Overriding the alkynophilicity of gold: Catalytic pathways from higher energy Au(i)-substrate complexes and reactant deactivation via unproductive complexation in the gold(i)-catalyzed propargyl Claisen rearrangement

Article abstract of DOI:10.1039/c2ob27231h

Computational and experimental analysis of unusual substituent effects in the Au-catalyzed propargyl Claisen rearrangement revealed new features important for the future development of Au(i) catalysis. Despite the higher stability of Au-alkyne complexes, they do not always correspond to the catalytically active compounds. Instead, the product emanates from the higher energy Au(i)-oxygen complex reacting via a low barrier cation-accelerated oxonia Claisen pathway. Additionally, both intra and intermolecular competition from other Lewis bases present in the system, for the Au(i) catalyst, can lead to unproductive stabilization of the substrate/catalyst complex, explaining hitherto unresolved substituent effects.

Full text of DOI:10.1039/c2ob27231h

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Overriding the Alkynophilicity of Gold: Catalytic Pathways from
Higher Energy Au(I)-Substrate Complexes and Reactant
Deactivation via Unproductive Complexation in the Gold (I)-
Catalyzed Propargyl Claisen Rearrangement
Dinesh V. Vidhani, John W. Cran, Marie E. Krafft* and Igor V. Alabugin*
Computational and experimental analysis of unusual substituent effects in the Auꢀcatalyzed propargyl Claisen rearrangement
revealed new features important for the future development of Au(I) catalysis. Despite the higher stability of Auꢀalkyne
complexes, they do not always correspond to the catalytically active compounds. Instead, the product emanates from the higher
energy Au(I)ꢀoxygen complex reacting via a low barrier cationꢀaccelerated oxonia Claisen pathway. Additionally, both intra and
intermolecular competition from other Lewis bases present in the system, for the Au(I) catalyst, can lead to unproductive
stabilization of the substrate/catalyst complex, explaining hitherto unresolved substituents effects.
Introduction
Results and Discussion
Our experimental design kept substituents at the terminal
alkyne atom constant while varying donor and acceptor
groups at the carbinol carbon as in the Toste’s study. Despite
the differences in the accelerating effects of the Ph3PAuSbF6
and [(Ph3PAu)3O]BF4 catalysts used in the two studies, we
observed the same unusual trend in which both electron
donors and acceptors slowed down the reaction (Table 2).
Goldꢀcatalyzed cycloisomerizations and rearrangements
of πꢀrich substrates find multiple applications in organic
synthesis.1 The common guiding principle in the design of
Auꢀcatalyzed organic reactions relies on the wellꢀprecedented
“alkynophilicity” of gold.2 Coordination at the triple bond
increases alkyne electrophilicity and provides the rational
foundation for the development of new Auꢀmediated reactions
of alkynes. However, successful optimization of such
catalytic processes in the presence of other functionalities
relies on our knowledge of the low energy mechanistic
pathways opened by catalyst/substrate interactions and on the
understanding of how these pathways are influenced by the
choice of reaction conditions and substituents.
Recently, Toste et al. reported an intriguing finding that
both electron donors and electron acceptors at C4 (entries 1, 3
and 4, Table 1) slow down the Claisen rearrangement of
propargylic vinyl ethers compared to the substrate with the
unsubstituted phenyl ring (entry 2, Table 1).3
Table 2. Experimental substituent effects in the Ph3PAuSbF6ꢀ
catalyzed propargyl Claisen rearrangement.
Substrate
X
OMe
Me
H
Cl
CF3
CN
% Conv.a
21
28
100
60
Allene
7
8
1
2
3
4
5
6
9
10
11
12
5
Traceb
aConversion in 5 minutes.b100% conversion could only be achieved
with 5% catalyst.
Table 1. Experimental investigation of the gold(I)ꢀcatalyzed
propargyl Claisen rearrangement performed by the Toste group.
O
1) 1% [(Ph3PAu)3O]BF4
DCM, rt
HO
X
To understand the origin of this anomalous trend, we
applied DFT calculations to the Auꢀcatalyzed and uncatalyzed
rearrangement of these substrates (see Computational
Methods). The uncatalyzed rearrangement was taken as the
reference point. Comparison of B3LYP/LANL2DZ and
B3LYP/6ꢀ31G(d,p) results for the nonꢀcatalyzed reaction (SI
section) found that the difference between the two basis sets
is small and suggested that the B3LYP/LANL2DZ level is
suitable for the further computational study.
R
2) NaBH4 /MeOH
X
R
Entry
X
R
% Conv.
89
89
Time
12h
0.5h
1
2
OMe
H
nꢀC4H9
OTBS
CH3
nꢀC4H9
3
4
CF3
Br
86
96
19h
6.5h
Considering the “alkynophilic” properties of Au(I), the
above processes are expected to originate from the
nucleophilic attack of the vinyl ether on the Au(I)ꢀcoordinated
alkyne. However, in our experimental study of the allenyl
vinyl ether Claisen rearrangement, we observed products
emanating from the coordination of Au (I) cations to the vinyl
ether (VE) moiety in the presence of an allene moiety.4
Considering the similarities between the allenyl vinyl ether
rearrangement and the propargyl Claisen rearrangement
reported by the Toste group, we undertook a mechanistic
study into the nature of these Auꢀcatalyzed processes.
Table 3. Computed activation and reaction energies (kcal/mol) for the
uncatalyzed Claisen rearrangement of aryl substituted propargyl vinyl
ethers at the B3LYP/LANL2DZ and B3LYP/6ꢀ31G(d,p) levels.
Ea,
Ea,
NICS,
ppma
kcal/mol
(LANL2DZ)
22.3
kcal/mola
15
16
17
Ph
PhNH2 TS2NH2
TS1H
23.4
22.6
23.4
ꢀ18.9
ꢀ17.6
ꢀ19.2
21.4
PhNO2 TS3NO2 22.0
aB3LYP/6ꢀ31G(d,p) level
1

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The energies of the twistꢀboat and the twistꢀchair
In concurrence with the earlier computational findings of
transition states are similar. Their geometries suggest
concerted weakly asynchronous pathways similar to the
uncatalyzed Claisen rearrangement of allyl vinyl ethers. The
negative NICS values5 in the geometric center of the forming
rings confirm the aromatic nature of these transition states
(Table 3).
the Toste group,21g we found only a single TS along this path
and even an extensive IRC search could not locate a
stationary point for the sixꢀmembered intermediate. The NICS
and the HOMA12 calculations for the three substrates showed
moderately aromatic and asynchronous transition states
(Table 4). Trends in the gas phase and solvent calculations
were similar (Table 4).
Analysis of the Auꢀcatalyzed reactions included three
alternative mechanisms AꢀC based on the three Auꢀ
coordinating sites of the substrates6 (Scheme 1Error!
Reference source not found.). The computed complexation
energies suggested an interesting coordinating preference:
vinyl ether>oxygen>alkyne.7
Several TS features are unusual and correspond to a
stepwise process occurring via a sixꢀmembered intermediate
instead of a concerted process. In particular, the C3ꢀO4 bond
cleavage (1.47ꢀ1.54 Å) (Figure 1Error! Reference source
not found.) was noticeably less pronounced in comparison to
that in the uncatalyzed rearrangement (1.49ꢀ2.03 Å).13
Figure 1. B3LYP/LANL2DZ TSs for the gold(I)ꢀcatalyzed
cyclizationꢀmediated Claisenꢀrearrangements of the three arylꢀ
substituted propargyl vinyl ethers.
The unusual reaction path, where the second “concealed”
transition state14 is buried in the PES continuum, combines
the characteristics of a stepwise and a concerted pathway.15
Although the IRC calculations did not locate the second
transition state, the RMS gradient revealed the presence of a
shallow inflection (Figure 2) corresponding to the concealed
transition state of the Grobꢀtype fragmentation. Moreover, the
NICS values showed the maximum aromaticity (ꢀ16.5 ppm)
as the system progresses from the TS towards this inflection
in a region where the calculated geometries are reminiscent of
the cyclic intermediate and the 2nd TS.
Scheme 1. Three mechanistic alternatives AꢀC for the Au(I)ꢀ
catalyzed propargyl Claisen rearrangement and B3LYP/6ꢀ31G(d,p)
binding energies for the three complexes.
A. Cyclization-mediated rearrangement and a “conce-
aled” TS. The cyclizationꢀmediated pathway8 was originally
considered for the [(Ph3Pau)3O]BF4ꢀcatalyzed propargyl
Claisen3 and propargyl ester9 rearrangements by Toste and
coworkers. The process is sensitive to reaction conditions: the
trapped cyclic products were absent when the reaction was
performed in wet CH2Cl2 but the formation of dihydropyran
derivatives was observed in wet dioxane.10 Our experiments
with Et3PauCl/AgBF4 also did not detect the trapped cyclic
products in the presence of MeOH or tꢀBuOH in CH2Cl2 (See
SI).11
Table 4. B3LYP/LANL2DZ activation and reaction energies for the
gold(I)ꢀcatalyzed propargyl Claisen rearrangements
O
Ar
a
b
ꢀH≠a ꢀG≠a
ꢀEra
Ea
Ea
NICSc
HOMA15
Me3PAu
6.0
(7.3d)
5.9
(7.1)
5.8
Ph
7.8
8.1
6.9
5.4
5.2
5.3
8.4
8.7
8.9
ꢀ26.7
ꢀ33.9
ꢀ24.3
ꢀ12.9
ꢀ12.8
ꢀ13.2
0.57
0.57
0.57
PhNH2
PhNO2
(6.8)
aB3LYP/LANL2DZ optimized geometries. bM05-2X optimized
geometries. cGIAO/B3LYP/6-311+G(d, p). dEnergies in parenthesis
include the solvation (CH2Cl2) correction.
Figure 2. B3LYP/LANL2DZ IRC results for the gold(I)ꢀcoordinated
substrate 15 (path A).
2

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The calculated geometries also reveal the source of
Since our results for paths A and B could not explain the
selective stabilization for these “concealed” species: the Au
cation changes its binding mode from a relatively weak πꢀ
coordination at the alkyne to the much tighter σꢀbonding at
the developing negative charge at C2 (the C2ꢀAu distance
change: 2.245 –2.121 Å).
unusually slow reaction for the electron donating substituents,
we considered the final mechanism via Au(I)ꢀcoordination at
the vinyl ether πꢀsystem.
The absence of a discernible sixꢀmembered intermediate is
consistent with our experimental findings whereas the
important role of gold as this reaction stage suggests that
slight modification in the nature of the catalyst (e.g., the
change from a mononuclear Au complex in our studies to the
multinuclear Au catalyst used in the work of Toste) or solvent
may indeed be sufficient for creating and trapping the cyclic
intermediate.
Although the calculated effect of substituents was
relatively small (Table 4 and Figure 1 in SI), the trend
indicated that, in contrast to the experimental substituent
effects in Tables 1 and 2, donors should accelerate the
reaction if it chooses to follow this path. Thus, we proceeded
further down the list of possible mechanismsError!
Reference source not found..
B. Cation-accelerated oxonia Claisen rearrangement.
Although cationic and anionic acceleration is wellꢀ
documented for Claisen16 and the oxyꢀCope rearrangements,17
this process depends on coordination of Au(I), a soft Lewis
acid, at oxygen instead of the polarizable πꢀbases. However,
the calculated complexation energies suggest that
coordination of the Au(I) catalyst to oxygen is favorable (vide
infra). This observation is consistent with our experimental
NMR ligand exchange studies where we observed the
preferential coordination of Ph3PAuSbF6 to the ethyl vinyl
ether in presence of 1ꢀhexyne18 and with the preferential
coordination of Au(I) to the vinyl ether in presence of alkyne
observed in the gasꢀphase study of Roithova et al.Error!
Bookmark not defined.
Figure 4. B3LYP/LANL2DZ IRC calculations for the gold(I)ꢀ
coordinated substrate 15 (path B).
Table 5. Computed activation and reaction energies for the Au(I)ꢀ
catalyzed cationꢀaccelerated oxonia Claisen rearrangement of aryl
substituted propargyl vinyl ethers at the B3LYP/LANL2DZ level.
a
Ea
NICSb HOMA
ꢀH≠a ꢀG≠a
ꢀEra
Ar = PhNH2
Ar = PhOMe
Ar = Ph
Ar = PhCF3
Ar = PhCN
Ar = PhNO2
4.9
6.8
8.8
8.4
8.8
9.0
3.7
6.1
7.3
6.9
7.4
7.4
5.8
5.0
8.9
9.7
10.0
10.6
ꢀ22.6
ꢀ23.9
ꢀ23.9
ꢀ23.9
ꢀ25.3
ꢀ26.2
ꢀ12.6
ꢀ14.0
ꢀ15.6
ꢀ15.6
ꢀ15.7
ꢀ15.7
0.23
0.52
0.74
0.75
0.75
0.83
Although most bond distances display moderate changes,
the C3ꢀO4 and C1ꢀC6 bonds are much more elongated in the
oxonia path than in the uncatalyzed and cyclizationꢀmediated
rearrangements (Figure 3).
aValues calculated at the B3LYP/LANL2DZ level and expressed in
kcal/mol. bValues calculated using GIAO/B3LYP/6-311+G(d,p) level
C. Au(I)-coordination at the vinyl ether. The calculated
transition states for this path display highly advanced C3ꢀO4
bond cleavage with the concomitant cationic character
accumulation at C3 which is even more pronounced than for
the cationꢀaccelerated oxonia Claisen rearrangement (Figure
5).
Figure 3. B3LYP/LANL2DZ TSs for the Au(I)ꢀcatalyzed cation
accelerated oxonia Claisenꢀrearrangements
The IRC calculations showed a smooth potential energy
surface indicative of a highly asynchronous but concerted
pathway (Figure 4).
Both energy and geometry of the highly polarized
dissociative TS are profoundly influenced by the substituents
(Table 5). In particular, the degree of asynchronicity is lower
for the Ph, PhCF3, PhCN and PhNO2 substituents (higher
HOMA and NICS values, Table 5). The effect of the electron
donating NH2 group on the developing cationic center is even
more pronounced than in path A and leads to a highly
fragmented but noticeably stabilized TS.
Figure 5. B3LYP/LANL2DZ TSs for the gold(I)ꢀcatalyzed Claisenꢀ
rearrangements emanating from a Au(I)ꢀVE complex.
As a result, a strong accelerating effect of the donating
substituents is observed. Acceptors have
a moderate
decelerating influence. However, all calculated barriers
remain significantly higher than for the previously discussed
3

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alternatives (Table 6). The calculated NICS values suggest
that the electron donating substituents at the carbinol carbon
stabilize the “fragmentedꢀTS” while electronꢀwithdrawing
substituents force the TS to adopt a more symmetric geometry
to avoid the buildꢀup of positive charge on the carbinol
carbon.
Table 6. Computed activation and reaction energies for the Au(I)ꢀ
catalyzed Claisen rearrangement of aryl substituted propargyl vinyl
ethers emanating from a Au(I)ꢀVE complex (B3LYP/LANL2DZ).
NICSb
a
ꢀH≠a ꢀG≠a
ꢀEra
Ea
Figure 7. Correlation of Hammett substituent constants and the
Ar = PhNH2
Ar = PhOMe
Ar = Ph
Ar = PhCl
Ar= PhCN
Ar = PhNO2
25.1 23.7 25.0
26.5 24.7 26.2
28.7 26.9 27.8
28.5 26.8 27.9
29.2 27.4 28.5
29.8 28.5 27.7
ꢀ15.6
ꢀ16.8
ꢀ17.2
ꢀ17.6
ꢀ18.2
ꢀ19.0
ꢀ8.1
ꢀ8.8
ꢀ9.9
ꢀ10.2
ꢀ10.9
ꢀ11.7
activation barrier for the three mechanisms (activation energies
adjusted based on CurtinꢀHammett correction). Red dashed line
correspond to Au(I)ꢀVE mechanism, blueꢀdashed line correspond to
cyclizationꢀmediated rearrangement and the solid green line
represents cationꢀaccelerated oxonia Claisen rearrangement.
All energies are in kcal/mol. aCalculated at B3LYP/LANL2DZ level.
bCalculated at GIAO/B3LYP/6-311+G(d,p) level
Interestingly, the two low energy pathways converge at the
electron withdrawing nitro substituent. A mechanistic shift
towards a lessꢀasynchronous pathway is predicted to occur in
order to avoid the buildꢀup of positive charge on the carbinol
carbon.
Thus, the CurtinꢀHammett analysis suggests a concerted
cationꢀaccelerated oxonia Claisen pathway via a “fragmentedꢀ
TS” to be the most favorable among the three mechanisms.
This pathway accounts for the failed attempts of trapping the
sixꢀmembered intermediate. However, neither this path nor
the two higher energy alternatives cannot fully account for the
experimentally observed substituent effects.
Curtin-Hammett analysis of the three pathways. The
relative energies of the three transition states and products are
presented in Figure 6 relative to the energies of the isolated
reactants. Although the Au(I)ꢀcoordinated vinyl ether
complex has the lowest energy, the transition state energy is
the highest among the three mechanisms. On the other hand,
the cationꢀaccelerated and the cyclizationꢀmediated
rearrangement are much closer in energies. The absolute TS
energy is lower for the cationꢀaccelerated Claisen
rearrangement due to greater stability of the Au(I)ꢀoxygen
complex compared to the Au(I)ꢀalkyne complex (Figure 6).
Non-bonding interactions. In order to find a reason for the
remaining discrepancy between the experimental and
computational trends, we investigated the possibility of
formation of Auꢀcomplexes with the “unproductive” Lewis
bases present in the substrates. Our hypothesis was that the
interaction of Au(I) with the loneꢀpairs of heteroatom or the
electron rich πꢀsystems that do not take part in the reaction
will influence the rate of the rearrangement. To test this
hypothesis, we investigated the effect of additives on the
rearrangement of vinyl ether 3 with unsubstituted phenyl
group on the carbinol carbon (Scheme 2).
Figure 6. CurtinꢀHammett analysis of the three mechanisms.
Energies for the three pathway are given relative to the two nonꢀ
interacting reagents.
The positive slope in the cationꢀaccelerated rearrangement
(slope = 2.8) and the rearrangement via Au(I)ꢀcoordinated
vinyl ether (slope = 2.9) suggested a buildꢀup of a positive
charge on the carbinol carbon while slight negative slope for
the cyclization mediated pathway (ꢀ1.0) indicated
development of negative charge on the carbinol carbon
(Figure 7).
Scheme 2. Effect of additives on the rearrangement
For electron withdrawing substituents, the rate is affected by
the electronic effect exerted by these groups on the
rearrangement and by catalyst coordination at the
heteroatoms. Both effects are decelerating. For the effect of
electron donors, it may also include coordination at the
aromatic πꢀsystems. Indeed, when a sterically demanding tꢀ
Bu group was introduced at the aromatic moiety, the
conversion improved from 28 to 100%. Clearly, this
reactivity increase stems from the steric protection offered by
4

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concealed and the “cyclizationꢀmediated” process avoids the
cyclization and follows instead an asynchronous concerted
pathway.
the bulky substituent, preventing the unproductive cationꢀπ
interaction with the Au(I)ꢀcatalyst (Scheme 3).
O
Finally, the decelerating effect of electron donor groups was
investigated through an experimental study of the effects of
additives. The origin of this reaction deceleration, not
predicted by computational study, was revealed to be the
result of unproductive coordination of Au(I) to either the
electron rich πꢀsystems or the heteroatomic Lewis bases
which led to the stabilization of the starting materials.
These findings should help to shed light on other metalꢀ
mediated alkyne reactions and aid the development of new
gold(I) catalyzed reactions.
1) 0.05% Ph3PAuSbF6
0.05M DCM, rt, 5 min
R
Conv.
HO
R
9:
14: tꢀBu 100%
Me 28%
Hexyl
2) NaBH4 /MeOH
R
Hexyl
3, 13
Scheme 3. Steric effect on the cation−π interaction.
Computational Methods
All stationary point geometries in the uncatalyzed and gold(I)
catalyzed Claisen rearrangements were optimized using the
B3LYP functional19 with LANL2DZ basis set,20 as
implemented in the Gaussian03 package.21 The effect of
solvent (dichloromethane: CH2Cl2) on the reaction barriers
was evaluated using single point calculations with the PCM
model at the SCRFꢀB3LYP/LANL2DZ level on the gasꢀphase
geometries. Performance of B3LYP method in studies of Auꢀ
catalyzed reactions has been tested extensively.22 Frequency
calculations confirmed that equilibrium geometries have all
positive frequencies whereas transition state (TS) geometries
had only one imaginary frequency (see SI). To test for the
concerted nature of these reactions, the aromaticity of the
selected TSs was examined using nucleus independent
chemical shift (NICS(0))23 and harmonic oscillator model of
aromaticity (HOMA) methods. The Nuclear Independent
Chemical Shift (NICS(0)) method introduced by Schleyer is
one of the most commonly used, convenient and informative
ways to study the aromaticity. It had been successfully
Acknowledgements
Financial support by NSF (Grant CHEꢀ1152491 to I.A. and
CHEꢀ0508969 to M. K.) and the MDS Research Foundation
are gratefully acknowledged. We would also like to thank Dr.
Edwin F. Hilinski and Dr. Manoharan Mariappan for their
valuable suggestions.
Notes and references
[∗] Dr. D. V. Vidhani, Dr. J. W. Cran, Prof. M. E. Krafft, Prof. I. V.
Alabugin. Department of Chemistry and Biochemistry, Florida State
University,
Tallahassee,
FL
32306
(USA)
Eꢀmail:
mekrafftfsu@yahoo.com, alabugin@chem.fsu.edu
applied to
a variety of unusual structures, reactive
1 Z. Li, C. Brouwer, C. He, Chem. Rev. 2008, 108, 3239. N. Shapiro,
F. D. Toste, Synlett 2010, 675. A. S. K. Hashmi, Angew. Chem. Int.
Ed. 2010, 49, 5232. A. Arcadi, Chem. Rev. 2008, 108, 3266. D.
Benitez, N. D. Shapiro, E. Tkatchouk, Y. Wang, W. A. Goddard, F.
D. Toste, Nature Chemistry 2009, 1, 482. A. Fürstner, P. W. Davies,
Angew. Chem. Int. Ed. 2007, 46, 3410. Gilmore, K.; Alabugin, I. V.
Chem. Rev. 2011. 111, 6513. Krafft, M. E.; Vidhani, D. V.; Cran, J.
W.; Manoharan, M. Chem. Commun., 2011,47, 6707. Cran, J. W.;
Krafft, M. E. Angew. Chem. Int. Ed. 2012, 51, 9398. Felix, R. J.;
Weber, D.; Gutierrez, O.; Tantillo, D. J.; Gagné, M. R. Nat. Chem.,
2012, 4, 405.
intermediates and transition states and lent itself as a tool for
better understanding of the allenic Claisen rearrangements.23
The NICS(0) values for the Au(I)ꢀcontaining species were
calculated by the NMRꢀGIAO procedure at the
B3LYP/LANL2DZ level. The B3LYP/6ꢀ311+G(d,p) level
was used to compute NICS(0) values for nonꢀcatalyzed TSs.
The HOMA, which is the geometryꢀbased criteria of
aromaticity, was calculated using the transition state geometry
of the standard Claisen rearrangement of the allyl vinyl ether
as a reference point (See SI for the detailed calculations).
Intrinsic reaction coordinate (IRC) calculations were used to
search for intermediates and additional transition states.
2
NietoꢀOberhuber, C.; Munoz, M. P.; Bunuel, E.; Nevado, C.;
Cardenas, D. J.; Echavarren, A. M. Angew. Chem. Int. Ed. 2004, 43,
2402. Zhang, L.; Sun, J.; Kozmin, S. A. Adv. Synth. Catal. 2006, 348,
2271.
3 Sherry, B. D.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 15978
Conclusions
4
Original report: Krafft, M. E.; Hallal, K. M.; Vidhani, D. V.; Cran,
In summary, the combination of experimental and
computational studies of the Auꢀcatalyzed propargyl Claisen
rearrangement provided us with the new insights into the
fundamental factors controlling the efficiency of Au(I)
catalysis. Significantly, it was found that the product
emanates from the higher energy Au(I)ꢀoxygen complex,
reacting via a low barrier cationꢀaccelerated oxonia Claisen
pathway, rather than via the more stable Au(I)ꢀVE complex.
Furthermore, calculations show that the “cyclizationꢀ
mediated” pathway originating from the Au(I)ꢀalkyne
complex may be the kinetically competitive rearrangement
mechanism as well.
From mapping the reaction potential energy surface with
nucleus independent chemical shift, a predicted 2nd TS for the
cyclizationꢀmediated pathway was found to be buried in the
PES continuum. Stabilization of the 2nd TS and related
intermediate by coordination to the Auꢀcatalyst explains why
this TS, corresponding to the Grobꢀtype fragmentation, is
J. W. Org. Biomol. Chem., 2011, 9, 7535.
5(a) Houk, K. N.; Gonzalez, J.; Li, Y. Acc. Chem. Res., 1995, 28, 81.
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6 Because experimental performance of Ph3PAuSbF6 and Et3PAuSbF6
is similar, we chose Me3PAu(I) as the model Au(I) species to
maximize the computational efficiency.
7
Gas phase experimental Me3PAu+ binding trends display a similar
trend: methyl vinyl ether>acetylene. (a) Roithová, J.; J. Hrušak, J.;
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9
Mauleon, P.; Krinsky, J. L.; Toste, F. D. J. Am. Chem.
Soc. 2009, 131, 4513.
5

Organic & Biomolecular Chemistry
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10
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The reaction was extremely fast compared to the phenyl analogs.
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11
Thus, BF4 counterꢀion, which showed a slower reaction compared to
the SbF6 counterꢀion, was used for this study.
12
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allyl vinyl ethers are known to rearrange via aromatic transition state.
Thus, for our case, R0 values were used as the reference point for
calculating the transition state geometries of the thermal Claisen
rearrangement of allyl vinyl ether. The αꢀvalue for each bond was
calculated separately.
13
Not only the CꢀO bond is not broken in the rateꢀlimiting step but
the other bonds showed relatively small changes relative to the
reactant (C1ꢀC2: 1.25ꢀ1.29Å, C2ꢀC3: 1.51ꢀ1.50Å, O4ꢀC5:
1.41ꢀ1.36Å, C5ꢀC6: 1.34ꢀ1.37Å).
14
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Alabugin, I. V. Submitted.
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18
Monitoring of NMR spectra of the 1:1 mixture of ethyl vinyl ether
and 1ꢀhexyne with 1 equivalent of Ph3PAuSbF6 in CD2Cl2 revealed
that vinyl ether protons completely disappear while alkyne protons
were still present. See SI for the additional details.
19
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6

Page 7 of 7
Organic & Biomolecular Chemistry
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Gold Catalysis
Dinesh V. Vidhani, John W. Cran, Marie
E. Krafft* and Igor V. Alabugin*
__________ Page – Page
Gold (I)-Catalyzed Propargyl Claisen
Rearrangement: Catalytic Pathways
from Higher Energy Au(I)-Substrate
Complexes and Reactant Deactivation
via Unproductive Complexation
Computational and experimental analysis of unusual substituent
effects in the Au-catalyzed propargyl Claisen rearrangement revealed
new features important for the future development of Au(I) catalysis.
Despite the higher stability of Au-alkyne complexes, they do not
always correspond to the catalytically active compounds. Instead, the
product emanates from the higher energy Au(I)-oxygen complex
reacting via a low barrier cation-accelerated oxonia Claisen pathway.
Additionally, both intra and intermolecular competition from other
Lewis bases present in the system, for the Au(I) catalyst, can lead to
unproductive stabilization of the substrate/catalyst complex,
explaining hitherto unresolved substituents effects.