Rh(I)-catalyzed transformation of propargyl vinyl ethers into (E, Z)-dienals: Stereoelectronic role of trans effect in a metal-mediated pericyclic process and a shift from homogeneous to heterogeneous catalysis during a one-pot reaction

Article abstract of DOI:10.1021/jo402505f

The combination of experiments and computations reveals unusual features of stereoselective Rh(I)-catalyzed transformation of propargyl vinyl ethers into (E,Z)-dienals. The first step, the conversion of propargyl vinyl ethers into allene aldehydes, proceeds under homogeneous conditions via a cyclization-mediated mechanism initiated by Rh(I) coordination at the alkyne. This path agrees well with the small experimental effects of substituents on the carbinol carbon. The key feature revealed by the computational study is the stereoelectronic effect of the ligand arrangement at the catalytic center. The rearrangement barriers significantly decrease due to the greater transfer of electron density from the catalytic metal center to the CO ligand oriented trans to the alkyne. This effect increases electrophilicity of the metal and lowers the calculated barriers by 9.0 kcal/mol. Subsequent evolution of the catalyst leads to the in situ formation of Rh(I) nanoclusters that catalyze stereoselective tautomerization. The intermediacy of heterogeneous catalysis by nanoclusters was confirmed by mercury poisoning, temperature-dependent sigmoidal kinetic curves, and dynamic light scattering. The combination of experiments and computations suggests that the initially formed allene-aldehyde product assists in the transformation of a homogeneous catalyst (or a cocktail of catalysts) into nanoclusters, which in turn catalyze and control the stereochemistry of subsequent transformations.

Full text of DOI:10.1021/jo402505f

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Article
Rh(I)-Catalyzed Transformation of Propargyl Vinyl Ethers into
(E, Z)-Dienals: Stereoelectronic Role of Trans-Effect in a Metal-
Mediated Pericyclic Process and a Shift from Homogeneous
to Heterogeneous Catalysis During a One-Pot Reaction
Dinesh V Vidhani, Marie E. Krafft, and Igor V. Alabugin
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 04 Dec 2013
Downloaded from http://pubs.acs.org on December 7, 2013
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Rh(I)-Catalyzed Transformation of Propargyl Vinyl Ethers into
(E, Z)-Dienals: Stereoelectronic Role of Trans-Effect in a Metal-
Mediated Pericyclic Process and a Shift from Homogeneous to
Heterogeneous Catalysis During a One-Pot Reaction
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Dinesh V. Vidhani,* Marie E. Krafft and Igor V. Alabugin*
Department of Chemistry & Biochemistry, Florida State University, Tallahassee, FL 32306. USA.
[Phone: (850) 644-5795, e-mail: dineshvidhani16@gmail.com & alabugin@chem.fsu.edu]
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Abstract:
The combination of experiments and computations reveals unusual features of stereoselective Rh(I)-catalyzed transformation
of propargyl vinyl ethers into (E, Z)-dienals. The first step, the conversion of propargyl vinyl ethers into allene aldehydes,
proceeds under homogeneous conditions via the “cyclization-mediated” mechanism initiated by Rh(I) coordination at the
alkyne. This path agrees well with the small experimental effects of substituents on the carbinol carbon. The key feature
revealed by the computational study is the stereoelectronic effect of the ligand arrangement at the catalytic center. The
rearrangement barriers significantly decrease due to the greater transfer of electron density from the catalytic metal center to
the CO ligand oriented trans to the alkyne. This effect increases electrophilicity of the metal and lowers the calculated
barriers by 9.0 kcal/mol. Subsequent evolution of the catalyst leads to the in-situ formation of Rh(I)-nanoclusters which
catalyze stereoselective tautomerization. The intermediacy of heterogeneous catalysis by nanoclusters was confirmed by
mercury poisoning, temperature-dependent sigmoidal kinetic curves, and dynamic light scattering. The combination of
experiments and computations suggest that the initially formed allene-aldehyde product assists in the transformation of a
homogeneous catalyst (or “a cocktail of catalysts”) into nanoclusters, which, in turn, catalyze and control the stereochemistry
of subsequent transformations.
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Introduction
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The metal-catalyzed Claisen rearrangement offers new mechanistic paths to this classic reaction
and significantly expands its synthetic utility.1 When metals coordinate with π-bases, such as
alkenes or alkynes, the first step of the rearrangement can be described as a 6-endo-dig
cyclization that leads to a cyclic six-membered intermediate (Figure 1). Thus, this mode of
rearrangement was termed “cyclization-mediated pathway”.2 On the other hand, Lewis acids,
such as Cu+2, Al+3 and H+ initiate the so-called “cation-accelerated oxonia Claisen”
rearrangement by coordinating with oxygen (Figure 1).3
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Recently, we reported a mechanistic study of Au(I)-catalyzed propargyl Claisen and allenyl
vinyl ether rearrangement, where Au(I), commonly considered as an alkynophilic Lewis acid,
coordinates with the oxygen and directs the Claisen rearrangement through an oxonia path.4 The
barrier for the alternative cyclization-mediated pathway is 1.5 kcal/mol higher. Two important
features of the calculated Au-catalyzed cyclization-mediated pathway includes: 1) lack of
substituent effects and 2) selective stabilization of the TS for the Grob fragmentation of the six-
membered intermediate by Au(I)-catalysts.
Figure 1. Three mechanistic alternatives for the metal-catalyzed propargyl Claisen rearrangement. Cyclization-
mediated pathway dipicted on left shows two possibilities emerging from the six-membered cyclic intermediate.
The latter effect lowers the barrier to the extent that this intermediate corresponds to a shallow
inflection on the potential energy surface, so the overall process blends the characteristics of a
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stepwise and a concerted process. The nature of this unusual potential energy surface depends
strongly on substrate-catalyst coordination and solvent, as illustrated by the successful trapping
of the six-membered intermediate by nucleophilic attack of water in dioxane reported by the
Toste group.5
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We were intrigued by the possibility of using deprotonation as a conceptually different approach
for trapping the six-membered intermediate. This approach would provide access to conjugated
(E, Z)-dienals via tandem rearrangement of the propargyl vinyl ethers. Such transformation
would be synthetically valuable because practical approaches to the thermodynamically less
stable Z-alkenes remain limited in comparison to the variety of methods available for
synthesizing the lower energy E isomer (Figure 2).6 Methods for the direct incorporation of the
unsaturated α,β carbonyl compounds, with the Z-stereochemistry at the double bond remains
especially limited.7
Figure 2. Selected cyclic intermediates in synthesis of Z-alkenes
Guided by this concept, we developed the transformation of propargyl vinyl ethers into (E, Z)-
dienals using a Rh(I)-catalyzed propargyl Claisen rearrangement and prototropic isomerization
sequence.8 This method provides α, β unsaturated aldehydes from an aldehyde and an alkyne in
three steps with excellent stereoselectivity (Figure 3). Catalyst screening showed that propargyl
Claisen rearrangement was efficiently catalyzed by several metals, but the stereoselective
prototropic rearrangement consistent with a six-membered intermediate was possible only with
[Rh(CO)2Cl]2. Although AuCl also promotes the formation of the dienals, but unlike Rh(I), it
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gives (E, E) dienals. Presence of donor ligands at the gold (LAu(I)) does not compromise its
ability to catalyze the propargyl Claisen rearrangement but stops the prototropic isomerization
step.9 Optimization studies further revealed that the tandem process was especially efficient in
weakly coordinating solvents such as benzene and toluene.
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C4H9
C4H9
CHO
CHO
CHO
CHO
CHO
CHO
F3C
MeO
Cl
1
85%
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85%
3
91%
4
90%
C4H9
Ph
CHO
CHO
CHO
NC
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87%
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92%
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78%
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82%c
Ph
O
C4H9
CHO
CHO
CHO
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62%
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95%
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80%c
50% b
Figure 3. Products and isolated yields of Rh(I)-catalyzed rearrangements obtained from their respective
propargyl vinyl ethers. Isomeric ratios were determined using NMR. In all cases the (E, Z):(E, E) was
a
found to be >95:5. Reaction Conditions: 0.1 M solution of 0.1 mmol propargyl vinyl ether in toluene in
o
b
the presence of 10% [Rh(CO)2Cl]2 at 50 C. Undergoes further rearrangement to give a mixture of
products. c Requires 70 oC.
The tandem rearrangement efficiently works for a range of substrates with aromatic, tertiary and
alkenyl substituents at the carbinol carbon (Figure 3). Primary and secondary substituents tend to
undergo a further rearrangement to give a mixture of products.
Results and Discussion
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While developing the methodology, we observed that the (E, Z)-dienal only starts to form after
the complete conversion of propargyl vinyl ether into the allene-aldehyde. Thus, we were
presented with the opportunity to investigate the kinetic of the two steps of this cascade reaction
separately. Initially, we expected that this study would help us to determine whether the
transformation of the allene-aldehyde into the (E, Z)-dienal involves a six-membered organo-
Rh(I) intermediate (Figure 2), but our attempts in trapping the proposed six-membered
intermediate with a nucleophile or detecting it spectroscopically were not successful, prompting
us to investigate this cascade in more details via a combination of experiments and computations.
In particular, we wanted to test whether the allene-diene transformation involves an allene-enol
formation, as suggested by Okamura for related reactions,7 or whether a new alternative exists.
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Non-Integral Order in Catalyst. As a first step of our kinetic study, we determined the reaction
order in respect to the catalyst by following the rearrangement of phenyl substituted substrate at
different concentrations of the catalyst. A non-linear fit of the data f(x)=a(x)n revealed a half
order of the Rh(I)-dimer (Figure 4). Such fractional order kinetic has been reported for reactions
in which either one of the reactants or the precatalyst dissociate prior to the rate limiting step.10
In this system, this observation confirms the dissociation of the dimeric precatalyst into a
catalytically active monomeric form (See SI for the derived rate law).
Figure 4. Rate constants determined at four different catalyst concentrations at 330K for the phenyl
substituted substrate. A non-linear fit of the data to the equation f(x) = a(x)n to obtain the order in catalyst
concentration
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These experimental results support the model suggested by our preliminary computational
study.8 It was suggested previously that the square planar d8 16e- [Rh(CO)2Cl]2 precatalyst
dissociates into the 14e- monomeric species prior to catalysis.11 However, thermodynamic data in
Figure 5 illustrate that such dissociation should be assisted by coordination with another ligand,
i.e. in this case the vinyl ether group of the substrate. This coordination produces new
monomeric Rh(I) species responsible for the catalysis of the propargyl Claisen step.
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Figure 5. Proposed catalytic cycle. Numbers in blue correspond to the PCM-SCRF-M05-2X/LANL2DZ
energies expressed in kcal/mol of the intermediate species relative to the uncomplexed Rh(I)-dimer
An important consequence of this model is that the fragmentation of the dimer occurs only
through an associative mechanism which leads to the formation of the square planar monomer
complex with the substrate. The key stereoelectronic feature of this complex is that it is not
symmetrical and it can have two orientation of the CO ligand relative to the substrate (Figure 6).
As we will show in one of the subsequent sections, such differences, which can be considered as
a manifestation of the trans-effect,12 play a key role in the differences observed transition state.
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Figure 6. Geometries of the Rh(I)-dimer and the Rh(I)-substrate complexes optimized at the M05-
2X/LANL2DZ level.
Substituent Effects. After establishing the order in catalyst, we proceeded in probing the
sequence of bond-forming and bond-breaking events in the Claisen part of the catalytic cycle. In
the cyclization-mediated pathway, the C4-O3 and C4-C5 bonds should be the least affected
(Figure 5). On the other hand, the oxonia Claisen rearrangement is expected to be an
asynchronous process, traversing through a dissociative type TS, in which the substituents on the
carbinol carbon would significantly influence the C4-O3 bond in the transition state.
Considering the expected differences between the two pathways, we carried out the kinetic
study of substrates corresponding to the products 1-5 (Figure 3) with the carbinol carbon
substituted by electronically different aromatic rings. A clean first-order conversion of all five
propargyl vinyl ethers into their respective allene-aldehydes occurs at the chosen range of
experimental temperatures. Conveniently, appearance of the final dienal product was not
observed at the times when the propargyl vinyl ether was still present. The activation energies,
enthalpies and entropies were obtained using Arrhenius and Eyring equations (see Figure 7 and
SI for the further details).
Figure 7. The representative Arrhenius (left) and Eyring (right) plots for the phenyl substituted substrate 2
obtained by monitoring the Claisen rearrangement at 323, 330 and 335 K.
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All five propargyl vinyl ethers show Arrhenius barriers in the range of 14-15 kcal/mol for
the transformation into their respective allene-aldehyde (Table 1, See SI for the kinetic plots).
The limited impact of substituents on the carbinol carbon is consistent with a cyclization-
mediated model (vide infra). Eyring plots showed large negative entropies of activation. At first
sight, this observation may appear counterintuitive and inconsistent with the fragmentation of
Rh(I)-dimer, however, the vinyl ether-assisted fragmentation of Rh(I)-dimer leads to the
decrease in the total number of molecules from 3 (Rh(I)-dimer and two substrates) to 2 (two
Rh(I)-VE complexes). As a result, this process involves a large negative entropy of activation.
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Table 1. Experimental activation parameters obtained using Arrhenius and Eyring plots.
ꢀH#
ꢀS#
Substrate
Ea
kcal/mol
15.1 0.7
14.5 0.7
14.2 0.1
14.6 0.3
15.1 0.7
kcal/mol
14.5 0.6
13.9 0.6
13.5 0.1
13.8 0.3
14.5 0.6
cal/K
PhOMe (1)
Ph (2)
PhCl (3)
p-CF3-Ph (4)
p-CN-Ph (5)
-19.4 0.9
-21.6 0.9
-22.7 0.2
-23.3 0.4
-22.5 1.0
In this selection of substrates, the effects of activation entropy (ꢀS#) and the activation
enthalpy (ꢀH#) oppose each other (Table 1, see Figure 45 of SI). For example, the electron
donor (OMe) showed the most favorable entropy of activation but the effect was compensated by
the relatively unfavorable activation enthalpy (ꢀH#=14.5 kcal/mol, ꢀS#=-19.3 cal/K mol). This
trend is not followed by the two most electron-deficient substrates 4 and 5. The deviation was
especially large for the nitrile group, where both the enthalpy and entropy of activation were
unfavorable, vide infra.
The experimental entropies suggested fragmentation of precatalyst in all five substrates. In
agreement with the proposed cyclization-mediated model, the measured activation barriers show
a subtle substituent effect, corroborating the lack of substantial carbinol C-O bond cleavage in
the TS. To understand these observations, we undertook a computational study where we
compared substituent effects for all three rearrangement pathways.
Computational Methods. The computational analysis of the reaction energy profile for the
present rearrangement was performed using DFT formalism as implemented in Gaussian 03.
Although the B3LYP is one of the most popular functionals used by the organic chemists, it is
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also known to often underestimate activation energies13 and provide unreliable bond energies in
transition metal catalysis.14 On the other hand, the M05-2X functional was shown to perform
well for transition metal chemistry, the main group elements and the calculation of activation
barriers.14 Thus, all geometries were optimized using M05-2X functional and the LANL2DZ
basis sets. Vibrational frequency calculations were performed to confirm the local minima or the
transition state corresponding to the given stationary point on the potential energy surface. The
transition states were located using quadratic synchronous transit (QST3) method.15 For the
structurally very similar substrates, the QST-optimized geometries were modified and refined by
the restricted transition state search using Berny algorithm. The solvation energies in toluene
were calculated using self-consisted reaction field on the optimized gas-phase geometries.16 The
Curtin-Hammett barriers were calculated from the most stable Rh(I)-VE complex.
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Computational results: Based on the possible coordinating sites on the propargyl vinyl ether,
we explored three pathways: 1) rearrangement via activation of vinyl ether, 2) Rh(I)-accelerated
oxonia Claisen rearrangement, and 3) cyclization-mediated pathway. In every case, we found
that position of the CO ligand (trans or cis) relative to the substrate had a large role in the
reaction.
A. Cyclization-mediated pathway: The geometries of reactant-like transition states show that the
carbinol C4-O3 and C4-C5 bonds are mostly unaffected during this process. As shown in Figure
8, the C4-O3 (cis: 1.47 Åꢀ1.48 Å, trans: 1.47 Åꢀ1.48 Å) and C4-C5 bonds are mostly intact in
the transition state. Interestingly, C4-C5 bond, which changes from a single bond to a double
bond in the final product, shows an initial bond elongation instead of shortening (~1.48 Å
ꢀ1.51Å for both isomers). The stereoelectronic effect of the trans-CO ligand is reflected in the
longer incipient C1-C6 distance (cis: 2.16 Å vs. trans: 2.22 Å).
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Figure 8. M05-2X/LANL2DZ optimized geometries displaying important bond parameters for the two
orientations of CO in the reactant and the TS of cyclization-mediated pathway. The values in blue color
correspond to the NBO charges on Rhodium.
Interestingly, this pathway combines the characteristics of a stepwise and a concerted process.
Although only a single TS was located as expected for a concerted reaction, the evolution of
aromaticity17 along the Internal Reaction Coordinate (IRC) (Figure 9) revealed that the
maximum aromaticity (NICS(0) = -11.5 ppm) and the most symmetrical geometry were attained
at a geometry ~4.2 kcal/mol downhill from the transition state (NICS(0) = -9.8 ppm). However,
even at the maximum of aromaticity, the RMS gradient revealed neither the additional minimum
corresponding to the six-membered intermediate nor an inflection indicative4 of a hidden second
transition state (see SI). These features suggest the interaction with the catalyst eliminates the
Grob fragmentation TS from the reaction hypersurface.
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Figure 9. IRC calculations performed at the M05-2X/LANL2DZ level for the Ph-substituted substrate 2
coordinated to Rh(I). The dashed blue line describes changes in energy. The dashed green line
corresponds to evolution of aromaticity along the IRC.
The role of trans-effect. The large differences for the calculated rearrangement energy
surfaces were observed for the two different positions of ligands at the Rh center. These
differences correspond to a manifestation of trans-effect. The trans effect is defined as the
ability of certain ligands to labilize trans groups during ligand substitution reactions in square
planar complexes.18 From a conceptual viewpoint, the trans effect can be broadly classified in
static and kinetic trans effect.19 Static trans effect, also known as trans-influence or structural-
trans-effect (STE),20 is a ground state phenomenon where the bonds trans to strong σ-donors are
significantly elongated. The kinetic trans effect, on the other hand, deals with the stabilization of
the trigonal bipyramidal transition state by the strong π-acceptors when such ligands occupy
equatorial positions.21
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Figure 10 Energy profile of cyclization-mediated pathway. Red and blue color depicts the cis and
the trans orientations of CO respectively in case of phenyl substituted substrate. Energies were
calculated relative to the most stable Rh(I)-VE complex at the M05-2X/LANL2DZ level.
In the present study, both the reactant-complex and the transition states for the “cyclization-
mediated” pathway were significantly stabilized by trans effects of the π-acceptor CO ligand but,
as shown in the Figure 10, the transition state is stabilized to a far greater extent (9.0 kcal/mol)
than the reactant complex (4.0 kcal/mol).22 Although barrier heights calculated from the trans
and cis Rh(I)-alkyne complex were only 9.7 kcal/mol and 14.6 kcal/mol respectively, the Curtin-
Hammett barrier, calculated from the most stable Rh(I)-vinyl ether complex, increases the barrier
(17.7 kcal/mol for the trans-CO geometry, Figure 10).
The direct involvement of the trans carbonyl ligand in the reaction process is further
confirmed by parallel trends in the calculated carbonyl IR stretching frequencies and the charge
on the metal. Combined, these changes are often used to determine the extent of back-donation
from the metal to the π*-orbital of the CO ligand. In particular, the IR stretching frequency of
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free CO (2143 cm-1) is reduced to 2120-1850 cm-1 when it coordinates to the metal which has the
ability to back-donate electrons into the CO π*-orbital.23 For the ground state Rh(I)-alkyne
complex, the CO trans to the alkyne showed a red shift in the IR CO stretching frequency
compared to its cis isomer (cis:2082 Vs. trans:2040cm-1). A similar effect was observed for the
transition states where the CO that is oriented trans to the alkyne is much more effective in
dispersing the progressively increasing electron density on Rh(I) and hence shows lower IR CO
stretching compared to the cis-orientation (cis:2036 Vs. trans:2027 cm-1).
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In this catalytic pathway, Rh(I) serves as a relay in the electronic communication between
alkyne and CO ligands. The NBO charges shown in Figure 8 suggest that the metal is far more
efficient in shunting electron density when the CO is present trans to the alkyne (charge on Rh(I)
in trans: -0.412 Vs. cis: -0.460). Together, the activation barriers, IR CO stretching frequencies
and NBO charges on the Rh paint a cohesive picture of a stereoelectronic interaction of the
trans-CO with the alkyne ligand through the metal center.
B.
Oxonia Claisen rearrangement. In the second pathway, coordination of Rh(I) to the
oxygen atom of the substrate triggers the cation-accelerated oxonia Claisen rearrangement. This
rearrangement proceeds via a highly asynchronous pathway with a dissociative-type transition
state. The fragmentation character is revealed by significant elongation of the carbinol C4-O3
bond (Figure 11, cis: 1.50 Åꢀ2.01 Å; trans: 1.50 Åꢀ2.02 Å) in the transition state geometries.
Figure 11. M05-2X/LANL2DZ optimized geometries displaying important bond parameters for the two
orientations of CO in the reactant and the TS of cyclization-induced pathway in case of phenyl substituted
substrate.
In stark contrast to the selective TS stabilization in the cyclization-mediated pathway, the
trans-orientation of the CO stabilized the ground state oxonia-Claisen reactant more than the
transition state (reactant stabilization: 11.1 kcal/mol, TS stabilization: 10.1 kcal/mol). Due to the
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unproductive reactant stabilization, the overall Curtin-Hammett barrier (24.4 kcal/mol for the
trans-CO geometry) remains higher than the barrier for the cyclization-mediated pathway
(Figure 12).
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Figure 12. Energy profile of oxonia-Claisen pathway in case of phenyl substituted substrate. Red and blue
color depicts the cis and the trans orientations of CO respectively. Energies were calculated relative to the
most stable Rh(I)-VE complex at the M05-2X/LANL2DZ level
C.
Rearrangement via activation of the vinyl ether. Among the three coordinating sites on
the substrate, the π-bond of the vinyl ether forms the most stable complex with the Rh(I) catalyst.
Similar to oxonia-Claisen rearrangement, the reaction involves a concerted highly asynchronous
pathway with fragmented-TS (See SI for the TS geometries). However, the activation barrier is
the highest among the three mechanisms (Figure 13, trans-CO: 41.2 kcal/mol). In this path, the
trans-effect provides only 1 kcal/mol of additional TS stabilization relative to the respective
ground state complex.
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Figure 13. Energy profile of pathway emanating from Rh(I)-vinyl ether complex in case of phenyl
substituted substrate. Red and blue color depicts the cis and the trans orientations of CO respectively.
Energies were calculated at the M05-2X/LANL2DZ level.
In summary, the computational analysis of the three mechanisms suggest that the
rearrangement should follow the cyclization-mediated pathway in which one of the CO ligand on
the Rh(I) is oriented trans to the alkyne.
Correlation of experimental barriers with calculated barriers. The theory predicts that the
carbinol C4-O3 bond is not significantly cleaved in the transition state of the cyclization-
mediated pathway. As a result, the substituents at the carbinol carbon are expected to produce
relatively small effects. As shown in Table 2, the absolute values of the Curtin-Hammett barriers
calculated from the Rh(I)-VE complex (Figure 14) depend on the nature of the most stable
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complex taken as a reference point in the calculations. Although agreement between the
experimental and computational trends is quite good if barriers are calculated relative to complex
A where the Rh-center displays a cation/π interaction with the alkyne, the more stable complexes
B, observed for arenes of good and moderate donor ability, correspond to the cation-π-
interaction of the Rh center with the arene (Figure 14).24 In the case of nitrile, the aromatic π-
system is a poor partner in the Rh(I)/π-interaction but the lone pair of nitrile provides a
secondary interaction assisting in the formation of the most stable reference complex (C,Figure
14). Once the more stable complexes were included in the computations, an excellent correlation
(R2=0.989) was found between experimental and computational trends for the four substrates
(Figure 15).
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Figure 14. The M05-2X optimized geometries of two conformations of the Rh(I)-VE complex. Structure
A depicts a secondary interaction between Rh(I) and alkyne while structure B depicts an interaction
between Rh(I) and arene. Structure C shows an interaction between Rh(I) and nitrogen lone pair of the
nitrile substituent. Values in blue color correspond to the NBO charges on Rh(I).
Table 2. Comparison of Experimental barriers with the M05-2X and the B3LYP level barriers.
Substrate
M052X/
B3LYP/
Ea,
LANL2DZ
LANL2DZ
kcal/mol
(Expt)
Curtin-Hammett Barrier from Curtin-Hammett Barrier from
barrier from the the Alkyne- barrier from the the Alkyne-
most stable Rh(I) Rh complex most stable Rh(I) Rh complex
complex
complex
PhOMe 15.1 0.7
19.4a (17.4)
18.5a (17.7)
17.8a (17.2)
17.6a (16.8)
19.4b (16.9)
9.6
9.7
9.0
8.4
8.5
15.5a (15.7)
15.5a (15.8)
15.1a (15.6)
14.7a (15.1)
22.2b (14.6)
7.6
7.7
7.1
6.7
6.8
Ph
PhCl
14.5 0.7
14.2 0.1
p-CF3-Ph 14.6 0.3
p-CN-Ph 15.1 0.7
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aValues corresponding to square pyramidal Rh(I)-VE complex analogous to structure B (Figure 14).
Values in parenthesis correspond to the square pyramidal Rh(I)-VE complex with alkyne structure A
(
Figure 14). bValue correspond to Rh(I)-nitrile complex.
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Further, we compared the performance of M05-2X functional with the widely used B3LYP
method. Although several B3LYP activation barriers were very close to the experimental values,
the overall trend in the B3LYP values failed to follow the experimental trend (Figure 15). The
discrepancy is likely to originate from the inability of B3LYP method to describe accurately the
non-covalent interactions between the arene and the Rh(I). Further, single point M06-2X
calculations with 6-311G(d, p) and aug-cc-pVTZ basis sets, showed similar trends in the
activation energy for the selected substrates (see SI for the total energies).
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Figure 15. Correlation of experimental and computational Curtin-Hammett barriers. Blue diamonds and
red squares correspond to the M05-2X and B3LYP values respectively. The blue diamond in the top right
corner represents two substrates, PhOMe and PhCN (See Table 2). Green triangle represents M05-2X
value corresponding to the CF3 substituted phenyl substrate 4. Inclusion of this point in the correlation
lowers R2 to 0.75
Unlike our previous hypothesis, the computational data indicated that deprotonation from the
proposed six-membered intermediate in our conditions was unlikely due to the lack of an energy
minima corresponding to such an intermediate. Thus, to understand the origin of
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stereoselectivity, we investigated the second step separately by isolating an allene-aldehyde and
subjecting it to the reaction conditions.
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Stereoselective Proton Transfer via Heterogeneous Catalysis. The combination of olefin
isomerization and Claisen rearrangement (the isomerization Claisen rearrangement, or ICR) has
been known for quite a long time. The Claisen rearrangement of allyl vinyl ethers which were
generated in-situ from allyl homoallyl ethers, were reported to occur in presence of transition
metals such as Ir(I),25 Ru(II),26 and Pd(II)27 catalysts. The tandem stereoselective transition
metal-catalyzed migration of the double bond in allyl homoallyl ethers and Claisen
rearrangement (ICR) was used by several groups to achieve multistep transformation including
enantioselective synthesis.28 However, unlike the literature ICR examples where tautomerization
precedes the Claisen step, our cascade involves a stereoselective prototropic rearrangement
which follows the Claisen rearrangement.
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A similar transformation of allene-aldehyde to the (E, Z)-dienal through tandem [1,5]
hydride shift, 6π electrocyclic ring closure and 6π electrocyclic ring opening, was reported by
Okamura. An essential step needed to enter the Okamura route is enolization of the allene-
aldehyde (Figure 16). Our experiments found a clean conversion of allene-aldehyde into the (E,
Z)-dienal (Figure 17) with no evidence for the involvement of any intermediates corresponding
to the Okamura route (Figure 16).
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Figure 16. The Okamura route to the formation of (E,Z) dienal.
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Figure 17. Stacked NMR spectra shows the clean conversion of the allene-aldehyde into the (E, Z)-dienal.
In addition, the transition state for Rh(I)-catalyzed formation of the (Z,Z) dienal was lower in
energy (10.2 kcal/mol) than the (E, Z) dienal (12.0 kcal/mol) (Figure 18). The formation of
single geometric isomer (E, Z) suggests that the true nature of the active catalyst is different from
the proposed monomeric Rh(I) species which is expected to give a mixture of (E, Z) and (Z, Z)
geometrical isomers.
Furthermore, the computational analysis of uncatalyzed [1,5] hydrogen shift in allene-enol
suggested similar low barriers for the formation of E, Z (10.7 kcal/mol) and Z, Z (10.5 kcal/mol)
dienals (Figure 18). Thus, the calculations predicted this process does not require catalysis once
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the allene-enol is formed from the allene-aldehyde and that the reaction should lead to a mixture
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of the isomers
.
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Figure 18. M05-2X optimized transition state geometries of unimolecular [1, 5] hydrogen shift. The
structures A and B correspond to the TS geometries of Rh(I)-catalyzed formation of (Z, Z) and (E, Z)
dienals respectively whereas structures C and D correspond to the TS geometries of uncatalyzed
formation of (Z, Z) and (E, Z) dienals respectively from the allene-enol
This scenario displays an interesting parallel to the work of Ananikov and Beletskaya who
reported the formation of a dynamically evolving mixture of catalytic species in different
aggregation states (“cocktail of catalysts”) in Pd(II)-catalyzed Heck reactions.29 The nature of the
catalytic species in such situations depends upon the substrate, concentration, temperature,
solvents and additives.
We suggest that a similar “cocktail of catalysts” is formed in our system and that the
catalytically active species are Rh nanoparticles. Several experimental observations support this
notion. In particular, a sigmoidal correlation between concentrations and reaction times was
found instead of exponential first order decay of allene-aldehyde (Figure 19).30 The initial
induction time was temperature-dependent. Additionally, over a period of 48 hours, the solution
turned dark brown and we observed precipitate formation. Several experimental observations
such as non-reproducible kinetics31 at different metal concentrations, inhibition of the reaction by
addition of excess of elemental mercury32 and in particular a sigmoidal correlation between
concentrations and reaction times instead of exponential first order decay of allene-aldehyde
(Figure 19) 33 lend support to the heterogeneous catalysis hypothesis.34
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Figure 19. Non-linear formation of (E, Z)-dienal 3 from the respective allene-aldehyde. In the plot on the
left, the blue diamonds, the red squares and the green triangles correspond to 323, 330 and 335 K
temperature respectively. Plot on right shows the temperature dependence of the induction time.
To verify the involvement of nanoparticles in the prototropic rearrangement, we perfromed
dynamic light scattering (DLS) experiments on the allene-aldehyde derived from the phenyl
substituted substrate 2. This technique is used to determine the size-distribution of particles in
suspension. Typically, in the DLS experiment, the solution containing the nanoclusters is
irradiated with the monochromatic light from the laser and the intensity of the light diffracted by
the nanocluster is measured. Since the scattered light from nanoclusters undergoes constructive
and destructive interference by the surrounding scatterers, a complex intensity fluctuation pattern
containing a detailed information about the time scale of the movement of the scatterers emerges.
To process this information, a mathematical tool called autocorrelation, is used to identify a
repeating pattern burried under the complex signal.
g2 (q; )
<I(t)I(t+ )>
: Autocorrelation function
g2 (q; )
=
q
: Wave vector
<I(t)>2
:
Delay time
I : Intensity
Generally, data is interpreted only when the plot of intensity vs. time shows a smooth and
continuous decay of intensity for autocorrelation function. Such plots are classified as “proceed-
category“. In the present study, the catalyst and the substrate solutions did not show the presence
of nanoclusters. Interestingly, the reaction mixture at 50% conversion of allene-aldehyde into
respective (E, Z)-dienal (Figure 20), showed the presence of 170 nm nanoclusters. Moreover,
low observed polydispersity (5%) suggested that the solution consisted of uniformly sized
particles (Figure 20).
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Figure 20. Dynamic light scattering experiment performed on phenyl substituted substrate 2. Top two
plots corresponds to the rates of decay of autocorrelation function for the catalyst and substrate solutions.
Bottom left plot corresponds to the rates of decay of autocorrelation function for the reaction mixture at
50% conversion. Bottom right plot correspond to the histogram dipicting the particle size (85 nm radius)
and 5.2% polydispersity.
Conclusion
In conclusion, experimental and computational analysis of the tandem process suggests a cascade
transformation that evolves from homogeneous to heterogeneous catalysis. The Rh(I)-catalyzed
propargyl Claisen rearrangement involves homogeneous catalysis whereas the subsequent
prototropic rearrangement shows the telltale signs of heterogeneous catalysis.
Kinetic studies of the Claisen rearrangement showed fractional order in the catalyst. Among
three pathways emanating from modes of coordination of Rh(I) with the substrate, the relatively
small effects of substituents at the carbinal carbon agreed best with the cyclization-induced
pathway. The NICS(0) values suggested that the transition state merged the characteristics of a
stepwise and a concerted process (NICS(0) = -12 ppm ). Furthermore, the orientation of CO
ligands on Rh(I) played a crucial role in determining the barrier heights. Due to the
stereoelectronic trans-effect, the trans orientation of one of the CO ligands relative to the
substrate stabilized both the ground state and, to a larger extent, the transition state. This
selective stereoelectronic transition state stabilization was estimated to be ~9 kcal/mol. Trends
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in substituent effects from the M05-2X calculations agreed well with the experimental order of
reactivity, presumably due to the relatively accurate description of the non-covalent interactions
by this method. On the other hand, the B3LYP results, despite being numerically close to the
experimental barriers, did not correlate well with the trends in experimental substituent effects.
The features indicative of heterogeneous catalysis in the prototropic rearrangement of the
allene-aldehyde include the temperature-dependent induction period, sigmoidal shaped curve,
non-reproducible kinetics at different catalyst concentrations and the inhibition of reaction in
presence of large excess of elemental mercury. Furthermore, DLS experiments confirmed the
involvement of 170 nm nanoparticles during the catalysis of second step. We plan to investigate
the nature of these clusters, dynamics of their formation as well as the correlation of the
nanoparticle structure with their catalytic activity in the future work.
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Experimental Section
General procedure for the synthesis of substrates. To a 0.1 M solution of 1-phenylbut-2-yn-1-
ol (0.146g, 1 mmol) in ethyl vinyl ether (10ml) was added mercuric acetate (0.6mmol, 0.190g) in
o
one portion. The reaction mixture was refluxed at 45 C for 12 hours before quenching with a
saturated aqueous sodium carbonate solution. The organic phase was extracted using diethyl
ether and dried over anhydrous potassium carbonate. The solvent was removed under vacuum
and the crude vinyl ether was purified on alumina gel column using hexane as an eluent. Phenyl
substituted substrate, (1-(vinyloxy)but-2-yn-1-yl)benzene, was obtained in 60% yield (0.1 g). 1H
NMR (500 MHz, CD2Cl2) δ: 7.55 (m, 2H), 7.43 (m, 3H), 6.56 (dd, J = 14.1, 6.6 Hz, 1H), 5.54
(q, J = 2.1Hz, 1H), 4.51 (dd, J = 14.1, 1.8 Hz, 1H), 4.21 (dd, J = 6.6, 1.8 Hz, 1H), 1.97 (d, J =
2.2 Hz, 3H). 13C NMR (125 MHz, CD2Cl2) δ: 149.7, 138.5, 128.5, 128.5, 127.2, 89.9, 84.9, 76.2,
71.1, 3.4. Synthesis and spectral data of all functionalized propargyl vinyl ethers corresponding
to the compounds 1-5, have also been described in our previous work on the stereoselective
synthesis of (E, Z) dienals.9
General procedure for kinetic studies. A stock solution of [Rh(CO)2Cl]2 (6 mg, 0.015 mmol)
was prepared in 0.3mL toluene. Another stock solution of (1-(vinyloxy)but-2-yn-1-yl)benzene
was prepared in 0.1 M toluene-d8. The catalyst solution (55 ꢁL,5%, 2.75 ꢁmol) was added to the
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0.55mL of the substrate solution at once using micropipette. The reaction mixture was
immediately transferred into the NMR tube and inserted in the 500 MHz NMR machine
equilibrated at 323K. The single pulse acquisitions were obtained automatically after every 120,
300 or 600 seconds depending upon the temperature. The rate of consumption of vinyl ether and
the rate of formation of the product, (E, Z) dienal 2, was monitored using toluene as internal
standard. 1H NMR (500 MHz, Toluene-d8) E, Z δ: 10.05 (d, J = 7.5 Hz, 1H), 7.20-7.03 (m, 5H),
7.53 (d, J = 15.9, 1H), 6.52 (d, J = 16.1 Hz, 1H), 5.71 (dq, J = 7.6, 1.1 Hz, 1H), 1.63 (d, J = 1.1
Hz, 3H). The full information about preparative procedure for the synthesis of the product, (E, Z)
dienal 1-5 was described in our previous work.9
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Computational Study. All geometries were optimized at the M05-2X/LANL2DZ and
B3LYP/LANL2DZ levels which frequently performs well for the transition metal compounds
using Gaussian 03 program (see reference). Force Field calculation indicated that optimized
equilibrium structures were found to be true minima with no imaginary frequency whereas
transition state (TS) geometries had only one imaginary frequency (see SI). The effect of solvent
(Toluene) on the reaction barriers was evaluated using single point calculations with the PCM
model at the SCRF-M05-2X/LANL2DZ level on the gas-phase geometries. Intrinsic reaction
coordinate (IRC) calculations were used to search for intermediates and additional transition
states.
Acknowledgements
Funding for this project was provided by MDS Research Foundation and NSF Grant CHE-
1152491 to I.A. We also would like to thank Dr. Virginie Maggiotti (FSU) for helpful
discussions, Dr. Steve Freitag (FSU) and Dr. Banghao Chen (FSU) for assistance with variable
temperature NMR spectroscopy, Dr. Claudius Mundoma (FSU) for dynamic light scattering
experiments and Dr. Umesh Goli (FSU) for acquiring mass spectra.
Supporting Information: Kinetic plots of substrates 1-5 at different temperatures. Kinetic plots
of substrate 2 at different concentrations. Arrhenius and Eyring plots of substarates 1-5. Details
of determination of order in catalyst and the rate law. Geometries and energies of all transition
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states, reactants and products. Additional experimental details. This material is available free of
charge via the internet at http://pubs.acs.org.
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21
Square planar complexes undergo ligand substitution reaction through an associative mechanism
whereby the metal receives electron density from the incoming ligand. Thus the ability of the strong π-
acceptors to disperse the developing negative charge on the metal gives rise to the kinetic trans effect.
Based on the strength of ligand, the spectrochemical series for the combined static and kinetic trans
-
-
effect, can be summarized as: C2H4, CO, CN- > PR3, H- > CH3 > C6H5, NO2 , SCN-, I-> Br-, CI- > Py,
NH3, OH-, H2O
22 Transition state stabilization is a particularly attractive strategy for accelerating pericyclic reactions. For
recent examples, see: (a) Gold, B.; Schevchenko, N.; Bonus, N.; Dudley, G. B.; Alabugin, I. V. J. Org.
Chem. 2012, 77, 75. (b) Gold, B.; Dudley, G. B.; Alabugin, I. V. J. Amer. Chem. Soc., 2013, 135, 1558.
23 The extent of the red shift depends upon the charge on the metal, the nature of other ligands
coordinated to the metal and the symmetry of the metal complex. Interestingly, the π-backbonding
weakens when the two strong π-acceptors are oriented trans to each other and strengthens when π-
acceptor is trans to the strong σ-donor. However, in case of alkynes which are both the σ-donor and π-
acceptor, compete with the CO for the MꢀL π-backdonation.
24
In the present study, the p-OMe group did not reveal the stereoelectronically governed dichotomous
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