Design of a versatile and improved precatalyst scaffold for palladium-catalyzed cross-coupling: (η3-1-tBu-indenyl)2(μ-Cl)2Pd2

Article abstract of DOI:10.1021/acscatal.5b00878

We describe the development of (η³-1-^tBu-indenyl)₂(μ-Cl)₂Pd₂, a versatile precatalyst scaffold for Pd-catalyzed cross-coupling. Our new system is more active than commercially available (η³-cinnamyl)₂(μ-Cl)₂Pd₂ and is compatible with a range of NHC and phosphine ligands. Precatalysts of the type (η³-1-^tBu-indenyl)Pd(Cl)(L) can either be isolated through the reaction of (η³-1-^tBu-indenyl)₂(μ-Cl)₂Pd₂ with the appropriate ligand or generated in situ, which offers advantages for ligand screening. We show that the (η³-1-^tBu-indenyl)₂(μ-Cl)₂Pd₂ scaffold generates highly active systems for a number of challenging cross-coupling reactions. The reason for the improved catalytic activity of systems generated from the (η³-1-^tBu-indenyl)₂(μ-Cl)₂Pd₂ scaffold compared to (η³-cinnamyl)₂(μ-Cl)₂Pd₂ is that inactive Pd^I dimers are not formed during catalysis.

Full text of DOI:10.1021/acscatal.5b00878

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Article
A New and Versatile Precatalyst Scaffold for Palladium
Catalyzed Cross-Coupling: (#3-1-tBu-indenyl)2(µ-Cl)2Pd2
Patrick R Melvin, Ainara Nova, David Balcells, Wei Dai, Nilay Hazari,
Damian P Hruszkewycz, Hemali P Shah, and Matthew T. Tudge
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.5b00878 • Publication Date (Web): 06 May 2015
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Design of a Versatile and Improved Precatalyst Scaffold for Palladium Catalyzed
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Cross-Coupling: (3-1-tBu-indenyl)2(-Cl)2Pd2
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Patrick R. Melvin,a Ainara Nova,b,* David Balcells,b Wei Dai,a Nilay Hazari,a,* Damian P.
Hruszkewycz,a Hemali P. Shaha and Matthew T. Tudgec
aThe Department of Chemistry, Yale University, P. O. Box 208107, New Haven, Connecticut, 06520,
USA, bCentre for Theoretical and Computational Chemistry (CTCC), Department of Chemistry,
University of Oslo, P.O. Box 1033 Blindern, 0315 Oslo, Norway and cDepartment of Process
Chemistry, Merck Research Laboratories, Rahway, New Jersey, 07065, USA. E-mail:
ainara.nova@kjemi.uio.no or nilay.hazari@yale.edu.
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Abstract
We describe the development of (3-1-tBu-indenyl)2(-Cl)2Pd2, a versatile precatalyst scaffold for Pd
catalyzed cross-coupling. Our new system is more active than commercially available (3-
cinnamyl)2(-Cl)2Pd2 and is compatible with a range of NHC and phosphine ligands. Precatalysts of
the type (3-1-tBu-indenyl)Pd(Cl)(L) can either be isolated through the reaction of (3-1-tBu-
indenyl)2(-Cl)2Pd2 with the appropriate ligand or generated in situ, which offers advantages for ligand
screening. We show that the (3-1-tBu-indenyl)2(-Cl)2Pd2 scaffold generates highly active systems for
a number of challenging cross-coupling reactions. The reason for the improved catalytic activity of
systems generated from the (3-1-tBu-indenyl)2(-Cl)2Pd2 scaffold compared to (3-cinnamyl)2(-
Cl)2Pd2 is that inactive PdI dimers are not formed during catalysis.
Keywords
Cross-coupling, catalysis, palladium, precatalyst, Suzuki-Miyaura reaction, Buchwald-Hartwig
reaction, -arylation, DFT calculations.
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Introduction
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Pd catalyzed cross-coupling has found applications in diverse areas of chemistry and is one of the most
powerful and general synthetic methods.1 A recent advance has been the development of specialized
phosphine and NHC based ligands,2 which can promote the fundamental steps in catalysis such as
oxidative addition and reductive elimination. The use of these ligands, has resulted in an expanded
substrate scope, milder reaction conditions and lower catalyst loadings. However, these specialized
ligands often have comparable expense with respect to the Pd precursor, which means that the
traditional route for generating the active species, addition of excess ligand to a Pd0 precursor, is not
attractive. Furthermore, in many cross-coupling reactions the optimal Pd to ligand ratio is 1:1 and the
active species is proposed to be monoligated Pd0.3 As a result, a number of well-defined PdII
precatalysts with a 1:1 Pd to ligand ratio, such as Buchwald’s palladacycles,4 Organ’s PEPPSI
complexes5 and Nolan’s allyl based systems6 (Figure 1) have been developed and are now
commercially available.
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Figure 1: Three well-defined precatalyst scaffolds with a 1:1 Pd to ligand ratio that are commercially available.
A major advantage of both the Buchwald and Nolan systems is the accessibility of the ligand free
precursors, (2-aminobiphenyl)2(-OMs)2Pd2 or (3-cinnamyl)2(-Cl)2Pd2, respectively, which can be
converted into the ligated precatalyst in situ. This allows for a variety of different ligands to be rapidly
screened, without the need for the isolation of well-defined precatalysts. At this stage Buchwald
precatalysts are more commonly utilized than Nolan type systems, but they have not been used with
NHC ligands, which generate superior catalysts for a number of cross-coupling reactions.1h In contrast,
Nolan type systems are compatible with both NHC and phosphine ligands, which is advantageous for
ligand screening.
Recently, we investigated the activation of Nolan type (3-allyl)Pd(Cl)(L) precatalysts.7 We
established that even in the case of the highly efficient (3-cinnamyl)Pd(Cl)(IPr) (Cin-IPr; IPr = 1,3-
Bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene) precatalyst, some of the IPr–Pd0
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active species undergoes comproportionation with unactivated PdII precatalyst to form an unreactive
PdI dimer, (μ-cinnamyl)(μ-Cl)Pd2(IPr)2, instead of entering the catalytic cycle (Figure 2).7a This
mechanistic insight prompted us to seek a related precatalyst scaffold that does not undergo
unproductive PdI dimer formation, and here we report that our efforts have resulted in the discovery of
(3-1-tBu-indenyl)2(-Cl)2Pd2 (Figure 2), a highly efficient precatalyst scaffold for cross-coupling. In
this work, we summarize our precatalyst development efforts, and illustrate that our new scaffold
produces highly active systems for a wide range of challenging cross-coupling reactions. Our new
precatalyst scaffold is compatible with both NHC and phosphine ligands, and catalytically active
systems can be generated either starting from isolated complexes of the type (3-1-tBu-
indenyl)Pd(Cl)(L) or by generating these species in situ. The dimeric precursor (3-1-tBu-indenyl)2(-
Cl)2Pd2, as well as complexes of the type (3-1-tBu-indenyl)Pd(Cl)(L) with several different ligands
are now commercially available from Strem Chemicals.8
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Figure 2: Comparison of state of the art cinnamyl based precatalysts with the new indenyl based systems
developed in this work.
Results and Discussion
Synthesis, Preliminary Catalytic Results and Mechanism
Our previous work on Nolan’s (3-allyl)Pd(IPr)(Cl) precatalysts demonstrated that the addition of
steric bulk to the 1-position of the 3-allyl ligand reduces PdI dimer formation, which in part explains
the efficiency of the Cin-IPr precatalyst.7a We hypothesized that the use of a di- or tri-substituted allyl
ligand may completely suppress dimer formation. Indenyl and 1-substituted indenyl ligands represent
simple di- or tri-substituted allyl ligands,9 which are synthetically accessible. Therefore, the
monomeric indenyl series of precatalysts, (3-1-R-indenyl)Pd(IPr)(Cl) (R = H (2a-IPr), Me (2b-IPr),
t
iPr (2c-IPr) or Bu (2d-IPr)), were synthesized using a robust and scalable sequence of reactions
(Scheme 1). The dimeric precursors, (3-1-R-indenyl)2(-Cl)2Pd2 (R = H (1a), Me (1b), iPr (1c) or tBu
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(1d)), were formed through an allylic hydrogen abstraction10 of the appropriate indene precursors by
Pd under mildly basic conditions. Subsequently, the monomeric (3-1-R-indenyl)Pd(IPr)(Cl)
precatalysts were generated by reacting these dimeric complexes with IPr. The new complexes 2b-IPr,
2c-IPr and 2d-IPr were fully characterized and their solid state structures (see ESI) are similar to that
previously described for 2a-IPr.11 Our reaction sequence enabled the synthesis of the new indenyl
complexes in high yield without the use of a glovebox, and the scalability of the protocol was
demonstrated through the preparation of 1d on a 20 gram scale and of 2d-IPr on a 10 gram scale (see
ESI).
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Scheme 1: Synthesis and yields of indenyl precatalyst scaffold and IPr supported precatalysts.
100
Condition A
90
Condition B
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Cin-IPr
2a-IPr
2b-IPr
PEPPSI-IPr
2c-IPr
2d-IPr
Figure 3: GC Yields of product for the SM reaction catalyzed by complexes of Cin-IPr, PEPPSI-IPr, 2a-IPr,
2b-IPr, 2c-IPr and 2d-IPr.
The indenyl complexes 2a-IPr, 2b-IPr, 2c-IPr and 2d-IPr were screened as precatalysts for the
Suzuki-Miyaura (SM) reaction of 4-chlorotoluene with phenylboronic acid, using both weak (K2CO3)
and strong (KOtBu) base in a 19:1 MeOH:THF mixture (Figure 3).12 For comparison, both Nolan’s
Cin-IPr and Organ’s (3-chloropyridine)Pd(Cl)2(IPr) (PEPPSI-IPr) precatalysts were included. The
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same trends in precatalyst performance were observed under both sets of reaction conditions. All of the
indenyl supported precatalysts are more active than Cin-IPr, and both 2c-IPr and 2d-IPr are also
significantly more active than PEPPSI-IPr. Strikingly, the indenyl-supported precatalysts become
more active as the size of the substituent on the indenyl ligand is increased, with 2d-IPr being the most
efficient system.
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A possible explanation for the trend seen in Figure 3 is that the formation of unreactive PdI dimers is
less likely to occur with more sterically demanding substituents. To probe this, the tendency of 2a-IPr
and 2d-IPr to dimerize was examined. Treatment of 2a-IPr with K2CO3 in MeOH at RT resulted in the
rapid formation of the unsubstituted indenyl dimer 3 in 85% yield, indicating that dimer formation is
facile (Eq 1). This is the same synthetic protocol we previously used to prepare PdI dimers with one
bridging allyl ligand and one bridging chloride ligand.7a Compound 3 was fully characterized,
including by X-ray crystallography (see ESI), and the binding of the indenyl ligand is similar to that
observed in other PdI dimers supported by a bridging indenyl ligand.13 In contrast to 2a-IPr, no dimer
formation was observed when 2d-IPr was treated with K2CO3 (Eq 2). Instead only Pd0 products, such
as Pd(IPr)2,14 were observed in the reaction mixture. This observation is consistent with PdI dimer
formation via comproportionation being more difficult for indenyl systems with greater steric bulk.
The relevance of the PdI dimer 3 to catalysis was confirmed by performing a reaction under slightly
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modified catalytic conditions to those described in Table 1, using 4 mol% 2a (see ESI). H NMR
spectroscopy indicated that 3 was present during the catalytic reaction and once full conversion was
achieved approximately 85% of the Pd was in the form of the PdI dimer. The deleterious nature of this
dimerization was confirmed by testing 3 as a precatalyst for the SM coupling using the reaction
conditions described in Figure 3. Complex 3 is inactive as a precatalyst under these conditions (see
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ESI). Thus, 3 represents an off-cycle deactivation product, which reduces the amount of the active
monoligated Pd0 catalyst in solution.
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Our proposed pathway for PdI dimer formation (see ESI for full pathway) involves initial activation of
the PdII precatalyst to generate a Pd0 olefin complex. This Pd0 complex can then comproportionate
with the starting PdII species to generate a PdI dimer (Table 1). DFT calculations were performed to
explore the thermodynamics of comproportionation of 2a-IPr, 2b-IPr, 2c-IPr and 2d-IPr with the
appropriate Pd-olefin complex to form the corresponding PdI dimer (Table 1). As the bulk of the 1-
substituent of the indene ligand is increased, dimer formation becomes less favorable. For example the
formation of 3 from 2a-IPr is thermodynamically favorable, consistent with 3 being isolable.
However, the generation of a PdI dimer from 2d-IPr and a Pd0 complex with a 1-tBu-indene ligand is
endoergic. This is due to the distortion of the metal core required to accommodate the 1-tBu
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i
substituent, which otherwise, would introduce steric clashes with the Pr substituents of the IPr ligand
(for more information see NBO and NCIPLOT calculations in the ESI). These calculations are in
agreement with our inability to synthetically access a PdI dimer with a bridging 1-tBu-indenyl ligand.
We conclude from these results that one of the main features explaining the superior catalytic activity
of 2d-IPr is the absence of the deactivation pathway shown in Table 1.
Table 1: Calculated Gibbs energies in MeOH for comproportionation of 2a-IPr, 2b-IPr, 2c-IPr and 2d-IPr
with the appropriate Pd0 olefin complex to form a PdI dimer and the free olefin (see ESI for computational
details).
G°MeOH (kcal
PdII Monomer
Olefin
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2d-IPr
indene
1-Me-indene
1- iPr-indene
1-tBu-indene
2.6
Further Catalytic Reactions with NHC Supported Complexes
A head to head comparison was performed between 2d-IPr and the commercially available Cin-IPr
for the SM reaction of a range of substrates using both weak (Figure 4) and strong base (see ESI). The
newly designed 2d-IPr significantly outperforms Cin-IPr in all of these examples, including
substrates with deactivating electron donating groups and substituents in the ortho positions. The
improvement from Cin-IPr to 2d-IPr is most pronounced using weak base compared to strong base.
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The quantitative yields obtained with 2d-IPr using weak base are unprecedented with Nolan type
precatalysts at RT.7a
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Figure 4: Yields of product for a series of SM reactions catalyzed by Cin-IPr and 2d-IPr.a
To show that our new precatalyst scaffold is compatible with state of the art NHC ligands, SM
reactions which generate tetra-ortho-substituted biaryl products were performed (Figure 5). For this
type of challenging reaction it has been demonstrated that the sterically hindered ancillary ligand
IPr*OMe (IPr*OMe
=
1,3-bis(2,6-bis-(diphenylmethyl)-4-methoxyphenyl)imidazol-2-ylidene) is
required.15 The complex 2d-IPr*OMe was prepared through the reaction of IPr*OMe with 1d (see ESI).
Using 2d-IPr*OMe as a precatalyst, a number of tetra-ortho-substituted products were prepared in high
yield. When aryl bromides were used as substrates, reactions could be performed at lower temperature
(80°C), compared to cinnamyl systems supported by IPr*OMe 15a
Furthermore, by increasing the
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catalyst loading to 1.0 mol%, aryl chlorides could be used as substrates under the same reaction
conditions. We believe that this method utilizes the mildest conditions reported to produce tetra-ortho-
substituted products in high yields using aryl chlorides.
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Figure 5: Yields of product for a series of SM reactions to generate tetra-ortho-substituted biaryl products
catalyzed by 2d-IPr*OMe a
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Catalytic Reactions with Phosphine Supported Complexes
Encouraged by our results with NHC ligands, we turned our attention to expanding the ligand scope to
include phosphines. Many important cross-coupling reactions are facilitated through the use of
electron-rich, sterically-demanding phosphines.1e To this end, a family of phosphine ligated complexes
with the general structure (3-tBu-indenyl)Pd(L)(Cl) were synthesized (Figure 6).16 Coordination was
achieved through the addition of two equivalents of ligand to the dimeric precursor, 1d, to afford a
variety of precatalysts with excellent yields (see ESI). A number of state of the art ligands, including
several Buchwald-type phosphines, were successfully coordinated to the dimeric scaffold.
Figure 6: Preparation and yields of phosphine supported precatalysts.
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With these complexes in hand, we screened the phosphine supported systems for several currently
challenging cross-coupling reactions. Heterocycles are commonly found in pharmaceuticals and
natural products but traditionally represent difficult substrates for cross-coupling.1e,17 For example, SM
reactions that employ boronic acids in the 2-position of 5-membered heterocycles are particularly
challenging due to their tendency to undergo rapid protodeboronation.4b Therefore, a rapid and
efficient precatalyst must be used to afford full conversion to product. Using 2d-XPhos as the
precatalyst, we were able to successfully couple a range of 2-heterocyclic boronic acids to produce
biaryl products in excellent yields under mild reaction conditions (Figure 7). Our precatalyst, which
gives comparable if not superior performance to the best known systems for this reaction,4b is also
tolerant to a wide range of functional groups on the aryl chloride, including phenols, Boc-protected
anilines and free amines.
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Figure 7: Yields of products for SM reactions involving 2-heterocyclic boronic acids.a
Until recently, Pd-catalyzed cross-coupling methodology was not compatible with substrates
containing acidic, free N-H moieties. In 2013, the Buchwald group reported drastic improvements for
the coupling of indazoles, benzimidazoles, pyrazoles, indoles, oxindoles, and azaindoles using their
SPhos supported palladacycle.18 Employing 2d-SPhos under similar conditions, we obtained yields of
greater than 90% for reactions where the aryl chloride was either indazole or benzimidazole (Figure 8).
With our catalyst system, the temperature could be lowered slightly (80°C), with excellent yields
obtained in 15 hours. As described previously, this methodology also supports the use of
heteroaromatic boronic acids.
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Figure 8: Yields of products for SM reactions involving unprotected indazoles or benzimidazoles.a
After the SM reaction, the Buchwald-Hartwig coupling is the next most commonly performed cross-
coupling reaction in the synthesis of pharmaceuticals.17 The RuPhos ligand has allowed for substantial
decreases in catalyst loading for challenging secondary amine substrates.4c Using reaction conditions
similar to those in the literature,4c 2d-RuPhos is able to generate a selection of symmetrical and
unsymmetrical tertiary amines in good to excellent yield (Figure 9). Various aryl chlorides containing
heteroatoms and ortho-substituents are compatible with our system.
Figure 9: Yields of products for BH reactions involving secondary amines.a
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The monoarylation of aryl methyl ketones is important due to prevelance of -aryl carbonyl moieties
in organic compounds with interesting pharmacological and biological properties.19 However, this is a
challenging reaction due to the possibility for diarylation of the ketone. The XPhos ligand has been
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shown to promote formation of the monoarylated product. Using 2d-XPhos we observed excellent
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results for the monoarylation of a variety of methyl ketones under moderate conditions (Figure 10).
Using a 1:1 THF/MeOH mixture and KOtBu as base, heterocyclic moieties in both the aryl chloride
and aryl methyl ketone were tolerated with yields greater than 90% in each case. In fact, in two cases,
the products contained heterocyclic fragments in both coupling partners.
Figure 10: Yields of products from -arylation of aryl methyl ketones.a
A very recent and important advance in cross-coupling has been the utilization of unactivated alkyl
coupling partners.21 In particular, alkyl trifluoroboronates have shown promise as boronic acid mimics
for the SM reaction with aryl chlorides.22 At this stage, good yields require high catalyst loadings (5-10
mol%), high temperatures (100°C) and long reaction times (24-48 hours). By using 2d-PtBu3 as the
precatalyst, we were able to make sizable improvements on the existing protocol. Specifically, in some
cases catalyst loadings could be reduced to 1 mol% and shorter reaction times (8 hours) utilized. Using
2d-PtBu3, both linear and cyclic alkyl trifluoroboronates salts could be coupled to a variety of aryl
chlorides, including one example of a nitrogen containing heterocycle (Figure 11). In fact, when
potassium cyclopropyl trifluoroboronate was used, the temperature could be lowered to 40°C without
any loss in activity (96% yield, see ESI).
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Figure 11: Yields of products for SM reactions involving alkyl trifluoroboronates.a
Finally, to demonstrate that (3-1-tBu-indenyl)2(-Cl)2Pd2 (1d) is suitable for rapid ligand screening,
without the need for the isolation of well-defined precatalysts, we performed a series of catalytic
reactions using an in situ generated solution of 1d and two equivalents of ligand (see ESI). When 1d
was mixed with the appropriate ligand for 10 minutes at RT excellent activity was observed for all of
the different reactions described in this work with isolated precatalysts. Comparative experiments
between systems containing 1d and IPr and Nolan’s cinnamyl dimer and IPr, showed that superior
catalytic activity was observed with 1d (see ESI). Taking this one step further, a successful reaction
was achieved without premixing 1d and ligand; Eq 3 shows a one-pot SM reaction where the
precatalyst is generated during the reaction. Under these conditions, there is no loss in activity
compared to both the in situ generated and isolated versions of 2d-XPhos. This methodology should
allow access to a variety of general and rapid screening procedures.
Conclusions
In conclusion, we have developed a highly active precatalyst scaffold for cross-coupling, which is
compatible with both NHC and phosphine ligands. The inability of precatalysts formed from our (3-1-
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tBu-indenyl)2(-Cl)2Pd2 scaffold to generate unreactive PdI dimers significantly improves the activity
of these systems compared to Nolan’s commercially available cinnamyl precatalysts. Indeed,
precatalysts based on our new scaffold are either the most active systems reported to date or
comparable to the best systems for a number of challenging cross-coupling reactions. Based on the
preliminary study of challenging reactions reported herein, we expect that the 1-tBu-indenyl scaffold
will have wide-ranging utility for many dfferent cross-coupling and related reactions that involve
monoligated Pd0.
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Experimental Section
General methods
Experiments were performed under a dinitrogen atmosphere in an M-Braun dry box or using standard
Schlenk techniques unless otherwise stated. Under standard glovebox conditions purging was not
performed between uses of diethyl ether, pentane, 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 dry box. Pentane, THF, diethyl ether and toluene were dried by passage through
a column of activated alumina followed by storage under dinitrogen. All commercial chemicals were
i
used as received except where noted. MeOH (J.T. Baker) and PrOH (Macron Fine Chemicals) were
not dried but were degassed by sparging with dinitrogen for 1 hour and stored under dinitrogen. Ethyl
acetate (Fisher Scientific) and hexanes (Macron Fine Chemicals) were used as received. Potassium
tert-butoxide (99.99%, sublimed) was purchased from Aldrich. Potassium carbonate was purchased
from Mallinckrodt and ground up with a mortar and pestle and stored in an oven at 130ºC prior to use.
Flash chromatography was performed on silica gel 60 (230-400 mesh, Fisher Scientific). All liquids
were degassed prior to use in a glove box through three freeze-pump-thaw cycles. Deuterated solvents
were obtained from Cambridge Isotope Laboratories. C6D6 was dried over sodium metal and stored
under nitrogen, while CDCl3, d4-MeOH, d8-iPrOH, and d8-THF were not dried but were degassed prior
to use through three freeze-pump-thaw cycles. NMR spectra were recorded on Agilent-400, -500 and -
600 spectrometers at ambient probe temperatures unless noted. For variable temperature NMR, the
sample temperature was calibrated by measuring the distance between the OH and CH2 resonances in
ethylene glycol (99%, Aldrich). Chemical shifts are reported with respect to residual internal protio
1
solvent for H and 13C{1H} NMR spectra. Robertson Microlit Laboratories, Inc. performed the
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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. High resolution mass spectrometry
was performed using an ion-cyclotron resonance (ICR) mass spectrometer equipped with a
superconducting (7T) magnet. Literature procedures were used to prepare the following compounds:
IPr,23 (3-cinnamyl)Pd(IPr)(Cl) (Cin-IPr)6d and PEPPSI-IPr.24
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Computational details
All stationary points were fully optimized at the DFT level with the hybrid meta-GGA M06
functional25 including dispersion, as implemented in the Gaussian09 software package (Rev. D.01).26
Geometry optimizations were carried out on the full system including solvation by MeOH with the
continuum SMD model.27 Frequencies were computed with the aim of classifying all stationary points
as minima and determining the thermochemistry corrections, (G – E), which include the zero-point
energies, thermal contributions and entropies. Two different basis sets were used, BS1, for geometry
optimizations and frequency calculations, and BS2, for single-points. BS1 includes polarization
functions and small-core pseudopotentials by combining the double- 6-31G** (C, N, O and H)28 and
triple- LANL08* (Pd)29 basis sets. With BS2, Pd was described at the same level, whereas C, N O
and H were described with the triple- 6-311+G** basis set,30 including polarization and diffuse
functions. The single-point calculations were performed at the DFT(M06)/SMD(MeOH)/BS2 level on
the DFT(M06)/SMD(MeOH)/BS1-optimized geometries with the aim of refining the potential energies
(Esol). The energies discussed in the text, Gsol, were obtained by adding the thermochemistry
corrections to the refined potential energies (Eq 4).
Gsol = Esol + (G – E)
(Eq. 4)
Acknowledgements
AN and DB 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). DB also thanks the EU
REA for a Marie Curie Fellowship (Grant CompuWOC/618303). PRM and DPH thank the NSF for
support as NSF Graduate Research Fellows. NH is a fellow of the Alfred P. Sloan Foundation and a
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Camille and Henry-Dreyfus Foundation Teacher Scholar. We are grateful to Dr. Paul Anastas’ group
for use of their GC instrument, Dr. Brandon Mercado for assistance with X-ray crystallography,
Professor Mark Johnson and Dr. Fabian Menges for acquiring mass spectra and Louise Guard for
valuable discussions.
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Supporting information available
Characterizing data, further experimental details, X-ray information for 2b-IPr, 2c-IPr, 2d-IPr and 3,
and details of DFT calculations are available free of charge via the internet at http://pubs.acs.org.
References
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