﬀerence at the transition states is a remarkable 14.1 kcal/mol.

Simple inspection of the transition-state and product

structures reveals that exchange of the 4-ﬂuorophenyl and (t-

Bu)₃P groups leads to dramatic distortion of the structures

resulting from steric repulsion between the extremely bulky

phosphine and the neighboring aryl groups attached to

palladium (Figure 11). This steric repulsion constitutes a

barrier to the migration of the 4-methoxyphenyl group to the

empty coordination site in N-TS-iso1. Contrariwise, migration

of the 4-methoxyphenyl group to the empty coordination site

in N-TS-iso2 relieves steric repulsion and advances the

intermediates toward the reductive elimination step.

Figure 11. Transition-state and complexed product structures for

transmetalation of 18 via the neutral (8-Si-4) pathway. Energies are in

kcal/mol; energies given in parentheses have been computed using the

CPCM solvent model (UFF radii, toluene) (hydrogens omitted for

clarity).

Thus, calculation of the dissociation event (and subsequent

reductive elimination) indicates a prohibitively endergonic

process (45.8 and 25.9 kcal/mol for N-FProd-iso1 and N-FProd-

iso2, respectively). Since we have unambiguously established

that the neutral process occurs in the absence of any

nucleophilic scavengers, we must assume that some kind of

bimolecular oligomerization takes place to remove the silanone

as a polysiloxane byproduct. Thus, to calculate the energy of the

pre-reductive elimination intermediates (N-FProd), the energy

of the silanone trimer, hexamethylcyclotrisiloxane (D₃), was

calculated, and one-third of that energy was added to the

palladium complex to arrive at much more realistic energies

(Figure 10).

4.3.2. Anionic (10-Si-5) Transmetalation Process. The

energy surface identiﬁed for the anionic pathway is summarized

in Figure 12. The starting points are the same neutral ground-

state structures (plus 5⁻), which must ﬁrst form the activated

10-Si-5 species (A-Inter-iso1 and A-Inter-iso2) by association

with a molecule of 5⁻. The calculations located the anionic

intermediates as stationary points, albeit they were structurally

and energetically quite similar to the transition states for their

formation (A-TS1-iso1 and A-TS1-iso2, respectively). As was

seen for the neutral pathway, the iso2 family of structures is

uniformly more stable than the iso1 family, though by a

signiﬁcantly lesser extent until the products are reached.

The immediate products from transmetalation of 18 are

diorganopalladium complexes that remain coordinated to the

silicon-containing byproduct (N-CProd). To enable reductive

elimination, presumably, the silicon moiety must dissociate to

form a tricoordinate or free diarylpalladium complex (N-

FProd). This step has been extremely problematic to address

computationally (and conceptually) because the silicon unit is

an extremely high-energy dimethylsilanone (Me₂SiO).⁵¹

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Figure 12. Energy proﬁle for the transmetalation of 20⁻via the anionic (10-Si-5) pathway. Energies are in kcal/mol; energies given in parentheses

have been computed using the CPCM solvent model (UFF radii, toluene).

Figure 13. Intermediates and transition-state structures for transmetalation of 20⁻via the anionic (10-Si-5) pathway. Energies are in kcal/mol;

energies given in parentheses have been computed using the CPCM solvent model (UFF radii, toluene) (hydrogens omitted for clarity).

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The structural details of the intermediates and trans-

metalation transition states warrant comment. Both inter-

mediates exist as trigonal bipyramidal siliconate species in

which both oxygen substituents occupy the apical positions, as

expected (Figure 13). The steric inhibition toward trans-

metalation in the iso1 family is easily seen by comparison of the

Pd−C distances in the intermediates, 3.425 Å for A-Inter-iso1 vs

2.352 Å for A-Inter-iso2, and transition states, 2.414 Å for A-

TS2-iso1 vs 2.269 Å for A-TS2-iso2. Moreover, the respective

transition states manifest diﬀerent geometries about the silicon

atom, which result in very diﬀerent Si−C bond distances, 2.395

Å for A-TS2-iso2 vs 2.127 Å for A-TS2-iso2. One possible

interpretation is that the silicon atom in A-TS2-iso1 places a

methyl group in an apical position to enhance the localization

of negative charge on the migrating aryl group, thereby assisting

in overcoming the sterically disfavored activation barrier.

As was seen in the neutral pathway, the activated reaction

proﬁle results in the formation of a diarylpalladium product

complexed to a silicon-containing byproduct (A-CProd).

However, in this case the dissociation of the disiloxane anion

is not terribly unfavorable because all of the silicon atoms are

tetracoordinate and can easily accommodate the negative

charge.

4.4. Mechanistic Picture of the Cross-Coupling of

Arylsilanolates. By combining the results from the kinetic

studies and the stoichiometric experiments, a detailed

mechanism for the cross-coupling of arylsilanolates can be

formulated that illustrates how both thermal and anionic

pathways can operate simultaneously (Figure 9). To initiate the

cycle, oxidative addition occurs directly from (t-Bu₃P)₂Pd to

generate the monomeric T-shaped complex, 17. Rapid

displacement of the halide occurs in which the key Pd−O−Si

moiety is forged with loss of the M⁺Br⁻salt. Now poised for

transmetalation, 18 can proceed down two independent

pathways that involve either: (1) a direct thermal trans-

metalation (8-Si-4) or (2) an anionically activated pathway

involving the formation of a hypervalent siliconate (M⁺20⁻, 10-

Si-5). Because under catalytic conditions an excess of silanolate

is employed and the reactions are considerably faster, the cross-

coupling of arylsilanolates employing t-Bu₃P likely proceeds via

the activation pathway.

By analogy, the catalytic cross-coupling reactions of Cs⁺5⁻

carried out starting with [allylPdCl]₂and dppp(O)₂(section

3.2.1.3.1) can now be conﬁdently understood to also be

operating under the activated regime.

Comparison of the activation free energies for the neutral

(N-TS-iso2) and anionic (A-TS2-iso2) pathways estimates that

the barrier for the anionic pathway is 1.8 kcal/mol lower.

Although it is diﬃcult to compare the rates of ﬁrst- (neutral)

and second-order (anionic) reactions, the kinetic data from

Tables 7 and 8 allow a qualitative comparison of the

fundamental rates. Experimentally, both pathways were

evaluated at 50 °C (for K⁺5⁻) and 25 °C (Cs⁺5⁻), and the

comparisons are compiled in Table 10. For K⁺5⁻, the activation

barrier for the anionic pathway is 1.61 kcal/mol lower than that

for the thermal pathway, whereas for K⁺5⁻, the diﬀerence is

2.59 kcal/mol. These values are within satisfyingly qualitative

agreement with the calculated diﬀerence.

The ability to computationally describe the energy proﬁles

for the transmetalation of intermediates 18 and 20⁻provides

compelling support for the experimentally documented

observation of two, simultaneously operating pathways for the

cross-coupling of organosilanolate salts. A critical discovery

from these calculations was that the crystallographically deﬁned

intermediate is not as kinetically competent as an isoenergetic

isomer, which allows for a much more facile transfer of the

migrating aryl group to the empty coordination site of the T-

shaped complex.

5. CONCLUSIONS

The mechanistic landscape of the cross-coupling of alkenyl- and

arylsilanolates with aryl halides has been signiﬁcantly reﬁned.

The isolation and characterization of many arylpalladium

silanolate complexes allowed for the unambiguous demon-

stration of both neutral (8-Si-4) and anionic (10-Si-5)

mechanistic pathways for transmetalation from silicon to

palladium. In general, alkenylsilanolates react via neutral (8-

Si-4) intermediates as the unassisted transmetalation is

suﬃciently rapid. However, if the direct transmetalation is

slower, as in the case of arylsilanolates (which require

interruption of aromaticity), then anionic activation via the

10-Si-5 intermediate will intervene. These conclusions mandate

a revision of the reigning paradigm that organosilicon

compounds must be anionically activated to engage in

transmetalation processes (Hiyama−Hatanaka paradigm).

Through the agency of intramolecularity, direct transmetalation

of silicon to palladium can be achieved under mild conditions.

The implications for transmetalation from silicon to other

transition metals via M−O−Si linkages are currently under

investigation.

ASSOCIATED CONTENT

■

S

* Supporting Information

Table 10. Comparison of Rates for Thermal and Anionic

Cross-Coupling

Full experimental procedures and characterization data, X-ray

coordinates for 7e, 7p, 7z, 7t, 10, and 18, H and ¹³C NMR

1

spectra, full kinetic data, and coordinates of calculated

structures. The Supporting Information is available free of

charge on the ACS Publications website at DOI: 10.1021/

jacs.5b02518.

M⁺5⁻

[M⁺5⁻], temp,

initial rate,

10⁻²mM/s

ΔΔG^⧧

AUTHOR INFORMATION

■

entry (amount, equiv)

mM

°C

kcal/mol

Corresponding Author

*sdenmark@illinois.edu

1

2

3

4

K⁺5⁻(1.0)

K⁺5⁻(7.5)

Cs⁺5⁻(1.0)

Cs⁺5⁻(7.5)

25.0

187.5

25.0

50

25

0.254

3.05

−1.61

−2.59

0.0251

1.99

Notes

187.5

The authors declare no competing ﬁnancial interest.

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(17) Attempts to diﬀerentiate these possibilities by studying the

cross-coupling reaction rates of stoichiometric amounts of 11 and

[allylPdCl]₂with varying amounts of Cs⁺5⁻were thwarted by the

requirement of a full equivalent of Cs⁺5⁻to reduce the [allylPdCl]₂.

Additional attempts using Pd(0) precatalysts led to slow oxidative

addition and irreproducible kinetics.

ACKNOWLEDGMENTS

■

We are grateful to the National Institutes of Health (GM R01-

63167) and the National Science Foundation (NSF CHE-

1151566) for generous ﬁnancial support.

(18) Calcagno, P.; Kariuki, B. M.; Kitchin, S. J.; Robinson, J. M. A.;

Philip, D.; Harris, K. D. M. Chem.Eur. J. 2000, 6, 2338−2349.

(19) (a) Mason, M. R.; Verkade, J. G. Organometallics 1992, 11,

2212−2220. (b) Amatore, C.; Jutand, A.; M’Barki, M. A. Organo-

metallics 1992, 11, 3009−3013. (c) Ozawa, F.; Kubo, A.; Hayashi, T.

Chem. Lett. 1992, 2177−2180. (d) Amatore, C.; Carre, E.; Jutand, A.;

M’Barki, M. A. Organometallics 1995, 14, 1818−1826. (e) Amatore, C.;

Jutand, A. J. Organomet. Chem. 1999, 576, 254−278.

REFERENCES

■

(1) Tymonko, S. A.; Smith, R. C.; Ambrosi, A.; Denmark, S. E. J. Am.

Chem. Soc. 2015, DOI: 10.1021/jacs.5b02515, (preceding paper in this

issue).

(2) For a deﬁnition of this atomic classiﬁcation scheme, see: Perkins,

C. W.; Martin, J. C.; Arduengo, A. J.; Lau, W.; Alegria, A.; Kochi, J. J.

Am. Chem. Soc. 1980, 102, 7753−7759.

(3) (a) Hiyama, T. J. Organomet. Chem. 2002, 653, 58−61.

(b) Hiyama, T. In Metal-Catalyzed, Cross-Coupling Reactions;

Diederich, F.; Stang, P. J., Eds.; Wiley-VCH: Weinhein, Germany,

1998; Chapter 10. (c) Hiyama, T.; Shirakawa, E. Top. Curr. Chem.

2002, 219, 61−85. Nakao, Y.; Hiyama, T. Chem. Soc. Rev. 2011, 40,

4893−4901.

(4) (a) Denmark, S. E.; Smith, R. C.; Chang, W.-t. T.; Muhuhi, J. M.

J. Am. Chem. Soc. 2009, 131, 3104−3118. (b) Chang, W.-t. T.; Smith,

R. C.; Regens, C. S.; Bailey, A. D.; Werner, N. S. Org. React. 2011, 75,

213−745. (c) Sore, H. F.; Galloway, W. R. J. D.; Spring, D. R. Chem.

Soc. Rev. 2012, 41, 1845−1866.

(5) Yamashita, M.; Vicario, J. V. C.; Hartwig, J. F. J. Am. Chem. Soc.

2003, 125, 16347−16360.

(6) To assist the reader in identifying the complexes, suﬃxes have

been appended to compound numbers to designate the ligand: e =

dppe, f = dppf, p = dppp, t = Ph₃P, z = dppbz.

(20) Grushin, V. V. Organometallics 2001, 20, 3950−3961.

(21) Andrews, M. A.; Gould, G. L.; Voss, E. J. Inorg. Chem. 1996, 35,

5740−5742.

(22) The exclusive observation of dppp(O)₂both from in situ

monitoring by ³¹P NMR and from isolation in the ¹⁸O labeling

experiment deserves some comment. The absence of dppp(O) is

unexpected because it requires the second oxidation from dppp(O) to

occur at a much greater rate than the ﬁrst oxidation. Otherwise, a

mixture of dppp(O) and dppp(O)₂should be observed. It is possible,

but unlikely, that dppp(O) is present but could not be diﬀerentiated in

its bound form by ³¹P NMR spectroscopy. That is, complex 7p mixed

with dppp(O)₂could be indistinguishable from (dpppO)₂aryl-

palladium(II) silanolate. While this cannot be rigorously ruled out,

(dpppO)₂arylpalladium(II) silanolate would be expected to have a

trans relationship between the phosphorus atoms unlike the cis chelate

in 7p and therefore be easily identiﬁed by the change in chemical shift

and coupling constant in the ³¹P NMR spectra. However, the isolation

of some monolabeled dppp(O)₂from the ¹⁸O incorporation

experiment is inconsistent with the ³¹P NMR data. The formation of

monolabeled dppp(O)₂suggests that dppp(¹⁸O) is present in the

reaction mixture. The monolabeled product would then arise from the

second oxidation which occurs upon quenching the reaction mixture.

This discrepancy cannot be explained at this time.

(7) All attempts to prepare a complex with 1,4-diphenylphosphino-

butane (dppb) led to theo formation of monomeric and oligomeric

arylpalladium(II) silanolate complexes. The formation of oligomers is

made possible by the ﬂexible butane backbone which cannot enforce a

cis-chelated bidentate structure. Unfortunately, the presence of

oligomers in solution prevented the isolation and characterization of

a discrete complex.

(8) The arylsilanolate displacement was also attempted on the trans-

Ph₃As derived complex without success. The longer Pd-As bond was

hypothesized to contain less steric crowding around the metal center

thus promoting a more facile exchange.

(9) The crystallographic coordinates of complexes 7e, 7p, 7z, 7t, and

10 have been deposited with the Cambridge Crystallographic Data

Centre; deposition nos. 765351, 645665, 765350, 645666, and

275186, resp. These data can be obtained free of charge from the

CCDC via www.ccdc.cam.ac.uk/conts/retreiving.html.

(10) Marciniec, B.; Maciejewski, H. Coord. Chem. Rev. 2001, 223,

301−335.

(11) The addition of 2-bromotoluene (11) was required as a

scavenger to consume dpppPd(0) formed as a byproduct.

(12) For reactions catalyzed by 7t, the coupling was found to have an

inverse ﬁrst-order dependence upon free Ph₃P.

(23) Preliminary communication: Denmark, S. E.; Smith, R. C. J. Am.

Chem. Soc. 2010, 132, 1243−1245.

(24) Stambuli, J. P.; Incarvito, C. D.; Buhl, M.; Hartwig, J. F. J. Am.

Chem. Soc. 2004, 126, 1184−1194.

(25) Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 2719−2724.

(26) Carrow, B. P.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132, 79−81.

(27) (a) Barrios-Landeros, F.; Carrow, B. P.; Hartwig, J. F. J. Am.

Chem. Soc. 2008, 130, 5842−5843. (b) Barrios-Landeros, F.; Carrow,

B. P.; Hartwig, J. F. J. Am. Chem. Soc. 2009, 131, 8141−8154.

(28) Standard NMR spectra were collected at room temperature,

however the longer requirements for the ¹³C NMR required the

spectrum to be collected at −30 °C.

(29) The only evidence that supports this hypothesis is associated

with the chemical shifts of monomeric and dimeric palladium alkoxides

complexes reported by Hartwig. The ³¹P NMR chemical shifts of the

palladium(II) alkoxide complexes that exist as dimeric structures are

located between 70−80 ppm. On the other hand, the reported shifts

for the monomeric, three-coordinate alkoxide complexes are displayed

in the 60−70 ppm region. Therefore, solely on the basis of the

stoichiometry and the expected chemical shifts, the mixed dimer is

proposed as a ﬂeeting intermediate. See: Stambuli, J. P.; Weng, Z.;

Incarvito, C. D.; Hartwig, J. F. Angew. Chem., Int. Ed. 2007, 46, 7674−

7677.

(13) (a) Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebeskind,

L. S. J. Org. Chem. 1994, 59, 5905−5911. (b) Allred, G. D.; Liebeskind,

L. S. J. Am. Chem. Soc. 1996, 118, 2748−2479.

(14) (a) A control experiment was carried out to eliminate other

possible roles of CuTC. The reaction of 7p was repeated under

identical conditions (Table 3, entry 3) except with 10 mol % of

potassium thienylcarboxylate (KTC) instead of CuTC. The initial rate

was 0.528 × 10⁻²mM/s which is ca. 3.5 times slower than the reaction

with CuTC, thus excluding an activating role of the carboxylate in

CuTC. The slower rate may be due to competitive binding to the

palladium center by KTC. (b) In addition, control experiments in the

cross-coupling of arylpalladium(II) alkenylsilanolates showed that

CuTC has no eﬀect on the rate of catalytic reactions in the absence of

phosphines, see accompanying manuscript..

(30) The monomeric form of palladium(II) silanolate complexes

correlates well to previously reported palladium(II) alkoxide

complexes.

(31) The crystallographic coordinates of 18 have been deposited with

the Cambridge Crystallographic Data Centre; deposition no. 744109.

These data can be obtained free of charge from the CCDC via www.

ccdc.cam.ac.uk/conts/retreiving.html.

(15) Denmark, S. E.; Smith, R. C. Synlett 2006, 2921−2928.

(16) Denmark, S. E.; Smith, R. C.; Tymonko, S. A. Tetrahedron 2007,

63, 5730−5738.

(32) Appleton, T. G.; Clark, H. C.; Manzer, L. E. Coord. Chem. Rev.

1973, 10, 335−422.

R

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J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society

Article

(33) (a) Fukuoka, A.; Sato, A.; Mizuho, Y.; Hirano, M.; Komiya, S.

Chem. Lett. 1994, 1641−1644. (b) Fukuoka, A.; Sato, A.; Kodama, K.-

y.; Hirano, M.; Komiya, S. Inorg. Chim. Acta 1999, 294, 266−274.

(c) Mintcheva, N.; Nishihara, Y.; Mori, A.; Osakada, K. J. Organomet.

Chem. 2001, 629, 61−67. (d) Mintcheva, N.; Nishihara, Y.; Tanabe,

M.; Hirabayashi, K.; Mori, A.; Osakada, K. Organometallics 2001, 20,

1243−1246.

(34) (a) The remaining mass balance was conﬁrmed to be the

dimerization of the arene derived from the aryl bromide. This product

may be a result of an unproductive bimolecular recombination of the

palladium(II) silanolate complexes. This amount of homocoupling was

not observed under the catalytic condition reported in ref 32 and may

be a result of the longer lived pre-transmetalation intermediate under

these conditions. (b) Reactions were performed at a lower

temperature compared to the catalytic reactions to obtain a reliably

measurable rate.

(35) (a) The saturated solubility of potassium bromide (KBr) is 32.8

mg in 1 L of acetone at 37 °C;. (b) Lannung, A. Z. Phys. Chiem (A)

1932, 161, 255−268. (c) in Solubilities of Inorganic and Mild Organic

Compounds; Linke, W.; Princeton, Van Nostrand, 1958; p 29.

(36) Both CsBr and KBr (>3 g each separately) were added to

boiling toluene (20 mL) and vigorously stirred for ca. 5 min. The

mixture was cooled to room temperature and the solids were allowed

to settle to the bottom. The supernatant solution was removed (6 mL)

using a 22G needle to ensure no solids transferred and added to a

oven-dried vial. The volatiles were removed in vacuo and no detectable

quantity of either CsBr or KBr was found even in 6 mL of a saturated

toluene solution.

at lower temperature, again favoring a lower saturation point for the

cesium silanolate.

(48) This behavior contrasts the dependence of the saturation point

on the electronic properties of the aryl residues. In the course of the

Hammett studies (ref 46) we discovered that palladium 4-triﬂuoro-

methylphenylsilanolate reached the saturation rate at signiﬁcantly

lower concentration compared to the palladium 4-methoxyphenyl-

silanolate. Thus, the more electronically deﬁcient silicon atom in the

palladium 4-triﬂuoromethylphenylsilanolate complex requires less

additional potassium silanolate to reach equilibrium saturation.

(49) For recent summaries of computational studies on palladium

catalyzed cross-coupling reactions see: (a) García-Melchor, M.; Braga,

́

A. A. C.; Lledos, A.; Ujaque, G.; Maseras, F. Acc. Chem. Res. 2013, 46,

2626−2634. (b) Xue, L.; Lin, Z. Chem. Soc. Rev. 2010, 39, 1692−1705.

(50) All geometry optimizations and frequency calculations were

performed in Gaussian 09 with the B3LYP functional and a combined

basis set BS1 in gas phase. BS1 uses LANL2DZ basis set for transition

metal Pd, and 6-31G(d) for other atoms. The transition states were

characterized by one imaginary frequency. Solvation free energy

corrections were computed by singlet point CPCM (Conductor-like

Polarizable Continuum Model) calculations using M06 functional, UFF

(Universal Force Field) atomic radii were used and toluene was

speciﬁed as the solvent. See Supporting Information for details.

(51) For a summary of the chemistry of silanones see (a) Brook, M.

A. Silicon in Organic, Organometallic and Polymer Chemistry John Wiley

& Sons: New York, 2000; pp 73−79. (b) Tokitoh, N.; Okazaki, R. In

The Chemistry of Organosilicon Compounds Vol. 2, Part 2; Rapoport, Z.;

Apeloig, Y., Eds.; John Wiley & Sons: Chichester, 1998; pp 1068−

1080. (c) Raabe, G.; Michl, J. In The Chemistry of Organosilicon

Compounds, Part 2; Patai, S.; Rapoport, Z.; Eds.; John Wiley & Sons:

Chichester, 1989; pp 1117−1127.

(37) Alternatively, at substoichiometric loadings of K⁺5⁻, the rate

could be associated with the rate of dissociation of the dimeric

complex 19 into the monomeric palladium silanolate and palladium

bromide species. Moreover, it is also possible that transmetalation

could take place directly from 19 since at 0.5 equiv of K⁺5⁻with

respect to 17 the predominant species visible by NMR spectroscopy is

19.

(38) (a) Kurts, A. L.; Macias, A.; Beletskaya, I. P.; Reutov, O. A.

Tetrahedron 1971, 27, 4759−4768. (b) Kurts, A. L.; Dem’yanov, P. I.;

Macias, A.; Beletskaya, I. P.; Reutov, O. A. Tetrahedron 1971, 27,

4769−4776. (c) Jackman, L. M.; Lange, B. M. Tetrahedron 1977, 34,

2737−2769.

(39) Inverse ﬁrst-order dependence in added Ph₃P would also be

observed if a second dissociation were turnover-limiting. Inverse

second-order dependence in added Ph₃P would be observed if the

second dissociation were reversible and transmetalation were turnover-

limiting.

(40) For ligand inﬂuence on other C−C bond forming events, see:

van Leeuwen, P. W. N. M.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P.

Chem. Rev. 2000, 100, 2741−2769 and references therein.

(41) Ledford, J.; Schultz, C. S.; Gates, D. P.; White, P. S.; DeSimone,

J. M.; Brookhart, M. Organometallics 2001, 20, 5266−5276.

(42) Attempts to determine quantitatively the aﬃnity of CuTC to

remove triphenylphosphine from complex 7t, were thwarted by the

inability to detect Ph₃P·CuTC complexes under cross-coupling

conditions.

(43) (a) Gilles, A.; Stille, J. K. J. Am. Chem. Soc. 1980, 102, 4933−

4941. (b) Nishihara, Y.; Onodera, H.; Osakada, K. Chem. Commun.

2004, 192−193.

(44) This rate equation is also consistent with an oﬀ-cycle rate

determining step such as ligand dissociation from (t-Bu₃P)₂Pd. This

scenario is viewed as less likely given the primarily associative oxidative

addition of aryl bromides with (t-Bu₃P)₂Pd, see ref 27b.

(45) However, if dissociation of t-Bu₃P is irreversible (i.e.,

transmetalation is much faster than reassociation) then no ligand

dependence would be observed.

(46) Denmark, S. E.; Smith, R. C.; Chang, W.-t. T. Tetrahedron 2011,

67, 4391−4396.

(47) The fact that these measurements were taken at diﬀerent

temperatures also leads to a counterintuitive conclusion. The entropic

cost of the pre-equilibrium (two particles forming one) would be less

S

DOI: 10.1021/jacs.5b02518

J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Article Doi

Mechanistic significance of the Si-O-Pd bond in the palladium-catalyzed cross-coupling reactions of arylsilanolates

DOI: 10.1021/jacs.5b02518

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Article abstract of DOI:10.1021/jacs.5b02518

Full text of DOI:10.1021/jacs.5b02518

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