Gold-catalyzed rearrangement of substituted allyl aryl ethers

Article abstract of DOI:10.1016/j.tetlet.2010.10.078

Triphenylphosphinegold(I) complexes catalyze the Claisen-type rearrangement of aryl allyl ethers to the corresponding branched and linear products. The product distribution depends on the olefin geometry of the allylic ether. Stereochemical transfer experiments support an ionic mechanism.

Full text of DOI:10.1016/j.tetlet.2010.10.078

Tetrahedron Letters 51 (2010) 6666–6669
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Tetrahedron Letters
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Gold-catalyzed rearrangement of substituted allyl aryl ethers
⇑
James R. Vyvyan , Heidi E. Dimmitt, Jennifer K. Griffith, Laura D. Steffens, Rebecca A. Swanson
Department of Chemistry, Western Washington University, 516 High Street, Bellingham, WA 98225-9150, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Triphenylphosphinegold(I) complexes catalyze the Claisen-type rearrangement of aryl allyl ethers to the
corresponding branched and linear products. The product distribution depends on the olefin geometry of
the allylic ether. Stereochemical transfer experiments support an ionic mechanism.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 15 September 2010
Revised 9 October 2010
Accepted 13 October 2010
Available online 21 October 2010
Dedicated to Professor Thomas R. Hoye on
the occasion of his 60th birthday
Keywords:
Claisen rearrangement
Gold catalysis
Mitsunobu etherification
Lewis acid
The [3,3]-sigmatropic rearrangement of allyl aryl ethers, more
commonly known as the aromatic Claisen rearrangement, has been
an important C–C bond-forming reaction for nearly a century.1 Le-
O
HO
Et2AlCl
wis acid catalysts,2 most notably BCl3 and Et2AlCl,5 TiCl4 and
3,4
6
hexanes
-78 °C
81 %
7
SnCl4 obviate the high temperatures required for the thermal
OMe
OMe
rearrangement, but must be used in stoichiometric quantities
and are not compatible with some functional groups. Other Lewis
acids (e.g., RuCl3/AgOTf/CuOTf,8 IrCl3/AgOTf,8b and Bi(OTf)39) and
guanidinium hydrogen bond donors10 may be used in sub-stoichi-
ometric quantities but have only been examined with simple mon-
osubstituted allyl ethers. We became interested in the aromatic
Claisen rearrangement in the context of our synthesis of heliannu-
ols C and E.11 Although Et2AlCl functioned well as a catalyst for the
rearrangement of diene 1 to yield ortho-allyl phenol 2,11 the use of
this catalyst with substrates like 3 containing more functionalized
allyl side chains led to complex mixtures of products resulting
from side reactions of the acetal group.12
2
1
O
Et2AlCl
complex
mixture
hexanes
-78 °C
O
OMe
O
3
of [3,3]-rearrangement product 5a along with small amounts of the
regioisomeric product 6a (Scheme 1 and Table 1, entry 1).18,19 The
constitution of 6a was deduced through observation of an nOe be-
tween the para-methyl group and the benzylic methylene as
shown. Reaction of E-4a under the same conditions also provided
5a and 6a along with the formal [1,3]-rearrangement product 7a
(Scheme 1 and Table 1, entry 2). Using the branched allyl aryl ether
8 in this reaction gave an excellent yield of 7a.
The use of Au(I) complexes as carbophilic p
-type Lewis acids13
for a variety of functional group-tolerant synthetic transformations
has exploded over the last decade.14 The use of Au(I) complexes to
catalyze a progargyl Claisen rearrangement15 and the preparation
of dihydrobenzofurans from simple allyl aryl ethers16 prompted
us to examine the rearrangement of substituted allyl aryl ethers
using gold complexes.
By way of comparison, treatment of 4a with Et2AlCl resulted in
a much lower selectivity for 5a (entries 3 and 4), while BCl320 gave
more 6a, but in poor yield (entries 5 and 6). Using BCl3 as catalyst
also gave additional products that were not fully characterized, but
appeared to be regioisomers of 6a and 7a based on analysis of their
1H NMR spectra. Use of either Ph3PAuCl or AgOTf alone resulted in
In early experiments, we were gratified to find that treatment of
ether Z-4a17 with Ph3PAuOTf (10 mol %, prepared in situ from
Ph3PAuCl and AgOTf) in 1,2-dichloroethane resulted in good yields
⇑
Corresponding author. Tel.: +1 360 650 3070; fax: +1 360 650 2826.
E-mail address: vyvyan@chem.wwu.edu (J.R. Vyvyan).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.078

J. R. Vyvyan et al. / Tetrahedron Letters 51 (2010) 6666–6669
6667
Table 1
Ph3PAuCl
(10 mol%)
AgOTf
Rearrangements of ether 4a17
Z or E 4a Conversionb
Yielda (%)
HO
HO
O
Entry Catalyst
(10 mol%)
5a
6a
7a
1,2-DCE
41 hours
room temp
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Ph3PAuCl/AgOTf
Ph3PAuCl/AgOTf
Et2AlClc
Z
E
Z
E
Z
E
Z
Z
Z
Z
Z
Z
Z
Z
Z
E
Z
E
Z
100
100
100
100
100
100
0
70
6
2
10
10
—
(58)
(46)
14
Trace 10
Trace 32
(8)
(6)
—
5
23
nOe
Et2AlCld
Z-4a
5a
70%
6a
6%
d,e
BCl3
d
BCl3
Ph3PAuCl
AgOTf
TfOH
Tf2NH
0
100
100
100
100
100
100
39
100
65
83
Complex mixturef
Complex mixturef
Complex mixturef
Complex mixturef
Complex mixturef
Complex mixturef
Ph3PAuCl
(10 mol%)
AgOTf
AgOTf/TfOH
AgNTf2/Tf2NH
Ph3PAuCl/TfOH
Ph3PAuCl/Tf2NH
Ph3PAuCl/AgNTf2
Ph3PAuCl/AgNTf2
Ph3PAuCl/AgBF4
Ph3PAuCl/AgBF4
Ph3PAuCl/
O
HO
(10 mol%)
5a
58%
6a
2%
+
+
1,2-DCE
41 hours
room temp
37
Trace Trace
5
4
6
(30)
(50)
(36)
65
(30)
E-4a
7a
8%
(4)
(31)
—
100
—
g
AgClO4
Ph3PAuCl
(10 mol%)
AgOTf
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35h
36h
37i
38i
39j
40j
Ph3PAuCl/AgPF6
Ph3PAuCl/AgPF6
Ph3PAuCl/AgOAc
Ph3PAuCl/AgTFA
Ph3PAuCl/AgTFA
Ph3PAuCl/AgOTs
Ph3PAuCl/AgOTs
10/AgOTf
11/AgOTf
11/AgOTf
12
12
13/AgOTf
14/AgOTf
14/AgOTf
(EtO)3PAuOTf
(EtO)3PAuOTf
AuCl3/AgOTf
AuCl3/AgOTf
AuCl3
Z
E
Z
Z
E
Z
E
Z
Z
E
Z
E
Z
Z
E
Z
E
Z
E
Z
E
28
32
0
0
0
0
0
0
Trace
6
—
—
—
—
HO
O
(10 mol%)
1,2-DCE
23 hours
room temp
7a
96%
28
46
0
8
31
—
Trace
—
—
8
Scheme 1. Rearrangements of substituted allyl aryl ethers with Ph3PAuOTf.
0
100
66
28
60
26
100
100
100
100
57
51
16
35
21
42
(6)
44
(25)
17
6
Trace
Trace
Trace
—
—
—
(10)
—
(8)
no conversion of Z-4a (entries 7 and 8), but treatment of Z-4a with
Brønsted acids resulted in complex product mixtures containing
only trace amounts of 5a and 6a (entries 9 and 10).20 Combining
Brønsted acids with Au(I) or Ag(I) produced complex mixtures of
products that, based on analysis of 1H NMR spectra, consisted pre-
dominantly of the cyclized dihydrobenzofuran product 9 (entries
11–14).8,16,20
—
—
—
—
9
8
24
AuCl3
The effect of the counter ion provided by the Ag(I) salt on the
rearrangement reaction was also examined. AgOTf gave the best
yield of Claisen product 5a, with AgNTf2 and AgBF4 being somewhat
less effective (entry 1 vs entries 15–18). It is noteworthy that in
these cases, E-4a gave a higher conversion than did Z-4a, but pro-
duced more of the linear rearrangement product 7a. Use of AgClO4
with triphenylphosphine gold chloride resulted in variable reaction
rates. At short reaction times, good yields of 5a could be obtained,
but at long reaction times produced only dihydrobenzofuran 9 (en-
try 13). We attribute this result to adventitious protons from water
due to the hygroscopic nature of the silver salt.21 In this case, addi-
tion of Proton SpongeÒ (3 mol %) prevented formation of 9, but rear-
rangement rates were still variable. The hexafluorophosphate,
acetate, trifluoroacetate, and p-toluenesulfonate silver salts were
ineffective in promoting the rearrangement of 4a (entries 20–26).
Although the Ph3PAuCl/AgOTf catalyst system worked well, we
also tried other gold(I) complexes as catalysts for the rearrange-
ment reaction. Au(I) complexes based on a hindered, electron-rich
biphenylbis(dialkyl)phosphine ligand (10–12) resulted in little or
no conversion of 4 (entries 27–31).
a
Yields reported are for isolated material from silica gel chromatography. Yields
in parentheses are based on integration of 1H NMR spectrum of the inseparable
mixture of 5a and 7a.
b
Based on amount of recovered 4a.
c
2 equiv of Lewis acid at À78 °C.
d
1.1 equiv of Lewis acid at À78 °C.
e
A regioisomer of 6a [tentatively identified as 2,4-dimethyl-3-(2-hexenyl)phe-
nol] was also isolated (32%).
f
Based on 1H NMR spectrum analysis, major components of this inseparable
mixture include diastereomeric dihydrobenzofurans 9 (see Refs. 16,20).
g
2 h reaction time.
h
Prepared in situ from (EtO)3P (10 mol %), Me2SAuCl (10 mol %) and AgOTf
(10 mol %).
i
AuCl3 (10 mol %) and AgOTf (30 mol %).
AuCl3 (10 mol %).
j
The more electron deficient tris(4-trifluoromethylphenyl) phos-
phine gold complex (13) gave good conversion of Z-4a to products
(entry 32). The N-heterocyclic carbene gold complex 14 gave only
moderate yields of 5 (entries 33 and 34). Use of a phosphite ligand
for gold(I) gave incomplete conversion, but high selectivity for for-
mation of 5a (entries 35 and 36). Gold(III) catalysts16 gave com-
plete conversion of 4a, but relatively low yields of rearrangement
products (entries 37–40). Thus, the triphenylphosphine gold chlo-
ride/silver triflate system remained the catalyst of choice.
O
A brief survey of solvents showed that weakly polar solvents
like 1,2-dichloroethane and dichloromethane gave the best yields
of rearranged products 5–7. Nonpolar solvents such as hexanes
and toluene gave only trace amounts of the rearranged products
even after extended reaction times at room temperature. Polar
9

6668
J. R. Vyvyan et al. / Tetrahedron Letters 51 (2010) 6666–6669
Table 2
AuCl
Cy
AuNTf2
P Cy
Effect of olefin geometry and steric bulk on the Au(I)-catalyzed rearrangement of
substituted allyl aryl ethers 4
AuCl
P
tBu
Cy
iPr
P
Cy
iPr
tBu
Ph3PAuOTf
(10 mol%)
HO
HO
O
iPr
iPr
N
R
R
iPr
11
iPr
1,2-DCE, 41 h
room temp
R
10
12
iPr
iPr
5
7
4
N
iPr
iPr
i
iPr
Pr
F3C
P AuCl
Entry
Substrate
R
Conversionb
Yield (%)a
Au
Cl
3
5
7
13
14
1
2
3
4
5
6
Z-4b
E-4b
Z-4c
E-4c
Z-4d
E-4d
n-C5H11
n-C5H11
Ph
Ph
t-Bu
100
100
100
100
0c
56
57
(21)
—
—
—
(42)
69
solvents like nitromethane were ineffective and only the starting
ether 4 was recovered. Catalyst loading was also examined briefly
using substrate E-4a. Use of 10 mol % Ph3PAuCl + AgOTf gave com-
plete conversion after 36 h, but reducing the amount of catalyst to
5 mol % gave only 71% conversion after 72 h. Further reducing the
catalyst loading to 2 mol % gave 65% conversion after 72 h.
From these results, it was clear that the Au(I)-catalyzed rear-
rangement of 4 cannot follow an entirely concerted mechanism.
At minimum, a competing ionic pathway is needed to explain
the isolation of 6 and the formal [1,3]-rearrangement product 7
from some reactions. The observation that the Z-isomers of 3 pro-
duce higher percentages of the formal [3,3]-rearrangement prod-
uct 5 than the corresponding E-isomers suggested that the olefin
geometry is important in dictating the reaction path. We next con-
ducted several experiments to refine our mechanistic understand-
ing of the reaction. When purified 5a was resubjected to the
reaction conditions, a very slow conversion to cyclic product 9
was observed by 1H NMR analysis, but no 6 or 7 was observed,
indicating the reaction is not reversible and that 5 is not an inter-
mediate that produces 6 or 7.
t-Bu
100d
—
56
a
Yields reported are for isolated material from silica gel chromatography. Yields
in parentheses are based on integration of 1H NMR spectrum of the inseparable
mixture of 5 and 7.
b
Based on amount of recovered 4.
Z-4d was recovered quantitatively after 72 h. Reaction time = 120 h.
Reaction time = 65 h; 2,4-dimethylphenol (31%) also isolated.
c
d
We have found that the steric bulk of the allyl substituent and
the stereochemistry of the olefin has significant effects on the
product distribution in the Au(I)-catalyzed rearrangement of allyl
aryl ethers 4 (Table 2). Good yields of branched products were ob-
tained from straight chain-substituted substrates 4b (entries 1 and
2). The phenyl-substituted substrates 4c gave good yields of rear-
ranged products, but relatively little branched product 5c was
formed from Z-4c, and E-4c produced only the linear product 7c
(entries 3 and 4). The tert-butyl substrate Z-4d failed to produce
any rearrangement products, allowing the starting material to be
recovered quantitatively (entry 5). Conversely, ether E-4e reacted
completely, but produced only the linear rearrangement product
7d along with a significant amount of 2,4-dimethylphenol (entry
6).
Stereochemical transfer experiments were conducted using
optically active substrates 15 and 17 (Scheme 2).22 When 15 and
17 were subjected to the rearrangement conditions, modest to
good yields of rearranged products 1622 and 18 were obtained,
but in all cases the products were racemic according to chiral GC
analysis, ruling out any possibility of a competing concerted rear-
rangement pathway. Thus, it seems clear that this transformation
proceeds via a solvent separated ion pair mechanism.
Au-phenoxide
allyl cation pair
AuPPh3
O
Ph3PAuCl
AgOTf
a
4 or 8
b
R
Ph3PAuCl (10 mol%)
a
b
O
OH
AgOTf (10 mol%)
1,2-dichloroethane
O
O
H
H
7
R
5
R
15
16
91% ee
47% yield, 0% ee
a
b
n
a
b
AuPPh3
R
O
Ph3PAuCl (10 mol%)
AgOTf (10 mol%)
1,2-dichloroethane
O
OH
n
Ph3PAuCl
AgOTf
4 or 8
Au-stabilized allyl
cation
17a n=1 98% ee
17b n=2 94% ee
18a 73% yield, 0% ee
18b 86% yield, 0% ee
Scheme 3. Mechanistic hypotheses for Au(I)-catalyzed rearrangement of allyl aryl
Scheme 2. Rearrangements of optically active allyl aryl ethers with Ph3PAuOTf.
ethers.

J. R. Vyvyan et al. / Tetrahedron Letters 51 (2010) 6666–6669
6669
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17. Allyl aryl ethers were prepared by Mitsunobu etherifcation (DIAD, PPh3, THF)
from the corresponding phenols and allylic alcohols: Mitsunobu, O. Synthesis,
1981, 1.
18. Typical experimental procedure: A culture tube was charged with Ph3PAuCl
(25.0 mg, 0.0505 mmol) and AgOTf (13.1 mg, 0.0510 mmol). The flask was put
under an argon atmosphere and dry 1,2-dichloroethane (5 mL) was added. The
suspension was stirred at room temperature for one hour. Ether 4a (102 mg,
0.499 mmol) was added via syringe. The septum and argon line were removed
and replaced with a screw cap. The solution was stirred at room temperature
for 41 h. The mixture was then opened to air and passed through a silica plug,
rinsing with 4:1 hexanes:ethyl acetate. The filtrate was concentrated by rotary
evaporation and purified via radial chromatography to yield 5a (71 mg,
0.35 mmol, 70%) and 6a (6.0 mg, 0.029 mmol, 6%).
We have two mechanistic hypotheses with respect to the role of
the gold catalyst.23 It is possible that the gold cation coordinates to
the electron-rich aryl ring, promoting cleavage of the allyl group
and formation of a gold phenoxide that traps the allylic cation
(Scheme 3, top).24 Alternatively, the gold cation may coordinate
to the olefin of the allyl aryl ether and lead to a gold-stabilized
allylic cation, that is subsequently trapped by the phenoxide
(Scheme 3, bottom). If the gold catalyst coordinates to the ether
oxygen to form a ‘free’ allylic carbocation intermediate, then sub-
strates Z-4a, E-4a, and 8 should all give the same products in sim-
ilar ratios.25 Thus, we favor a mechanism that involves interaction
between the gold catalyst and the allyl cation intermediate.
In summary, Au(I) complexes catalyze the rearrangement of al-
lyl aryl ethers to produce both formal [3,3] and [1,3]-rearrange-
ment products through an ionic mechanism. Further
investigation of the reaction mechanism with respect to the role
of the gold catalyst is on going, as well as studies aimed at deter-
mining the scope and limitations of this reaction, particularly with
respect to functional group tolerance.
Acknowledgment
Acknowledgment is made to the Donors of the American Chem-
ical Society Petroleum Research Fund (49441-UR 1) for partial sup-
port of this research and the National Science Foundation (CHE-
0616995) and the Herman Frasch Foundation (522-HF02) for sup-
port of initial experiments. The authors thank Jacqueline A. Haw-
kins for the preparation of some allyl aryl ethers and Profs
Timothy B. Clark and Gregory W. O’Neil for helpful discussions.
We also thank Dr. John Greaves (University of California-Irvine)
for assistance with mass spectrometry.
19. Characterization data for new compounds may be found in Supplementary
data.
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Int. Ed. 2009, 48, 2510; (e) Fürstner, A.; Morency, L. Angew. Chem., Int. Ed. 2008,
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Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.10.078.
References and notes
1. (a) Castro, A. M. M. Chem. Rev. 2004, 104, 2939; (b) Ichikawa, H.; Maruoka, K. In
The Claisen Rearrangement; Hiersemann, M., Nubbemeyer, U., Eds.; Wiley-VCH:
Weinheim, Germany, 2007; p 45. Chapter 3.