Kinetics and Mechanism of Allene Racemization Catalyzed by a Gold N-Heterocyclic Carbene Complex

Article abstract of DOI:10.1021/acs.organomet.6b00307

The kinetics of the racemization of 1,3-disubstituted allenes catalyzed by (IPr)AuOTf (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidine) has been investigated. The rate of gold-catalyzed allene racemization obeyed the following second-order rate law: rate = k_rac[allene][Au]. An analysis of the rate of the gold-catalyzed racemization of 1-aryl-1,2-butadienes as a function of allene electron donor ability established moderate depletion of electron density on the C1 allenyl carbon atom in the rate-limiting transition state for racemization. Analysis of the temperature dependence of the rate of racemization of 1-(p-tolyl)-1,2-butadiene established the activation parameters ΔH^∞ = 8.3 ± 1 kcal mol^-1 and ΔS^∞ = -28 ± 4 eu. These observations were in accord with a mechanism for allene racemization involving turnover-limiting, intermolecular allene exchange followed by rapid allene stereomutation.

Full text of DOI:10.1021/acs.organomet.6b00307

Article
pubs.acs.org/Organometallics
Kinetics and Mechanism of Allene Racemization Catalyzed by a Gold
N‑Heterocyclic Carbene Complex
Hao Li, Robert J. Harris, Kohki Nakafuku, and Ross A. Widenhoefer*
Department of Chemistry, French Family Science Center, Duke University, Durham, North Carolina 27708, United States
*
S Supporting Information
ABSTRACT: The kinetics of the racemization of 1,3-disubstituted allenes
catalyzed by (IPr)AuOTf (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-
ylidine) has been investigated. The rate of gold-catalyzed allene racemization
obeyed the following second-order rate law: rate = k [allene][Au]. An analysis
rac
of the rate of the gold-catalyzed racemization of 1-aryl-1,2-butadienes as a
function of allene electron donor ability established moderate depletion of
electron density on the C1 allenyl carbon atom in the rate-limiting transition
state for racemization. Analysis of the temperature dependence of the rate of
racemization of 1-(p-tolyl)-1,2-butadiene established the activation parameters
⧧
−1
⧧
ΔH = 8.3 ± 1 kcal mol and ΔS = −28 ± 4 eu. These observations were in
accord with a mechanism for allene racemization involving turnover-limiting,
intermolecular allene exchange followed by rapid allene stereomutation.
INTRODUCTION
detected prior to the onset of intermolecular allene exchange
■
⧧
−1
with an energy barrier of ΔG
≥ 17.4 kcal mol .
The proliferation of gold(I)-catalyzed methods for the
functionalization of C−C multiple bonds represents one of
the most significant developments in homogeneous catalysis
298
Scheme 1
1
over the past decade. In addition to alkynes, alkenes, and allylic
alcohols, allenes have proven to be particularly active and
2
versatile substrates for gold-catalyzed functionalization. Gold-
catalyzed transformations of allenes include cycloaddition with
3
alkenes and dienes and hydrofunctionalization with carbon
4
and heteroatom nucleophiles. A distinguishing feature of
allenes is the potential for axial chirality, and as such, there has
been considerable interest in the gold-catalyzed stereospecific5
functionalization of enantiomerically enriched chiral allenes.
Although high levels of chirality transfer have been realized,
efficient chirality transfer is often compromised by concomitant
6
7
gold-catalyzed allene racemization. Alternatively, we and
8
others have exploited gold(I)-catalyzed allene racemization
to realize the stereoconvergent enantioselective hydrofunction-
alization of chiral racemic allenes and propargylic acetates.
Despite the relevance of allene racemization to the gold(I)-
catalyzed functionalization of allenes, our understanding of
gold(I)-catalyzed allene racemization has been largely restricted9
to the information gleaned from computational analyses.
Toward an experimentally grounded understanding of the
coordination chemistry of gold allene complexes, we have
investigated the dynamic behavior of well-defined cationic gold
We subsequently investigated the kinetics of the racemization
of axially chiral 1-aryl-1,2-butadienes catalyzed by cationic gold
11
phosphine complexes. These studies supported a mechanism
involving rapid and reversible intermolecular allene exchange
from cationic gold π-allene complexes (I) followed by turnover-
10
1
π-allene complexes. In particular, variable-temperature NMR
limiting formation of an achiral η -allylic cation intermediate
⧧
−1
2
(
(
II) with energy barriers of ΔG
= 17−20 kcal mol
analysis of the gold(I) π-4,5-nonadiene complex {(P)Au[η -n-
298
+
−
Scheme 2). The significant transfer of electron density from
Pr(H)CCC(H)n-Pr]} SbF (P = P(t-Bu) o-biphenyl)
6
2
and related compounds established facile π-face exchange
< 10 kcal mol ) through chiral η -allene intermediates
Scheme 1). In comparison, allene stereomutation was not
⧧
−1
1
(ΔG
Received: April 16, 2016
298
(
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.6b00307
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Article
Scheme 2
Scheme 3
the allene ligand to the gold phosphine moiety in the transition
state for racemization (TS1) was established through Hammett
analysis of gold-catalyzed allene racemization as a function of
allene and phosphine electron-donor ability. Rapid intermo-
lecular allene exchange relative to racemization was independ-
ently confirmed through spin saturation transfer analysis of gold
π-allene complexes in the presence of free allene. Recently,
Ballesteros and co-workers have directly observed and
1
spectroscopically characterized gold η -allylic cations generated
via ring-opening cycloaddition of 6-aryl-6-(arylethynyl)-
12
bicyclo[3.1.0]hex-2-enes.
Figure 1. Pseudo-first-order plots for the racemization of (S)-1 (100
N-heterocyclic carbenes (NHCs) such as 1,3-bis(2,6-
diisopropylphenyl)imidazol-2-ylidine (IPr) are common sup-
porting ligands for gold catalysis, including gold-catalyzed
mM, 97% ee) catalyzed by a 1:1 mixture of (IPr)AuCl and AgOTf (2.5
(×), 5.0 (△), 7.5 (□
), and 10 mM (○)) in toluene at 25 °C.
13
allene hydrofunctionalization. Owing to the relevance of gold
NHC complexes in allene functionalization, we sought to gain
information regarding the mechanism and energetics of allene
racemization catalyzed by gold IPr complexes. To this end, we
have investigated the kinetics of the racemization of 1,3-
disubstituted allenes catalyzed by cationic gold IPr complexes.
Herein we report the results of these investigations along with
additional experiments involving allene racemization catalyzed
by gold phosphine complexes that reveal some notable
Table 1. Pseudo-First-Order Rate Constants for the
Racemization of Axially Chiral Allenes Catalyzed by a 1:1
Mixture of (L)AuCl (L = IPr, P) and AgOTf in Toluene
a
entry
allene
L
[cat.] (mM) temp (°C)
104kobs (s−1
)
1
2
3
4
(S)-1
IPr
IPr
IPr
IPr
IPr
IPr
IPr
IPr
IPr
IPr
IPr
IPr
IPr
P1
P1
P1
2.5
5.0
25
25
25
25
25
25
25
25
25
25
9
3.96 ± 0.13
5.52 ± 0.14
10.6 ± 0.3
14.9 ± 0.7
13.7 ± 0.4
2.46 ± 0.05
5.17 ± 0.05
16.7 ± 0.4
0.580 ± 0.009
0.323 ± 0.005
3.28 ± 0.06
15.9 ± 0.3
(S)-1
(S)-1
7.5
(S)-1
10.0
10.0
10.0
b
+
+
5
(S)-1
differences in the behavior of (IPr)Au and (P)Au allene
complexes. These differences provide new insights into the
subtle differences in σ-donor/π-acceptor behavior of phos-
phines and NHC ligands bound to a cationic gold(I) fragment.
c
6
(S)-1
7
8
9
(R)-3a
(R)-3b
(R)-3c
(R)-3d
(R)-3a
(R)-3a
(R)-3a
(S)-1
0.20
0.20
0.20
0.20
0.20
0.20
0.10
10
11
12
13
14
15
16
RESULTS
■
Allene Racemization Catalyzed by (IPr)AuOTf. When a
toluene solution of (S)-2,3-pentadienyl benzoate ((S)-1, 97%
ee) (100 mM) and a catalytic amount of (IPr)AuOTf (5.0 mM;
40
51
25
35
45
11.6 ± 0.3
10.0
0.543 ± 0.006
1.49 ± 0.06
5.01 ± 0.19
14
generated in situ from (IPr)AuCl and AgOTf ) was stirred at
5 °C and monitored periodically by HPLC equipped with a
chiral stationary phase, (S)-1 underwent complete racemization
≤2% ee) within 2 h with concomitant formation of a small
amount (∼5%) of penta-1,3-dien-2-yl benzoate (2) via a formal
3,3]-sigmatropic rearrangement (Scheme 3) previously
(S)-1
9.6
2
(S)-1
10.2
a
Error limits refer to the standard deviation of the corresponding
(
b
c
linear regression plot. AgOTf/(IPr)AuCl = 2. AgOTf/(IPr)AuCl =
.5.
0
[
15
documented by Gagosz. A plot of ln [ee((S)-1)] versus
time was linear to >3 half-lives with a pseudo-first-order rate
constant of kobs = (5.52 ± 0.14) × 10
constants for the racemization of (S)-1 catalyzed by (IPr)-
AuOTf were determined as a function of catalyst concentration
from 2.5 to 10.0 mM (Figure 1; Table 1, entries 1−4). A plot of
−
4 −1
s
(Figure 1; Table 1,
entry 2), which established the first-order dependence of the
rate of racemization on [(S)-1]. Continued stirring at 25 °C for
k
versus catalyst concentration was linear (Figure 2), which
obs
24 h led to complete consumption of (S)-1 to form 2 in 88%
established the first-order dependence of the rate on catalyst
yield as a 1.2:1 mixture of isomers.
To determine the dependence of the rate of allene
racemization on catalyst concentration, pseudo-first-order rate
concentration and overall the following second-order rate law:
rate = k [(S)-1][Au], where k = 0.146 ± 0.013 s−
1
M
−1
rac
rac
−1
⧧
(ΔG 2 = 18.6 ± 0.1 kcal mol ). In comparison, the second-
98
B
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Article
+
Figure 3. Plot of log krac versus the Hammett σ parameter for the
racemization of (R)-3a−d (20 mM) catalyzed by a 1:1 mixture of
Figure 2. Plot of kobs versus catalyst concentration for the racemization
of (S)-1 (100 mM, 97% ee) catalyzed by a 1:1 mixture of (IPr)AuCl
and AgOTf in toluene at 25 °C.
+
(
IPr)AuCl and AgOTf (0.20 mM) in toluene at 25 °C (ρ = −1.56 ±
0
.02).
order rate constant for the conversion of (S)-1 to 2 was k =
2
−3
−1 −1
⧧
(
2.57 ± 0.07) × 10
M
s
(ΔG
= 20.97 ± 0.01 kcal
2
98
−1
mol ; see the Supporting Information). The rate of gold(I)-
catalyzed racemization of (S)-1 was independent of [AgOTf],
provided that sufficient silver triflate was present to fully
14
convert (IPr)AuCl to (IPr)AuOTf (Table 1, entries 5 and 6),
and treatment of (S)-1 (100 mM) with AgOTf (10 mM) in the
absence of (IPr)AuCl led to no detectable racemization after 2
h at 25 °C. Interestingly, employment of 0.5 equiv of AgOTf
relative to (IPr)AuCl led to reduction in the rate of
racemization which far exceeded that predicted by the
decreased concentration of (IPr)AuOTf, presumably due to
the formation of the catalytically inactive chloride-bridged gold
+
−
16−19
species {[(IPr)Au] (μ-Cl)} OTf .
2
Figure 4. Eyring plot of the second-order rate constants (k ) for the
racemization of (R)-3b (20 mM, 99% ee) catalyzed by a 1:1 mixture of
rac
To evaluate the dependence of the rate of allene
racemization catalyzed by (IPr)AuOTf on the electron donor
ability of the allene, we determined pseudo-first-order rate
constants for the racemization of the 1-aryl-1,2-butadienes (R)-
(IPr)AuCl and AgOTf (0.20 mM) in toluene over the temperature
range 9−51 °C.
(
(
(
4-X-C H )C(H)CC(H)Me (X = H (3a), Me (3b), CF
6
4
3
3c), NO (3d); 20 mM) catalyzed by a 1:1 mixture of
of 1-aryl-1,2-butadienes catalyzed by gold phosphine com-
2
11
IPr)AuCl and AgOTf (0.20 mM) at 25 °C (eq 1; Table 1,
plexes, kinetic data are absent regarding the racemization of
chiral, 1,3-dialkyl allenes that would allow direct comparisons to
the energetics of the racemization of (S)-1 catalyzed by
(
IPr)AuOTf. To this end, a toluene solution of (S)-1 (100
mM) and a catalytic amount of (P)AuOTf (10.0 mM generated
2
0
in situ from a 1:1 mixture of (P)AuCl and AgOTf ) was stirred
at 25 °C and monitored periodically by HPLC. A plot of ln
[ee((S)-1)] versus time was linear to >3 half-lives with a
pseudo-first-order rate constant of kobs = (5.43 ± 0.06) × 10−
entries 7−10). The corresponding second-order rate constants
(k = k /[Au]) increased 50-fold as the electron donor
5
k
rac
rac
obs
−1
ability of the allene aryl group increased from X = NO (3d) to
s , which corresponds to a second-order rate constant of krac
=
2
+
−3
−1 −1
X = Me (3b). A plot of log krac versus the Hammett σ
k
obs/[Au] = 5.43 × 10
M
s
(Table 1, entry 14). Pseudo-
parameter provided an excellent fit with a reaction constant of
first-order rate constants for the racemization of (S)-1 catalyzed
by (P)AuCl/AgOTf were likewise determined at 35 and 45 °C
(Table 1, entries 15 and 16). An Eyring plot of the
corresponding second-order rate constants provided the
+
ρ = −1.56 ± 0.02 (Figure 3), which established the depletion
of electron density at the C1 allenyl carbon atom in the
transition state for racemization.
⧧
−1
⧧
To determine the activation parameters for allene
racemization catalyzed by (IPr)AuOTf, pseudo-first-order rate
constants for the racemization of (R)-3a catalyzed by a 1:1
mixture of (IPr)AuCl and AgOTf in toluene were determined
as a function of temperature from 9 to 51 °C (Table 1, entries 7
and 11−13). An Eyring plot of the corresponding second-order
activation parameters: ΔH = 20 ± 1 kcal mol and ΔS =
−2 ± 2 eu (Figure 5), which are fully consistent with our
previously proposed mechanism for allene racemization
catalyzed by gold phosphine complexes involving turnover-
limiting unimolecular stereomutation of a π-allene complex to a
1
11
η -allylic cation.
⧧
rate constants krac provided the activation parameters ΔH =
−
1
⧧
DISCUSSION
8
.4 ± 1.3 kcal mol and ΔS = −28 ± 4 eu (Figure 4).
■
Allene Racemization Catalyzed by (P)AuOTf. Although
Comparison of Allene Racemization Catalyzed by
(IPr)AuOTf and (P)AuOTf. Three points regarding the
we have previously investigated the kinetics of the racemization
C
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Article
Scheme 4
Figure 5. Eyring plot of the second-order rate constants (k ) for the
rac
racemization of (S)-1 (100 mM, 97% ee) catalyzed by a 1:1 mixture of
(
P)AuCl and AgOTf (∼10 mM) in toluene over the temperature
2
⧧
range 25−45 °C.
cationic gold complex (IPr)Au(η -H CCMe ) (ΔH = 8 ± 1
2
2
kcal mol− and ΔS = −27 ± 4 eu). Similarly, the reaction
constant determined for the racemization of 1-aryl-1,2-
butadienes catalyzed by (IPr)AuOTf (ρ = −1.56) is similar
to that determined for the equilibrium displacement of
1
⧧
21
comparative kinetic data for the racemization of axially chiral,
+
1
(
,3-disubstituted allenes catalyzed by (IPr)AuOTf and
P)AuOTf are noteworthy. First, the activation parameters
determined for the racemization of (R)-3a catalyzed by
trifluoromethanesulfonate from (P)AuOTf with 1-aryl-1,2-
⧧
−1
⧧
+
11
(
IPr)AuOTf (ΔH = 8.4 ± 1.3 kcal mol ; ΔS = −28 ± 4
butadienes (ρ = −1.4). It should be noted, however, that
the former value presumably reflects the depletion of electron
density from the attacking allene in transition state for allene
exchange (TS2) relative to free allene, whereas the latter value
reflects the depletion of electron density of the allene ligand in
the ground-state, two-coordinate gold π-allene complex I
relative to free allene. Furthermore, our analyses of the
intermolecular π-ligand exchange of (P)Au+ π complexes
established the presence of competing ligand-dependent and
ligand-independent pathways, the latter of which may involve
transient coordination of the proximal o-biphenyl aryl group
that likewise maintains weak coordination to gold in the solid
However, the observed negative reaction constant
for the racemization of 1-aryl-1,2-butadiene catalyzed by
(IPr)AuOTf requires that allene exchange occur through a
eu) differ significantly from those determined for racemization
⧧
−1
of (S)-1 catalyzed by (P)AuOTf (ΔH = 20 ± 1 kcal mol ;
⧧
ΔS = −2 ± 2 eu). Second, the racemization of 1-aryl-1,2-
butadienes catalyzed by (IPr)AuOTf is much less sensitive to
+
the electron donor ability of the 2-aryl group (ρ = −1.56 ±
0
+
.02) than is racemization catalyzed by (P)AuOTf (ρ = −2.8
±
0.4). Third, (IPr)AuOTf is a more reactive catalyst for allene
racemization than is (P)AuOTf, especially for less electron-rich
allenes. For example, racemization of 1-(4-nitrophenyl)-1,2-
butadiene (3d) catalyzed by (IPr)AuOTf at 25 °C is ∼190
times faster than is racemization of 3d catalyzed by (P)-
10
1
1
10,22,23
AuOTf, while racemization of (S)-1 catalyzed by (IPr)AuOTf
is ∼28 times faster (ΔΔG = 1.9 kcal mol ) than is
racemization of (S)-1 catalyzed by (P)AuOTf.
state.
⧧
−1
24
Mechanism of Allene Racemization Catalyzed by
ligand-dependent, associative pathway.
(
IPr)AuOTf. Our observations regarding the racemization of
,3-disubstituted allenes catalyzed by (IPr)AuOTf, in particular
Our kinetic data for the racemization of 1,3-disubstituted
allenes catalyzed by gold phosphine and NHC complexes
highlight some notable differences regarding the behavior of
(IPr)Au(π-allene)+ and (P)Au(π-allene)+ complexes. For
example, the energy barriers for associative allene exchange
1
the modest reaction constant for the racemization of 1-aryl-1,2-
+
butadienes (ρ = −1.56 ± 0.02) and modest enthalpy of
⧧
−1
activation (ΔH = 8.3 ± 1 kcal mol ) and large negative
⧧
+
entropy of activation (ΔS = −28 ± 4 eu) for the racemization
for (IPr)Au(π-allene) complexes must be significantly larger
of (R)-3b, argue against a mechanism for racemization
than for (P)Au(π-allene)+ complexes, which presumably
reflects the greater steric shielding of the gold center by the
involving turnover-limiting, unimolecular stereomutation of a
gold π-allene complex via an η -allylic cation intermediate, as
1
25
aryl isopropyl groups of the IPr ligand relative to the P ligand.
was invoked for the racemization of 1-aryl-1,2-butadienes
catalyzed by cationic gold phosphine complexes (Scheme 2).
We have previously documented the strong dependence of the
rate of intermolecular π-ligand exchange of two-coordinate gold
π complexes on the steric bulk of the supporting ligand, in
particular the low energy barriers for π-ligand exchange
11
Rather, these data are consistent with a mechanism for allene
racemization involving turnover-limiting, associative allene
exchange of π-allene complexes I via the cationic three-
coordinate bis(allene) intermediate (S,R)-III followed by rapid
observed for sterically unencumbered Ph PAu π-complexes
3
⧧
−1 26
(ΔG ≤ 10 kcal mol ).
1
allene stereomutation, presumably via an η -allylic cation
As noted above, allene racemization catalyzed by (IPr)-
AuOTf is faster than is racemization catalyzed by (P)AuOTf.
Furthermore, because ligand exchange is turnover-limiting in
the former cases, the observed energy barriers for racemization
represent the upper limit of the energy barriers for allene
stereomutation, which suggests that the energy barriers for
intermediate II (Scheme 4). Superimposed on the productive
pathway for racemization are degenerate, nonproductive
pathways involving intermolecular exchange of coordinated
(
(
S)-allene with free (S)-allene and exchange of coordinated
R)-allene with free (R)-allene.
+
Supporting the proposed mechanism, the activation param-
unimolecular stereomutation of (IPr)Au(π-allene) complexes
+
eters for the racemization of (R)-3b catalyzed by (IPr)AuOTf
are not significantly different from those determined for the
intermolecular exchange of bound and free isobutylene with the
are much lower than for (P)Au(π-allene) complexes. In light
of the ligand effects identified in our investigation of allene
11
racemization catalyzed by gold phosphine complexes, this is
D
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Article
2
1,22
most surprising conclusion drawn from these kinetic inves-
tigations. In particular, we previously showed that the rate of
racemization of 1-(4-biphenyl)-1,2-butadiene catalyzed by gold
respect to alkene binding.
Most interesting is their
32
computational analysis of cationic metal carbonyl complexes,
which indicated that, in contrast to nickel tricarbonyl complexes
of the form (L)Ni(CO) that serve as the basis for the Tolman
electronic parameter, the C−O stretching frequency of
L)Au(CO) complexes is affected only by Au→L π back-
donation owing to inefficient transfer of the σ-donor electron
density from L to the C−O π* orbital. The calculated C−O
stretching frequencies for complexes (P)Au(CO) and (IPr)-
(
triaryl)phosphine complexes of the form [(4-C H X) P]-
6
4
3
3
34
AuOTf increased significantly with the decreasing electron
11
+
donor ability of the phosphine ligand (ρ = 2.4), consistent
(
with the transfer of electron density from the allene ligand to
the (PR )Au fragment in the transition state for allene
3
stereomutation (TS1).
+
The observations outlined in the preceding paragraph
therefore imply that IPr is less electron donating than is P,
which appears to contradict both the general perception of IPr
+
Au(CO) are similar, implying comparable Au→L π back-
donation for both ligands. However, the calculated total L→Au
electron donation is significantly greater for P (0.40 e) than for
IPr (0.27 e) owing to greater L→Au σ-donation in the case of
13
as a strong donor ligand to gold and our experimental
evaluation of the electrophilicity of the 12-electron fragments
32
+
+
21,22
P.
(
P)Au and (IPr)Au with respect to alkenes.
Specifically,
On the basis of these results, it appears plausible that, for the
Hammett analyses of the equilibrium binding affinities of para-
substituted vinyl arenes to the 12-electron cationic gold
fragments (P)Au and (IPr)Au relative to 3,5-bis-
stereomutation of (L)Au(π-allene)+ complexes, electron
depletion from the allene ligand in the ground state π-allene
complex increases with the increasing Au→L π back-donation
to the supporting ligand, which is greater for P than for IPr.
Conversely, electron depletion from the allene fragment in the
transition state for allene stereomutation (TS1) increases with
the decreasing net L→Au electron donation (L→Au σ
donation + Au→L π back-donation) from the supporting
ligand, which is greater for P than for IPr. Therefore, despite
(
trifluoromethyl)benzonitrile served as a measure of d→π*
back-bonding to the alkene ligand and, hence, the electro-
philicity of the respective (L)Au fragments. Significantly, the
reaction constant for vinyl arene complexation to (P)Au (ρ =
+
+
+
−
−
3.4) was significantly larger than was that for (IPr)Au (ρ =
2
1,22
2.4),
which established the greater depletion of electron
+
density from the vinyl arene upon complexation to (P)Au in
+
+
comparison to that to (IPr)Au and the greater electrophilicity
the greater electrophilicity of the (P)Au fragment relative to
(IPr)Au toward alkenes, the latter more effectively accepts
+
+
+
of the (P)Au fragment relative to the (IPr)Au fragment with
respect to alkene binding. However, it should be noted that
both of these values are significantly more negative than are the
reaction constants determined for the binding of vinyl arenes to
cationic Ag(I) (ρ = −0.77), Pt(II) (ρ = −1.32), and Pd(II)
electron density from the allene fragment in the transition state
for stereomutation owing to lower net L→Au electron
donation, thereby decreasing the energy of the transition
state for allene stereomutation.
As a final comment, it was noted in the Introduction that in
our investigation of the fluxional behavior of gold π-allene
complexes we were able only to assign a lower limit for the
energy barrier for allene stereomutation of ΔG ≥ 17.4 kcal
mol owing to the onset of intermolecular allene exchange.
The experimentally determined energy barrier for the
racemization of (S)-1 catalyzed by (P)AuOTf (ΔG = 20.5
kcal mol ) confirms our previous analysis and provides the
final value required for the complete energetic mapping of the
dynamic behavior of 1,3-dialkylallenes bound to the 12-electron
P)Au fragment, albeit with slightly different 1,3-dialkylallenes.
27
complexes (ρ = −1.44).
The most obvious rationale to this apparent contradiction is
+
+
that the relative electrophilicities of the (P)Au and (IPr)Au
fragments do not accurately reflect their ability to accept
electron density from the allene ligand in the transition state for
allene stereomutation (TS1). Whereas the π-allene ligand binds
to gold through a combination of allene→gold σ-donation and
gold→allene π-back bonding according to the Dewar−Chatt−
⧧
−1
10
⧧
−
1
2
8,29
Duncanson model,
there is a node on the C2 carbon atom
1
1
in the HOMO of the η -allylic cation π system and the η -allylic
cation should therefore behave as pure σ-donor ligand.
Therefore, Au→C π* back-bonding in the transition state for
allene stereomutation will be diminished relative to the ground
state with a concomitant increase in C→Au σ donation.
Because the σ-bonding framework of two-coordinate gold
complexes involves a three-center, four-electron L−Au−C σ
hyperbond through which both ligands compete for σ donation
+
(
CONCLUSIONS
■
We have studied the kinetics of the racemization of axially
chiral 1,3-disubstituted allenes catalyzed by (IPr)AuOTf, and
we have compared these kinetic data to relevant kinetic data for
the racemization of 1,3-disubstituted allenes catalyzed by gold
phosphine complexes such as (P)AuOTf. These results support
a mechanism for allene racemization catalyzed by (IPr)AuOTf
involving turnover-limiting intermolecular π-allene exchange
25
into a partially occupied sd(σ) gold(I) orbital, greater L→Au
σ donation from P relative to IPr would therefore destabilize
the transition state for allene stereomutation (TS1) for
+
+
(
P)Au(π-allene) relative to (IPr)Au(π-allene) .
Recent computational work by Belpassi and co-workers
1
coupled with rapid allene stereomutation, presumably via η -
directed toward disentangling the σ-donor and π-acceptor
behavior of supporting ligands in gold π complexes supports
allyic cation intermediates. Although the (P)Au+ fragmen+t
possesses greater electrophilicity than does the (IPr)Au
fragment with respect to alkene binding, allene racemization
catalyzed by (IPr)AuOTf was faster than was allene
racemization catalyzed by (P)AuOTf. This observation implies
3
0−33
this hypothesis.
First, their computational analysis of
(
NHC)AuL′ complexes indicates that the extent of Au→NHC
30
π back-donation is dependent on the nature of L′. In the case
+
of (L)Au(π-ethylene) complexes, Au→π* back-bonding to the
+
ethylene ligand is greater for IPr than for PCy , implying
that the (IPr)Au fragment is better able to accept electron
3
31
diminished Au→L back-donation for IPr relative to PCy3,
density from the allene ligand in the transition state for allene
stereomutation than is the (P)Au+ fragment, which was
attributed to the greater σ-donor character of P relative to IPr.
which is consistent with our experimental observations
+
regarding the electrophilicity of (L)Au gold fragments with
E
DOI: 10.1021/acs.organomet.6b00307
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(
5) (a) Patil, N. T. Chem. - Asian J. 2012, 7, 2186. (b) Bongers, N.;
EXPERIMENTAL SECTION
Kinetic Analysis of Racemization. A solution of (IPr)AuOTf
■
Krause, N. Angew. Chem., Int. Ed. 2008, 47, 2178.
6) (a) Nishina, N.; Yamamoto, Y. Angew. Chem., Int. Ed. 2006, 45,
(
(
(
0.010 mmol) in toluene was prepared by stirring a mixture of
−2
−2
3314. (b) Patil, N. T.; Lutete, L. M.; Nishina, N.; Yamamoto, Y.
Tetrahedron Lett. 2006, 47, 4749. (c) Zhang, Z.; Liu, C.; Kinder, R. E.;
Han, X.; Qian, H.; Widenhoefer, R. A. J. Am. Chem. Soc. 2006, 128,
IPr)AuCl (6.2 mg, 1.0 × 10 mmol) and AgOTf (2.6 mg, 1.0 × 10
1
4
mmol) in toluene (1.0 mL) for 5 min at 25 °C. To this was added a
solution of (S)-1 (37.6 mg, 0.20 mmol) in toluene (1.0 mL) (total
volume 2.0 mL, [(S)-1] = 100 mM, [(IPr)AuOTf] = 5.0 mM), and the
resulting solution was stirred in a thermostated oil bath at 25 ± 0.5 °C.
To monitor reaction progress, aliquots were removed periodically via
syringe and analyzed by HPLC equipped with a chiral stationary phase
9066. (d) Liu, Z.; Wasmuth, A. S.; Nelson, S. G. J. Am. Chem. Soc.
2006, 128, 10352. (e) Morita, N.; Krause, N. Angew. Chem., Int. Ed.
2006, 45, 1897. (f) Belting, V.; Krause, N. Org. Lett. 2006, 8, 4489.
(
g) Sherry, B. D.; Maus, L.; Laforteza, B. N.; Toste, F. D. J. Am. Chem.
Soc. 2006, 128, 8132. (h) Morita, N.; Krause, N. Org. Lett. 2004, 6,
121. (i) Hoffmann-Roder, A.; Krause, N. Org. Lett. 2001, 3, 2537.
(
t (major) = 21.0 min, t (minor) = 18.3 min; hexanes:isopropyl
r
r
4
alcohol 99.8:0.2 @ 0.5 mL/min). The pseudo-first-order rate constant
−
4
−1
(j) Boutier, A.; Kammerer-Pentier, C.; Krause, N.; Prestat, G.; Poli, G.
Chem. - Eur. J. 2012, 18, 3840. (k) Kinder, R. E.; Zhang, Z.;
Widenhoefer, R. A. Org. Lett. 2008, 10, 3157. (l) Sherry, B. D.; Toste,
F. D. J. Am. Chem. Soc. 2004, 126, 15978. (m) Morita, N.; Krause, N.
Eur. J. Org. Chem. 2006, 2006, 4634. (n) Zhang, Z.; Widenhoefer, R. A.
Org. Lett. 2008, 10, 2079. (o) Lee, J. H.; Toste, F. D. Angew. Chem., Int.
Ed. 2007, 46, 912. (p) Deutsch, C.; Gockel, B.; Hoffmann-Ro
Krause, N. Synlett 2007, 2007, 1790.
(7) (a) Butler, K. L.; Tragni, M.; Widenhoefer, R. A. Angew. Chem.,
Int. Ed. 2012, 51, 5175. (b) Zhang, Z.; Bender, C. F.; Widenhoefer, R.
A. J. Am. Chem. Soc. 2007, 129, 14148.
for racemization (kobs = (5.52 ± 0.14) × 10 s ) was determined
from a plot of ln [ee((S)-1))] versus time (Figure 1; Table 1, entry
3
5,36
1).
Pseudo-first-order rate constants for the racemization of (S)-1
catalyzed by a 1:1 mixture of (IPr)AuCl and AgOTf were determined
as a function of [catalyst] and [AgOTf] (Table 1, Figure 1, and Figure
S1 in the Supporting Information) employing analogous procedures.
The second-order rate constant (krac = 0.146 ± 0.013 M− s ) for the
racemization of (S)-1 catalyzed by (IPr)AuOTf was determined from a
plot of kobs versus [catalyst] (Figure 2). Error limits for kinetic data
refer to the standard deviation of the corresponding linear regression
plot. Additional experimental details and plots for the kinetic analysis
of the racemization of 1-aryl-1,2-butadienes catalyzed by (IPr)AuOTf,
the racemization of (S)-1 catalyzed by (P)AuOTf and for the
conversion of (S)-1 to 2 are included in the Supporting Information.
1 −1
̈
der, A.;
(8) Wang, Y.-M.; Kuzniewski, C. N.; Rauniyar, V.; Hoong, C.; Toste,
F. D. J. Am. Chem. Soc. 2011, 133, 12972.
(9) (a) Montserrat, S.; Ujaque, G.; Lop
Lledos, A. Top. Curr. Chem. 2011, 302, 225. (b) Benitez, D.;
Tkatchouk, E.; Gonzalez, A. Z.; Goddard, W. A., III; Toste, T. D. Org.
Lett. 2009, 11, 4798. (c) Trillo, B.; Lopez, F.; Montserrat, S.; Ujaque,
G.; Castedo, L.; Lledos, A.; Mascarenas, J. L. Chem. - Eur. J. 2009, 15,
3336. (d) Malacria, M.; Fensterbank, L.; Gandon, V. Top. Curr. Chem.
2011, 302, 157. (e) Fernandez, I.; Cossío, F. P.; de Cozar, A.; Lledos
A.; Mascarenas, J. L. Chem. - Eur. J. 2010, 16, 12147. (f) Trillo, B.;
Lopez, F.; Montserrat, S.; Ujaque, G.; Castedo, L.; Lledos, A.;
Mascarenas, J. L. Chem. - Eur. J. 2009, 15, 3336. (g) Alonso, I.; Trillo,
B.; Lopez, F.; Montserrat, S.; Ujaque, G.; Castedo, L.; Lledos, A.;
Mascarenas, J. L. J. Am. Chem. Soc. 2009, 131, 13020. (h) Gandon, V.;
Lemiere, G.; Hours, A.; Fensterbank, L.; Malacria, M. Angew. Chem.,
Int. Ed. 2008, 47, 7534. (i) Soriano, E.; Fernandez, I. Chem. Soc. Rev.
014, 43, 3041.
́
̃
ez, F.; Mascarenas, J. L.;
́
ASSOCIATED CONTENT
■
́
*
S
Supporting Information
́
̃
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.6b00307.
́
́
,
̃
́
́
General methods, experimental details regarding the
synthesis of enantiomerically enriched allenes and gold
complexes, kinetic data, and in situ spectroscopic analysis
of catalytic reactions (PDF)
̃
́
́
̃
́
́
2
AUTHOR INFORMATION
■
*
(10) (a) Brown, T. J.; Sugie, A.; Dickens, M. G.; Widenhoefer, R. A.
Organometallics 2010, 29, 4207. (b) Brown, T. J.; Sugie, A.; Dickens,
M. G.; Widenhoefer, R. A. Chem. - Eur. J. 2012, 18, 6959.
Corresponding Author
E-mail for R.A.W.: rwidenho@chem.duke.edu.
(
11) Harris, R.; Nakafuku, N.; Li, H.; Widenhoefer, R. A. Chem. - Eur.
J. 2014, 20, 12245.
12) Tudela, E.; Gonzalez, J.; Vicente, R.; Santamaría, J.; Rodríguez,
Notes
The authors declare no competing financial interest.
(
M. A.; Ballesteros, A. Angew. Chem., Int. Ed. 2014, 53, 12097.
(13) (a) Gatineau, D.; Goddard, J.-P.; Mouris-Mansuy, V.;
Fensterbank, L. Isr. J. Chem. 2013, 53, 892. (b) Nolan, S. P. Acc.
Chem. Res. 2011, 44, 91. (c) Díez-Gonzalez, S.; Marion, N.; Nolan, S.
P. Chem. Rev. 2009, 109, 3612. (d) Lin, J. C. Y.; Huang, R. T. W.; Lee,
C. S.; Bhattacharyya, A.; Hwang, W. S.; Lin, I. J. B. Chem. Rev. 2009,
109, 3561. (e) Marion, N.; Nolan, S. P. Chem. Soc. Rev. 2008, 37, 1776.
(f) Klahn, P.; Kirsch, S. F. ChemCatChem 2011, 3, 649.
ACKNOWLEDGMENTS
■
We acknowledge the NSF (CHE-1465209) for support of this
research.
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Organometallics XXXX, XXX, XXX−XXX

Organometallics
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21
(
IPr)Au(η -H CCMe ) supports a mechanism for catalytic allene
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G
DOI: 10.1021/acs.organomet.6b00307
Organometallics XXXX, XXX, XXX−XXX