Gold-catalyzed 1,2-/1,2-bis-acetoxy migration of 1,4-bis-propargyl acetates: A mechanistic study

Article abstract of DOI:10.1002/chem.201103472

The late transition metal catalyzed rearrangement of propargyl acetates offers an interesting platform for the development of synthetically useful transformations. We have recently shown that gold complexes can catalyze a highly selective tandem 1,2-/1,2-bis-acetoxy migration in 1,4-bis-propargyl acetates to form 2,3-bis-acetoxy-1,3-dienes. In this way, (1Z,3Z)- or (1Z,3E)- and (1E,3Z)-1,3-dienes could be obtained in a stereocontrolled manner depending on the electronic and steric features of the ancillary ligand bound to gold and the substituents at the propargylic positions. In this work, we report an experimental study on the scope of this transformation, plus a detailed theoretical examination of the reaction mechanism, which has revealed the key features responsible for the reaction stereoselectivity. Synthetic applications towards the one-pot synthesis of quinoxaline heterocycles and tandem Diels-Alder processes have also been devised. Copyright

Full text of DOI:10.1002/chem.201103472

FULL PAPER
DOI: 10.1002/chem.201103472
Gold-Catalyzed 1,2-/1,2-Bis-Acetoxy Migration of 1,4-Bis-Propargyl
Acetates: A Mechanistic Study
Teresa de Haro,[a] Enrique Gꢀmez-Bengoa,[b] Riccardo Cribiffl,[a] Xiaogen Huang,[a] and
Cristina Nevado*[a]
Abstract: The late transition metal cat-
alyzed rearrangement of propargyl ace-
tates offers an interesting platform for
the development of synthetically useful
transformations. We have recently
shown that gold complexes can cata-
lyze a highly selective tandem 1,2-/1,2-
bis-acetoxy migration in 1,4-bis-prop-
argyl acetates to form 2,3-bis-acetoxy-
1,3-dienes. In this way, (1Z,3Z)- or
(1Z,3E)- and (1E,3Z)-1,3-dienes could
be obtained in
a
stereocontrolled
on the scope of this transformation,
plus a detailed theoretical examination
of the reaction mechanism, which has
revealed the key features responsible
for the reaction stereoselectivity. Syn-
thetic applications towards the one-pot
synthesis of quinoxaline heterocycles
and tandem Diels–Alder processes
have also been devised.
manner depending on the electronic
and steric features of the ancillary
ligand bound to gold and the substitu-
ents at the propargylic positions. In this
work, we report an experimental study
Keywords: gold
catalysis · ligand effects · propargyl
acetates · stereoselectivity
·
homogeneous
Introduction
The rearrangement of propargylic acetates in the presence
of catalytic amounts of late transition metal complexes is
recognized as a useful synthetic tool in organic chemistry.[1]
The first examples of this chemistry, reported by Ohloff in
the late 1970s, used zinc salts to promote the reaction.[2] In
contrast, the synthetic applications developed by Rauten-
strauch in the 1980s to construct cyclopentenones using
1-ethynyl-2-propenyl acetates as starting materials used pal-
ladium salts as catalysts.[3] Other research groups have con-
tributed in the meantime to the development of these trans-
formations utilizing other transition metals. Thus, Ohe and
Uemura reported the use of ruthenium complexes,[4] where-
as Malacria exploited the alkynophilicity of platinum salts[5]
to develop novel transformations. The rise to prominence of
gold in the catalysis arena also contributed to the further ex-
pansion of these processes.[6] All of these precedents have
helped to define a clearer mechanistic picture of these trans-
formations (Scheme 1).[1,7] It is widely accepted that, upon
Scheme 1. Mechanistic proposal for the metal-catalyzed rearrangement
of propargyl acetates.
activation of the alkyne by coordination of the metal (I),
terminal alkynes or alkynes substituted with electron-defi-
cient groups react by 1,2-migration of the carboxylate
moiety,[8] whereas internal alkynes prefer to undergo a
AHCTUNGTRENNUNG
[3,3]-sigmatropic acyloxy rearrangement[9] (paths A and B in
Scheme 1, respectively). 1,2-Migration is proposed to pro-
ceed via a metal carbene (III), whereas [3,3]-sigmatropic re-
arrangement might occur via an allenyl acetate (V) in
a single process or stepwise by a second acetate migration
from III, meaning that these two competitive processes are
mechanistically connected (Scheme 1). Metal carbenes (III)
[a] T. de Haro, Dr. R. Cribiffl, Dr. X. Huang, Prof. Dr. C. Nevado
Organic Chemistry Institute
University of Zürich
Winterthurerstrasse 190, 8057 Zürich (Switzerland)
Fax : (+41)44-6356812
can undergo prototypical reactions such as alkene or diene
[10]
E-mail: nevado@oci.uzh.ch
À
cyclopropanation, insertion into C H bonds, and so on.
[b] Prof. Dr. E. Gómez-Bengoa
Departamento de Química Orgµnica I
Universidad del Pais Vasco
Apdo 1072
On the other hand, allenyl acetates (V) can be further acti-
vated in the presence of a metal catalyst, leading to further
transformations.[11]
The general behavior summarized in Scheme 1 for termi-
nal versus internal alkynes is subject to a few exceptions.
Ohe and co-workers demonstrated that 1,3-diynes and
20080 Donostia - San Sebastiµn (Spain)
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triynes bearing acetoxy groups at the propargylic positions
undergo a 1,2-OAc migration followed by a [1,3]-carbene
shift triggering subsequent transformations in the presence
of ruthenium catalysts.[12] Transformations triggered by plati-
num complexes have also been reported in this context.[13]
Zhang and co-workers recently reported a gold-catalyzed
1,2-acyloxy migration in internal alkynes to give the corre-
sponding 2-pivaloxy-1,3-dienes, for which both a bulky mi-
grating group and catalyst were required.[14] In this context,
we also discovered that 1,4-bis-propargyl acetates can be
transformed into 2,3-bis-acetoxy-1,3-dienes through a highly
selective tandem 1,2-/1,2-bis-acetoxy migration catalyzed by
gold.[15] In addition, depending on the electronic and steric
features of the ancillary ligand bound to gold, (1Z,3Z)- or
(1Z,3E)- and (1E,3Z)-1,3-dienes could be obtained in a ste-
reocontrolled manner.[16] The reaction was proposed to pro-
ceed through the formation of Au carbene VIII upon the
first 1,2-migration of an acetoxy group. A second migration
in VIII to give the 1,3-allenyl acetate is disfavored due to
the presence of a second ester group at the alfa position of
the carbenic carbon, which migrates to give bis-acetoxy
diene IX (Scheme 2).
vent. In the presence of 5 mol% catalyst at room tempera-
ture, a completely unselective mixture of (Z,Z)-, (E,Z)-, and
(E,E)-2,3-bis
tained (Table 1, entry 1). The reaction in the presence of
[(IPr)Au(NTf2)] (IPr=bis(2,6-diisopropylphenyl)imidazol-2-
ACHTUNGTREN(NUNG acetoxy)-1,3-dienes (2a, 3a, and 2a’) was ob-
AHCTUNGTRENNUNG
ylidene) afforded only 2a and 3a in a 10:1 ratio, so that 2a
could be isolated in 86% yield (Table 1, entry 2).[17] The cat-
alyst loading could be decreased below 1 mol%, although
longer reaction times were then required (Table 1, entries 3–
5). We also evaluated the effect of the solvent on the reac-
tion outcome. More polar solvents such as THF or CH3CN
afforded comparable levels of efficiency while improving
the reaction selectivity (Table 1, entries 6 and 7). However,
a less polar solvent such as toluene provided higher selectiv-
ity in favor of 2a (28:1) although the conversion was lower
(Table 1, entry 8). The use of a more electron-deficient
phosphite ligand on gold shifted the selectivity of the reac-
tion in favor of 3a (Table 1, entry 9). However, the selectivi-
ty seems to be related to steric factors, as [(PPh3)AuACHTUNGTRENNUNG(NTf2)]
afforded a 1:18:1 mixture of isomers, from which 3a could
be isolated in 80% yield (Table 1, entry 10). Again, polar
solvents afforded comparable levels of selectivity (Table 1,
entries 11 and 12), but in con-
trast to entry 8, the use of tolu-
ene not only eroded the effi-
ciency but also the selectivity of
the reaction (Table 1, entry 13).
We decided to continue our
study with the conditions corre-
sponding to entry 2 (protocol 1)
Scheme 2. Tandem 1,2-/1,2-bisACTHUNTGRNEUNG(acetoxy) migration.
and entry 10 (protocol 2) of
Herein, we report a detailed study on the scope of this
transformation. In addition, a detailed computational study
at the DFT level has been carried out, revealing the rather
complex mechanistic picture governing these transforma-
tions, and explaining the key role that the ancillary
Table 1, which selectively furnished (Z,Z)- and (Z,E)-dienes,
respectively. We focused on symmetrically substituted sub-
strates related to 1a. Under the abovementioned conditions,
a meta-methoxy- (1b) and a 3,5-dimethoxyphenyl-substitut-
ligand on gold plays in determining their stereose-
Table 1. Optimization of the reaction conditions.
lectivity. Two different synthetic applications taking
advantage of the 2,3-bis-acetoxy-1,3-dienes pro-
duced in these reactions have also been devised:
first, as diene partners for Diels–Alder cycloaddi-
tions, and second, as precursors of 1,2-diketones for
the one-pot construction of quinoxalines in the
Entry
Catalyst
Mol%
Solvent
Time [h]
Conv.[a]
Ratio[b]
presence of 1,2-diACHTUNGTRENNUNGamines.
1
2
3
4
5
6
7
8
[(L)AuCl2]
5
5
2
1
0.5
2
2
2
2
2
2
2
2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
CH3CN
toluene
CH2Cl2
CH2Cl2
THF
2
0.7
1.5
3
12
2
3
3
0.3
0.7
2
78
94 (86)
90
81
78
80
68
46
83
1:1:1
A
R
10:1:0[c]
10:1:0
10:1:0
10:1:0
20:1:0
15:1:0
28:1:0
4:14:1
1:18:1
1:14:1
1:21:1
1.5:9:1
A
U
A
U
Results and Discussion
A
U
A
U
Reaction scope and limitations: Due to the highly
carbocationic nature of the reaction intermediates
proposed in Scheme 2, we decided to use 1,4-diphe-
nylbut-2-yne-1,4-diyldiacetate 1a as a benchmark
substrate, so that the aromatic ring could stabilize
the developing positive electron density generated
in the course of the reaction. Our screening of reac-
tion conditions commenced with dichloro(pyridine-
A
U
A
U
9
T
N
10
11
12
13
A
U
82 (80)
56
82
A
U
A
U
CH3CN
toluene
2
2
A
U
53
[a] Yield (%). [b] Ratio determined by 1H NMR spectroscopy. [c] The same ratio was
obtained in a reaction catalyzed by [(IPr)Au(SbF6)] (5 mol%) generated in situ from
AHCTUNGTRENNUNG
2-carboxylato)goldACHTUNGTRENNUNG(III) in dichloromethane as sol- [(IPr)AuCl] and AgSbF6 (Ref. [18]). L=Pyridine-2-carboxylate.
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Mechanistic Study of Acetoxy Migration
FULL PAPER
ed substrate (1c) could be con-
verted into the corresponding
(Z,Z)- and (Z,E)-1,3-dienes
2b,c and 3b,c, respectively
(Table 2, entries 1/2 and 5/6).
As observed for 1a, the reac-
tions of 1b in the presence of
dichloro(pyridine-2-
carboxylato)goldACHTUNGTRENNUNG(III) or a phos-
phite ligand were also less se-
lective (Table 2, entries 3 and
4). Surprisingly, the para-me-
Scheme 3. Reactivity of bis-cinnamyl-substituted substrate 1 f in the presence of different catalysts (L=pyri-
dine-2-carboxylato).
thoxyphenyl-substituted
bis-
acetate 1d afforded much lower
levels of selectivity compared
in solution. In the presence of AuCl as catalyst, the major
product was the (E,E,E,E)-tetraene 2 f’. Higher selectivity in
favor of the all-trans product, with a 1:4:20 ratio, was ob-
Table 2. Reaction scope in symmetrically substituted substrates.
tained using dichloro(pyridine-2-carboxylato)gold
ACHTUNGTRENNUNG(III) as
catalyst in toluene.
We then set out to explore the chemistry of unsymmetri-
cally substituted substrates. The results are summarized in
Table 3. Substrates such as 4a and 4b, in which both R1 and
R2 are capable of stabilizing a positive electron density,
showed a clear (Z,Z)-selectivity under [(IPr)AuACTHUNRGTNEUNG(NTf2)] cat-
alysis, affording dienes 5a and 5b in yields of 73% and
Entry
Substrate
Proto- 2/3/2’[b] Product
col[a]
[%][c]
1
2
3
4
5
6
7
8
1
2
3
4
1
2
1
2
1
2
8:1:0
1:8:0
1:5:1.5 n.d.
5:10:1 n.d.
2b (87)
3b (83)
1b
R=3-OMe-C6H4
80%, respectively (Table 3, entries 1 and 3). [(PPh3)Au-
AHCTUNGRTEG(NNUN NTf2)] favored the (1Z,3E)- and (1E,3Z)-1,3-dienes 6a,b
13:1:0
1:10:0
2c (92)
3c (92)
1c R=3,5-dimethoxyphenyl
2.5:1:0 2d+3d (99)[d]
and 7a,b (Table 3, entries 2 and 4), in analogy with the re-
sults shown in Table 2. Substrate 4c, featuring a pull-push
system, was converted to the corresponding dienes (Z,Z)-5c
and (1Z,3E)-6c as a 1:1 mixture in the presence of both cat-
alysts, thus reflecting the importance of electronic factors in
the stereocontrol of the reaction (Table 3, entries 5 and 6).
To study the effect of steric factors, we tested substrates
bearing substituents with similar electron-donating proper-
ties at C1 (R1 =para-methoxyphenyl) but of different sizes at
1d
1e
R=4-OMe-C6H4
R=4-CF3-C6H4
1.5:1:0 2d+3d (97)[d]
9
10
–
–
1e
1e
[a] Protocol 1: Table 1, entry 2; Protocol 2: Table 1, entry 10; Protocol 3:
as protocol 2 but with dichloro(pyridine-2-carboxylato)gold(III) as cata-
(SbF6)] as catalyst.
AHCTUNGTRENNUNG
lyst; Protocol 4: as protocol 2, but with [(PhO)3PAuACHTGNUTRENNUNG
[b] Ratio calculated by 1H NMR spectroscopy. [c] Yield of the product
isolated after column chromatography. [d] Yield of the mixture. n.d.=
yield not determined.
Table 3. Reaction scope in non-symmetrically substituted substrates 4.
to the previous cases (Table 2, entries 7 and 8).
[(IPr)Au(NTf2)] and [(PPh3)Au(NTf2)] afforded
N
ACHTUNGTRENNUNG
mixtures of 2d and 3d in ratios of 2.3:1 and 1.5:1,
respectively. The lack of reactivity of the bis-para-
trifluoromethylphenyl-substituted substrate 1e is
a strong indication of the importance of the stabili-
zation of positive electron density in these reac-
tions.
Under the conditions of protocol 1, substrate 1 f,
bearing cinnamyl groups at the propargylic posi-
tions, underwent a clean rearrangement reaction
with concomitant isomerization of the cinnamyl
moiety to the thermodynamically favored
(Z,Z,Z,Z)-1,3,5,7-tetraene 2 f (Scheme 3). With
Entry
Substrate
4a
R1 =Ph
R2 =3,5-dimethoxyphenyl
4b R1 =Ph
Protocol[a]
5/6/7[b]
Yield [%][c]
1
2
3
4
5
6
7
8
1
2
1
2
1
2
1
2
1
2
>23:1:1
1:14:10
8:1:0
1:4.5:4
1:1:0
1:1:0
1:9:0
1:8:0
1:15:0
1:10:0
5a (73)
6a (53), 7a (40)
5b (85)
R2 =3-OMe-C6H4
6b+7b (80)[d]
5c+6c (91)[d]
5c+6c (78)[d]
6d (86)
4c
R1 =4-OMe-C6H4
R2 =4-CF3-C6H4
4d R1 =4-OMe-C6H4
R2 =Me
6d (80)
6e (81)
6e (69)
9
10
4e
R1 =4-OMe-C6H4
R2 =iPr
[(PPh3)Au
ACHTUNGTRENNUNG(NTf2)] as catalyst, the (E,Z,E,E)-tet-
[a] Protocol 1: Table 1, entry 2; Protocol 2: Table 1, entry 10. [b] Ratio calculated by
1H NMR spectroscopy. [c] Yield of the major isomer isolated after column chromatog-
raene could be isolated in 80% yield, although this
compound rapidly isomerized to 2 f upon standing raphy. [d] Yield of the isolated mixture after column chromatography.
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C. Nevado et al.
C4 (R2 =Me, iPr), 4d and 4e. The (1Z,3E)-dienes 6d,e were
always the major products of these reactions, irrespective of
the catalyst used (Table 3, entries 7–10). In addition, the
bulkier the group at C4 (methyl to isopropyl), the higher the
selectivity of the reaction (Table 3, entries 7,8 vs. 9,10).
The individual effect of the propargylic substituent at-
tached to the acyloxy migrating group on the stereochemis-
try of the resulting vinyl acetate was evaluated using bis-ace-
tates derived from commercially available 2-methyl-3-butyn-
2-ol (Table 4). Sterically hindered substrate 8a reacted selec-
Table 4. Reaction scope in bis-acetates derived from acetone.
Scheme 4. Initial mechanistic proposal.
Although this mechanistic manifold was useful for ration-
alizing most of these double-migration processes, a detailed
understanding of the reaction was lacking. In fact, some of
the experimental results described above could not be ex-
plained within the framework of this model. First, assuming
that for stabilizing groups at the propargyl position the first
acyloxy migration occurs to give the (Z)-olefin, it was not
clear why the stereochemistry of the second migration de-
pends on the ancillary ligand on gold (Table 2). In contrast,
if the second migrating group was “less” stabilized (R=
alkyl), only the (1Z,3E)-products 6 were obtained, irrespec-
tive of the catalyst (e.g., 4e in Table 3, entries 9 and 10).
Furthermore, for a combination of “stabilizing”/“non-stabi-
lizing” groups at the propargylic position, the reaction was
completely unselective (e.g., 4c in Table 3, entries 5 and 6).
Another puzzling result was the different outcomes of reac-
tions of substrates derived from 2-methyl-3-butyn-2-ol, 8a
and 8b, as summarized in Table 4 (entries 1–4). With 8a
(R1 =Ph, R2 =Me), the ligand effect was observed, whereas
with 8b (R1 =Ph, R2 =H) only the (Z)-product was ob-
tained.
A detailed computational analysis at the DFT level was
performed to unravel the mechanism governing these trans-
formations.[20,21] The overall process was found to consist of
four discrete steps, as illustrated for substrate 1a in Figure 1.
As expected, upon gold activation of the triple bond, two
transition states (TS1 and TS2) connect the starting material
1a-0 with the corresponding carbene intermediate 1a-B as
a result of the 1,2-migration of the first acetoxy moiety.
Next, the second 1,2-migration through transition states TS3
and TS4 connects intermediate 1a-B with the final product
1a-D. The stereochemistry of the alkene(s) generated in the
reaction is defined at TS2 and TS4.
Entry Substrate
Protocol[a] Z/E[b,c] Product [%][d]
1
2
3
4
5
6
7
8
R1 =Ph
1
2
1
2
1
2
1
2
>20:1
>1:20
10:1
9:1
18:1
17:1
1:4
9a-Z (80)
9a-E (82)
9b-Z (90)
9b-Z (64)
9c-Z (93)
9c-Z (34)
9d (83)[e]
9d (81)[e]
8a
8b
8c
8d
R2 =Me
R1 =Ph
R2 =H
R1 =4-OMe-C6H4
R2 =H
R1 =4-CF3-C6H4
R2 =H
1:7
[a] Protocol 1: Table 1, entry 2; Protocol 2: Table 1, entry 10. [b] Ratio
1
calculated by H NMR spectroscopy. [c] Considering R1 of higher priority
than R2. [d] Yield of the major isomer (when applicable) after column
chromatography. [e] Yield of the mixture isolated after column chroma-
tography.
tively upon treatment with different catalysts, with the cata-
lyst bearing an NHC-ligand affording (Z)-9a in 80% yield,
whereas the one bearing triphenylphosphine as ligand fur-
nished (E)-9a in 82% yield (Table 4, entries 1 and 2). How-
ever, secondary acetates at the C4 position (substrates 8b–d)
behaved differently. Phenyl- (8b) and para-methoxyphenyl-
substituted (8c) substrates provided 9b and 9c, respectively,
with high (Z)-selectivity under catalysis by both [(IPr)Au-
ACHTUNGTRENNUNG(NTf2)] and [(PPh3)AuAHCUTGNTREN(NUNG NTf2)] (entries 3–6). This observa-
tion was in sharp contrast to the results summarized in
Tables 2 and 3. Furthermore, para-trifluoromethylphenyl-
substituted 8d preferentially afforded the (E)-olefin product
with both catalysts (entries 7 and 8).
Reaction mechanism: In our previous work, a general mech-
anism was outlined, in which, upon gold activation of the
triple bond, the acetoxy moiety adjacent to groups capable
of stabilizing the developing positive electron density would
migrate first. This first migration should always occur with
(Z)-selectivity due to the 1,3-allylic strain between the metal
[Au] and R1 in the transition state (Scheme 4). When the
second acetate is also attached to stabilizing groups, the ste-
reochemical outcome of the second acetoxy migration de-
First, the reactions of 1a in the presence of [(IPr)Au-
ACHUNTGRENN(UG NTf2)] or [(PPh3)AuAHCTUTGNREN(NGUN NTf2)] were studied. In the presence
of the NHC ligand (Figure 2), the first migration occurs to
give the (Z)-configured intermediate 1a-IPr-B. In the transi-
tion state 1a-IPr-TS2, steric factors disfavor the formation
of the (E)-intermediate (DE1a-IPr[TS2(E)ÀTS2(Z)] =1.5 kcalmolÀ1).
In this case, the first migration is higher in energy than the
second one (TS1 and TS2 @ TS3 and TS4), meaning that
pends on the nature of the catalyst. While [(IPr)Au
afforded the (Z)-alkene, [(PPh3)Au(NTf2)] favored forma-
tion of the (E)-alkene.[19]
ACHTUNGERTN(NUNG NTf2)]
AHCTUNGTRENNUNG
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Mechanistic Study of Acetoxy Migration
FULL PAPER
11.1 kcalmolÀ1).[22] The (Z)-se-
lectivity in the first migration
can be easily explained by com-
paring the structures of the two
transition states 1a-IPr-TS2-E
and 1a-IPr-TS2-Z (Figure 3).
For the formation of a trans
olefin, the phenyl group needs
to move towards one of the 2,6-
diisopropylphenyl substituents
of the IPr ligand, thus increas-
ing the steric congestion in the
TS compared to that in the (Z)-
isomer.[23] The steric interaction
between the phenyl ring and
the IPr ligand distorts the linear
disposition of the ligands
around the AuI metal center, so
that the C2-Au-C5 angle is re-
duced from 178.78 in 1a-IPr-
TS2-Z to 171.28 in 1a-IPr-TS2-
E (Figure 3).
Figure 1. General mechanism for the transformation of 1a-0 into 1a-D. For the sake of clarity, only one of the
possible stereoisomers of the final product is shown here.
The reaction carried out in
the presence of a phosphine
ligand showed a complementary
profile (Figure 4). As in
Figure 2, TS2 determines the
stereochemistry of the first mi-
gration, but in this case in the
opposite direction, since the
formation of the (Z)-isomer is
energetically disfavored. Thus,
the first migration occurs with
complete (E)-selectivity (DE1a-
PPh3[(TS2(E)ÀTS2(Z)] =4.1 kcal
molÀ1). The second migration,
after intermediate 1a-PPh3-B,
is then (Z)-selective as the
energy barrier associated with
1a-PPh3-TS4 is about 2 kcal
molÀ1 higher for the (E,E)-
isomer than that for the (E,Z)-
isomer
(E1a-PPh3-TS4(E,E)
=
13.0 kcalmolÀ1
vs. E1a-PPh3-
TS4(E,Z) =11.1 kcalmolÀ1). Thus,
our previous assumption for
substrates bearing stabilizing
groups at C1 and C4, involving
a (Z)-selective first acyloxy mi-
gration followed by a ligand-
dependent migration, turned
out not to be correct.[15] In fact,
Figure 2. Reaction coordinate diagram for the reaction of 1a with [(IPr)Au
the M062X/6-311+G(d,p) (C,H,O,N), SDD (Au)//B3LYP/6-31G(d) (C,H,O,N), LANL2DZ (Au) level. Single-
point energy calculations were also performed at the B3LYP/6-311+G(d,p) (C,H,O,N), SDD (Au) level and
the results are given in brackets. The solid blue line shows the more favorable pathway. Au=(IPr)Au.
ACHTUNGRTEN(NUNG NTf2)]. Single-point calculations at
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
the formation of (Z)-1a-IPr-B can be considered irreversi-
ble. From this intermediate, the reaction proceeds via transi-
tion states 1a-IPr-TS3 and 1a-IPr-TS4 to give (Z,Z)-2a (i.e.,
(Z,Z)-1a-IPr-D), which is favored over the (Z,E)-isomer by
the ancillary ligand on gold determines the stereochemical
outcome of the first migration, with the second migration
always being (Z)-selective in substrates of this type.
The strong influence of the ligand on the stereoselectivity
of the reaction seems to be directly related to the presence
3.1 kcalmolÀ1 (E1a-IPr-TS4(Z,Z) =8.0 kcalmolÀ1 vs. E1a-IPr-TS4(Z,E)
=
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C. Nevado et al.
Figure 4. Reaction coordinate diagram for the reaction of 1a with
[(PPh3)AuACHTNUGTRENNUG(NTf2)]. Single-point calculations at the M062X/6-311+GACHTUNGTRENNUNG(d,p)
(C,H,O,N), SDD (Au)//B3LYP/6-31G(d) (C,H,O,N), LANL2DZ (Au)
level. Single-point energy calculations were also performed at the
B3LYP/6-311+GACTHUNTGRNEUNG(d,p) (C,H,O,N), SDD (Au) level and the results are
given in brackets. The solid red line shows the more favorable pathway.
Au =(Ph3P)Au.
Figure 3. Structures of the transition states a) 1a-IPr-TS2-E and b) 1a-
IPr-TS2-Z, highlighting the relative disposition of the phenyl group with
respect to the aromatic substituents of the IPr ligand. Relevant distances
and angles are shown. a) C2-Au-C5 =171.28, C2-C3-C4-C6 =À40.68. b) C2-
Au-C5 =178.78, C2-C3-C4-C6 =À128.68.
of two stabilizing groups (aromatic rings) in the propargylic
positions. Thus, a substrate combining a para-methoxyphen-
yl group at C1 with a “less” stabilizing isopropyl group at C4
(4e) afforded predominantly the (1Z,3E)-product 6e, irre-
spective of the catalyst (e.g., Table 3, entries 9 and 10). As
expected, the migration starts at the acyloxy group flanked
by the aromatic group at the propargylic position, which is
associated with an energy of 11.8 kcalmolÀ1 (Z-4e-IPr-TS2)
as compared to 18.8 kcalmolÀ1 for the acyloxy group near
the iPr substituent (Figure 5). Concerning the stereochemis-
Figure 5. Reaction coordinate diagram for the reaction of 4e with
[(IPr)AuACHTUNGTRENNUNG(NTf2)]. Single-point calculations at the M062X/6-311+GACHTUNGTERN(NUGN d,p)
(C,H,O,N), SDD (Au)//B3LYP/6-31G(d) (C,H,O,N), LANL2DZ (Au)
level. Single-point energy calculations were also performed at the
B3LYP/6-311+GACHTUNGTRENNUNG(d,p) (C,H,O,N), SDD (Au) level and the results are
given in brackets. The solid black line shows the more favorable pathway.
Au =(IPr)Au.
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Mechanistic Study of Acetoxy Migration
FULL PAPER
try of the reaction, the profile of substrate 4e in the pres-
ence of [(IPr)AuACHTUNGTRENNUNG(NTf2)] shows a completely different sce-
similar, the reaction seems to be at equilibrium at this stage
so that, according to the Curtin–Hammett principle, the ste-
reochemical outcome will be determined by the relative en-
ergies of the respective isomeric TS4 transition states. The
lower TS4 relates to the (Z,E)-isomer, which is indeed the
major product observed (E4e-PPh3-TS4(Z,E) =11.1 kcalmolÀ1 vs.
nario to that for compound 1a in Figure 2. The reaction
transition state TS2 is relatively low in energy and gives rise
to the (E)- and (Z)-carbene intermediates 4e-IPr-B in simi-
lar proportions. However, this fact is irrelevant, since the se-
lectivity of the whole process is determined later during the
second migration, in TS3 and TS4. As shown in Figure 5,
the formation of the major (Z,E)-diastereoisomer follows
the lowest-energy pathway, while the other isomers must
overcome high-energy transition states, (E,E)-4e-IPr-TS3
(13.1 kcalmolÀ1), (E,Z)-4e-IPr-TS3 (15.1 kcalmolÀ1), and
(Z,Z)-4e-IPr-TS4 (14.5 kcalmolÀ1). Thus, it is due to steric
factors (congestion between the isopropyl group and the
metal in TS3 and TS4) that the stereochemical outcome of
the second migration is now (E), and is thus opposite to that
observed for 1a. The congestion in TS4 also explains the
higher selectivity obtained for the reaction of 4e compared
to that of 4d bearing a smaller methyl group at C4 (Table 3,
entries 7 vs. 9).
E
4e-PPh3-TS4(Z,Z) =12.1 kcalmolÀ1).
The lack of selectivity in the reactions of substrate 4c
(Table 3, entries 5 and 6) prompted us to study its reactivity
in more detail. The reaction profile in the presence of
[(PPh3)AuACHTNUGRTENUNG(NTf2)] is shown in Figure 7. Because of the dif-
ferent electronic characters of the groups at propargylic po-
sitions C1 and C4 (para-methoxyphenyl vs. para-trifluorome-
thylphenyl), the first migration preferentially involves the
acyloxy group near the para-methoxyphenyl moiety. The
general picture is very similar to that for compound 4e in
Figure 6, so that the overall stereoselectivity of the reaction
is determined at TS4. In this case, however, the energy dif-
ference between the final transition states (Z,Z)-TS4 and
(Z,E)-TS4 is lower (10.7 vs. 11.1 kcalmolÀ1), justifying the
formation of an approximately 1:1 mixture of (Z,Z)- and
(Z,E)-6c isomers.
Seemingly, the (E)-selectivity of the first migration in the
reaction of 4e with [(PPh3)AuACHTNUGRTENUNG(NTf2)] is not relevant to the
outcome of the reaction (Figure 6). In this case, the point of
highest energy along the reaction coordinate is located at
TS4, due to insufficient stabilization of the positive electron
density by the isopropyl group. As the ranges of energy
values found for 4e-PPh3-TS2 and 4e-PPh3-TS3 are very
The relative ability of the substituent at the propargylic
position to stabilize the vicinal acyloxy migration was con-
firmed by NBO analysis[24] of 4c-PPh3-TS2-E (in which the
acetoxy group next to the para-methoxyphenyl substituent
migrates first, C1) and 4c-PPh3-TS2’-E (in which the migra-
Figure 6. Reaction coordinate diagram for the reaction of 4e with [(PPh3)AuACTHUNGTREN(NNUG NTf2)]. Single-point calculations at the M062X/6-311+GACHTUNGTRENNNUG
SDD (Au)//B3LYP/6-31G(d) (C,H,O,N), LANL2DZ (Au) level. Single-point energy calculations were also performed at the B3LYP/6-311+G
(C,H,O,N), SDD (Au) level and the results are given in brackets. The solid black line shows the more favorable pathway. Au=(Ph3P)Au.
ACHTUNGTRENNUNG
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C. Nevado et al.
termined in 8a-PPh3-TS2, fa-
voring the (E)-isomer (the red
line is lower than the blue line
throughout the whole energy
profile) and accounting for the
formation of the reaction prod-
uct (E)-9a. As shown above in
Figures 2 and 5, for a bulky
NHC ligand, a (Z)-migration
would be favored at this stage,
thus explaining the preferential
formation of (Z)-9a under
these circumstances (not calcu-
lated).
In sharp contrast to the pre-
vious case, the reaction of sub-
strate 8b exclusively afforded
(Z)-9b irrespective of the cata-
lyst. As shown in Figure 10, for
substrates derived from 2-
methyl-3-butyn-2-ol, the group
that migrates first again deter-
mines the final reaction selec-
tivity. As expected, the most fa-
vorable migration occurs from
the Me,Me-substituted acetate.
Thus, the stereochemical out-
come is defined by 8b-PPh3-
TS4, for which the pathway
leading to the (Z)-isomer is
Figure 7. Reaction coordinate diagram for the reaction of 4c with [(PPh3)Au
at the M062X/6-311+G(d,p) (C,H,O,N), SDD (Au)//B3LYP/6-31G(d) (C,H,O,N), LANL2DZ (Au) level.
Single-point energy calculations were also performed at the B3LYP/6-311+G(d,p) (C,H,O,N), SDD (Au) level
and the results are given in brackets. The black and blue solid lines show the more favorable pathways. Au=
(Ph3P)Au.
ACHTUNGRTEN(NUNG NTf2)]. Single-point calculations
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
preferred
(E8b-PPh3-TS4(E) =17.5 kcalmolÀ1 vs.
8b-PPh3-TS4(Z) =14.0 kcalmolÀ1).
by
3.5 kcalmolÀ1
E
tion starts with the ester adjacent to the para-trifluorome-
thylphenyl substituent, C4) (Figure 8). In the former case,
a strong interaction between the p-system of the aromatic
ring (through Carom) and the developing carbocation at C1
can be observed. This interaction is 28% smaller in the case
of 4c-PPh3-TS2’-E at C4. This stabilizing contribution is also
reflected in the analysis of the partial charges, which shows
an increasing positive charge at C4 in 4c-PPh3-TS2’-E
(+0.031) compared to that measured at C1 for 4c-PPh3-
Based on this computational study, we envisaged that the
migrating abilities of different carboxylic groups could be
evaluated by preparing substrates with phenyl substituents
at the propargylic position and bearing different ester func-
tions (10, Table 5). According to the results shown in
Figure 2, these substrates should afford (Z,Z)-1,3-dienes 11
with [(IPr)Au
ACHTUNGTRENNUNG
with [(PPh3)Au
AHCTUNGTRENNUNG
tive (Figure 4), the (1Z,3E)-12 versus (1E,3Z)-13 ratio
should correlate with the migrating abilities of the different
groups.
Four substrates combining acetyl, benzoyl, pivaloyl, and
para-nitrobenzoyl migrating groups (10a–d) were prepared
and evaluated under the two sets of standard conditions
(Table 5). As predicted, reactions in the presence of
À
TS2-E (+0.011). In line with this analysis, the C1 Carom dis-
tance increases from 1.423 Š in 4c-PPh3-TS2-E to 1.443 Š
in 4c-PPh3-TS2’-E.
Finally, we set out to study the puzzling results obtained
with substrates derived from 2-methyl-3-butyn-2-ol, 8a and
8b. In the reactions of 8a (Table 4, entries 1 and 2), the
ligand determines the stereoselectivity of the reaction. As
observed for 4c and 4e, the determining factor in the reac-
[(IPr)Au
d) in good yields (Table 5, entries 1, 3, 5, and 7). The reac-
tion of 10a with [(PPh3)Au(NTf2)] afforded (Z,E)-12a and
ACHTUNGRTEN(NUNG NTf2)] afforded the (Z,Z)-diastereoisomers (11a–
tion with [(PPh3)Au
N
ACHTUNGTRENNUNG
gration of the first group (Figures 6 and 7). In 8a, the differ-
ence in energy between migration of the Me,Ph-substituted
acetoxy group and migration of the Me,Me-substituted ace-
toxy group is significantly high (13.6 vs. 20.1 kcalmolÀ1) and
thus the reaction proceeds exclusively through the former
(Figure 9). The stereoselectivity in this migration is thus de-
(E,Z)-13a in an approximately 1:2 ratio, thus reflecting that
the migration of acetate is twice as favorable as that of ben-
zoate (Table 5, entry 2). A similar outcome was obtained for
substrate 10b bearing acetate and pivaloate migrating
groups (Table 5, entry 4). Thus, we can deduce that the mi-
gration abilities of pivaloyl and benzoyl groups are compa-
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Mechanistic Study of Acetoxy Migration
FULL PAPER
Figure 9. Reaction coordinate diagram for the reaction of 8a with
[(PPh3)AuACHTNUGTRENNUG(NTf2)]. Single-point calculations at the M062X/6-311+GACHTUNGTRENNUNG(d,p)
(C,H,O,N), SDD (Au)//B3LYP/6-31G(d) (C,H,O,N), LANL2DZ (Au)
level. Single-point energy calculations were also performed at the
B3LYP/6-311+GACTHUNTGRNEUNG(d,p) (C,H,O,N), SDD (Au) level and the results are
given in brackets. The solid red line shows the more favorable pathway.
Au =(Ph3P)Au.
Figure 8. Top: structure of the transition state 4c-PPh3-TS2-E, in which
the acetoxy at C1 migrates first (close to the para-methoxyphenyl group).
Bottom: structure of the transition state 4c-PPh3-TS2’-E, in which the
first migrating ester group is the one next to the para-trifluoromethyl-
phenyl substituent (C4).
AHCTUNGRTEG(NNUN NTf2)] afforded 12e and 13e in a 1:2 ratio in yields of 25%
and 63%, respectively.
Synthetic applications: In the course of our studies, we ob-
served that substrates bearing only alkyl substituents at the
propargylic positions afforded mixtures of 1,4-bis-acetoxy
dienes and their corresponding 1,2-diketones[26] upon in situ
hydrolysis of the vinyl acetate moieties under the reaction
conditions. This process could be optimized by treatment of
the crude reaction mixtures with K2CO3 in MeOH
(Scheme 6).
We envisaged that non-symmetrical 1,2-diketones could
be formed by hydrolysis of the crude reaction mixtures after
gold catalysis, which could then be further condensed with
aromatic 1,2-diamines to give quinoxalines.[27] Quinoxalines
are an important class of N-containing heterocyclic com-
pounds that can be found in the scaffolds of many pharma-
ceuticals.[28] They have also found application in materials
science[29] and in the dye industry.[30] Symmetrically and non-
symmetrically substituted quinoxalines 15–20 were obtained
in moderate to good yields by a one-pot, three-step protocol
(Table 6).
rable, which was corroborated by the lack of selectivity of
substrate 10c in the presence of [(PPh3)AuACTHUNTRGNENG(U NTf2)] (Table 5,
entry 6), from which 12c and 13c were obtained in a 1:1
ratio. Finally, substrate 10d bearing acetate and para-nitro-
benzoate migrating groups provided, under phosphine-gold
catalysis, a mixture of 12d and 13d in a 2:1 ratio (Table 5,
entry 8). Thus, the migrating aptitude in these transforma-
tions can be summarized as follows: OBz=OPiv<OAc <
O-p-NO2-Bz, which seems to correlate more with the leav-
ing-group ability than with the nucleophilic character of the
carboxylic moieties, thus emphasizing the partial ion-pair
nature of TS1.[25]
An alternative reaction pathway involving a double 1,3-
bis-carboxylate migration can be ruled out since compound
10e was cleanly transformed into compound 11e in the pres-
ence of [(IPr)Au
results summarized in Table 5, the reaction with [(PPh3)Au-
(NTf2)] (Scheme 5). As expected from the
We also utilized the 2,3-bis-acetoxy-1,3-dienes produced
in these reactions as partners for Diels–Alder cycloaddi-
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C. Nevado et al.
Scheme 6. Synthesis of 1,2-diketones from 1,4-bis-propargyl acetates.
tions. We decided to focus on (Z,Z)-dienes, which could be
easily obtained using [(IPr)Au(NTf2)] as shown in Tables 1–
AHCTUNGTRENNUNG
5. Using N-phenyl maleimide as dienophile, we sought to
optimize the reaction conditions in the presence of different
Lewis acids, such as ZnCl2, AlCl3, and Me2AlCl2.[31] At-
tempted reactions in the presence of such Lewis acids
showed no conversion at temperatures ranging from 0 to
608C. On the other hand, decomposition of both the diene
and dienophile occurred when the mixtures were heated to
1008C. Although 2,3-disubstituted dienes are known to be
sluggish substrates in [4+2]-cycloadditions, as the transoid
conformation is favored to avoid steric repulsion between
bulky substituents,[32] we were pleased to observe that pro-
longed heating afforded the corresponding adducts in good
yields and with moderate endo selectivity.[33] Our results are
summarized in Table 7.
Figure 10. Reaction coordinate diagram for the reaction of 8b with
[(PPh3)Au(NTf2)]. Single-point calculations at the M062X/6-311+G(d,p)
(C,H,O,N), SDD (Au)//B3LYP/6-31G(d) (C,H,O,N), LANL2DZ (Au)
level. Single-point energy calculations were also performed at the
B3LYP/6-311+GACHTUNGTRENNUNG(d,p) (C,H,O,N), SDD (Au) level and the results are
given in brackets. The solid blue line shows the more favorable pathway.
G
ACHTUNGTRENNUNG
Au =(Ph3P)Au.
Table 5. Reaction scope combining different migrating groups.
Conclusion
We have presented an experimental study on the
scope of the 1,2-/1,2-bis-acetoxy migration of 1,4-
bis-propargyl acetates both in terms of substrates
and gold catalysts. Molecular modeling studies have
provided a mechanistic rationale for the reaction
outcome in terms of the stereoselectivity observed
in the formation of the 1,3-bis-acetoxy dienes. Our
computational studies have revealed that the ancil-
lary ligand on gold determines the stereochemistry
of the double bond upon the first acetoxy migra-
tion, with the second migration always being (Z)-se-
lective in the case of substrates bearing stabilizing
groups at the propargylic positions. When the stabi-
lization provided by the substituent at the propar-
gylic position is decreased, the reaction selectivity is
Entry
Substrate
Protocol[a] 11/12/13[b] Yield [%][c]
1
2
1
2
9:1:2
1:6:10
11a (75)
12a (30)
13a (50)
11b (80)
12b (25)
13b (55)
11c (81)
10a
X1 =Ac, X2 =Bz
3
4
1
2
92:1:7
1:5:9
10b
10c
X1 =Ac, X2 =Piv
X1 =Piv, X2 =Bz
5
6
7
8
1
2
1
2
9:1:0
1:5:5
3:1:0
1:2:1
12c+13c (79)[d]
11d (56)
12d (46)
10d X1 =Ac, X2 =CO-p-NO2-C6H4
[a] Protocol 1: Table 1, entry 2; Protocol 2: Table 1, entry 10. [b] Ratio calculated by
1H NMR spectroscopy. [c] Yield of the product isolated after column chromatography.
[d] Yield of the mixture isolated after column chromatography.
Scheme 5. 1,2- versus 1,3-Bis-carboxylate migration.
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Mechanistic Study of Acetoxy Migration
Table 6. One-pot synthesis of quinoxalines.
FULL PAPER
(Thermo Finnigan, San Jose, CA, USA) double-focusing magnetic sector
mass spectrometer. Ten spectra were acquired. A mass accuracy ꢀ2 ppm
was obtained in the peak-matching acquisition mode by using a solution
containing PEG200 (2 mL), PPG450 (2 mL), and NaOAc (1.5 mg) (all ob-
tained from Sigma–Aldrich, Buchs, Switzerland) dissolved in MeOH
(100 mL; HPLC Supra grade, Scharlau, Barcelona, Spain) as an internal
standard. GC-MS analysis was carried out on
a Finnigan Voyager
GC8000 Top system. Elemental analyses were performed on a Leco
CHN-932 analyzer. Optical rotations were measured at 258C on
a JASCO P-2000 polarimeter using filtered light from a Hg lamp (l=
589 nm).
Entry
Substrate
Product
Yield [%][a]
1
2
3
1a
1c
4c
R1 =R2 =Ph
15
16
17
65
64
65
R1 =R2 =3,5-dimethoxyphenyl
R1 =4-OMe-C6H4
R2 =4-CF3-C6H4
Materials and methods: All reactions were carried out under a nitrogen
atmosphere using standard Schlenk-line techniques. Unless otherwise
stated, starting materials were purchased from Aldrich and/or Fluka. All
4
5
6
4e
4 f
4g
R1 =4-OMe-C6H4
R2 =iPr
18
19
20
70
41
48
reagents were used as received. [(IPr)Au
AHCTUNGTRENNUNG
(NTf2)][34] and [(PPh3)Au-
ACHTUNGTRENNUNG
(NTf2)][35] were prepared according to previously reported procedures.
R1 =cinnamyl
Compounds 1a, 1b, 1c, 1e, 1 f, 2a, 2a’, 3a, 2b, 3b, 2c, 3c, 2 f, 3 f, 4a, 4b,
4c, 4d, 4e, 4 f, 4g, 5a, 5b, 5c+6c, 6a, 6b+7b, 6d, 6e, 8a, 8b, 8c, 8d,
8e, 8 f, 9a-Z, 9a-E, 9b-Z, 9c-Z, 9d, 10e, 11e, 14e, and 14 f have been de-
scribed previously.[15] Solvents were purchased as HPLC grade, degassed
by purging thoroughly with nitrogen, and dried over activated molecular
sieves of appropriate size. Alternatively, they were purged with argon
and passed through columns of alumina in a solvent purifica-
tion system (Innovative Technology). Conversion was moni-
tored by thin-layer chromatography (TLC) using Merck TLC
silica gel 60 F254. Flash column chromatography was performed
on silica gel (230–400 mesh).
R2 =3,5-dimethoxyphenyl
R1 =Ph, R2 =iPr
[a] Yield of the product isolated over three steps after column chroma-
tography.
Table 7. One-pot Diels–Alder reactions.
General procedure for the gold-catalyzed stereocontrolled syn-
thesis of 2,3-carboxylate-1,3-dienes: [(IPr)AuACTHNUGTREN(NNUG NTf2)] (proto-
col 1, 0.005 mmol, 0.05 equiv), or [(PPh3)Au(NTf2)] (protocol 2,
AHCTUNGTRENNUNG
0.005 mmol, 0.05 equiv, 0.05m solution freshly prepared in
CH2Cl2 by mixing 1 equivalent of [(PPh3)AuCl] and 1 equiva-
Entry Substrate
t
endo/
endo
exo
[h] exo[a]
[%][b]
[%][b]
lent of AgNTf2), or dichloro(pyridine-2-carboxylato)gold
ACHTUNGTRENNUNG(III)
1
2
1a R1 =R2 =Ph, R3 =H
48 2.5:1
120 2.5:1
21 (65)
23 (51)
22 (27)
24 (18)
(protocol 3, 0.005 mmol, 0.05 equiv), or [(PhO)3PAu(SbF6)]
ACHTUNGTRENNUNG
1c R1 =R2 =3,5-dimethoxyphenyl
(protocol 4, 0.005 mmol, 0.05 equiv) was added to a solution of
the bis-acetate (0.1 mmol, 1 equiv) in anhydrous CH2Cl2
(4 mL). The mixture was stirred for 2–3 h and then worked-up
by column chromatography on silica gel. The yields and full
characterization data are presented below. Note: structural as-
signments were supported by full characterization, including
1H NMR, 13C NMR, HSQC, HMBC, and 1D-NOESY experi-
ments.
R3 =H
3
4a R1 =Ph, R2 =3,5-dimethoxy
R3 =H
phenyl,
96 2:1
25 (64)
26 (26)
4
5
4b R1 =Ph, R2 =3-OMe-C6H4, R3 =H
8b R1 =Ph, R2 =R3 =Me
96 2:1
120 2.5:1
27 (59)
29 (7)
28 (24)
30 (21)
[a] Ratio calculated by 1H NMR spectroscopy. [b] Yield of the product isolated after
column chromatography.
Compounds 2d and 3d: The title compounds were obtained
following general protocol 2 in 97% yield as a 1.5:1 mixture.
2d: 1H NMR (400 MHz, CDCl3): d=7.39 (dd, J=9.4 Hz, 4H),
further influenced by the order of the migrating groups,
6.86 (dd, J=9.4 Hz, 4H), 6.36 (s, 2H), 3.81 (s, 6H), 2.31 ppm (s, 6H);
13C NMR (100 MHz, CDCl3): d=168.4, 159.8, 140.8, 130.7, 126.9, 116.7,
114.6, 55.7, 21.5 ppm; IR (film): n˜ =2956, 2910, 2838, 1743, 1604, 1508,
1250, 1210, 1174, 1028, 800, 730 cmÀ1. 3d: 1H NMR (400 MHz, CDCl3):
d=7.42 (dd, J=8.5 Hz, 2H), 7.32 (dd, J=8.5 Hz, 2H), 6.83 (dd, J=
2.2 Hz, 2H), 6.82 (dd, J=2.2 Hz, 2H), 6.35 (s, 1H), 6.34 (s, 1H), 3.80 (s,
3H), 3.79 (s, 3H), 2.26 (s, 3H), 1.83 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3): d=169.8, 168.6, 160.0, 159.6, 141.0, 139.3, 131.3, 131.0, 126.7,
126.6, 121.9, 121.7, 114.5, 114.0, 55.7 (2C), 21.5, 20.7 ppm.
which ultimately outweighs the influence of the ligand. The
new mechanistic picture revealed by this computational
modeling set the stage for a subsequent detailed analysis of
the migrating ability of different ester groups. Additionally,
two synthetic applications have been developed; first, an ef-
ficient one-pot synthesis of quinoxaline heterocycles, and
second, a one-pot tandem Diels–Alder process to obtain bi-
cyclic compounds with moderate endo selectivities.
Compound 2 f’: The title compound was obtained from dichloro(pyri-
dine-2-carboxylato)goldACTHNUTRGNEUG(N III) (protocol 3) and characterized directly in the
reaction mixture due to its instability. 1H NMR (400 MHz, CDCl3): d=
7.24–7.07 (m, 10H), 6.84 (dd, J=11.3, 4.3 Hz, 2H), 6.62 (d, J=15.6 Hz,
2H), 6.26 (d, J=11.3 Hz, 2H), 2.09 ppm (s, 6H); 13C NMR (100 MHz,
CDCl3): d=169.8, 140.1, 137.4, 136.6, 129.0, 128.6, 127.1, 125.9, 123.8,
21.3 ppm; IR (film): n˜ =3033, 2961, 2924, 2212–1975, 1760, 1368, 1197,
Experimental Section
General information: NMR spectra were recorded on Bruker AV2
400 MHz or AV2 500 MHz spectrometers. Chemical shifts are given in
ppm. The spectra were calibrated to the residual 1H and 13C signals of
the solvents. Multiplicities are abbreviated as follows: singlet (s), doublet
(d), triplet (t), quartet (q), doublet of doublets (dd), quintet (quint),
septet (sept), multiplet (m), and broad (br). Infrared spectra were record-
ed on a JASCO FTIR-4100 spectrometer. High-resolution electrospray
ionization mass spectrometry was performed on a Finnigan MAT900
1122, 1061, 968, 842, 750, 691 cmÀ1
C24H22O4Na: 397.1416, found: 397.1416.
; HRMS (ESI): m/z: calcd for
Compound 11a: The title compound was obtained following general pro-
tocol 1 in 75% yield; 1H NMR (400 MHz, CDCl3): d=8.23 (dd, J=7.9,
0.9 Hz, 2H), 7.68 (tt, J=7.3, 1.3 Hz, 1H), 7.57–7.42 (m, 6H), 7.33–7.19
(m, 6H), 6.60 (s, 1H), 6.53 (s, 1H), 2.30 ppm (s, 3H); 13C NMR
(100 MHz, CDCl3): d=167.9, 163.5, 141.5, 141.4, 134.0, 133.7, 133.5,
Chem. Eur. J. 2012, 00, 0 – 0
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C. Nevado et al.
130.3, 129.0, 128.9, 128.9, 128.8, 128.6, 128.6, 128.1, 128.1, 117.7, 117.4,
1082, 1064, 1025, 709, 695 cmÀ1
C28H26O4Na: 449.1729, found: 449.1731.
;
HRMS (ESI): m/z: calcd for
21.0 ppm; IR (film): n˜ =3056, 2932, 2916, 1768, 1741, 1240, 1191, 1177,
1080, 1063, 1027, 752, 692 cmÀ1
;
HRMS (ESI): m/z: calcd for
Compound 11d: The title compound was obtained following general pro-
1
C25H20O4Na: 407.1259, found: 407.1263.
tocol 1 in 56% yield; H NMR (400 MHz, CDCl3): d=8.40 (s, 4H), 7.44–
Compound 12a: The title compound was obtained following general pro-
tocol 2 in 30% yield; 1H NMR (500 MHz, CDCl3): d=8.20 (dd, J=8.5,
1.2 Hz, 2H), 7.65 (tt, J=7.4, 1.2 Hz, 1H), 7.54–7.51 (m, 4H), 7.34–7.22
(m, 8H), 6.60 (s, 1H), 6.57 (s, 1H), 1.70 ppm (s, 3H); 13C NMR
(125 MHz, CDCl3): d=168.0, 164.8, 141.5, 140.2, 133.9, 133.7, 133.3,
130.2, 129.5, 129.3, 129.0, 128.7, 128.5, 128.2, 128.1, 127.9, 122.3, 121.7,
20.1 ppm; IR (film): n˜ =3056, 2932, 2848, 2379, 1764, 1739, 1260, 1194,
1084, 1066, 752, 706, 695 cmÀ1; HRMS (ESI): m/z: calcd for C25H20O4Na:
407.1259, found: 407.1257.
7.22 (m, 10H), 6.63 (s, 1H), 6.49 (s, 1H), 2.31 ppm (s, 3H); 13C NMR
(100 MHz, CDCl3): d=167.7, 161.7, 151.1, 141.1, 141.0, 134.0, 133.3,
133.1, 131.4, 128.8, 128.8, 128.7, 128.6, 128.4, 128.3, 124.0, 118.0, 117.7,
21.0 ppm; IR (film): n˜ =3058, 2988, 1759, 1737, 1525, 1347, 1319, 1254,
1198, 1091, 736, 710 cmÀ1; HRMS (ESI): m/z: calcd for C25H19NO6Na:
452.1104, found: 452.1106.
Compound 12d: The title compound was obtained following general pro-
1
tocol 2 in 46% yield; H NMR (400 MHz, CDCl3): d=8.37 (s, 4H), 7.53–
7.26 (m, 10H), 6.62 (s, 1H), 6.45 (s, 1H), 1.73 ppm (s, 3H); 13C NMR
(125 MHz, CDCl3): d=168.5, 163.6, 151.6, 141.9, 140.2, 135.2, 134.0,
133.6, 131.9, 130.0, 129.6, 129.1, 129.0, 128.8, 128.4, 124.4, 122.8, 123.3,
20.7 ppm; IR (film): n˜ =3111, 3061, 2928, 2849, 1763, 1742, 1607, 1525,
1491, 1347, 1257, 1191, 1147, 1091, 1013, 752, 714, 692 cmÀ1; HRMS
(ESI): m/z: calcd for C25H19NO6Na: 452.1104, found: 452.1110.
Compound 13a: The title compound was obtained following general pro-
tocol 2 in 50% yield; 1H NMR (500 MHz, CDCl3): d=7.92 (dd, J=8.5,
1.4 Hz, 2H), 7.58 (tt, J=8.8, 1.4 Hz, 1H), 7.55–7.53 (m, 2H), 7.43–7.34
(m, 4H), 7.24–7.10 (m, 6H), 6.50 (s, 1H), 6.49 (s, 1H), 2.18 ppm (s, 3H);
13C NMR (125 MHz, CDCl3): d=169.7, 164.5, 142.5, 140.6, 134.5, 134.2,
133.9, 130.6, 129.8, 129.7, 129.3, 129.1, 129.0, 128.8, 128.1, 123.3, 122.9,
21.5 ppm (one carbon signal is missing due to overlapping); IR (film):
n˜ =3067, 3025, 1765, 1737, 1449, 1368, 1176, 1150, 1082, 1064, 1041, 707,
693 cmÀ1; HRMS (ESI): m/z: calcd for C25H20O4Na: 407.1259, found:
407.1260.
Compound 12e: The title compound was obtained following general pro-
tocol 2 in 25% yield; 1H NMR (400 MHz, CDCl3): d=8.19 (dd, J=8.3,
1.3 Hz, 2H), 7.66–7.61 (m, 1H), 7.53–7.49 (m, 4H), 7.34–7.30 (m, 3H),
7.18–7.15 (m, 1H), 6.90–6.88 (m, 2H), 6.78–6.75 (m, 1H), 6.58 (s, 1H),
6.43 (s, 1H), 3.73 (s, 3H), 1.68 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3): d=168.4, 165.3, 160.0, 142.0, 140.9, 135.1, 134.4, 134.2, 130.7,
130.0, 129.9, 129.8, 129.2, 128.7, 128.1, 123.0, 122.2, 122.1, 114.8, 114.6,
55.7, 20.6 ppm; IR (film): n˜ =3062, 2927, 1765, 1739, 1259, 1191, 1084,
1066, 1023, 914, 748, 707 cmÀ1; HRMS (ESI): m/z: calcd for C26H22O5Na:
437.1365, found: 437.1363.
Compound 11b: The title compound was obtained following general pro-
tocol 1 in 80% yield; 1H NMR (400 MHz, CDCl3): d=7.45–7.42 (m,
4H), 7.35–7.22 (m, 6H), 6.54 (s, 1H), 6.41 (s, 1H), 2.30 (s, 3H), 1.35 ppm
(s, 9H); 13C NMR (100 MHz, CDCl3): d=174.8, 167.7, 141.6, 141.6,
133.6, 133.5, 129.0, 128.8, 128.6, 128.3, 128.1, 128.0, 117.8, 117.1, 39.1,
27.2, 21.0 ppm; IR (film): n˜ =3046, 2974, 1753, 1631, 1480, 1446, 1194,
1101, 1042, 826, 749, 693 cmÀ1; HRMS (ESI): m/z: calcd for C23H24O4Na:
387.1572, found: 387.1571.
Compound 13e: The title compound was obtained following general pro-
tocol 2 in 63% yield; 1H NMR (400 MHz, CDCl3): d=7.93 (dd, J=8.3,
1.3 Hz, 2H), 7.60–7.56 (m, 1H), 7.43–7.35 (m, 4H), 7.24–7.07 (m, 6H),
6.66–6.63 (m, 1H), 6.51 (s, 1H), 6.47 (s, 1H), 3.67 (s, 3H), 2.19 ppm (s,
3H); 13C NMR (100 MHz, CDCl3): d=169.0, 163.9, 159.3, 142.0, 139.9,
135.1, 133.5, 133.2, 130.0, 129.2, 129.0, 128.7, 128.5, 128.4, 128.2, 122.7,
122.2, 121.7, 114.0, 113.8, 55.1, 20.9 ppm; IR (film): n˜ =3062, 2937, 2837,
1762, 1738, 1243, 1203, 1174, 1083, 1065, 1041, 908, 730, 692 cmÀ1; HRMS
(ESI): m/z: calcd for C26H22O5Na: 437.1365, found: 437.1363.
Compound 12b: The title compound was obtained following general pro-
tocol 2 in 25% yield; 1H NMR (400 MHz, CDCl3): d=7.50–7.48 (m,
2H), 7.34–7.23 (m, 8H), 6.40 (s, 1H), 6.37 (s, 1H), 1.75 (s, 3H), 1.37 ppm
(s, 9H); 13C NMR (125 MHz, CDCl3): d=177.1, 168.3, 142.1, 140.7,
134.5, 133.9, 129.9, 129.4, 128.9, 128.7, 128.6, 127.9, 122.4, 122.0, 39.5,
27.6, 20.6 ppm; IR (film): n˜ =3056, 2973, 2869, 1758, 1483, 1447, 1369,
1194, 1111, 751, 693 cmÀ1; HRMS (ESI): m/z: calcd for C23H24O4Na:
387.1572, found: 387.1572.
Computational details: All reported structures were optimized at the
DFT level by using the B3LYP[36] hybrid functional as implemented in
Gaussian 09.[37] Optimizations were carried out by using the standard 6–
31G(d) basis set for C, H, O, N, F, and P. The LANL2DZ basis set, which
includes the relativistic effective core potential (ECP) of Hay and Wadt
and employs a split-valence (double-z) basis set, was used for Au.[38]
Single-point calculations were also performed, employing Truhlarꢁs last-
generation M06 functional[39] and the aforementioned basis sets. As
befits intramolecular processes, the computed E, E+ZPVE, H, and G
values of the designated structures were found to lie within a narrow 0–
2 kcalmolÀ1 energy difference, and are indicative of the same reactivity
trend. Therefore, only E values are shown herein and in Table S1. The
critical stationary points were characterized by frequency calculations in
order to verify that they had the right number of imaginary frequencies,
and the intrinsic reaction coordinates (IRC)[40] were followed to verify
the energy profiles connecting these transition structures to the correct
associated local minima.
Compound 13b: The title compound was obtained following general pro-
tocol 2 in 55% yield; 1H NMR (400 MHz, CDCl3): d=7.62–7.69 (m,
2H), 7.32–7.19 (m, 8H), 6.41 (s, 1H), 6.38 (s, 1H), 2.22 (s, 3H), 1.20 ppm
(s, 9H); 13C NMR (125 MHz, CDCl3): d=176.0, 168.9, 142.2, 140.0,
133.8, 133.2, 129.3, 129.0, 128.3, 128.2, 128.1, 127.6, 123.2, 122.2, 38.9,
27.0, 20.9 ppm; IR (film): n˜ =3067, 2984, 1752, 1480, 1368, 1269, 1206,
1150, 1109, 1044, 906, 729, 649 cmÀ1
C23H24O4Na: 387.1572, found: 387.1569.
; MS (ESI): m/z: calcd for
Compound 11c: The title compound was obtained following general pro-
tocol 1 in 81% yield; 1H NMR (400 MHz, CDCl3): d=8.24 (dd, J=8.2,
1.1 Hz, 2H), 7.68 (tt, J=7.6, 1.1 Hz, 1H), 7.55 (t, J=8.0 Hz, 2H), 7.45 (d,
J=6.9 Hz, 2H), 7.40 (d, J=6.9 Hz, 2H), 7.30–7.18 (m, 6H), 6.59 (s, 1H),
6.58 (s, 1H), 1.34 ppm (s, 9H); 13C NMR (100 MHz, CDCl3): d=175.5,
164.0, 142.2, 142.1, 134.5, 134.2, 134.1, 130.9, 129.6, 129.5, 129.4, 129.2,
128.8, 128.6, 128.5, 118.4, 118.0, 39.7, 27.8 ppm (one carbon signal is miss-
ing due to overlapping); IR (film): n˜ =3056, 2971, 2874, 1739, 1627, 1598,
1479, 1446, 1239, 1105, 1080, 1064, 749 cmÀ1; HRMS (ESI): m/z: calcd for
C28H26O4Na: 449.1729, found: 449.1730.
Compounds 12c and 13c: The title compounds were obtained as a 1:1
isomeric mixture following general protocol 2 in 79% combined yield.
Characterization of the mixture: 1H NMR (400 MHz, CDCl3): d=8.16
(dd, J=8.4, 1.2 Hz, 2H), 7.91 (dd, J=8.4, 1.4 Hz, 2H), 7.68–7.08 (m,
26H), 6.56 (s, 1H), 6.49 (s, 1H), 6.46 (s, 1H), 6.45 (s, 1H), 1.24 (s, 9H),
1.10 ppm (s, 9H); 13C NMR (100 MHz, CDCl3): d=176.6, 176.1, 164.7,
163.8, 142.5, 142.2, 140.1, 140.0, 134.1, 134.0, 133.6, 133.5, 133.3, 133.3,
130.1, 130.1, 129.3, 129.4, 129.2, 129.1, 128.7, 129.0, 128.5, 128.4, 128.4,
128.2, 128.2, 128.1, 128.1, 127.6, 127.3, 123.3, 122.5, 122.0, 121.8, 39.0,
38.9, 27.1, 27.0 ppm (one carbon signal is missing due to overlapping); IR
(film): n˜ =3062, 3020, 2971, 1744, 1600, 1479, 1450, 1245, 1150, 1107,
Acknowledgements
We thank the Organic Chemistry Institute of the University of Zürich,
the Legerlotz Stiftung, and the Swiss National Science Foundation for fi-
nancial support and the SGI/IZO-SGIker UPV/EHU and Schrçdinger
(UZH) for allocation of computational resources. We thank Dr. A.
Linden for performing the X-ray crystal structure determinations of 21
(CCDC-849632) and 22 (CCDC-849631).
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Mechanistic Study of Acetoxy Migration
FULL PAPER
[16] For other examples of Au-catalyzed diene formation, see: a) A.
Buzas, F. M. Istrate, F. Gagosz, Org. Lett. 2007, 9, 985–988; b) S. Z.
Wang, L. Zhang, Org. Lett. 2006, 8, 4585–4587; c) A. S. Dudnik, T.
Schwier, V. Gevorgyan, Tetrahedron 2009, 65, 1859–1870; d) A. S.
Dudnik, T. Schwier, V. Gevorgyan, J. Organomet. Chem. 2009, 694,
482–485.
[17] The structure of 2a has been confirmed by X-ray analysis. For more
information, see ref. [15].
[18] D. Weber, M. R. GagnØ, Org. Lett. 2009, 11, 4962–4965.
[19] a) D. J. Gorin, B. D. Sherry, F. D. Toste, Chem. Rev. 2008, 108, 3351–
3378; b) N. Marion, S. P. Nolan, Chem. Soc. Rev. 2008, 37, 1776–
1782.
[1] a) N. Marion, S. P. Nolan, Angew. Chem. 2007, 119, 2806–2809;
Angew. Chem. Int. Ed. 2007, 46, 2750–2752; b) J. Marco-Contelles,
E. Soriano, Chem. Eur. J. 2007, 13, 1350–1357; c) C. Nevado,
Chimia 2010, 64, 247–251.
[2] H. Strickler, J. B. Davis, G. Ohloff, Helv. Chim. Acta 1976, 59, 1328–
1332.
[3] a) V. Rautenstrauch, J. Org. Chem. 1984, 49, 950–952; b) V. Rauten-
strauch, U. Burger, P. Wirthner, Chimia 1985, 39, 225–226.
[4] a) K. Miki, K. Ohe, S. Uemura, Tetrahedron Lett. 2003, 44, 2019–
2022; b) K. Miki, K. Ohe, S. Uemura, J. Org. Chem. 2003, 68, 8505–
8513.
[5] a) E. Mainetti, V. Mouri›s, L. Fensterbank, M. Malacria, J. Marco-
Contelles, Angew. Chem. 2002, 114, 2236–2239; Angew. Chem. Int.
Ed. 2002, 41, 2132–2135; b) Y. Harrak, C. Blaszykowski, M. Bern-
hard, K. Cariou, E. Mainetti, V. Mouri›s, A.-L. Dhimane, L. Fen-
sterbank, M. Malacria, J. Am. Chem. Soc. 2004, 126, 8656–8657;
c) E. Soriano, P. Ballesteros, J. Marco-Contelles, Organometallics
2005, 24, 3182–3191.
[20] The coordination of gold to each of the four possible isomers of the
starting material produces several conformationally distinct com-
plexes. Unless otherwise stated, the calculations shown here were
performed on the most stable system, in which the smallest substitu-
ents at the propargylic positions are eclipsed with the bulky metal
center.
[6] a) X. Shi, D. J. Gorin, F. D. Toste, J. Am. Chem. Soc. 2005, 127,
5802–5803; b) G. Lemi›re, V. Gandon, K. Cariou, A. Hours, T. Fu-
kuyama, A.-L. Dhimane, L. Fensterbank, M. Malacria, J. Am.
Chem. Soc. 2009, 131, 2993–3006; c) N. Marion, G. Lemi›re, A.
Correa, C. Costabile, R. S. Ramón, X. Moreau, P. FrØmont, R. Dah-
mane, A. Hours, D. Lesage, J.-C. Tabet, J.-P. Goddard, V. Gandon,
L. Cavallo, L. Fensterbank, M. Malacria, S. P. Nolan, Chem. Eur. J.
2009, 15, 3243–3260.
[7] a) A. Correa, N. Marion, L. Fensterbank, M. Malacria, S. P. Nolan,
L. Cavallo, Angew. Chem. 2008, 120, 730–733; Angew. Chem. Int.
Ed. 2008, 47, 718–721; b) R. Fang, L. Yang, Y. Wang, Org. Biomol.
Chem. 2011, 9, 2760–2770; c) P. Mauleón, J. L. Krinsky, F. D. Toste,
J. Am. Chem. Soc. 2009, 131, 4513–4520; d) D. Garayalde, E.
Gòmez-Bengoa, Q. Wang, C. Nevado, A. Goeke, J. Am. Chem. Soc.
2010, 132, 4720–4730; e) O. Nieto Faza, C. Silva López, R. lvarez,
A. R. de Lera, J. Am. Chem. Soc. 2006, 128, 2434–2437.
[8] For selected references: a) V. Mamane, T. Gress, H. Krause, A.
Fürstner, J. Am. Chem. Soc. 2004, 126, 8654–8655; b) M. J. Johans-
son, D. J. Gorin, S. T. Staben, F. D. Toste, J. Am. Chem. Soc. 2005,
127, 18002–18003; c) A. Buzas, F. Gagosz, Org. Lett. 2006, 8, 515–
518; d) N. Marion, P. de FrØmont, G. Lemi›re, E. D. Stevens, L. Fen-
sterbank, M. Malacria, S. P. Nolan, Chem. Commun. 2006, 2048–
2050; e) C. A. Witham, P. Mauleón, N. D. Shapiro, B. D. Sherry, F. D.
Toste, J. Am. Chem. Soc. 2007, 129, 5838–5839; f) C. H. M. Amijs,
V. López-Carrillo, A. M. Echavarren, Org. Lett. 2007, 9, 4021–4024.
[9] See, among others: a) L. Zhang, J. Am. Chem. Soc. 2005, 127,
16804–16805; b) N. Marion, S. Díez-Gonzµlez, P. de FrØmont, A. R.
Noble, S. P. Nolan, Angew. Chem. 2006, 118, 3729–3732; Angew.
Chem. Int. Ed. 2006, 45, 3647–3650; c) A. Buzas, F. Gagosz, J. Am.
Chem. Soc. 2006, 128, 12614–12615; d) L. Zhang, S. Wang, J. Am.
Chem. Soc. 2006, 128, 1442–1443; e) Y. Zou, D. Garayalde, Q.
Wang, C. Nevado, A. Goeke, Angew. Chem. Int. Ed. 2008, 47,
10110–10113.
[21] For the sake of clarity, the figures depicted here correspond to the
reaction path yielding the major product observed in these transfor-
mations.
[22] Complete schemes, including further reaction pathways, computed
energy values for other possible intermediates, and three-dimension-
al representations of the most relevant transition states, can be
found in the Supporting Information.
[23] E. Soriano, J. M. Contelles, Chem. Eur. J. 2008, 14, 6771–6779.
[24] a) A. E. Reed, R. B. Weinstock, F. Weinhold, J. Chem. Phys. 1985,
83, 735–746; b) A. E. Reed, L. A. Curtiss, F. Weinhold, Chem. Rev.
1988, 88, 899–926.
[25] Distance C1-O1 in 1a=1.444 Š. Distance C1-O1 in 1a-PPh3-TS1=
1.473 Š.
[26] Y. Landais, J.-M. Vincent, in Science of Synthesis, Vol. 26, (Eds.: D.
Bellus, S. Ley, R. Noyori, B. G. Trost), Thieme, Stuttgart, 2005,
pp. 647–743.
[27] D. J. Brown, in The Chemistry of Heterocyclic Compounds: Qui-
noxalines: Supplement II, (Eds.: E. C. Taylor, P. Wipf), John Wiley
& Sons, New York, 2004.
[28] a) A. Gazit, H. App, G. McMahon, J. Chen, A. Levitzki, F. D.
Bohmer, J. Med. Chem. 1996, 39, 2170–2177; b) U. Sehlstedt, P.
Aich, J. Bergman, H. Vallberg, B. Norden, A. Graslund, J. Mol.
Biol. 1998, 278, 31–56; c) A. Dell, D. H. William, H. R. Morris,
A. G. Smith, J. Feeney, G. C. K. Roberts, J. Am. Chem. Soc. 1975,
97, 2497.
[29] T. Yamamoto, K. Sugiyama, T. Kushida, T. Inoue, T. Kanbara, J.
Am. Chem. Soc. 1996, 118, 3930–3937.
[30] E. D. Brock, D. M. Lewis, T. I. Yousaf, H. H. Harper, WO9951688,
1999.
[31] J. G. Martin, R. K. Hill, Chem. Rev. 1961, 61, 537–562.
[32] a) C. M. Cimarusti, J. Wolinsky, J. Am. Chem. Soc. 1968, 90, 113–
120; b) W. R. Roush, D. A. Barda, J. Am. Chem. Soc. 1997, 119,
7402–7403.
[10] a) C. Fehr, J. Galindo, Angew. Chem. 2006, 118, 2967–2970; Angew.
Chem. Int. Ed. 2006, 45, 2901–2904; b) A. Fürstner, P. Hannen,
Chem. Eur. J. 2006, 12, 3006–3019; c) C. Fehr, B. Winter, I. Magpan-
tay, Chem. Eur. J. 2009, 15, 9773–9784.
[11] a) J. Zhao, C. O. Hughes, F. D. Toste, J. Am. Chem. Soc. 2006, 128,
7436–7437; b) A. Buzas, F. Gagosz, J. Am. Chem. Soc. 2006, 128,
12614–12615; c) T. Luo, S. L. Schreiber, Angew. Chem. 2007, 119,
8398–8401; Angew. Chem. Int. Ed. 2007, 46, 8250–8253.
[33] The structures of 21 and 22 were unambiguously assigned by X-ray
diffraction analysis. CCDC-849632 (21) and CCDC-849631 (22) con-
tain the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. For
further detail see the Supporting Information.
[12] K. Ohe, M. Fujita, H. Matsumoto, Y. Tai, K. Miki, J. Am. Chem.
Soc. 2006, 128, 9270–9271.
[13] a) E. J. Cho, M. Kim, D. Lee, Eur. J. Org. Chem. 2006, 3074–3078;
b) E. J. Cho, D. Lee, Adv. Synth. Catal. 2008, 350, 2719–2723; c) K.-
G. Ji, X.-Z. Shu, J. Chen, S.-C. Zhao, Z.-J. Zheng, L. Lu, X.-Y. Liu,
Y.-M. Liang, Org. Lett. 2008, 10, 3919–3922.
[34] L. Ricard, F. Gagosz, Organometallics 2007, 26, 4704–4707.
[35] Y. Li, P. Tang, Y. Chen, B. Yu, J. Org. Chem. 2008, 73, 4323–4325.
[14] G. Li, L. Zhang, J. Am. Chem. Soc. 2008, 130, 3740–3741.
[15] X. Huang, T. de Haro, C. Nevado, Chem. Eur. J. 2009, 15, 5904–
5908.
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
13
&
ÞÞ
These are not the final page numbers!

C. Nevado et al.
[36] a) C. Lee, W. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785–789;
b) A. D. Becke, J. Chem. Phys. 1993, 98, 5648–5652; c) W. Kohn,
A. D. Becke, R. G. Parr, J. Phys. Chem. 1996, 100, 12974–12980.
[37] Gaussian 09, Revision B.01; M. J. Frisch, G. W. Trucks, H. B. Schle-
gel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V.
Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X.
Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Son-
nenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa,
M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven,
J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J.
Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, T. Keith, R. Ko-
bayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant,
S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene,
J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gom-
perts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Po-
melli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzew-
ski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D.
Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, and
D. J. Fox, Gaussian, Inc., Wallingford CT, 2010.
[38] a) P. J. Hay, W. R. Wadt, J. Chem. Phys. 1985, 82, 270–283; b) W. R.
Wadt, P. J. Hay, J. Chem. Phys. 1985, 82, 284–298; c) P. J. Hay, W. R.
Wadt, J. Chem. Phys. 1985, 82, 299–310.
[39] Y. Zhao, D. G. Truhlar, Theor. Chem. Acc. 2008, 120, 215.
[40] C. Gonzalez, H. B. Schlegel, J. Phys. Chem. 1990, 94, 5523–5527.
Received: November 4, 2011
Revised: January 23, 2012
Published online: && &&, 0000
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Mechanistic Study of Acetoxy Migration
FULL PAPER
Acetoxy Migration
T. de Haro, E. Gꢀmez-Bengoa,
R. Cribiffl, X. Huang,
C. Nevado* .................... &&&& — &&&&
Gold-Catalyzed 1,2-/1,2-Bis-Acetoxy
Migration of 1,4-Bis-Propargyl
Acetates: A Mechanistic Study
Gold catalysis: The gold-catalyzed
tandem 1,2-/1,2-bis-acetoxy migration
of 1,4-bis-propargyl acetates stereose-
lectively affords 2,3-bis-acetoxy-1,3-
dienes depending on the electronic
and steric features of the ancillary
ligand bound to gold and the substitu-
ents at the propargylic positions (see
scheme). Computational studies have
revealed the subtle mechanistic differ-
ences governing these transformations.
Chem. Eur. J. 2012, 00, 0 – 0
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www.chemeurj.org
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