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Pure and Applied Chemistry Manuscript PAC-CON-14-11-08
REVISED Version: 12 January 2015
Gas-Phase Studies of Metal Catalyzed Decarboxylative
Cross-Coupling Reactions of Esters.†
Richard A. J. O’Hair* a-c
(a) School of Chemistry, University of Melbourne, Victoria 3010, Australia. Fax: +61
3 9347 5180; Tel: +61 3 8344 2452; Email: [email protected]
(b) Bio21 Institute of Molecular Science and Biotechnology, The University of
Melbourne, Victoria 3010, Australia.
(c) ARC Centre of Excellence in Free Radical Chemistry and Biotechnology.
* Correspondence and PROOFS to: Professor Richard O’Hair:
Fax: +61 3 9347 5180; Tel: +61 3 8344 2452; E-mail: [email protected]
†
Respectfully dedicated to the memory of recently departed pioneers of gas-phase
physical organic chemistry: Professors Roger F. C. Brown; Charles “Chuck” H.
DePuy and Nico M. M. Nibbering.
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Abstract
Metal-catalyzed decarboxylative coupling reactions of esters offer new opportunities
for formation of C-C bonds with CO2 as the only coproduct. Here I provide an
overview of: key solution phase literature; thermochemical considerations for
decarboxylation of esters and thermolysis of esters in the absence of a metal catalyst.
Results from my laboratory on the use of multistage ion trap mass spectrometry
experiments and DFT calculations to probe the gas-phase metal catalyzed
decarboxylative cross-coupling reactions of allyl acetate and related esters are then
reviewed. These studies have explored the role of the metal carboxylate complex in
the gas phase decarboxylative coupling of allyl acetate proceeding via a simple twostep catalytic cycle. In Step 1, an organometallic ion, [CH3ML]+/- (where M is a group
10 or 11 metal and L is an auxillary ligand), is allowed to undergo ion-molecule
reactions with allyl acetate to generate 1-butene and the metal acetate ion,
[CH3CO2ML]+/-. In Step 2, the metal acetate ion is subjected to collision-induced
dissociation to reform the organometallic ion and thereby close the catalytic cycle.
DFT calculations have been used to explore the mechanisms of these reactions.
The organometallic ions [CH3CuCH3]-, [CH3Cu2]+, [CH3AgCu]+ and [CH3M(phen)]+
(where M = Ni, Pd and Pt) all undergo C-C bond coupling reactions with allyl acetate
(Step 1), although the reaction efficiencies and product branching ratios are highly
dependant on the nature of the metal complex. [CH3Ag2]+ does not undergo C-C bond
coupling. Using DFT calculations, a diverse range of mechanisms have been explored
for these C-C bond-coupling reactions including: oxidative-addition, followed by
reductive elimination; insertion reactions and SN2-like reactions. Which of these
mechanisms operate is dependant on the nature of the metal complex.
A wide range of organometallic ions can be formed via decarboxylation (Step 2)
although these reactions can be in competition with other fragmentation channels.
DFT calculations have located different types of transition states for the formation of
[CH3CuCH3]-, [CH3Cu2]+, [CH3AgCu]+ and [CH3M(phen)]+ (where M = Ni, Pd and
Pt).
Of the catalysts studied to date, [CH3Cu2]+ and [CH3Pd(phen)]+ are best at promoting
C-C bond formation (Step 1) as well as being regenerated (Step 2). Preliminary
results on the reactions of [C6H5M(phen)]+ (M = Ni and Pd) with
C6H5CO2CH2CH=CH2 and C6H5CO2CH2C6H5 are described.
Running title: Metal Catalyzed Decarboxylative Coupling of Esters
Keywords: C-C bond formation; cross-coupling reactions; gaseous state;
computational chemistry; mass spectrometry.
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1. Introduction.
“I would not like to neglect to mention that we are still very poor in synthetic
methods in organic chemisty. Most of the synthetic work is done with organic
reactions of the type which have been known for a long time. If you know 20 organic
reactions you probably know most of the steps used in synthetic work, particularly in
industry, but I am quite sure there must be hundreds of other organic reactions to be
discovered.” Barton, 1973 [1]
“.. chemists today are asked to develop perfect chemical reactions that proceed with
100% yield and 100% selectivity without forming any waste products. Molecular
catalysis, together with traditional heterogeneous catalysis, significantly contributes
to the realization of this goal.” Nyori, 2005 [2]
The above quotes highlight that every recent generation of organic chemists
has received a clarion call to “invent” new reactions to benefit the synthesis of
organic molecules [1-3]. In a world of finite and diminishing resources that faces
environmental threats from pollution associated with increasing waste production, the
imperative for inventing new reactions has shifted from solely expanding the
synthetic “toolbox” [1] to also developing atom efficient reactions [2-5]. Metal
catalyzed transformations continue to be a rich vein to mine for new reactions. Apart
from opportunities in designing new catalysts, there is plenty of scope to move
towards more environmentally benign organic substrates [6]. A case in point is the
widely used transition metal catalyzed biaryl cross-coupling reaction [7], which
requires the preparation and use of the stoichiometric nucleophilic organometallic,
Ar1-M, to couple with the electrophilic partner, Ar2-X (eq. 1). This reaction results in
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the metal halide, MX, as a waste byproduct. By switching to a carboxylic acid
substrate, Goossen et al were able to develop a dual metal catalyzed decarboxylative
cross-coupling reaction [8], which produces CO2 and HX as waste byproducts (eq. 2).
This method takes advantage of the fact that copper(I) salts have long been known to
promote the Pesci decarboxylation reaction [9] of copper(I) carboxylates to produce
organocopper species that can be isolated [10] or that can undergo a range of
reactions including protonation [11], cross-coupling [12] or transmetallation, as in the
case of Goossen’s biaryl coupling reaction [8].
Carboxylic acids, RCO2H, are valuable organic substrates since they: (i)
exhibit structural diversity; (ii) are readily available as bulk chemicals or via existing
synthetic procedures (e.g. oxidation of primary alcohols or alkylarenes); (iii) are
stable, allowing ease of storage and handling; (iv) have the potential to become
“green chemistry” alternatives to existing substrates in synthetic processes. Metal
catalyzed decarboxylative coupling reactions have been widely studied over the past
decade, as highlighted in several reviews and a book chapter [13].
Esters have also been widely used as substrates in metal catalyzed crosscoupling reactions (eq. 3). For example, allylic alkylation reactions have fascinated
organic chemists in terms of their regiochemical and stereochemical outcomes [14] as
well as for the diverse range of possible mechanisms [15]. Unfortunately the R1 group
of the carboxylate is wasted in these reactions.
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Metal catalyzed decarboxylative cross-coupling reactions of esters are highly
desirable. These single substrate reactions exhibit high atom economy since both R 1
and R2 groups are used, and only CO2 is produced as a waste byproduct (eq. 4,
Scheme 1). Not surprisingly, this class of reaction has also received considerable
recent attention from the organic chemistry community [16]. However, the concept of
using metal catalysts to selectively decompose esters is not new, and dates back over
a century ago, to Sabatier’s work on the reactions of esters with metal oxide catalysts
[17]. In the English translation of Sabatier’s classic book on catalysis in organic
chemistry, W. D. Bancroft noted that a nickel catalyst decomposed ethyl acetate into
propane while a titanium oxide catalyst gave acetic acid [18]. He also highlighted the
need to better understand the interactions of the substrate with the metal catalyst in
order to explain these differences in reactivity, thereby foreshadowing modern
mechanistic studies in homogenous and heterogenous catalysis. Subsequent careful
experiments by Pearce and Ott, in which products were isolated and quantified,
revealed that decomposition of ethyl acetate by nickel is complex and gives rise to a
range of products that do not include propane [19].
In an authoritative review, Tunge has discussed decarboxylative crosscoupling reactions of esters in terms of: their mechanistic features; the scope of the
ester substrates (Scheme 1); and applications in total synthesis [16a]. While several
metal catalysts have been used, by far the most widely used metal-ligand combination
has been Pd(0) with phosphine ligands. An attractive feature of these reactions is that
they formally generate a nucleophilic carbon (R1) and an electrophilic carbon (R2) in
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situ. This helps explain the scope of the reaction (Scheme 1a), which has tended to
require the formation of stabilized anions (R1) and cations (R2).
Scheme 1: (a) Metal catalyzed decarboxylative cross-coupling reactions of esters (eq.
4), with synthetic scope of the ester substrate. (b) Generic mechanism showing steps
of: (1) oxidative-addition; (2) decarboxylation; and (3) reductive elimination steps.
Tunge has noted that “decarboxylative allylation is a field that would benefit
from more in-depth mechanistic knowledge” [16a], which has been my motivation for
using physical organic techniques to study these reactions in the gas-phase. In
particular, my group has used multistage mass spectrometry experiments in ion trap
mass spectrometers in conjunction with DFT calculations to explore the details of
each step in the catalytic cycle. This follows the motivation of solution phase
chemists such as Yamamoto, who have adopted a physical organic chemistry
approach to study the elementary processes associated with catalytic reactions of
relevance to organic chemistry [20]. For example, Yamamoto has measured reaction
kinetics and isolated and characterized both organic and metal containing products
from stoichiometric variants of metal catalyzed reactions involving esters [21]. His
studies have highlighted that the nature of the metal complex and the ester substrate
can dictate which of the bonds in the ester are activated. Two selected examples given
in Scheme 2 show the role of the substrate: (A) in allyl acetate the R1CO2-R2 bond is
activated; (B) in phenyl acetate the R1C(O)-OR2 bond is activated.
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Scheme 2: Examples of metal containing products that have been isolated from
stoichiometric reactions of metal complexes with esters that highlight activation of
different C-O bonds: (A) activation of the R1CO2-R2 bond in allyl acetate to give a allyl O-Ac complex, 1; activation of the R1C(O)-OR2 bond in phenyl acetate to give a
O-Ph, Ac complex, 2, which then decarbonylates to give complex 3 [21]. PCy3 =
tricyclohexylphosphine, COD = 1,5-cyclooctadiene, bpy = 2,2'-bipyridine.
Here I provide an overview of: thermochemical considerations for
decarboxylation of esters; thermolysis of esters in the absence of a metal catalyst;
results from my laboratory on the use of mass spectrometry experiments and DFT
calculations to probe the gas-phase metal catalyzed decarboxylative cross-coupling
reactions of allyl acetate (Scheme 3) and related esters.
[CH3M(L)]+/-
O
O
CO2
CID
2
1
IMR
systems studied:
[CH3CuCH3][CH3Cu2]+, [CH3CuAg]+, [CH3Ag2]+
[CH3Ni(phen)]+, [CH3Pd(phen)]+, [CH3Pt(phen)]+
[CH3CO2M(L)]+/-
Scheme 3: Generic two step catalytic cycle for the gas-phase metal catalyzed
decarboxylative coupling of allyl acetate: step 1 involves the ion-molecule reaction
(IMR) of an organometallic ion with allyl acetate; step 2 involves collision-induced
dissociation of the metal acetate ion to reform the organometallic catalyst.
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2. Thermochemical considerations for decarboxylation of esters.
In terms of bond homolysis [22], the weakest bond in acetic acid is the C-C
bond (Scheme 4a). For methyl acetate, the C-C and C-O bonds that are associated
with the desired decarboxylation reaction (eq. 4) are the weakest bonds (Scheme 4b).
The C-O bond can be substantially weakened by changing R2 to a benzyl group
(Scheme 4c).
Scheme 4: Selected bond dissociation energies (kJ mol-1) in: (a) acetic acid; (b)
methyl acetate; (c) benzyl acetate. Data from [22].
With regards to the overall enthalpy change for decarboxylation of esters (eq.
4) there is dearth of experimentally determined enthalpies of formation of esters,
which precludes tabulation of such data for a range of esters. Using gas-phase
enthalpies of formation [23], the enthalpy change for decarboxylation of methyl
acetate, ethyl acetate and methyl benzoate are predicted to be -100, -157 and +174 kJ
mol-1 respectively.
3. Thermolysis of esters in the absence of a metal catalyst.
The pyrolysis of esters has been widely studied for over a hundred years and
has been the subject of several reviews [24] that have appeared since Hurd’s classic
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book [25]. The structure of the ester plays a key role in dictating what type(s) of
reactions are observed, making these reactions of limited synthetic use. Readers
interested in the range of reactions that have been observed are directed to detailed
literature reviews [24]. Here I focus on three classes of esters (Scheme 5): (1) if the
ester group (R2) has 2 or more carbons and possesses one or more non-vinylic 
hydrogens, then a cis-elimination readily occurs to yield a carboxylic acid and an
alkene, as illustrated for ethyl acetate (Scheme 5a). This reaction has been widely
studied [24] and recent DFT calculations on a wide range of possible decomposition
reactions of ethyl propanoate reveal that the activation energy for cis-elimination is
much lower than radical pathways involving bond homolysis [26]. (2) For vinyl esters
possessing a R1 group with one or more  hydrogens, acetaldehyde and a ketene are
formed (Scheme 5b). (3) Based on the detection of cross-over products from the copyrolysis of CH3CO2CH2CH=CH2 and CD3CO2CH2CH=CH2, allyl acetate has been
proposed to decompose via a radical chain mechanism involving bond homolysis
followed by attack of the methyl radical onto a second allyl acetate to either produce
1-butene (path (a) of Scheme 5c) or acrolein (path (b)) [27].
Scheme 5: Mechanisms for pyrolytic decomposition reactions of esters: (a) ciselimination [22]; (b) six centred TS for vinyl ester decomposition [22d]; (c) radical
decompositions in allyl acetates [27].
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4. Metal-catalyzed decarboxylative cross-coupling reactions in the gas-phase.
As highlighted previously [28], the combination of electrospray ionisation
(ESI) [29] with ion-trap mass spectrometers provides a “complete chemical
laboratory” to study metal catalyzed reactions in the gas-phase. Mass-selected
charged metal carboxylates, formed via ESI of solutions of appropriate metal salts,
can undergo decarboxylation under conditions of low-energy collision-induced
dissociation (CID) to produce organometallic ions (eq. 5). These can be further mass
selected for studies aimed at examining their unimolecular or bimolecular reactions
with organic substrates. It is worth noting the benefits of these studies: (i) each of the
elementary steps of a catalytic cycle can be examined in detail [20]; (ii) CID is like
an “on/off” switch so that organometallic ions formed via decarboxylation are rapidly
thermalized to room temperature of the helium bath gas [30], (iii) ionic contaminants
are removed via mass selection. With regards to the latter point, this contrasts with the
condensed phase, where trace metal impurities can be the real catalysts [31].
[RCO2M(L)n]+/-

[RM(L)n]+/- + CO2
(5)
Since an overview of metal mediated decarboxylation reactions in ion trap mass
spectrometers has been given in a recent accounts article [32], the focus here is on
summarizing recent published and unpublished work on the chemistry of ester
substrates. While there have been several studies on the gas-phase reactions of metal
ions and complexes with esters [33], only those involving metal catalyzed
decarboxylative cross-coupling (eq. 4 and Scheme 3) are considered. I will:
summarize the types of mechanisms that have been considered for the C-C bond
coupling reaction (step 1 of Scheme 3); compare the DFT calculated energetics
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associated with both steps of Scheme 3 for the following three different catalytic
systems: (1) [CH3CuCH3]- [34]; (2) [CH3M1M2]+ (where M1 and M2 = Cu or Ag) [35];
(3) [RM(phen)]+ [36] (where R = CH3 and C6H5; M = Ni, Pd or Pt); discuss the C-C
bond coupling reaction and competing off-cycle reactions and decarboxylation step
and its competition with off-cycle decomposition reactions for each of these catalysts.
4.1 Types of mechanisms for metal catalyzed allylic alkylation reactions of
relevance to step 1 of Scheme 3.
As noted above, metal catalyzed allylic alkylation reactions of ester substrates
have been widely used in organic synthesis (eq. 3). Sawamura has recently
summarized the range of mechanisms that can operate (Scheme 6) [15b]. Importantly,
the reaction mechanism followed dictates the regiochemical and stereochemical
outcomes for non-symmetric allyl acetate substrates. In metal catalyzed reactions
involving a π-allyl metal intermediate, competition between - and γ- substitution
occurs (Scheme 6A). When strongly nucleophilic organometallic reagents are used, γregioselectivity is often observed due to oxidative addition via SN2′ attack to form a
(σ-allyl)metal species, which then undergoes reductive elimination (Scheme 6B). In
cases where the - substituted isomer is also observed, it forms via allylmetal
intermediates that undergo σ-π-σ isomerization. In contrast, -selective substitution
(Scheme 6C) can occur when a strongly nucleophilic (low-valent) transition metal
complex, M (e.g. rhodium, ruthenium or iron) attacks in an SN2′ manner to form (σallyl)metal complexes, which then undergoes a second SN2′ displacement with a soft
carbon nucleophile, R- (e.g. malonate anion). Once again, the regioselectivity of this
-selective substitution manifold can be compromised by a related σ-π-σ allylic
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isomerization pathway prior to attack of the carbon nucleophile. Sawamura developed
a new γ-selective strategy that entirely avoids the issue of isomerization of the
allylmetal species (Scheme 6D). Here, the C-C double bond inserts into an
organometallic reagent, with subsquent -acetoxy fragmentation giving rise to the γselective product.
Scheme 6: Mechanisms for the metal catalyzed allylic alkylation reactions of ester
substrates. Adapted from [15b].
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4.2 Simplified energy diagram for the 2 step metal catalyzed decarboxylative
cross-coupling of allyl acetate.
Irregardless of the precise mechanism involved in the allylic alkylation step
(Scheme 6), all metal catalysts that promote the decarboxylative cross-coupling of
allyl acetate do so in two discreet steps (Figure 1) and so it is informative to compare
the DFT calculated energetics of the highest transition state (TS) for each step as a
function of the metal catalyst (Table 1).
Step 2 CID requires energy
Step 1 IMR occurs without energy
TS for CO2 loss
[CH3M(L)]+/+ CH3CO2C3H5
DH TS1
DH eq. 4
DH step1
E
DH TS2
reactant
complex
M(L)]+/-
TS for allylic
alkylation
product
complex
[CH3CO2
+ C 4H 8
product
complex
[CH3M(L)]+/+ CO2 + C4H8
ion is collisionally
cooled by the He
bath gas
reaction coordinate
Figure 1: Simplified energy diagram to allow ready comparision of the DFT
calculated energetics (Table 1) associated with steps 1 and 2 of the metal catalyzed
decomposition of allyl acetate (Scheme 2).
Allylic alkylation (Step 1) is an ion-molecule reaction. The DFT calculations predict
that this reaction is exothermic for all organometallic ions (Table 1, column 3). The
energy of TS1 should be below that of the separated reactants for this reaction to
occur under the near thermal conditions of ion-trap mass spectrometers [30], which is
the case for all organometallic ions (Table 1, column 2), except [CH3CuCH3]-, which
only reacts very slowly (see section 4.3 below).
As will be discussed for the
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individual classes of organometallic ions, whether on not allylic alkylation occurs also
depends on whether there are other, more competitive off cycle reactions.
Table 1: Key energetics in kJ mol-1 for the gas-phase transition metal catalyzed
decarboxylative alkylation of allyl acetate (Figure 1).
Organometallic
H TS1
H step1
H TS2
catalyst
[CH3CuCH3]- (a)
+26 (b)
-203.8
145.2
+ (c)
(d)
[CH3Cu2]
-132.2
-80.1
193.9
[CH3CuAg]+ (c)
-78.2 (e)
-77.2
178.5
+ (c)
(f)
[CH3Ag2]
-9.6
-81.0
198.8
[CH3Ni(phen)]+ (g)
-106.3 (h)
-231.0
188.1 (i)
[CH3Pd(phen)]+ (g) -104.6 (h)
-154.4
179.5 (i)
+ (g)
(h)
[CH3Pt(phen)]
-112.1
-184.1
178.5 (i)
(a) ref. 34f. Energetics calculated at the B3LYP/Def2-QZVP//B3LYP/SDD6-31+G(d) level of theory.
(b) Step 1 involves oxidative addition (OA) followed by reductive elimination (RE). Only the energy of
the highest reductive elimination TS is given as H TS1.
(c) ref. 35c. Energetics calculated at the MO6/SDD6-31+G(d) level of theory.
(d) Step 1 involves OA/RE. Only the energy of the highest OA TS is given as H TS1.
(e) Step 1 involves OA/RE. The lowest energy pathway involves allyl group transfer to the Cu centre.
Only the energy of the highest OA TS is given as H TS1.
(f) Step 1 involves OA/RE. Only the energy of the highest RE TS is given as H TS1.
(g) ref. 36d. Energetics calculated at the MO6/SDD6-31+G(d) level of theory.
(h) Step 1 involves insertion followed by -OAc transfer. Only the energy of the highest insertion TS is
given as H TS1.
(i) ref. 36c. Energetics calculated at the MO6/SDD6-31+G(d) level of theory. Decarboxylation
involves 2 transition states. Only the energy of the highest isomerization TS is given.
The metal carboxylate ionic product of allylic alkylation, [CH3CO2M(L)]+/-, is cooled
back to room temperature via collisions with the helium bath gas. In order to be
decarboxylated, it must be mass selected and allowed to undergo an endothermic CID
reaction in step 2. The DFT calculations reveal that each metal acetate has a different
activation energy of decarboxylation and there are differences in the geometries for
the transition state for decarboxylation. For [CH3CO2CuCH3]- a three centred TS is
found (Figure 2A), while all of the cations [CH3C(OM1)(OM2)]+ undergo a complex
rearrangement in which one of the metals inserts into the C-CH3 bond (Figures 2BD). Finally decarboxylation of the group 10 acetates, [CH3CO2M(phen)]+, involves a
4 centred TS (Figures 2E-G) which sets up to yield a four coordinate intermediate in
which the CO2 is O-coordinated to the metal centre.
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Figure 2: TS geometries and imaginary frequencies for decarboxylation of: (a)
[CH3CO2CuCH3]-; (b) [CH3C(OCu)2]+; (c) [CH3C(OCu)(OAg)]+; (d) [CH3C(OAg)2]+;
(e) [CH3CO2Ni(phen)]+; (f) [CH3CO2Pd(phen)]+; (g) [CH3CO2Pt(phen)]+. Energies
(kJ mol-1) are relative to the parent carboxylate, [CH3CO2M(L)]+/- (DFT methods
detailed in refs 34f, 35c and 36c respectively).
4.3 [CH3CuCH3]- catalyzed decarboxylative cross-coupling of allyl acetate.
[CH3CuCH3]- reacts with allyl acetate via C-C cross-coupling, which is the
major reaction channel (Scheme 6, 81 % yield) and generates the product ion
[CH3CO2CuCH3]- [34f]. However, the rate of the reaction is slow (11 x 10-13
cm3.molecules-1.s-1) with a reaction efficiency of only 0.032 %. This is consistent with
the DFT calculated energy for TS1, which is +26 kJ mol-1 (Table 1). Several other
minor product ions were observed, which represent off cyle reactions. When
[CD3CuCD3]- is used as the reactant ion, a small amount of [CH3CuCD3]- is observed,
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which arises from decomposition of “hot” [CH3CO2CuCD3]-. This is entirely
consistent with the DFT calculations (Figure 1, Table 1), which highlight that H TS2
(+145.2 kJ mol-1) is easily surmounted by the exothermicity of step 1 (-203.8 kJ mol1
).
off cycle unimolecular (CID) reactions:
[HCuH]
+ CH2=CH2 (7a)
[CH3Cu] + CH3
(7b)
3
off cycle reaction:
CH3CO2
[CH3CuCH3]
+ CuCH3 (6)
O
O
CO2
2
1
[CH3CO2CuCH3]
several off cycle
competing reactions
produce byproducts.
Scheme 7: Two step (1 and 2) catalytic cycle for the gas-phase metal catalyzed
decarboxylative coupling of allyl acetate by [CH3CuCH3]- and showing off cycle
reactions (eqs 6 and 7) [34b,c and f].
DFT calculations predict that the lowest energy manifold involves stepwise oxidative addition proceeding via an 2-(C3H5O2CCH3) intermediate with extrusion
of the acetate leaving group [34f]. This is followed by a reductive elimination from a
3- π-allyl copper intermediate, with the acetate being recaptured by the copper center
to form [CH3CO2CuCH3]-. Thus the reaction mechanisms is essentially a variant of
Scheme 6B.
To close the catalytic cycle, [CH3CuCH3]- is formed in high yield via CID of
[CH3CO2CuCH3]-, although a minor loss of acetate is observed as well (eq. 6, Scheme
7) [34b].
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Finally, since thermal decarboxylative allylic alkylation reactions in solution
mean that the resultant organometallics are vulnerable to thermal decomposition, we
have also subjected mass selected [CH3CuCH3]- to CID to examine its unimolecular
fragmentation. Two main fragmentation channels were observed: dehydro-coupling to
form [HCuH]- and ethene (eq. 7a), a reaction that proceeds via a dyotropic
rearrangement mechanism; bond homolysis (eq. 7b) [34c].
4.4 [CH3M1M2]+ catalyzed decarboxylative cross-coupling of allyl acetate.
The nature of the metals present in the bimetallic systems [CH3M1M2]+
strongly influence allylic alkylation by allyl acetate [35a]. When both metals are
copper, good efficiency (essentially at the collision rate) and good selectivity (52.7%)
for the C-C cross-coupling reaction is observed. In contrast, while [CH3AgCu]+ and
[CH3Ag2]+ are also both highly reactive towards allyl acetate, the yields for allylic
alkylation (1.2% and 0% respectively) are compromised by the off cycle metal cation
abstraction reaction (eq. 8 of Scheme 8), which dominates and destroys (poisons) the
metal catalyst.
DFT calculations suggest that the most likely mechanism for allylic alkylation
of [CH3M1M2]+ involves discrete oxidative addition and reductive elimination steps,
with both metal centres playing a role in both steps. All reactions are predicted to be
thermodynamically and kinetically viable, but in the cases of [CH3AgCu]+ and
[CH3Ag2]+, the off cycle metal cation abstraction reaction is thermodynamically
preferred.
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All of the bimetallic systems [CH3M1M2]+ are formed upon decarboxylation.
The yield of [CH3Cu2]+ is highest (83.3%), followed by [CH3Ag2]+ (44.5%) and
[CH3CuAg]+ (20.4%) [35a]. The main off cycle reactions involve loss of the metal
cation (eq. 9a) or formation of [CO2M]+ (eq. 9b), a reaction that is part of the
decarboxylation manifold, but involves decomposition of the nascent organometallic
via loss of CH3M. An examination of the TS for decarbxylation (Figures 2b-d)
reveals why this can compete with formation of [CH3M1M2]+, which requires
rearrangement of the metal complex after decarboxylation.
off cycle unimolecular (CID; PID) reactions:
Ag
+ CH3Ag
CH3Ag
Ag2
(10a)
+ Ag
+ CH3
(10b)
(10c)
3
off cycle reaction:
(M1/2)
H
+ CH3CO2M2/1 (9a)
(CO2M1/2)
O
+ CH3M2/1 (9b)
CO2
H
C H
M1
M2
O
1
2
CH3
O
O
M1
M2
off cycle competing reaction:
M1/2
O
+ M2/1CH3 (8)
O
Scheme 8: Two step (1 and 2) catalytic cycle for the gas-phase metal catalyzed
decarboxylative coupling of allyl acetate by [CH3M1M2]+ and showing off cycle
reactions (eqs 8, 9 and 10) [35a].
Organosilver compounds are susceptible to thermal and photolytic
decomposition. Thus we have examined the CID and photoinduced decomposition
(PID) reactions of [CH3Ag2]+ [35b]. Only Ag+ is formed (eq. 10a) upon CID, which
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contrast to the additional formation of products of excited state radical decomposition
reactions (eqs. 10b,c) under PID conditions.
4.5 [CH3M(phen)]+ catalyzed decarboxylative cross-coupling of allyl acetate.
All of the group 10 organometallic cations [CH3M(phen)]+ undergo allylic
alkylation, with the reaction efficiencies relative to the collision rate: [CH3Ni(phen)]+
(36%) > [CH3Pd(phen)]+ (28%) > [CH3Pt(phen)]+ (2%) [36d]. Adduct formation is in
competition, but CID of these adducts forms the metal acetates, suggesting that the
adducts are collisionally stabilized intermediates along the C-C bond coupling
pathway. In contrast to [CH3CuCH3]- and [CH3M1M2]+, DFT calculation predict that
the lowest energy pathway for allylic alkylation involves insertion followed by –
OAc elimination (Scheme 6D).
H2 O
off cycle"reaction:
CH4
1b
N
N
M
+ CH3
N
N
M
(10)
O
CH3
CO2
1a
2
O
N
N
M
OH
N
N
M
O
O
3
CH3
O
O
HO
Scheme 9: Two step (1a and 2) catalytic cycle for the gas-phase metal catalyzed
decarboxylative coupling of allyl acetate by [CH3M(phen)]+ and showing off cycle
reaction (eq. 10) and a competing cycle (steps 1b and 3) for the water catalyzed
decomposition of allyl acetate (eq. 11) [36d].
Page 21 of 29
In the case of [CH3Pt(phen)]+ a major competing off cycle reaction involves
addition of allyl acetate followed by loss of methane (reaction efficiency 10%).
Deuterium labelling experiments reveal that this reaction involves competitive C-H
bond activation to either give coordinated enolate, [(phen)Pt(CH2CO2CH2CHCH2)]+,
or allyl, [(phen)Pt(CH2CHCHO2CCH3)]+.
All of the group 10 organometallic cations [CH3M(phen)]+ are reformed upon
decarboxylation, thereby closing the catalytic cycle [36d]. The experimentally
determined ease of decarboxylation follows the order: [CH3CO2Pd(phen)]+ >
[CH3CO2Pt(phen)]+ > [CH3CO2Ni(phen)]+. DFT calculations reveal that
decarboxylation involves two transition states. The first involves a conformational
change of the acetate from a bidentate to a monodentate binding mode, which then
allows decarboxylation via the second TS shown in Figures 2e-g. The main
competing fragmentation pathway involves bond homolysis to form the M(I) species,
[M(phen)]+. (eq. 10, Scheme 9).
The group 10 organometallic cations [CH3M(phen)]+ are all three coordinate
and thus possess a vacant coordination site, which not only facilitates the allylic
alkylation reaction, but provides a site for reaction with other neutral substrates. In the
case of [CH3Ni(phen)]+ this results in a competing catalytic cycle for the water
catalyzed decomposition of allyl acetate (eq. 11) which involves hydrolysis (step 1b
of Scheme 8) followed by reaction with allyl acetate to give allyl alcohol and the
metal acetate, [CH3CO2Ni(phen)]+ (step 3), which can then undergo decarboxylation
(step 2) to close the cycle. Overall this cycle is not that competitive due to a sluggish
step 3.
Page 22 of 29
CH3CO2CH2CH=CH2 + H2O → HOCH2CH=CH2 + CO2 + CH4
(11)
4.6 [RM(phen)]+ catalyzed decarboxylative cross-coupling of allyl and benzyl
carboxylates.
Since [CH3Pd(phen)]+ and [CH3Ni(phen)]+ were found to be effective
catalysts for the cross-coupling of allyl acetate [36d], we are currently exploring the
scope of the decarboxylative cross-coupling (eq. 4) by examining the reactions of
[R1M(phen)]+ with other ester substrates, R1CO2R2. Preliminary results reveal that:
allyl benzoate and benzyl benzoate both undergo decarboxylative cross-coupling (eq.
4) catalyzed by [R1M(phen)]+; the decarboxylation of [PhCO2M(phen)]+ requires less
energy than for the acetate complexes, [CH3CO2M(phen)]+, which is consistent with
the preference for decarboxylation of benzoate over acetate observed for the copper
and silver anions [PhCO2MO2CCH3]- (M = Cu or Ag) [34b,h].
5. Conclusions and outlook
By examining the gas-phase reactions of a single substrate with a range of
different metal complexes, it is possible to gain insights into how the properties of the
metal complex (charge, metal oxidation state, cluster nuclearity and ligand(s))
influence reactivity. To date only a few organic substrates have been subject to such
scrutiny, with methane being one of the most widely studied substrates [37]. Metal
catalyzed allylation reactions exhibit a diverse range of metal dependant mechanistic
behaviour [15b], and this holds true for step 1 of the metal catalyzed decarboxylative
cross-coupling of allyl acetate (Scheme 2): [CH3CuCH3]- reacts via oxidative-addition
Page 23 of 29
to form a  allyl intermediate that then undergoes reductive elimination [34f];
[CH3Cu2]+ and [CH3CuAg]+ react via oxidative-addition involving both metal centers,
followed by reductive elimination [35b]; while [CH3M(phen)]+ (where M = Ni, Pd
and Pt) react via insertion followed by -OAc transfer [36d]. Of all the catalysts
studied to date, the organometallic cations [CH3Cu2]+ and [CH3Pd(phen)]+ are the best
catalysts for both steps of the catalytic cycle, while [CH3Ni(phen)]+ is also a
promising catalyst. Our preliminary studies on the [(phen)M(O2CPh)]+ (M = Ni and
Pd) catalyzed decarboxylative coupling of PhCO2Allyl and PhCO2CH2Ph suggest that
the following new decarboxylative coupling reactions should be explored in solution:
[ArCO2M(phen)]+ (M = Ni and Pd) with ArCO2Allyl and ArCO2CH2Ph.
Metal catalyzed decarboxylative alkylation reactions remain limited by the
scope of ester substrates that can be used. To date the solution phase decarboxylation
of alkyl carboxylates, R1CO2-, has been a challenge due to the high basicities of the
resultant alkyl anions, R1-. Tunge has recently reported the decarboxylative allylation
of amino alkanoic esters using a dual catalyst systems consisting of a palladium
catalysis and an iridium photocatalyst (Scheme 10) [38]. A key feature is that
photochemical oxidation of the carboxylate anion gives a carboxylate radical, which
is known to readily decarboxylate [39] to generate a radical intermediate, which then
undergoes allylation. This represents a promising new approach to extend the scope of
ester substrates that can be used in metal catalyzed decarboxylative alkylation
reactions.
Page 24 of 29
Scheme 10: Overcoming decarboxylation of recalcitrant carboxylate anions using a
dual metal photocatalysis approach [38].
6. Acknowledgements
I thank: the ARC for financial support via grant DP110103844 and through the ARC
CoE program; all the students, post-doctoral fellows and collaborators involved in
helping develop a mechanistic understanding of metal-mediated decarboxylation in
the gas-phase, especially Dr George Khairallah.
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