Insight into the efficiency of cinnamyl-supported precatalysts for the suzuki-miyaura reaction: Observation of Pd(I) dimers with bridging allyl ligands during catalysis

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pubs.acs.org/JACS

Insight into the Eﬃciency of Cinnamyl-Supported Precatalysts for

the Suzuki−Miyaura Reaction: Observation of Pd(I) Dimers with

Bridging Allyl Ligands During Catalysis

Damian P. Hruszkewycz,^†David Balcells,*^,‡Louise M. Guard,^†Nilay Hazari,*^,†and Mats Tilset^‡

^†The Department of Chemistry, Yale University, P.O. Box 208107, New Haven, Connecticut 06520, United States

^‡Centre for Theoretical and Computational Chemistry (CTCC), Department of Chemistry, University of Oslo, P.O. Box 1033

Blindern, 0315 Oslo, Norway

S

* Supporting Information

ABSTRACT: Despite widespread use of complexes of the

type Pd(L)(η³-allyl)Cl as precatalysts for cross-coupling, the

chemistry of related Pd^Idimers of the form (μ-allyl)(μ-

Cl)Pd₂(L)₂has been underexplored. Here, the relationship

between the monomeric and the dimeric compounds is

investigated using both experiment and theory. We report an

eﬃcient synthesis of the Pd^Idimers (μ-allyl)(μ-Cl)Pd₂(IPr)₂

(allyl = allyl, crotyl, cinnamyl; IPr = 1,3-bis(2,6-

diisopropylphenyl)imidazol-2-ylidene) through activation of

Pd(IPr)(η³-allyl)Cl type monomers under mildly basic

reaction conditions. The catalytic performance of the Pd^II

monomers and their Pd^Iμ-allyl dimer congeners for the

Suzuki−Miyaura reaction is compared. We propose that the (μ-allyl)(μ-Cl)Pd₂(IPr)₂-type dimers are activated for catalysis

through disproportionation to Pd(IPr)(η³-allyl)Cl and monoligated IPr−Pd⁰. The microscopic reverse comproportionation

reaction of monomers of the type Pd(IPr)(η³-allyl)Cl with IPr−Pd⁰to form Pd^Idimers is also studied. It is demonstrated that

this is a facile process, and Pd^Idimers are directly observed during catalysis in reactions using Pd^IIprecatalysts. In these catalytic

reactions, Pd^Iμ-allyl dimer formation is a deleterious process which removes the IPr−Pd⁰active species from the reaction

mixture. However, increased sterics at the 1-position of the allyl ligand in the Pd(IPr)(η³-crotyl)Cl and Pd(IPr)(η³-cinnamyl)Cl

precatalysts results in a larger kinetic barrier to comproportionation, which allows more of the active IPr−Pd⁰catalyst to enter

the catalytic cycle when these substituted precatalysts are used. Furthermore, we have developed reaction conditions for the

Suzuki-Miyaura reaction using Pd(IPr)(η³-cinnamyl)Cl which are compatible with mild bases.

and Nolan’s allyl-based systems⁹(Figure 1), have been

developed and are now commercially available.

A key feature in determining the eﬀectiveness of these

INTRODUCTION

■

Pd-catalyzed cross-coupling is an area of intense research

interest because it has numerous applications in the synthesis of

precatalysts is the rate and eﬃciency of their conversion into

pharmaceuticals, ﬁne chemicals, and materials.¹In the last 20

the monoligated L−Pd⁰active species under the reaction

years one of the major advances in the ﬁeld has been the

development of specialized phosphine- and NHC-based

conditions.^1c,h,iExtensive studies have been performed on the

mechanism of activation of the Buchwald^7band Organ

ligands, such as those designed by Fu,²Buchwald,³Hartwig,⁴

and Stradiotto,⁵which promote many of the fundamental steps

in catalysis such as oxidative addition and reductive

elimination.^1g,hUse of these relatively new ligands has resulted

in an expanded substrate scope, milder reaction conditions, and

lower catalyst loadings.^1g,hUnfortunately, these specialized

ligands often have comparable expense to the Pd source, which

means that the traditional route for generating the Pd⁰active

species, addition of excess ligand to a Pd⁰or Pd^IIprecursor, is

Figure 1. Three popular well-deﬁned precatalyst scaﬀolds with a 1:1

Pd to ligand ratio.

not always attractive. Furthermore, in many cases it has been

determined that the optimal Pd to ligand ratio is 1:1 and that

the active species is monoligated L−Pd⁰.⁶As a result, a number

of well-deﬁned Pd^IIprecatalysts with a 1:1 Pd to ligand ratio,

Received: December 10, 2013

such as Buchwald’s palladacycles,⁷Organ’s PEPPSI complexes,⁸

Published: April 24, 2014

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Scheme 1. Two Steps Which Are Proposed to Be Relevant to Activation of Allyl-Containing Precatalysts: (a) Conversion of Pd^II

to Pd⁰and (b) Comproportionation of Pd⁰with Pd^IIto Generate Pd^I

Figure 2. (a) Summary of allyl-based precatalysts reported by Nolan and co-workers. (b) Generic structure of cinnamyl-supported Pd^IIprecatalysts

that are often used in cross-coupling. (c) Dimeric precursor which is often combined with a bulky ligand in situ in cross-coupling.

a

Scheme 2. Our Proposed Pathway for Activation of Precatalysts of the Type Pd(IPr)(η³-allyl)Cl

a

Both the rates of activation to Pd⁰and comproportionation to Pd^Iaﬀect overall catalytic activity.

precatalysts,^8b,10and these activation pathways are now

relatively well understood. In contrast, relatively little is

known about the mechanism of activation of allyl-based

precatalysts. It is proposed that activation of these species can

be split into two steps (Scheme 1):¹¹(a) activation of the

ligated precatalyst scaﬀold to form the catalytically active

monoligated L−Pd⁰species⁶and (b) comproportionation,

which forms a Pd^Iμ-allyl dimer¹²and removes the L−Pd⁰from

the reaction mixture. Preliminary studies on activation^9b,13and

comproportionation¹¹have been reported, but both need to be

understood in greater detail. This current work investigates

both steps shown in Scheme 1, with an emphasis on b.¹⁴

To perform these studies we revisit precatalysts of the type

Pd(NHC)(η³-allyl)Cl (NHC = IPr or SIPr),⁹which were

originally reported by Nolan and co-workers in 2002.^9a,b

Subsequently, Nolan demonstrated that addition of substituents

in the 1-position of the allyl ligand results in a dramatic

improvement in catalytic eﬃciency for the Suzuki−Miyaura and

Buchwald−Hartwig reactions compared to unsubstituted allyl

precatalysts.^9d,15This work has led to the widespread use of

complexes of the type Pd(NHC)(η³-cinnamyl)Cl (NHC = IPr

or SIPr) as precatalysts for both cross-coupling and related

reactions¹⁶and the general use of cinnamyl-supported Pd

complexes with other bulky ligands in the cross-coupling

literature (Figure 2b).¹⁷In fact, based on these results the

dimeric precursor (η³-cinnamyl)₂(μ-Cl)₂Pd₂, in conjunction

with an appropriate ligand, is also extensively used in cross-

coupling reactions (Figure 2c).¹⁸Nolan postulated that the

substitution on the allyl ligand weakens bonding between the

Pd and the allyl moiety and makes activation to the catalytically

active IPr−Pd⁰more facile,^9dbut the precise reason for this

enhanced rate of activation and the more eﬃcient performance

of cinnamyl-supported species is still unclear. In this

contribution, we provide insight into the eﬃciency of the

cinnamyl-supported precatalyst 3. It is demonstrated that Pd^Iμ-

allyl dimers of the type (μ-allyl)(μ-Cl)Pd₂(IPr)₂form via

comproportionation between the corresponding Pd(IPr)(η³-

allyl)Cl monomers and IPr−Pd⁰in Suzuki−Miyaura reactions

that use the monomeric precatalysts (Scheme 1b). The

presence of substituents in the 1-position of the allyl ligand

raises the kinetic barrier to comproportionation, thus increasing

the concentration of the monoligated active catalyst that can

enter the catalytic cycle via oxidative addition with the aryl

halide substrate (Scheme 2).

Surprisingly, despite the close relationship between com-

plexes of the type Pd(L)(η³-allyl)Cl and their Pd^Iμ-allyl dimers

analogues little has been done to compare these systems or

study the reactivity of Pd^Iμ-allyl dimers.^11a,19This is even more

noteworthy given that in recent years binuclear Pd^I−Pd^I

complexes have repeatedly been isolated from reaction mixtures

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previously thought to involve complexes only in the Pd⁰and

Pd^IIoxidation states.^11,19,20Furthermore, several binuclear Pd^I−

Pd^Icomplexes,²¹including Pd^Iμ-allyl dimers,^11a,19,22have been

shown to be eﬀective precatalysts for Pd-catalyzed cross-

coupling, and their mechanisms of activation have been a topic

of ongoing research.^21d,23In this work, we conduct a detailed

comparison of the catalytic eﬃciency of a series of precatalysts

of the type Pd(IPr)(η³-allyl)Cl and their Pd^Iμ-allyl dimer

analogues for a simple Suzuki−Miyaura reaction. We propose

that the Pd^Iμ-allyl dimers access the catalytically active IPr−

Pd⁰via disproportionation, and we present a detailed study of

the disproportionation pathway (Scheme 1b). In addition,

through our studies of the synthesis of Pd^Iμ-allyl dimers we

have discovered a mild way to activate the Pd(NHC)(η³-allyl)

Cl scaﬀold (Scheme 1a) and describe reaction conditions for

the Suzuki−Miyaura reaction using precatalysts of the type

Pd(L)(η³-allyl)Cl with milder bases.

for all of the isolated Pd^Iμ-allyl dimers. Complexes 5 and 6 are

rare examples of Pd^Iμ-allyl dimers with 1-substituted μ-allyl

ligands.^20d,e,25Consistent with literature precedent, the μ-allyl

ligands in the thermodynamically preferred isomers of both 5

and 6 exhibit an anti geometry,²⁵where the 1-substituent is on

the opposite side of the allyl ligand to the central proton, as

determined from NOE experiments. In the reaction to form 5,

a mixture of syn and anti isomers is initially formed, which

equilibrates almost exclusively to the anti isomer (the

thermodynamic product) when 5 is left in solution for 48 h

at room temperature.²⁴In contrast, in the reaction to form 6

only the anti isomer is observed under our standard synthetic

conditions.²⁴The μ-allyl ligands in 4, 5, and 6 exhibit distinct

¹H NMR features compared to their monomeric η³-allyl

counterparts.^9b,dIn all three cases the anti protons of the μ-allyl

ligands resonate at abnormally low chemical shifts, in the range

of 0.5−0.9 ppm, and the anti methyl and phenyl resonances of

5 and 6 are also shifted upﬁeld. The central protons of

monomeric η³-allyl ligands exhibit a chemical shift in the

oleﬁnic region,^9b,dwhereas the signals corresponding to the

central protons of 4, 5, and 6 are observed between 1.55 and

1.75 ppm. These abnormally low chemical shifts may result in

part from the signiﬁcant electron density present on the μ-allyl

ligand due to back-bonding from the Pd−Pd bond into the π*

orbital of the μ-allyl ligands, an interaction ﬁrst proposed by

Kurosawa and co-workers.^25b,26

Compounds 5 (Figure 3) and 6 (Figure 4) were

characterized by X-ray crystallography. They exhibit similar

structural characteristics to 4 and other Pd^Iμ-allyl dimers which

also contain a μ-chloride ligand.^11a,19,27Consistent with

analogous structures, the central carbon atoms of the μ-allyl

ligands interact with both Pd centers (Pd−C_cent2.34−2.39 Å),

while the terminal carbon atoms only interact with one Pd

atom. Crystallographic analysis suggests that the Pd−C bond

distances to the terminal carbon atoms of the μ-allyl ligands are

not equivalent, although due to disorder this cannot be

concluded with absolute certainty.²⁸Longer Pd−C bond

distances are observed for the carbon atoms, which are

attached to either the Me (5) or the Ph (6) substituents.

Nolan previously observed a similar Pd−C elongation in the η³-

cinnamyl ligand in the monomeric species 3.^9dA feature of the

structures of 5 and 6 is that the central carbon atoms of the μ-

allyl ligands are canted toward the Pd−Pd−Cl plane (Figure 5a,

θ = 69.3° in 5 and 74.1° in 6), whereas in monomeric

complexes with η³-allyl ligands the central carbon is canted

away from the L−Pd−Cl plane (Figure 5b).²⁹Kurosawa and

co-workers previously observed this structural feature in related

μ-allyl dimers and propose that it is due to back-bonding from

the ﬁlled d orbitals of the Pd−Pd bond into the empty π*

orbital of the μ-allyl ligand.^25b,26Another noteworthy character-

RESULTS AND DISCUSSION

■

Activation of Pd(IPr)(η³-allyl)Cl. Although it has pre-

viously been postulated that complexes with 1-substituted allyl

ligands are activated faster in complexes of the type Pd(IPr)(η³-

allyl)Cl,^9dthere is no direct experimental evidence to support

this claim. Therefore, our mechanistic investigation began with

a study of the activation of 1−3 with excess KO^tBu and

PhB(OH)₂at 25 °C (eq 1). The reaction conditions used for

these experiments correspond closely to the conditions used for

the Suzuki−Miyaura coupling (vide infra), but the aryl halide

substrate is absent. A mixed solvent system was used to ensure

that the reaction was homogeneous, which allows for a more

exact comparison of rates. We were surprised that all three

monomeric precatalysts formed their corresponding Pd^Iμ-allyl

dimer as the major product, as determined by ¹H NMR

spectroscopy (vide infra for characterization of 4−6).²⁴

However, a large diﬀerence in rate was observed between the

systems, with 3 being activated completely in less than 5 min,

while after 1 h 50−60% of 1 or 2 was still present in solution,

and complete conversion was only observed after heating for an

additional hour at 40 °C.²⁴These results suggest that it is

plausible that Pd^Iμ-allyl dimers play a role in cross-coupling

and that under these conditions the speed of activation never

becomes suﬃciently fast to prevent dimer formation,

presumably through comproportionation between the starting

complex of the type Pd(IPr)(η³-allyl)Cl and monoligated IPr−

Pd⁰(vide infra).

Synthesis and Characterization of Pd^Iμ-Allyl Dimers.

To probe the role of dimers further, we synthesized the IPr-

supported Pd^Iμ-allyl dimer congeners to Nolan’s monomeric

species through the reaction of 1−3 with a slight excess of

K₂CO₃in warm ethanol (eq 2). Excellent yields were obtained

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ligands, so that the Pd−Pd−IPr angles are between 164° and

169°.

Our new synthetic route for preparation of Pd^Iμ-allyl dimers

is a vast improvement on previous methods,^27,30which required

formation of air- and moisture-sensitive intermediates. A

proposed mechanism for dimer formation is depicted in

Scheme 3.³¹The primary alcohol ﬁrst displaces the chloride

ligand. This acidiﬁes the hydroxyl group, which is deprotonated

by the weak carbonate base. The resultant Pd^IIalkoxide species

is then reduced to a monoligated IPr−Pd⁰complex via β-

hydride elimination and reductive elimination of an oleﬁn.

Finally, the IPr−Pd⁰species is trapped by starting material to

form the Pd^Iμ-allyl dimer. Several experimental observations

support this mechanism: (i) Propene was observed as a

1

byproduct in the H NMR spectrum when the reaction of 1

with K₂CO₃was monitored using ¹H NMR spectroscopy in d₄-

methanol, and propionaldehyde was detected by GC after the

reaction of 1 with K₂CO₃in PrOH. (ii) Reaction of 1 with

Figure 3. ORTEP of 5 (hydrogen atoms have been omitted for

clarity). The crotyl fragment crystallized in two conformations, and the

major one is shown. Selected bond lengths (Angstroms) and angles

(degrees): Pd(1)−Pd(2) 2.5814(7), Pd(1)−C(1) 2.05(2), Pd(1)−

C(2) 2.34(1), Pd(2)−C(2) 2.37(2), Pd(2)−C(3) 2.11(2), Pd(1)−

Cl(1) 2.433(1), Pd(2)−Cl(1) 2.4368(8), Pd(1)−C(5) 2.013(4),

Pd(2)−C(6) 2.017(3), Pd(1)−Pd(2)−C(6) 166.86(8), C(5)−

Pd(1)−Pd(2) 164.9(1).

n

K₂CO₃in d₄-methanol was inhibited by the presence of excess

ⁿBu₄NCl in solution, as this presumably prevented initial

coordination of d₄-methanol. (iii) Facile activation of the

monomeric precatalysts by K₂CO₃to form Pd^Iμ-allyl dimers

was observed only in primary alcohol solvents, such as MeOH,

n

EtOH, PrOH, and BuOH, with a decrease in rate as the size

of the alcohol increased, most likely due to steric factors. (iv)

Only slow dimer formation was observed when 1 was heated at

40 °C in a d₈-isopropanol suspension of K₂CO₃, as the

increased steric bulk of ⁱPrOH probably prevents it from readily

displacing the chloride ligand and entering the proposed

reaction pathway. (v) No reaction was observed when 1 and

K₂CO₃were heated for 12 h at 60 °C in ^tBuOH, which is both

sterically bulky and lacks the β-hydrogen necessary for

activation. Overall, our synthetic protocol represents a novel

and mild way to activate the (NHC)Pd(η³-allyl)Cl scaﬀold and

suggests that the harsh base KO^tBu used by Nolan and others

for catalysis is not necessary in the presence of primary alcohol

solvents.^9b,d

Catalytic Studies. The catalytic eﬃciency for the Suzuki−

Miyaura reaction of the Pd^IImonomers and their Pd^Iμ-allyl

dimer congeners was compared using conditions similar to

those reported by Nolan and co-workers from 25 to 40 °C

(Table 1).^9dA mixed solvent system³²was utilized to ensure a

homogeneous reaction mixture,³³in contrast to the heteroge-

neous conditions used by Nolan. Unsubstituted complexes 1

and 4 are both poor precatalysts for this reaction, and dimer 4

outperforms 1 at all temperatures. The crotyl systems 2 and 5

are slightly more eﬃcient precatalysts than the analogous

unsubstituted allyl systems at all temperatures, but the same

pattern holds, and dimer 5 always gives higher yields than 2. A

combination of factors could account for the improved catalytic

activity of the dimers in the allyl and crotyl systems. As

demonstrated in eq 1, 1 and 2 are not eﬃciently activated

under our reaction conditions, whereas the dimeric systems are

already partially activated and may generate the Pd⁰active

species faster than the monomer. Moreover, the IPr−Pd⁰that is

formed upon activation of 1 and 2 could be reacting with

unreacted 1 and 2 to form the corresponding dimers 4 and 5

instead of entering the catalytic cycle. In contrast to the allyl

and crotyl systems, the monomeric cinnamyl precatalyst 3

vastly outperforms its dimeric congener 6. For example, a 95%

yield was obtained after 60 min at 25 °C using precatalyst 3,

whereas the yield was only 3% using the corresponding dimer

6. This disparity is inconsistent with complete conversion of 3

Figure 4. ORTEP of 6 (hydrogen atoms have been omitted for

clarity). The cinnamyl fragment crystallized in two conformations, and

the major one is shown. Selected bond lengths (Angstroms) and

angles (degrees): Pd(1)−Pd(2) 2.5999(7), Pd(1)−C(1) 2.04(1),

Pd(1)−C(2) 2.390(7), Pd(2)−C(2) 2.377(7), Pd(2)−C(3) 2.09(1),

Pd(1)−Cl(1) 2.421(1), Pd(2)−Cl(1) 2.422(1), Pd(1)−C(5)

2.017(5), Pd(2)−C(6) 2.024(5), Pd(1)−Pd(2)−C(6) 166.2(2),

C(5)−Pd(1)−Pd(2) 168.0(2).

Figure 5. Diﬀerent orientations of the central carbon atoms of the allyl

ligand with respect to the Pd bonding planes in (a) μ-allyl and (b) η³-

allyl ligands. X is a generic anionic ligand such as Cl.

istic that 5 and 6 share with similar compounds is that the Pd−

Pd−IPr angles are not linear.^27,30Instead, the IPr ligands are

oriented away from the central carbon atoms of the μ-allyl

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Scheme 3. Proposed Mechanism for Formation of the μ-Allyl Dimers 4−6 from Monomers 1−3 with Weak Base

a

Table 1. Yields of Product for the Suzuki−Miyaura

Supporting Information), whereas under our conditions only 3

b

activates quickly (eq 1).²⁴

Reaction Catalyzed by Complexes of the Type (IPr)Pd(η³-

allyl)Cl (1−3) and Related Pd^Iμ-Allyl Dimers (4−6)

Direct evidence for the presence of Pd^Iμ-allyl dimers under

the catalytic conditions was obtained using NMR spectroscopy.

1

When catalytic reactions with 1, 2, and 3 were tracked by H

NMR spectroscopy under conditions virtually identical to those

described in Table 1 at room temperature (Scheme 4), signals

corresponding to 4, 5, and 6, respectively, were detected in the

baseline of the ¹H NMR spectra. In all three systems

resonances associated with the Pd^Iμ-allyl dimers could be

observed while the catalytic reactions were proceeding,²⁴which

indicates that Pd^Iμ-allyl dimer formation is a process that can

remove some of the active IPr−Pd⁰species during catalysis.

The distinct ¹H NMR signals of the μ-allyl ligands (vide supra)

permitted unambiguous assignment of the dimers, but the trace

concentration of these complexes compared to the catalytic

substrates prevented accurate quantiﬁcation of Pd^Iμ-allyl dimer

formation.²⁴

% yields for precatalysts

temp (°C) time (min)

1

4

2

5

3

6

25

30

35

40

30

60

30

60

30

60

30

60

<1

2

3

5

93

1

7

14

19

36

35

67

58

80

22

30

69

51

97

92

99

95

3

4

>99

4

13

8

17

15

52

32

93

26

20

97

74

99

28

20

81

a

Yields were calculated using gas chromatography with naphthalene as

b

an internal standard and are the average of two runs. Reaction

conditions: ⁱPrOH solution containing 0.625 M 4-chlorotoluene,

0.3125 M naphthalene, and 0.6875 M KO^tBu (800 μL); MeOH

solution containing 3.5 M phenylboronic acid (150 μL); THF solution

containing 0.1 M [Pd]_tot(50 μL).

Using modiﬁed catalytic conditions (eq 3) it was possible to

1

quantify the formation of Pd^Iμ-allyl dimers by H NMR

spectroscopy in reactions using 1, 2, and 3 as the precatalyst.²⁴

In the cases of the unsubstituted precatalyst 1 and the crotyl

precatalyst 2, a gradual increase in the dimer concentrations

occurred as the catalytic reactions proceeded. When catalysis

was complete, approximately 76% of the Pd was in the form of

dimer 4 for precatalyst 1, whereas for precatalyst 2, only 25% of

the Pd was in the form of 5. For precatalyst 3, approximately

35% of the Pd was in the form of 6 straight after mixing, and

this percentage stayed relatively constant as the catalytic

reaction proceeded. It is proposed that this increased rate of

formation of 6 compared to 4 and 5 is due to the fast rate of

activation of 3.

to 6 under the reaction conditions. The full set of monomeric

and dimeric precatalysts was also screened for the Suzuki−

Miyaura of more sterically hindered substrates (Table S1,

Supporting Information), and similar catalytic results were

obtained.²⁴An interesting feature of the catalytic studies is the

poor performance of precatalyst 2. Under Nolan’s heteroge-

neous reaction conditions 2 and 3 both had high activity,^9d

whereas under our conditions 3 gives signiﬁcantly higher

activity than 2. Our control experiments indicate that under

Nolan’s conditions both 2 and 3 activate rapidly (see eq S1,

On the basis of the signiﬁcant concentration of 4 observed

under these modiﬁed conditions, we propose that that the low

1

Scheme 4. Conditions Used for Detection of Dimers 4−6 by H NMR Spectroscopy in Catalytic Reactions Using 1−3

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a

Scheme 5. Proposed Disproportionation of μ-Allyl Dimers

a

Addition of a trapping ligand L* shifts the equilibrium to favor formation of two monomers.

Scheme 6. Summary of Disproportionation Experiments with 4−6 Using (a) dvds, (b) Dimethyl Fumarate, and (C) Allyl Ether

as the Trapping Reagents

activity observed with precatalyst 1 is due not only to slow

activation but also to the formation of signiﬁcant quantities of

the Pd^Iμ-allyl dimer 4. In contrast, only a fraction of the Pd in

the substituted systems undergoes Pd^Iμ-allyl dimer formation.

One explanation for the low yields of the 1-substituted dimers

is that formation of 5 and 6 from 2 and 3, respectively, is less

facile than formation of 4 from 1. In this scenario, more of the

IPr−Pd⁰formed from the activation can enter the catalytic

cycle instead of reacting with 2 or 3 to form the corresponding

dimers (Scheme 2). This hypothesis was tested by quantifying

the formation of the Pd^Iμ-allyl dimers under identical reaction

conditions to eq 3 in the absence of the 4-chlorotoluene

substrate (eq 4). Consistent with the scenario proposed in

Scheme 2, the yield of the unsubstituted dimer 4 was unaﬀected

by the presence of 4-chlorotoluene in solution, whereas the

yields of the substituted dimers 5 and 6 were lower in the

presence of 4-chlorotoluene. The proposed reaction pathway

outlined in Scheme 2 is also consistent with the observation

that precatalyst 2 outperforms 1 in catalysis (Table 1), even

though the two precatalysts are activated at a comparable rate

under our reaction conditions (eq 1). In the case of 2 more

IPr−Pd⁰can enter the catalytic cycle. 'The speciﬁc reasons for

the diﬀerences in yields of the dimers from precatalysts 1−3

were investigated in detail and are discussed below.

NMR Studies of the Activation of Pd^Iμ-Allyl Dimers

via Disproportionation. Although several studies report the

use of Pd^Iμ-allyl dimers as precatalysts for cross-coupling, the

mechanism of activation of these species is unclear.^19,22Our

catalytic results with 4, 5, and 6 indicate that the substitution on

the μ-allyl ligand has a profound eﬀect on the activity.

Furthermore, the similar catalytic performance of the dimers at

elevated temperature suggests that in all three cases the same

active catalyst is formed and that the disparity in activity at

lower temperatures could simply be related to diﬀerences in the

rates of activation. Therefore, we were interested in probing the

mechanism of activation of Pd^Iμ-allyl dimer precatalysts.

Previously, while studying the insertion of CO₂into Pd^Idimers

with two μ-allyl ligands we suggested that these dimers can

disproportionate into a monoligated Pd⁰species and a Pd^II

species, and others have proposed similar reactions.^{20e,25a,27,34}

In this case, we propose that 4−6 are activated through an

analogous disproportionation, in which Pd(IPr)(η³-allyl)Cl

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Figure 6. Reaction coordinate diagram illustrating two diﬀerent scenarios for the relative rates of comproportionation of 1-substitued species

compared to unsubstituted species, based on the relative rates of disproportionation summarized in Scheme 6. In Scenario A, 1-substituted Pd^Iμ-allyl

dimers are thermodynamically stabilized and no information from the relative rates of disproportionation can be obtained about the relative rates of

comproportionation (we have arbitrarily shown the barrier as smaller). In Scenario B, 1-substituted Pd^Iμ-allyl dimers are not thermodynamically

stabilized and the relative rates of comproportionation will be directly related to the rates of disproportionation.

(1−3) and catalytically active IPr−Pd⁰are formed (Scheme 5).

The disproportionation is thermodynamically unfavorable but

can be driven by trapping the IPr−Pd⁰product. We

hypothesized that the rate of disproportionation will be related

to the catalytic performance of μ-allyl dimer precatalysts.

The rates of disproportionation of 4−6 in the presence of 10

equiv of 1,3-divinyl-1,1,3,3-tetramethyldisiloxane (dvds)

(Scheme 6a), 2 equiv of dimethyl fumarate (Scheme 6b), and

1 equiv of allyl ether (Scheme 6c) were measured. The

determine the exact role that the trapping reagent plays in the

reaction, and this is explored further computationally (vide

infra). Interestingly, the rate of disproportionation is also

dependent on the solvent. Trapping experiments were

performed in the presence of d₄-methanol (with some C₆D₆

present to solubilize the reaction mixtures) because coordinat-

ing solvents enhance the rate of disproportionation. For

example, reaction of 5 with 10 equiv of dvds proceeded faster

in the presence of the more strongly coordinating d₃-ACN

instead of d₄-methanol. Speciﬁcally, the reaction was complete

after 30 min in a 3:2 d₃-ACN:C₆D₆mixture, whereas the

reaction was complete after 90 min in 3:2 d₄-methanol:C₆D₆.

Studies on Comproportionation to form Pd^Iμ-Allyl

Dimers. In catalysis using dimers as the precatalyst it is

proposed that the rate of disproportionation to form the active

IPr−Pd⁰species is important for high activity. However, in

systems where a monomeric precatalyst is utilized, dimer

formation from comproportionation of IPr−Pd⁰and the

starting precatalyst (the microscopic reverse of disproportio-

nation of the dimer) will lead to reduced rates by sequestering

active catalyst. Therefore, we were interested in probing the

kinetics of comproportionation from 1−3 and monoligated

Pd⁰. Although the experiments in Scheme 6 show that

increasing the sterics at the 1-position of the μ-allyl ligand

raises the kinetic barrier to disproportionation compared to the

unsubstituted species, we cannot conclude from these experi-

ments alone that this same relationship holds for compro-

portionation. As shown in Figure 6, the kinetic barrier to

disproportionation could arise from thermodynamic stabiliza-

tion of the 1-substituted Pd^Iμ-allyl dimers (Figure 6, Scenario

A), in which case the kinetic barrier to comproportionation

could be smaller, the same, or larger than that observed for an

unsubstituted species, and our disproportionation experiments

do not provide us with any information about comproportio-

nation. (In Figure 6, Scenario A, we have arbitrarily drawn the

barrier as smaller.) On the other hand, if the substituted dimers

are thermodynamically destabilized relative to the unsubstituted

1

disappearance of dimer over time was tracked using H NMR

spectroscopy, and the rate of trapping is 4 > 5 ≫ 6 for all three

trapping reagents. We conclude from these experiments that

increasing the steric bulk at the 1-position of the μ-allyl ligand

increases the kinetic barrier to disproportionation. At ﬁrst

glance these results appear inconsistent with our catalytic

results, which indicated that under all conditions the crotyl

dimer 5 was more active than the unsubstituted dimer 4 and

that under some conditions the cinnamyl dimer 6 is more active

than 4. However, we believe that the overall eﬃciency of a Pd^I

dimer for catalysis is determined by both the rate of

disproportionation and the rate at which the subsequent

(IPr)Pd(η³-allyl)Cl product is activated and can enter the

catalytic cycle. For example, although disproportionation of the

crotyl dimer 5 is slower than the unsubstituted dimer 4, the

crotyl monomer 2 is a better precatalyst than 1, so overall 5

outperforms 4. A similar argument explains why 6, which

undergoes slow disproportionation, is a better precatalyst than

4 under some reaction conditions.

Our experiments clearly indicate that the rate of

disproportionation is dependent on the trapping reagent.

Allyl ether is the fastest trapping reagent, while the more

sterically hindered dvds is the slowest. In fact, in the case of

dvds, addition of 10 equiv was required to ensure that the

reaction proceeded at a reasonable rate. Under these pseudo-

ﬁrst-order conditions we were able to demonstrate that there is

a ﬁrst-order dependence on both the Pd dimer and dvds.²⁴

Unfortunately from these experiments it is not possible to

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Scheme 7. Summary of Cross-Over Experiments Between the Pd^Iμ-Allyl Dimers 5 and 6 and the Pd^IIMonomer 1

Figure 7. Structures of model compounds used in our calculations.

dimer then the higher kinetic barrier to disproportionation in 1-

substituted species must arise from an increase in the relative

transition state energies (Figure 6, Scenario B). In this case the

relative kinetic barrier for the microscopic reverse compro-

portionation process will also be higher in 1-substituted

systems.

the cinnamyl ligand increases the transition state energy for

disproportionation and comproportionation. Precatalyst 6 is

ineﬃcient because its kinetic barrier to disproportionation

prevents it from readily accessing the catalytically active IPr−

Pd⁰. Precatalyst 3 is highly eﬀective not only because it is

rapidly activated to the catalytically active IPr−Pd⁰but also

because a relatively large kinetic barrier to comproportionation

slows down formation of the less active 6 from unreacted 3 and

IPr−Pd⁰, a deleterious process that removes the active catalyst

from the reaction mixture. In this precatalyst system oxidative

addition with the aryl halide substrate is more likely to

outcompete comproportionation of IPr−Pd⁰with unreacted 3

compared to unsubstituted 1, thus increasing the concentration

of IPr−Pd⁰that enters the catalytic cycle (Scheme 2). However,

direct observation of dimer 6 in catalytic reactions with 3

indicates that comproportionation still occurs in this system. In

principle, even more active precatalysts could be designed by

further increasing the barrier to dimerization. Alternatively, if

the speed of activation is increased further by modifying the

precatalyst, it may be possible to develop highly active systems

in which all of the Pd^IIprecatalyst is converted to Pd⁰, before

deleterious comproportionation between Pd^IIand Pd⁰can

occur.

To determine if Scenario A or Scenario B is operative, cross-

over experiments were run in which the unsubstituted

monomer 1 was mixed with the substituted dimers 5 and 6

(Scheme 7a).³⁵The cross-over reactions can be described as

the combination of the disproportionation of the substituted

dimers and the comproportionation of 1 with IPr−Pd⁰

(Scheme 7b). The equilibrium strongly favors formation of

the unsubstituted allyl dimer 4 from the substituted allyl dimers

5 and 6. This indicates that the comproportionation reaction to

form 4 is more exergonic than the comproportionation

reactions to form 5 or 6 (|ΔG°_all| > |ΔG°_1‑sub| in Scheme 7b).

Given that 5 and 6 are less thermodynamically stabilized than 4,

the slower rates of disproportionation for 5 and 6 must arise

from an increase in the transition state energy for

disproportionation/comproportionation (Scenario B in Figure

6).

The experiments in Schemes 6 and 7 provide a rationale for

the disparity in the catalytic performance between monomeric

precatalyst 3 and its dimeric congener 6 (Table 1). The

increased steric bulk of the phenyl group on the 1-position of

Computational Studies on Comproportionation and

Disproportionation. DFT calculations were performed to

further evaluate the eﬀect of substituents on the 1-position of

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the allyl ligand on the kinetics and thermodynamics of the

disproportionation/comproportionation pathway. Calculations

were performed with two diﬀerent simpliﬁed NHC ligands,

IDM and IPh, where the steric bulk of the IPr ligand was

reduced to diﬀerent degrees (Figure 7).³⁶In the case of the 1-

substituted monomers and dimers, isomers with both syn and

anti conformations of the η³-allyl or μ-allyl ligand were

modeled. In general, the relative energies of the isomers are

in agreement with our experimental results, and isomers with

syn conformations of the 1-substituted η³-allyl ligand are the

most stable for monomeric compounds, while isomers with anti

conformations of the μ-allyl ligand are the most stable for the

dimeric compounds.²⁴This suggests that our computational

method is suitable for modeling the relative stabilities of these

complexes. Furthermore, where calculated structures could be

directly compared with experimental structures, close agree-

ment between the theoretical and the experimental bond

distances and angles was observed.²⁴

Experimentally, when the unsubstituted monomer 1 was

mixed with the 1-substituted dimers 5 or 6, we observed

essentially complete conversion to the unsubstituted dimer 4

and the 1-substituted monomers 2 or 3 (Scheme 7). Within

error, the calculated equilibrium constants for cross-over

reactions between the monomer 1^IPhand the dimers anti-5^IPh

and anti-6^IPhare consistent with these results. The calculated

K_eqat 25 °C for cross over between 1^IPhand anti-5^IPhis 130,

while for 1^IPhand anti-6^IPhthe value is 3. When the full IPr

ligand was used,²⁴the calculations give even better agreement

with the experimental results. At 25 °C, the calculated K_eqvalue

for cross over between 1 and 5 is 83, while for 1 and 6 the value

is 1091. Therefore, we conclude that in an analogous fashion to

experimental results calculations with the more sterically bulky

IPh and IPr ligands suggest that formation of 1-substituted

dimers through comproportionation is less thermodynamically

favorable than formation of the unsubstituted dimer.

Three main pathways were computationally tested to provide

information about the activation of μ-allyl dimers: (i)

disproportionation to generate a solvent (ⁱPrOH) stabilized

monoligated Pd⁰species and a complex of the type Pd(NHC)-

(η³-allyl)Cl, (ii) homolytic scission of the Pd−Pd bond to

generate two Pd^Imonomers, and (iii) disproportionation to

generate an anionic Pd⁰monomer and a cationic Pd^II

monomer. Pathways (ii) and (iii) are signiﬁcantly higher in

energy than pathway (i) and are discussed further in the

Supporting Information.²⁴Pathway (i) is a two-step process,

which requires solvent assistance (Scheme 8). In the ﬁrst step,

the bridging chloride ligand on one Pd atom is displaced by

ⁱPrOH to form an intermediate with a μ-allyl ligand and

terminal Pd−Cl and Pd-ⁱPrOH groups. The coordination of

ⁱPrOH is slightly energetically uphill and goes through a

relatively low-energy transition state in which one of the Pd−Cl

bonds is almost completely cleaved and a new bond between

Pd and ⁱPrOH is being formed. This transition state is similar to

those observed for ligand substitution at monomeric centers

which proceed via a dissociative interchange mechanism.²⁹An

The thermodynamics of μ-allyl dimer formation through

comproportionation of Pd^IIcomplexes of the type Pd(L)(η³-

allyl)Cl and L−Pd⁰were calculated (Table 2). The

monoligated Pd⁰complexes were modeled with an explicit

solvent molecule coordinated to Pd to complete the

i

coordination sphere. PrOH was selected as the solvent,

because this was the primary solvent used in catalytic reactions

(vide supra). The calculations indicate that dimer formation is

strongly preferred in all cases, in agreement with the exergonic

character of the comproportionation reactions observed

experimentally. For systems supported by the IDM ligand,

formation of anti-5^IDMis the most thermodynamically

favorable, although there is only a small diﬀerence in the

calculated energy of dimer formation for the unsubstituted,

crotyl and cinnamyl species. Calculations with IPh reveal a

diﬀerent trend. In this case formation of the unsubstituted

species 4^IPhis the most thermodynamically favored. The small

yet signiﬁcant energy diﬀerences between the three systems

with the IPh ligand show the inﬂuence of steric bulk in the 1-

position of the μ-allyl ligand on the relative stability of the Pd^I

dimers.

i

alternative pathway in which PrOH coordination results in

conversion of the μ-allyl ligand into an η¹-allyl ligand and the

bridging chloride ligand remains intact is considerably higher in

energy.²⁴In the second step, a Pd−C bond of the μ-allyl ligand

and the Pd−Pd bond are cleaved to generate two monomeric

fragments. The Pd atom to which ⁱPrOH binds undergoes Pd−

C bond cleavage. The transition state for Pd−C and Pd−Pd

bond breakage is the highest energy point on the reaction

pathway. The transition state for disproportionation of 4^IPh

(TS-4^IPh_dis), which is virtually identical to the transition state

for disproportionation of 4^IDM, is shown in Figure 8. In this late

transition state the dimer has almost been completely cleaved,

Table 2. Calculated Thermodynamics for Formation of Pd^I

μ-Allyl Dimers through Comproportionation of Monomers

of the Type Pd(NHC)(η³-allyl)Cl and Monoligated Pd⁰

and the Pd−Pd distance is 3.18 Å, compared to 2.65 Å in 4^IPh

.

One of the Pd atoms is essentially two coordinate and in a

i

linear geometry, with IPh and PrOH supporting ligands. The

ΔG°_com(kcal mol⁻¹

−16.7

)

closest Pd−C contact from a carbon atom of the initial μ-allyl

ligand to the two coordinate Pd atom is 2.74 Å, while the Pd−

Cl distance is 3.53 Å. The other Pd atom is four coordinate and

in a distorted square planar geometry, with IPh, and chloride

ligands, along with the incipient η³-allyl ligand. The incipient

η³-allyl ligand is bound through two C atoms with Pd−C bond

lengths of 2.10 and 2.28 Å, respectively, while the other Pd−C

distance is 2.72 Å. The Pd−Cl distance of 2.68 Å is slightly

elongated compared with the calculated Pd−Cl distance in 1^IPh

(2.52 Å). Finally, it should be noted that a pathway in which

4^IDM

a

anti-5^IDM

anti-6^IDM

4^IPh

−17.3

−15.0

a

−16.2

−13.4

−15.5

a

anti-5^IPh

anti-6^IPh

a

Calculated numbers are for comproportionation from the syn isomers

of the 1-substituted monomers to the anti isomers of the μ-allyl

dimers, as these are the thermodynamically preferred isomers.

i

isopropoxide assists in cleavage of the dimer instead of PrOH

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a

Scheme 8. Calculated Pathway and Free Energies for Solvent-Assisted Disproportionation of 4^IDMor 4^IPh

a

i

The energy of the dimer and PrOH is deﬁned as being at 0 kcal mol⁻¹.

Table 3. Calculated Barriers for Solvent (ⁱPrOH) Assisted

Disproportionation and Comproportionation of Pd^Iμ-Allyl

Dimers with Monomers of the Type Pd(NHC)(η³-allyl)Cl

and Monoligated Pd⁰

has the same kinetic barrier to disproportionation as the

i

pathway involving PrOH but is unlikely due to the relative

i

concentrations of isopropoxide versus PrOH under the

catalytic reaction conditions.²⁴

ΔG^‡(kcal mol⁻¹

)

ΔG^‡(kcal mol⁻¹

)

dis

com

4^IDM

29.7

29.3

28.4

25.9

32.6

33.8

13.0

a

anti-5^IDM

anti-6^IDM

4^IPh

12.0

a

13.4

9.6

a

anti-5^IPh

anti-6^IPh

syn-5^IDM

syn-6^IDM

syn-5^IPh

syn-6^IPh

19.2

a

18.3

10.2

11.1

16.8

14.6

a

Calculated numbers are the barrier for comproportionation starting

from the syn isomer of the 1-substituted monomers. The pathway for

this process presumably involves isomerization from the syn isomer of

the monomer to the anti isomer.

Figure 8. Calculated transition state for disproportionation of 4^IPh

(TS-4^IPh_dis) (selected hydrogen atoms have been omitted for clarity).

Selected bond lengths (Angstroms) and angles (degrees): Pd(1)−

Pd(2) 3.18, Pd(1)−C(1) 2.10, Pd(1)−C(2) 2.28, Pd(1)−C(3) 2.72,

Pd(1)−C(4) 2.20, Pd(1)−Cl(1) 2.68, Pd(2)−C(5) 1.99, Pd(1)−

O(1) 2.27, Pd(2)−C(3) 2.74, C(1)−C(2) 1.44, C(2)−C(3) 1.39,

C(1)−Pd(1)−C(4) 94.4, C(1)−Pd(1)−Cl(1) 167.6, C(5)−Pd(2)−

O(1) 169.1.

of unsubstituted, crotyl and cinnamyl μ-allyl dimers are virtually

identical with the sterically undemanding IDM ligand, and the

structures are similar to that described for TS-4^IPh_dis(Figure 8).

In contrast, when the sterically bulky IPh ligand is utilized, the

transition state energies for the 1-substituted species are

signiﬁcantly higher than that for the unsubstituted species. This

is qualitatively in agreement with our experimental results that

disproportionation is faster for the unsubstituted species, and

our comparative calculations with the IDM and IPh ligands

indicate that the origin of this eﬀect is related to steric rather

than electronic factors. A comparison of the calculated structure

of the transition state for disproportionation of anti-6^IPh(TS-

6^IPhFigure 9) with TS-4^IPhreveals major diﬀerences. For

The energies of the transition states for disproportionation of

1-substituted and unsubstituted μ-allyl dimers with both IDM

and IPh supporting ligands are compared in Table 3. In the case

of the 1-substituted dimers, calculations were performed

starting from the anti isomers. The computed reaction pathway

leads to formation of the thermodynamically disfavored anti

isomer of the 1-substituted monomers of the type Pd(NHC)-

(η³-allyl)Cl. However, these types of monomeric systems are

known to undergo facile isomerization from anti to syn,³⁷which

is consistent with our observation that the syn isomers were

exclusively the ﬁnal product in our trapping experiments.³⁸The

transition state energies and structures for disproportionation

dis

example, in TS-6^IPh_disthe two Pd-containing fragments are even

more separated. The Pd−Pd distance is 3.59 Å, and the closest

Pd−C contact from a carbon atom of the initial μ-cinnamyl

ligand to the two-coordinate Pd atom is 3.00 Å. Furthermore,

although the incipient η³-cinnamyl ligand on the square planar

Pd is still bound through two C atoms, the Pd−C distances are

longer (2.10, 2.41, and 3.07 Å). Apart from the increased

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ethylene initially binding to one Pd atom along with cleavage

of a Pd−Cl bond. However, the critical energy barrier

associated with cleavage of the Pd−Pd and Pd−C bonds is

lowered for all three systems when compared to that found for

ⁱPrOH. This may be due to back-donation from the metal to

ethylene, which should stabilize the incipient Pd⁰oxidation

state in the transition state. Our computational results clearly

indicate that the nature of the coordinating solvent or trapping

agent can directly aﬀect the rate of disproportionation,

consistent with our experimental results. Also in agreement

with our experimental results, the calculated barriers for

disproportionation with ethylene follow the order 4^IPh≈ anti-

5^IPh≪ anti-6^IPh. Thus, the calculations predict that increasing

the sterics at the 1-position of the μ-allyl ligand results in an

increased calculated barrier to disproportionation in both the

Figure 9. Calculated transition state for disproportionation of anti-6^IPh

(TS-6^IPh_dis) (selected hydrogen atoms have been omitted for clarity).

Selected bond lengths (Angstroms) and angles (degrees): Pd(1)−

Pd(2) 3.59, Pd(1)−C(1) 2.10, Pd(1)−C(2) 2.41, Pd(1)−C(3) 3.07,

Pd(1)−C(4) 2.00, Pd(1)−Cl(1) 2.67, Pd(2)−C(5) 1.99, Pd(1)−

O(1) 2.23, Pd(2)−C(3) 3.00, C(1)−C(2) 1.44, C(2)−C(3) 1.39,

C(1)−Pd(1)−C(4) 98.7, C(1)−Pd(1)−Cl(1) 174.4, C(5)−Pd(2)−

O(1) 180.0.

i

ethylene- and the PrOH-assisted pathways. However, in the

ⁱPrOH-assisted pathway, the barrier for disproportionation of

anti-5^Phis signiﬁcantly closer in energy to that of anti-6^IPhthan

4^IPh

.

Overall, our calculations provide clear support for the

hypothesis that the disproportionation of Pd^Idimers into a

monoligated Pd⁰complex and a Pd^IIcomplex of the type

Pd(L)(η³-allyl)Cl is the pathway for generation of the Pd⁰

active species in catalysis. Although this process is thermody-

namically unfavorable, under catalytic conditions the aryl halide

substrate can trap the Pd⁰species via oxidative addition, which

provides a driving force for disproportionation. Given that the

pathway for disproportionation is assisted by solvent

coordination, we suggest that for faster activation in coupling

reactions with μ-allyl dimer precatalysts a weakly coordinating

separation of the two fragments, the other major diﬀerence

between TS-4^IPhand TS-6^IPhis the orientation of the IPh

dis

ligand around the two-coordinate Pd center. In TS-4^IPhthe

dis

ﬁve-membered imidazol-2-ylidene ring of this IPh ligand is

perpendicular to the plane containing the two Pd atoms and the

carbon donor of the IPh ligand. In contrast, in TS-6^IPhthe

dis

imidazol-2-ylidene ring is almost parallel to this plane,

presumably for steric reasons. The transition state structure

i

for disproportionation of anti-5^IPhis more similar to TS-6^IPh

solvent such as PrOH or ACN should be present and that

dis

than to TS-4^IPh_dis, consistent with the increased barrier.

In our experiments exploring the disproportionation of

dimers 4−6 we noticed a pronounced eﬀect of both the

trapping agent and the solvent on the rate of the reaction. As a

simple model for our oleﬁn-based trapping reagents dis-

proportionation of the dimers 4^IPh, anti-5^IPh, and anti-6^IPhwere

modeled in the presence of ethylene (Scheme 9). The

calculated pathway for disproportionation is virtually identical

these reactions should not be performed in pure hydrocarbon

solvents, which are the conditions most commonly utilized in

the literature.^19,22c,d

The calculated trends for the activation energies of

i

comproportionation in the presence of PrOH are the same

as for disproportionation (Table 3). Formation of compounds

with 1-substituted μ-allyl ligands species have signiﬁcantly

larger barriers than unsubstituted species when steric factors are

considered. In the case of 1-substituted species, the kinetic

i

to that described for the PrOH-mediated process, with

a

Scheme 9. Calculated Pathway and Free Energies for Ethylene-Assisted Disproportionation of 4^IPh, anti-5^IPh, and anti-6^IPh

a

The energy of the dimer and ethylene is deﬁned as being at 0 kcal mol⁻¹.

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Scheme 10. Inhibition of the Catalytic Activity of 3 by 1

a

b

products of comproportionation are predicted to be the syn

isomers of the dimers, formed from the thermodynamically

more stable syn isomers of monomers of the type Pd(NHC)-

(η³-allyl)Cl. This is consistent with our experimental results,

where during the synthesis of 5 initially a mixture of syn and

anti isomers was formed, which equilibrated exclusively to the

anti isomer over time. We believe that the pathway for

formation of the thermodynamically preferred anti μ-crotyl or

μ-cinnamyl dimers involves the initial facile isomerization of the

starting η³-allyl monomer to the anti conformation³⁷followed

by comproportionation of the anti monomer with L−Pd⁰. The

computational results suggest that the crotyl monomer 2 is

slightly less likely to undergo comproportionation with L−Pd⁰

than the cinnamyl monomer 3. This is in agreement with the

experiments summarized in eq 3, where approximately equal

yields of the substituted dimers 5 and 6 were observed under

modiﬁed catalytic conditions using precatalysts 2 and 3,

respectively. On this basis we propose that the reason 2 is

not a good precatalyst under our reaction conditions is due

primarily to slow activation, not signiﬁcant dimer formation.

Further evidence in support of this hypothesis is provided by

the results of Nolan and co-workers, who observed that 2 is a

very eﬃcient precatalyst under their heterogeneous reaction

conditions,^9dwhere we believe that activation of 2 is rapid.²⁴

Essentially, if precatalysts 2 and 3 are activated at the same rate

both species will give similar catalytic results as they are both

equally likely to form the oﬀ-cycle dimer. In contrast, even if 1

is activated at the same rate as 2 and 3, it will give lower activity

in catalysis because it is more likely to comproportionate and

form 4.

Table 4. Yields of Product for Suzuki−Miyaura Reactions

Inhibited by the Presence of 1 in Solution

% yields for precatalyst mixtures

temp (°C)

time (min)

1 + 3

1 mol % 4

25

30

60

30

60

30

60

30

60

11

24

11

79

74

92

83

94

3

9

30

35

40

6

28

21

64

46

92

a

Yields were calculated using gas chromatography with naphthalene as

b

an internal standard and are the average of two runs. Reaction

conditions: ⁱPrOH solution containing 0.625 M 4-chlorotoluene,

0.3125 M naphthalene, and 0.6875 M KO^tBu (800 μL); MeOH

solution containing 3.5 M phenylboronic acid (150 μL); THF solution

containing 0.1 M 1 and 0.1 M 3 or 0.1 M 4 (50 μL).

reaction 68% of the Pd was in the form of 4, with no signiﬁcant

amounts of 6 present. A control reaction was also performed to

show that 4 is simply an oﬀ-cycle side product in this

experiment that does not itself inhibit catalysis and that the

perturbation in catalytic eﬃciency in Table 4 is due strictly to

removal of active IPr−Pd⁰catalyst by comproportionation with

1. When a stock solution containing 1 mol % 3 and 0.5 mol % 4

was used for catalysis, the reaction proceeded at the same rate

as the corresponding reaction in the absence of 4.²⁴The results

in Table 4 show that the extent of inhibition decreased with

increasing temperature, presumably in part because at higher

temperature 4 is more readily converted into monoligated IPr−

Pd⁰. If all the IPr−Pd⁰formed from 3 had been trapped as 4

then the catalyst mixture of 1 mol % 1 and 3 would exhibit the

same catalytic eﬃciency as 1 mol % 4. The mixture of 1 and 3

outperforms a 1 mol % solution of 4, suggesting that not all the

IPr−Pd⁰is trapped as the Pd^Iμ-allyl dimer. Nevertheless, the

perturbation in the eﬃciency of precatalyst 3 in the presence of

1 demonstrates that a signiﬁcant fraction of the active IPr−Pd⁰

catalyst can be removed from the reaction mixture through Pd^I

μ-allyl dimer formation.

Inhibition of Catalysis by Precatalyst 1. On the basis of

the experiments in Schemes 6 and 7 and our computational

results, it is clear that the barrier to comproportionation to

form 4 from 1 and IPr−Pd⁰is signiﬁcantly lower than the

barrier to comproportionation in the 1-substituted systems.

Therefore, we postulated that 1 could inhibit the catalytic

performance of 3 by trapping the IPr−Pd⁰produced from

activation of 3 as dimeric 4 (Scheme 10).

When a stock solution containing 1 mol % 1 and 1 mol % 3

was used for catalysis, a marked decrease in reaction rate was

observed compared to the corresponding reaction in which 1

was absent, despite the increase in the overall Pd loading

(Table 4). To provide support for our hypothesis that this

reduced eﬃciency was due to formation of 4, we performed a

Suzuki−Miyaura reaction under modiﬁed catalytic conditions

(2.5 mol % 1, 2.5 mol % 3, 40 °C) and monitored the Pd

Catalysis under Milder Conditions. As noted earlier, our

new synthesis of Pd^Iμ-allyl dimers using K₂CO₃under mild

conditions suggests that the strong base KO^tBu is not necessary

24

1

speciation using H NMR spectroscopy. At the end of the

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for catalysis with precatalysts of the type (IPr)Pd(η³-allyl)Cl

(eq 2) provided a primary alcohol is present. Table 5

precatalyst and mild bases. Solvent-assisted disproportionation

of the dimers generate the monoligated L−Pd⁰active catalyst as

well as Pd^IIcomplexes of the type Pd(IPr)(η³-allyl)Cl. This

further demonstrates the close relationship between Pd^II

complexes with η³-allyl ligands and Pd^Idimers with μ-allyl

ligands and indicates that interconversion between the two

species is signiﬁcantly more facile than previously thought.

Overall, we expect that this work will aid in the design of more

eﬃcient Pd precatalysts for cross-coupling that are supported

by η³-allyl or related ligands, and further studies toward this end

are being conducted in our laboratory.

a

b

Table 5. Yields of Product for Suzuki−Miyaura Reactions

Using Precatalyst 3 and Weak Bases

% yields for diﬀerent base/solvent combinations

K₂CO₃

ⁱPrOH

K₃PO₄

ⁱPrOH

temp

(°C)

time

(min)

K₂CO₃

EtOH

K₃PO₄

EtOH

25

40

30

60

30

60

59

88

92

42

75

56

66

<1

3

<1

2

EXPERIMENTAL SECTION

■

General. Experiments were performed under a dinitrogen

atmosphere in an M-Braun drybox or using standard Schlenk

techniques unless otherwise stated. Under standard glovebox

conditions purging was not performed between uses of pentane,

diethyl ether, benzene, toluene, and THF; thus, when any of these

solvents were used, traces of all these solvents were in the atmosphere

and could be found intermixed in the solvent bottles. Moisture- and

air-sensitive liquids were transferred by stainless steel cannula on a

Schlenk line or in a drybox. Pentane, THF, and toluene were dried by

passage through a column of activated alumina followed by storage

under dinitrogen. All commercial chemicals were used as received

9

8

a

Yields were calculated using gas chromatography with naphthalene as

b

an internal standard and are the average of two runs. Reaction

conditions: EtOH or ⁱPrOH solution containing 0.5263 M 4-

chlorotoluene, 0.2632 M naphthalene, and 0.5526 M phenylboronic

acid (950 μL); 0.75 mmol of K₂CO₃or K₃PO₄; THF solution

containing 0.1 M 3 (50 μL).

summarizes our catalytic results using K₂CO₃and K₃PO₄as

bases for the Suzuki−Miyaura reaction with precatalyst 3 in

i

except where noted. MeOH (J. T. Baker), PrOH (Macron Fine

Chemicals), and 200 proof EtOH (Decon Laboratories Inc.) were not

dried but degassed by sparging with dinitrogen for 1 h and stored

under dinitrogen. Ethyl acetate (Fisher Scientiﬁc) and hexanes

(Macron Fine Chemicals) were used as received. Potassium phosphate

(97%), potassium tert-butoxide (99.99%, sublimed), naphthalene

(99%), propionaldehyde (97%), dimethyl fumarate (97%), 4-

chlorotoluene (98%), and 2-chloro-m-xylene (97%) were purchased

from Aldrich. Potassium carbonate was purchased from Mallinckrodt.

1,3-Divinyltetramethyldisiloxane, allyl ether (98%), and 4-methylbi-

phenyl were purchased from TCI. Phenylboronic acid (98%), 2,6-

dimethoxytoluene (98%), 1-napthaleneboronic acid, ⁿBuOH (99%),

39

i

EtOH and PrOH. Use of EtOH instead of PrOH greatly

improves the eﬃciency of the reactions using weak bases, and

eﬃcient conversions are observed even at 25 °C. This is the

ﬁrst time a milder base has been shown to promote eﬃcient

Suzuki−Miyaura reactions at mild temperature using Nolan’s

cinnamyl precatalyst, and this result could expand the substrate

scope of this catalytic system. Furthermore, it may be applicable

to cinnamyl-supported systems which use other ancillary

ligands.

t

and BuOH (99%) were purchased from Alfa Aesar. Phenylboronic

CONCLUSIONS

acid was puriﬁed via ﬂash chromatography using 2:1 ethyl acetate/

hexanes.^32,40Flash chromatography was performed on silica gel 60

(230−400 mesh, Fisher Scientiﬁc). Potassium phosphate and

potassium carbonate were ground with a mortar and pestle and

stored in an oven at 130 °C prior to use. 4-Chlorotoluene, 2-chloro-m-

xylene, ⁿPrOH, 1,3-divinyltetramethyldisiloxane, and ⁿBuOH were

degassed prior to use through three freeze−pump−thaw cycles.

Deuterated solvents were obtained from Cambridge Isotope

Laboratories. C₆D₆was dried over sodium metal and stored under

nitrogen, while d₄-methanol, d₈-isopropanol, and d₈-THF were not

dried but degassed prior to use through three freeze−pump−thaw

cycles. NMR spectra were recorded on Bruker AMX-400 and -500 and

Varian-300 and -500 spectrometers at ambient probe temperatures

unless noted. For variable-temperature NMR, the sample temperature

was calibrated by measuring the distance between the OH and the

CH₂resonances in ethylene glycol (99%, Aldrich). Chemical shifts are

■

This work has established that the eﬃciency of the Pd(IPr)(η³-

cinnamyl)Cl precatalyst and most likely other related 1-

substituted species for the Suzuki−Miyaura reaction is not

only due to facile activation of the precatalyst scaﬀold but also

because this system exhibits an increased kinetic barrier to

comproportionation to form the corresponding Pd^Iμ-allyl

dimer. However, Pd^Iμ-allyl dimer formation, which is a

deleterious process that removes the IPr−Pd⁰active species

from the reaction mixture, was still observed under catalytic

conditions with this highly active precatalyst and shown to be a

facile process in all the systems that were studied in this report.

On the basis of these results, we propose that Pd^Iμ-allyl dimer

formation is a general phenomenon in reaction mixtures that

use precatalysts of the type Pd(L)(η³-allyl)Cl, which were

previously thought to only involve Pd⁰and Pd^IIcomplexes. By

increasing the barrier to comproportionation between Pd⁰and

Pd^IIor by developing systems that activate suﬃciently quickly

so that all of the Pd^IIis converted to Pd⁰before

comproportionation can occur it should be possible to develop

precatalysts that are even more active.

1

reported with respect to residual internal protio solvent for H and

¹³C{¹H} NMR spectra. Atom numbering for the peak assignments is

13

1

given below. All assignments are based on two-dimensional H, C-

HMQC, and HMBC experiments. Robertson Microlit Laboratories,

Inc. performed the elemental analyses (inert atmosphere). Gas

chromatography analyses (GC) were performed on a Shimadzu GC-

2010 Plus apparatus equipped with a ﬂame ionization detector and a

Shimadzu SHRXI-5MS column (30 m, 250 μm inner diameter, ﬁlm

0.25 μm). The following conditions were utilized for GC analyses:

ﬂow rate 1.23 mL/min constant ﬂow, column temperature 50 °C (held

for 5 min), 20 °C/min increase to 300 °C (held for 5 min), total time

22.5 min. The response factor used to calculate GC yields was

determined using a purchased sample of 4-methylbiphenyl (TCI).

Literature procedures were used to prepare the following compounds:

IPr,⁴¹Pd(IPr)(η³-allyl)Cl (1),^9aPd(IPr)(η³-crotyl)Cl (2),^9dand

This study has also elucidated new pathways for activation of

precatalysts of the type Pd(NHC)(η³-allyl)Cl as well as their

dimeric Pd^Icongeners. Eﬃcient activation of

Pd(IPr)(η³-allyl)Cl type precatalysts was observed under

weakly basic reaction conditions in primary alcohol solvents,

and reaction conditions for the Suzuki−Miyaura reaction were

subsequently developed using the Pd(IPr)(η³-cinnamyl)Cl

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Pd(IPr)(η³-cinnamyl)Cl (3).^9dCompounds 1−3 were stored on the

benchtop, while IPr was stored in a glovebox under dinitrogen.

X-ray Crystallography. X-ray diﬀraction experiments were carried

out on a Rigaku MicroMax-007HF diﬀractometer coupled to a

Saturn994+ CCD detector with Cu Kα radiation (λ = 1.54178 Å) at

−180 °C. Crystals were mounted on MiTeGen polyimide loops with

immersion oil. Data frames were processed using Rigaku CrystalClear

and corrected for Lorentz and polarization eﬀects. Using Olex2⁴²the

structure was solved with the XS⁴³structure solution program by

Patterson methods and reﬁned with the XL⁴³reﬁnement package

using least-squares minimization. Non-hydrogen atoms were reﬁned

anisotropically. Hydrogen atoms were reﬁned using the riding model.

Details of the crystal structure and reﬁnement data for 5 and 6 are

given in the Supporting Information.

Computational Details. DFT calculations were carried out using

the Gaussian09 program.⁴⁴Due to the rather large size of the systems

studied, two diﬀerent basis sets, BS1 and BS2, were used. With BS1, all

elements were described with the full-electron double-ζ quality 6-31G

basis set,⁴⁵except the heaviest, Cl and Pd, which were described with

the small-core SDD pseudopotential basis set.⁴⁶BS1 was used in the

geometry optimization and frequency calculations at the DFT-

(M06L)⁴⁷/SMD⁴⁸level. The SMD continuum model was used to

model the eﬀects of the solvent (ⁱPrOH; ε = 19.264). Geometries were

fully optimized in solution without any geometry or symmetry

constraints. Frequencies were computed analytically with the aim of

identifying each stationary point as either a minimum (reactants,

intermediates, and products) or a saddle point (transition states, TS).

Transition state geometries were relaxed to reactants and products

using the vibrational frequency data. Frequency calculations were also

used to determine the diﬀerence between the potential (E) and Gibbs

(G) energies, G − E, which contains the zero-point, thermal, and

entropy energies. Potential energies were reﬁned, E_sol, by means of

single point (SP) calculations at the DFT(M06)/SMD level with a

larger basis set, BS2. With BS2, all elements were described with a

triple-ζ + polarization quality basis set, including the SDD(f,d) for Cl

and Pd and the 6-311+G** for all other elements.⁴⁹The ΔG and ΔG^‡

values given in the text were obtained from the Gibbs energy in

solution, G_sol, which was calculated by adding the thermochemistry

corrections, G − E, to the reﬁned SP energies, E_sol, i.e., G_sol= E_sol+ G

− E.

(septet, J = 6.8 Hz, 2H, H4), 3.14−3.04 (m, 5H, H4 and H8), 1.91

(dd, J = 8.3, 2.1 Hz, 1H, H6-syn), 1.68 (m, 1H, H7), 1.37 (d, J = 6.8

Hz, 6H, H5), 1.34 (d, J = 6.8 Hz, 6H, H5), 1.31 (d, J = 6.8 Hz, 6H,

H5), 1.26 (d, J = 6.8 Hz, 6H, H5), 1.13 (d, J = 6.8 Hz, 6H, H5), 1.12

(s, J = 6.4 Hz, 6H, H5), 1.10 (d, J = 6.6 Hz, 6H, H5), 1.08 (d, J = 6.9

Hz, 6H, H5), 0.85 (dd, J = 12.3, 2.2 Hz, 1H, H6-anti), 0.24 (d, J = 6.2

Hz, 3H, H9). ¹³C{¹H} NMR (126 MHz, C₆D₆) 192.36, 191.91,

146.02, 146.01, 145.96, 145.90, 137.26, 137.20, 128.85, 128.83, 123.45,

123.33, 123.33, 123.29, 122.28, 122.13, 55.07, 36.45, 28.49, 28.45,

28.36, 25.58, 25.27, 25.24, 23.32, 23.16, 23.14, 23.08, 20.12, 15.21.

Syn isomer (minor product): Some unobscured peaks are visible in

the ¹H NMR spectrum. ¹H NMR (400 MHz, C₆D₆) 6.65 (s, 2H, H3),

6.59 (s, 2H, H3), 2.23 (dd, J = 8.0, 1.9 Hz, 1H, H6-syn), 0.44 (dd, J =

12.1, 1.9 Hz, 1H, H6-anti).

(μ-Cinnamyl)(μ-Cl)Pd₂(IPr)₂(6). Pd(η³-cinnamyl)(IPr)Cl (3)

(119.5 mg, 0.185 mmol) and potassium carbonate (127 mg, 5

equiv) were transferred to a Schlenk ﬂask and placed under dinitrogen.

Degassed ethanol (5 mL) was transferred by cannula into the Schlenk

ﬂask at rt, and the reaction mixture was stirred at 40 °C for 3 h.

Volatiles were removed under vacuum. The residue was extracted

using toluene (5 mL) and ﬁltered using a cannula. Volatiles were then

removed under vacuum, and the remaining residue was washed with

pentane (3 × 2 mL) and dried to give 6 (87.2 mg, 83%) as a yellow

solid. Crystals for X-ray analysis were grown by layering MeOH over a

concentrated solution of 6 in THF. Anal. Calcd for C₆₃H₈₁ClN₄Pd₂: C,

66.22; H, 7.15; N 4.90. Found: C, 66.34; H, 7.29; N, 4.84.

Synthetic Procedures and Characterizing Data for New

Compounds. (μ-Allyl)(μ-Cl)Pd₂(IPr)₂(4). Pd(IPr)(η³-allyl)Cl (1)

(101.7 mg, 0.178 mmol) and potassium carbonate (37 mg, 1.5

equiv) were transferred to a Schlenk ﬂask and placed under dinitrogen.

Degassed ethanol (5 mL) was transferred by cannula into the Schlenk

ﬂask at rt, and the reaction mixture was stirred at 40 °C for 3 h.

Volatiles were removed under vacuum. The residue was extracted

using a 3:1 pentane/toluene (5 mL) solution and ﬁltered through a

silica plug. Volatiles were removed under vacuum to give 4 (79.0 mg,

¹H NMR (500 MHz, C₆D₆, geometry determined by irradiating the

central proton signal at δ 1.75 in a 1D NOESY experiment) 7.28−7.19

(m, 4H, H1), 7.13 (d, J = 8.0 Hz, 4H, H2), 7.09 (d, J = 7.7 Hz, 2H,

H2), 7.04 (d, J = 7.6 Hz, 2H, H2), 6.91 (t, J = 7.8 Hz, 1H, H11), 6.76

(t, J = 7.6 Hz, 2H, H10), 6.62 (s, 2H, H3), 6.62 (s, 2H, H3), 6.54 (d, J

= 7.3 Hz, 2H, H9), 3.86 (d, J = 8.2 Hz, 1H, H8), 3.21 (septet, J = 6.9

Hz, 2H, H4), 3.16−3.06 (m, 4H, H4), 3.01 (septet, J = 7.0 Hz, 2H),

1.87 (dd, J = 8.8, 1.5 Hz, 1H, H6-syn), 1.75 (m, 1H, H7), 1.37 (d, J =

6.8 Hz, 6H, H5), 1.30 (d, J = 6.8 Hz, 6H, H5), 1.26 (d, J = 6.8 Hz, 6H,

H5), 1.10 (m, 18H, H5), 0.98 (d, J = 6.9 Hz, 6H, H5), 0.94 (d, J = 6.7

Hz, 6H, H5), 0.67 (dd, J = 12.3, 1.8 Hz, 1H, H6-anti). ¹³C{¹H} NMR

(126 MHz, C₆D₆) 192.29, 191.12, 146.54, 146.24, 146.09, 144.48,

137.95, 137.54, 129.90, 129.38, 129.24, 126.81, 123.82, 123.76, 123.72,

123.66, 123.34, 122.92, 122.69, 51.69, 44.50, 28.91, 28.90, 28.88,

28.78, 25.94, 25.93, 25.65, 25.53, 23.50, 23.44, 23.37, 22.78, 21.06.

One of the ¹³C peaks in the aromatic region was obscured by solvent.

Suzuki−Miyaura Cross-Coupling Reactions, General Proce-

dures. Tables 1 and 4. Each reaction was performed under dinitrogen

in a 1 dram vial containing a ﬂea stir bar and sealed with a septum cap.

1

83%) as a pale yellow solid. H and ¹³C NMR data were consistent

with those that have been previously reported.³⁰

(μ-Crotyl)(μ-Cl)Pd₂(IPr)₂(5). Pd(η³-crotyl)(IPr)Cl (2) (75.0 mg,

0.128 mmol) and potassium carbonate (27 mg, 1.5 equiv) were

transferred to a Schlenk ﬂask and placed under dinitrogen. Degassed

ethanol (5 mL) was transferred by cannula into the Schlenk ﬂask at rt,

and the reaction mixture was stirred at 40 °C for 3 h. Volatiles were

removed under vacuum. The residue was extracted using a 3:1

pentane/toluene (5 mL) solution and ﬁltered through a silica plug.

Volatiles were removed under vacuum to give 5 (60.4 mg, 87%) as a

yellow solid, which contained a 9:1 mixture of anti and syn isomers.

Redissolving the mixture in C₆H₆and leaving it to stand for 12 h at

room temperature allowed for isolation of only the anti isomer of 5.

Crystals for X-ray analysis were grown through slow evaporation of a

saturated solution in pentane/toluene. Anal. Calcd for

C₅₈H₇₉ClN₄Pd₂: C, 64.47; H, 7.37; N, 5.18. Found: C, 64.38; H,

7.39; N, 5.20.

i

To each vial was added 800 μL of an PrOH stock solution (0.625 M

4-chlorotoluene, 0.6875 M KO^tBu, 0.3125 M naphthalene) and 150

μL of a MeOH stock solution (3.5 M phenylboronic acid). Each vial

was then heated using an aluminum block heater set to the appropriate

temperature. After thermal equilibration, each reaction was initiated via

addition of 50 μL of the appropriate precatalyst solution in THF (0.1

M [Pd]_totfor Table 1, 0.2 M [Pd]_totfor Table 4). Aliquots (∼50−100

μL) were removed at reaction times of 30 and 60 min. Aliquots were

Anti isomer (major product, geometry determined by irradiating the

central proton signal at δ 1.68 in a 1D NOESY experiment): ¹H NMR

(400 MHz, C₆D₆) 7.22 (m, 4H, H1), 7.15−7.07 (m, 8H, H2), 6.64 (s,

2H, H3), 6.63 (s, 2H, H3), 3.22 (septet, J = 6.8 Hz, 2H, H4), 3.17

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puriﬁed by ﬁltration through pipet ﬁlters containing approximately 1

cm of silica and eluted with 1−1.2 mL of ethyl acetate directly into GC

vials. Conversion was determined by comparison of the GC responses

of product and the internal naphthalene standard.

1147. (h) Johansson Seechurn, C. C. C.; Kitching, M. O.; Colacot, T.

J.; Snieckus, V. Angew. Chem., Int. Ed. 2012, 51, 5062. (i) Valente, C.;

Calimsiz, S.; Hoi, K. H.; Mallik, D.; Sayah, M.; Organ, M. G. Angew.

Chem., Int. Ed. 2012, 51, 3314.

Table 5. Potassium carbonate (0.75 mmol) or potassium phosphate

(0.75 mmol) was transferred on the benchtop into a 1 dram vial

containing a ﬂea stir bar. The vial was sealed with a septum cap and

placed under dinitrogen (by cycling three times between vacuum and

dinitrogen) on a Schlenk line through a needle. To each vial was added

950 μL of an EtOH or ⁱPrOH stock solution (0.526 M 4-

chlorotoluene, 0.553 M phenylboronic acid, 0.263 M naphthalene).

Each vial was then heated using an aluminum block heater set to 25 or

40 °C. After thermal equilibration, each reaction was initiated via

addition of 50 μL of a 0.1 M solution of the precatalyst in THF.

Aliquots (∼50−100 μL) were removed at reaction times of 30 and 60

min. Aliquots were puriﬁed by ﬁltration through pipet ﬁlters

containing approximately 1 cm of silica and eluted with 1−1.2 mL

of ethyl acetate directly into GC vials. Conversion was determined by

comparison of the GC responses of product and the internal

naphthalene standard.

(2) (a) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1999, 38, 2411.

(b) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020.

(3) (a) Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald, S. L. J. Am.

Chem. Soc. 1999, 121, 9550. (b) Aranyos, A.; Old, D. W.; Kiyomori, A.;

Wolfe, J. P.; Sadighi, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121,

4369. (c) Wolfe, J. P.; Buchwald, S. L. Angew. Chem., Int. Ed. 1999, 38,

2413.

(4) (a) Shelby, Q.; Kataoka, N.; Mann, G.; Hartwig, J. J. Am. Chem.

Soc. 2000, 122, 10718. (b) Kataoka, N.; Shelby, Q.; Stambuli, J. P.;

Hartwig, J. F. J. Org. Chem. 2002, 67, 5553.

(5) (a) Lundgren, R. J.; Hesp, K. D.; Stradiotto, M. Synlett 2011,

2443. (b) Lundgren, R. J.; Stradiotto, M. Chem.Eur. J. 2012, 18,

9758.

(6) Christmann, U.; Vilar, R. Angew. Chem., Int. Ed. 2005, 44, 366.

(7) (a) Biscoe, M. R.; Fors, B. P.; Buchwald, S. L. J. Am. Chem. Soc.

2008, 130, 6686. (b) Kinzel, T.; Zhang, Y.; Buchwald, S. L. J. Am.

Chem. Soc. 2010, 132, 14073. (c) Bruno, N. C.; Tudge, M. T.;

Buchwald, S. L. Chem. Sci. 2013, 4, 916.

ASSOCIATED CONTENT

* Supporting Information

■

S

(8) (a) O’Brien, C. J.; Kantchev, E. A. B.; Valente, C.; Hadei, N.;

Chass, G. A.; Lough, A.; Hopkinson, A. C.; Organ, M. G. Chem.Eur.

J. 2006, 12, 4743. (b) Organ, M. G.; Chass, G. A.; Fang, D.-C.;

Hopkinson, A. C.; Valente, C. Synthesis 2008, 2776. (c) Nasielski, J.;

Hadei, N.; Achonduh, G.; Kantchev, E. A. B.; O’Brien, C. J.; Lough, A.;

Organ, M. G. Chem.Eur. J. 2010, 16, 10844.

Further experimental details including (i) procedures for

reactions investigating activation of 1−3 and synthesis of

dimers in diﬀerent solvents, (ii) protocols for observing and

quantifying the presence of dimers 4−6 under catalytic

conditions, (iii) procedures for investigating disproportionation

and comproportionation reactions involving 1−6, and (iv) X-

ray crystallographic information for 5 and 6; computational

details including (i) optimized coordinates and energies, (ii) a

comparison of experimental and calculated bond lengths and

distances, (iii) test calculations performed using the full IPr

ligand, and (iv) information about alternative mechanisms. This

material is available free of charge via the Internet at http://

pubs.acs.org.

(9) (a) Viciu, M. S.; Germaneau, R. F.; Nolan, S. P. Org. Lett. 2002, 4,

4053. (b) Viciu, M. S.; Germaneau, R. F.; Navarro-Fernandez, O.;

Stevens, E. D.; Nolan, S. P. Organometallics 2002, 21, 5470.

(c) Navarro, O.; Kaur, H.; Mahjoor, P.; Nolan, S. P. J. Org. Chem.

2004, 69, 3173. (d) Marion, N.; Navarro, O.; Mei, J.; Stevens, E. D.;

Scott, N. M.; Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101.

(10) (a) Nasielski, J.; Hadei, N.; Achonduh, G.; Kantchev, E. A. B.;

O’Brien, C. J.; Lough, A.; Organ, M. G. Chem.Eur. J. 2012, 16,

10844. (b) Sayah, M.; Lough, A. J.; Organ, M. G. Chem.Eur. J. 2013,

19, 2749.

(11) (a) Hill, L. L.; Crowell, J. L.; Tutwiler, S. L.; Massie, N. L.;

Hines, C. C.; Griffin, S. T.; Rogers, R. D.; Shaughnessy, K. H.; Grasa,

G. A.; Johansson Seechurn, C. C. C.; Li, H.; Colacot, T. J.; Chou, J.;

Woltermann, C. J. J. Org. Chem. 2010, 75, 6477. (b) Johansson

Seechurn, C. C. C.; Parisel, S. L.; Colacot, T. J. J. Org. Chem. 2011, 76,

7918.

AUTHOR INFORMATION

■

Corresponding Authors

david.balcells@kjemi.uio.no

nilay.hazari@yale.edu

Notes

(12) (a) Werner, H. Adv. Organomet. Chem. 1981, 19, 155.

(b) Murahashi, T.; Kurosawa, H. Coord. Chem. Rev. 2002, 231, 207.

(c) Hazari, N.; Hruszkewycz, D. P.; Wu, J. Synlett 2011, 1793.

(13) (a) Egbert, J. D.; Chartoire, A.; Slawin, A. M. Z.; Nolan, S. P.

Organometallics 2011, 30, 4494. (b) Fantasia, S.; Nolan, S. P. Chem.

Eur. J. 2008, 14, 6987. (c) Denmark, S. E.; Smith, R. C. Synlett 2006,

18, 2921. (d) Ortiz, D.; Blug, M.; Goff, X.-F. L.; Floch, P. L.; Mezailles,

N.; Maître, P. Organometallics 2012, 31, 5975. (e) Alsabeh, P. G.;

Lundgren, R. J.; McDonald, R.; Johansson Seechurn, C. C. C.;

Colacot, T. J.; Stradiotto, M. Chem.Eur. J. 2013, 19, 2131.

(14) Colacot and co-workers brieﬂy speculated about the role of Pd^I

μ-allyl dimers when monomeric η³-allyl Pd complexes are used as

precatalysts in ref 11a. They also conducted some interesting

preliminary mechanistic studies, which imply the intermediacy of Pd^I

μ-allyl dimers in catalysis in ref 11b. These two studies served as a

large inspiration for the current study.

(15) Monomeric Pd complexes with substituents in the 2-position of

the allyl ligand have also been reported in the literature, but only

complexes with 2-methylallyl substituents have been explored as

precatalysts for cross-coupling: (a) ref 11b. (b) Cawley, M. J.; Cloke,

F. G. N.; Fitzmaurice, R. J.; Pearson, S. E.; Scott, J. S.; Caddick, S. Org.

Biomol. Chem. 2008, 6, 2820. (c) Navarro, O.; Oonishi, Y.; Kelly, R. A.;

Stevens, E. D.; Briel, O.; Nolan, S. P. J. Organomet. Chem. 2004, 689,

3722. In these reports, the 2-methylallyl-supported precatalysts

displayed similar catalytic efficiency to the corresponding unsub-

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

■

N.H. gratefully acknowledges support through a Doctoral New

Investigator Grant from the ACS Petroleum Research Fund

(51009-DNI3). D.B. and M.T. acknowledge support from the

Norwegian Research Council through the Center of Excellence

for Theoretical and Computational Chemistry (CTCC) (Grant

No. 179568/V30) and the Norwegian Metacenter for

Computational Science (NOTUR; Grant nn4654k). D.P.H.

thanks the NSF for support both through the Nordic Research

Opportunity and as an NSF Graduate Research Fellow. D.P.H.

also acknowledges the Norwegian Research Council for a

mobility grant (Grant No. 220360/F11). We are grateful to Dr.

Paul Anastas’ group for use of their GC instrument.

REFERENCES

■

(1) (a) Hartwig, J. F. Acc. Chem. Res. 2008, 41, 1534. (b) Martin, R.;

Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461. (c) Marion, N.; Nolan,

S. P. Acc. Chem. Res. 2008, 41, 1440. (d) Fu, G. C. Acc. Chem. Res.

2008, 41, 1555. (e) Wurtz, S.; Glorius, F. Acc. Chem. Res. 2008, 41,

̈

1523. (f) Magano, J.; Dunetz, J. R. Chem. Rev. 2011, 111, 2177. (g) Li,

H.; Johansson Seechurn, C. C. C.; Colacot, T. J. ACS Catal. 2012, 2,

7314

dx.doi.org/10.1021/ja412565c | J. Am. Chem. Soc. 2014, 136, 7300−7316

Journal of the American Chemical Society

Article

stituted allyl precatalysts. Overall, at this stage the effect of substituents

in the 2-position in precatalysts of the type Pd(L)(η³-allyl)Cl has not

been evaluated in detail and is a topic that is currently being explored

in our laboratory.

(16) Cinnamyl-supported 3 and its SIPr analogue were used as

precatalysts in the following reports: (a) Navarro, O.; Marion, N.; Mei,

J.; Nolan, S. P. Chem.Eur. J. 2006, 12, 5142. (b) Lipshutz, B. H.;

Petersen, T. B.; Abela, A. R. Org. Lett. 2008, 10, 1333. (c) Berini, C.;

Brayton, D. F.; Mocka, C.; Navarro, O. Org. Lett. 2009, 11, 4244.

(d) Prasad, B. A. B.; Buechele, A. E.; Gilbertson, S. R. Org. Lett. 2010,

12, 5422. (e) Woodmansee, D. H.; Mueller, M.-A.; Neuburger, M.;

Pfaltz, A. Chem. Sci. 2010, 1, 72. (f) Landers, B.; Berini, C.; Wang, C.;

Navarro, O. J. Org. Chem. 2011, 76, 1390.

(17) For select examples of the use of cinnamyl-supported

precatalysts using other ligands, see: (a) Luan, X.; Mariz, R.; Robert,

C.; Gatti, M.; Blumentritt, S.; Linden, A.; Dorta, R. Org. Lett. 2008, 10,

5569. (b) Schoeps, D.; Sashuk, V.; Ebert, K.; Plenio, H. Organo-

metallics 2009, 28, 3922. (c) Vieille-Petit, L.; Luan, X.; Mariz, R.;

Blumentritt, S.; Linden, A.; Dorta, R. Eur. J. Inorg. Chem. 2009, 1861.

(d) Luan, X.; Wu, L.; Drinkel, E.; Mariz, R.; Gatti, M.; Dorta, R. Org.

Lett. 2010, 12, 1912. (e) Wu, L.; Drinkel, E.; Gaggia, F.; Capolicchio,

S.; Linden, A.; Falivene, L.; Cavallo, L.; Dorta, R. Chem.Eur. J. 2011,

17, 12886. (f) Chartoire, A.; Lesieur, M.; Falivene, L.; Slawin, A. M. Z.;

Cavallo, L.; Cazin, C. S. J.; Nolan, S. P. Chem.Eur. J. 2012, 18, 4517.

(g) Terashima, T.; Inomata, S.; Ogata, K.; Fukuzawa, S.-i. Eur. J. Inorg.

Chem. 2012, 2012, 1387. (h) Wu, L.; Falivene, L.; Drinkel, E.; Grant,

S.; Linden, A.; Cavallo, L.; Dorta, R. Angew. Chem., Int. Ed. 2012, 51,

2870. (i) Wheaton, C. A.; Bow, J.-P. J.; Stradiotto, M. Organometallics

2013, 32, 6148.

(18) The chloride-bridged dimeric precursor to the cinnamyl-

supported precatalysts was demonstrated to be a superior Pd source

compared to other common Pd sources in the following reports:

(a) Martin, R.; Buchwald, S. L. Org. Lett. 2008, 10, 4561. (b) Lundgren,

R. J.; Stradiotto, M. Angew. Chem., Int. Ed. 2010, 49, 8686.

(c) Lundgren, R. J.; Sappong-Kumankumah, A.; Stradiotto, M.

Chem.Eur. J. 2010, 16, 1983. (d) Rousseaux, S.; Garcia-Fortanet,

J.; Del Aguila Sanchez, M. A.; Buchwald, S. L. J. Am. Chem. Soc. 2011,

133, 9282. (e) Hermange, P.; Gogsig, T. M.; Lindhardt, A. T.;

Taaning, R. H.; Skrydstrup, T. Org. Lett. 2011, 13, 2444. (f) Hesp, K.

D.; Lundgren, R. J.; Stradiotto, M. J. Am. Chem. Soc. 2011, 133, 5194.

(g) Gøgsig, T. M.; Nielsen, D. U.; Lindhardt, A. T.; Skrydstrup, T. Org.

Lett. 2012, 14, 2536. (h) Schranck, J.; Tlili, A.; Neumann, H.; Alsabeh,

P. G.; Stradiotto, M.; Beller, M. Chem.Eur. J. 2012, 18, 15592.

(i) Salvi, L.; Davis, N. R.; Ali, S. Z.; Buchwald, S. L. Org. Lett. 2012, 14,

170.

(21) (a) Vilar, R.; Mingos, D. M. P.; Cardin, C. J. J. Chem. Soc.,

Dalton Trans. 1996, 4313. (b) Stambuli, J. P.; Kuwano, R.; Hartwig, J.

F. Angew. Chem., Int. Ed. 2002, 41, 4746. (c) Christmann, U.; Vilar, R.;

White, A. J. P.; Williams, D. J. Chem. Commun. 2004, 1294. (d) Barder,

T. E. J. Am. Chem. Soc. 2006, 128, 898. (e) Han, X.; Weng, Z.; Hor, T.

S. A. J. Organomet. Chem. 2007, 692, 5690. (f) Das, R. K.; Saha, B.;

Rahaman, S. M. W.; Bera, J. K. Chem.Eur. J. 2010, 16, 14459.

(22) (a) Elliott, E. L.; Ray, C. R.; Kraft, S.; Atkins, J. R.; Moore, J. S. J.

Org. Chem. 2006, 71, 5282. (b) Finke, A. D.; Elleby, E. C.; Boyd, M. J.;

Weissman, H.; Moore, J. S. J. Org. Chem. 2009, 74, 8897. (c) Denmark,

S. E.; Baird, J. D. Org. Lett. 2006, 8, 793. (d) Denmark, S. E.; Baird, J.

D.; Regens, C. S. J. Org. Chem. 2008, 73, 1440.

(23) (a) Christmann, U.; Pantazis, D. A.; Benet-Buchholz, J.;

McGrady, J. E.; Maseras, F.; Vilar, R. Organometallics 2006, 25, 5990.

(b) Christmann, U.; Pantazis, D. A.; Benet-Buchholz, J.; McGrady, J.

E.; Maseras, F.; Vilar, R. J. Am. Chem. Soc. 2006, 128, 6376. (c) Jimeno,

C.; Christmann, U.; Escudero-Adan, E. C.; Vilar, R.; Pericas, M. A.

Chem.Eur. J. 2012, 18, 16510. (d) Proutiere, F.; Aufiero, M.;

Schoenebeck, F. J. Am. Chem. Soc. 2012, 134, 606.

(24) See Supporting Information for more details.

(25) (a) Osakada, K.; Chiba, T.; Nakamura, Y.; Yamamoto, T.;

Yamamoto, A. Organometallics 1989, 8, 2602. (b) Kurosawa, H.;

Hirako, K.; Natsume, S.; Ogoshi, S.; Kanehisa, N.; Kai, Y.; Sakaki, S.;

Takeuchi, K. Organometallics 1996, 15, 2089.

(26) Sakaki, S.; Takeuchi, K.; Sugimoto, M.; Kurosawa, H.

Organometallics 1997, 16, 2995.

(27) Hruszkewycz, D. P.; Wu, J.; Green, J. C.; Hazari, N.; Schmeier,

T. J. Organometallics 2012, 31, 470.

(28) In support of our proposal that the Pd−C bond distances to the

terminal carbon atoms of the μ-allyl ligand are inequivalent, the DFT-

optimized structures of 5 and 6 have diﬀerent Pd−C bond distances.

See the Supporting Information for more information.

(29) Crabtree, R. H. The Organometallic Chemistry of the Transition

Metals, 5th ed.; Wiley: New York, 2009.

(30) Hruszkewycz, D. P.; Wu, J.; Hazari, N.; Incarvito, C. D. J. Am.

Chem. Soc. 2011, 133, 3280.

(31) For a similar mechanism of activation that involves the

isopropoxide anion, see ref 13b.

(32) Dible, B. R.; Cowley, R. E.; Holland, P. L. Organometallics 2011,

30, 5123.

(33) In ref 32 a very dilute (∼0.1 M) solution of substrates in ⁱPrOH

(no MeOH cosolvent) and precatalyst in THF was utilized. We added

MeOH as a cosolvent in order to perform our reactions at higher

concentration.

(34) Krause, J.; Cestaric, G.; Haack, K.-J.; Seevogel, K.; Storm, W.;

(19) Weissman, H.; Shimon, L. J. W.; Milstein, D. Organometallics

2004, 23, 3931.

Porschke, K.-R. J. Am. Chem. Soc. 1999, 121, 9807.

̈

(35) For related cross-over experiments, see ref 25b.

(36) Given the extremely large size of the IPr ligand, it was not

possible to run a full series of calculations with the complete

experimental systems. A limited number of calculations with the IPr

ligand are described in the Supporting Information.

(37) Faller, J. W.; Thomsen, M. E.; Mattina, M. J. J. Am. Chem. Soc.

1971, 93, 2642.

(20) (a) Yamamoto, T.; Saito, O.; Yamamoto, A. J. Am. Chem. Soc.

1981, 103, 5600. (b) Yamamoto, T.; Akimoto, M.; Saito, O.;

Yamamoto, A. Organometallics 1986, 5, 1559. (c) Portnoy, M.;

Frolow, F.; Milstein, D. Organometallics 1991, 10, 3960. (d) Tromp,

M.; Sietsma, J. R. A.; van Bokhoven, J. A.; van Strijdonck, G. P. F.; van

Haaren, R. J.; van der Eerden, A. M. J.; van Leeuwen, P. W. N. M.;

Koningsberger, D. C. Chem. Commun. 2003, 128. (e) Markert, C.;

Neuburger, M.; Kulicke, K.; Meuwly, M.; Pfaltz, A. Angew. Chem., Int.

Ed. 2007, 46, 5892. (f) Baya, M.; Houghton, J.; Konya, D.;

Champouret, Y.; Daran, J.-C.; Almeida, L. K. Q.; Schoon, L.; Mul,

W. P.; van Oort, A. B.; Meijboom, N.; Drent, E.; Orpen, A. G.; Poli, R.

J. Am. Chem. Soc. 2008, 130, 10612. (g) Ragaini, F.; Larici, H.;

Rimoldi, M.; Caselli, A.; Ferretti, F.; Macchi, P.; Casati, N.

Organometallics 2011, 30, 2385. (h) Agrawal, D.; Schroder, D.;

Frech, C. M. Organometallics 2011, 30, 3579. (i) Boyd, P. D. W.;

Edwards, A. J.; Gardiner, M. G.; Ho, C. C.; Lemee-Cailleau, M.-H.;

McGuinness, D. S.; Riapanitra, A.; Steed, J. W.; Stringer, D. N.; Yates,

B. F. Angew. Chem., Int. Ed. 2010, 49, 6315. (j) Bedford, R. B.;

Haddow, M. F.; Mitchell, C. J.; Webster, R. L. Angew. Chem., Int. Ed.

2011, 50, 5524. (k) Aufiero, M.; Proutiere, F.; Schoenebeck, F. Angew.

Chem., Int. Ed. 2012, 51, 7226.

1

(38) In the trapping experiments, products with H NMR chemical

shifts that are consistent with those expected for the anti isomer of

complexes of the type Pd(IPr)(η³-allyl)Cl were observed on some

occasions. However, these peaks rapidly decreased in intensity, while

peaks associated with the syn isomers of complexes of the type Pd(IPr)

(η³-allyl)Cl increased. Therefore, no attempts were made to

characterize the putative anti isomers.

(39) The loading of the weak base in these reactions is similar to that

described by Organ and co-workers in ref 8a, which reports a family of

highly active precatalysts for the Suzuki−Miyaura coupling with weak

base. Our precatalyst system seems to be slightly more active than the

precatalysts described in ref 8a, although there are diﬀerences in the

exact reaction conditions, which make direct comparison diﬃcult.

(40) Genov, M.; Almorín, A.; Espinet, P. Chem.Eur. J. 2006, 12,

9346.

7315

dx.doi.org/10.1021/ja412565c | J. Am. Chem. Soc. 2014, 136, 7300−7316

Journal of the American Chemical Society

Article

(41) (a) Arduengo, A. J., III; Krafczyk, R.; Schmutzler, R.; Craig, H.

A.; Goerlich, J. R.; Marshall, W. J.; Unverzagt, M. Tetrahedron 1999,

55, 14523. (b) Tang, P.; Wang, W.; Ritter, T. J. Am. Chem. Soc. 2011,

133, 11482.

(42) Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.;

Puschmann, H. J. Appl. Crystallogr. 2009, 42, 339.

(43) Sheldrick, G. Acta Crystallogr., Sect. A: Found. Crystallogr. 2008,

64, 112.

(44) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;

Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci,

B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.

P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.;

Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,

T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A.;

Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin,

K. N.; Staroverov, V. N.; Keith, T.; Kobayashi, R.; Normand, J.;

Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.;

Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.;

Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.;

Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.;

Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador,

P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.;

Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian09;

Gaussian, Inc.: Wallingford, CT, 2013.

(45) Hehre, W. J.; Ditchfield, R.; Pople, J. A. J. Chem. Phys. 1972, 56,

2257.

(46) (a) Bergner, A.; Dolg, M.; Kuchle, W.; Stoll, H.; Preuss, H. Mol.

̈

Phys. 1993, 80, 1431. (b) Peterson, K. A.; Figgen, D.; Dolg, M.; Stoll,

H. J. Chem. Phys. 2007, 126, 124101.

(47) (a) Zhao, Y.; Truhlar, D. G. Theor. Chem. Acc. 2008, 120, 215.

(b) Zhao, Y.; Truhlar, D. G. Acc. Chem. Res. 2008, 41, 157.

(48) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B

2009, 113, 6378.

(49) Krishnan, R.; Binkley, J. S.; Seeger, R.; Pople, J. A. J. Chem. Phys.

1980, 72, 650.

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Insight into the efficiency of cinnamyl-supported precatalysts for the suzuki-miyaura reaction: Observation of Pd(I) dimers with bridging allyl ligands during catalysis

DOI: 10.1021/ja412565c

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