Gold(I)-catalyzed synthesis of dihydrobenzofurans from aryl allyl ethers

Article abstract of DOI:10.1055/s-2006-932491

Formation of dihydrobenzofurans from aryl allyl ethers was catalyzed by in situ generated PPh₃AuOTf. This reaction appears to proceed by a Claisen rearrangement, followed by addition of the resulting phenol to the allyl group. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-932491

1
278
LETTER
Gold(I)-Catalyzed Synthesis of Dihydrobenzofurans from Aryl Allyl Ethers
1
G
N
old(I)-Catalyzed
i
Synthe
c
sis of Dihy
h
drobenzofur
o
A
ry
l
l
A
llyl
a
Ethers s W. Reich, Cai-Guang Yang, Zhangjie Shi, Chuan He*
Department of Chemistry, University of Chicago, Chicago, IL 60637, USA
Fax +1(773)7020805; E-mail: chuanhe@uchicago.edu
Received 16 November 2005
tical use, thus requiring higher temperatures (80 °C) for
completion. Unfortunately, good yields were only ob-
tained with the use of carbon tetrachloride as solvent
Abstract: Formation of dihydrobenzofurans from aryl allyl ethers
was catalyzed by in situ generated PPh AuOTf. This reaction
3
appears to proceed by a Claisen rearrangement, followed by addi-
tion of the resulting phenol to the allyl group.
(
Table 1). Based on our recent success in employing
PPh AuOTf to activate olefins for addition of weak
nucleophiles, we tested the catalyst in this system as well.
3
Key words: homogeneous catalysis, gold, cyclization, alkenes,
Claisen rearrangement
6
PPh AuOTf proved to be the ideal catalyst for conducting
3
this reaction, which when employed in toluene (Table 1)
gave an excellent yield of 2. We found that silver(I)
triflate alone as well as triflic acid were capable of
catalyzing the same reaction, but at significantly lower
yields. Without the phosphine ligand, gold(I) chloride
with silver(I) triflate was still able to catalyze the reaction,
but with a far lower efficiency.
The Claisen rearrangement represents one of the oldest
and most effective carbon–carbon bond formation
methods. Though traditionally this reaction is conducted
2
thermally at high temperatures, a large number of catalyt-
ic systems have been developed for both the aryl and ali-
2
,3
phatic variants of the reaction. In addition to carbon–
carbon bond formation, the product of the aryl Claisen
rearrangement is well suited to undergo ring closure via
an intramolecular addition reaction to give a dihydro-
benzofuran (Scheme 1). As part of our continued interest
in cationic gold species as effective Lewis acid catalysts,
we sought to catalyze the synthesis of dihydrobenzofurans
Table 1 Survey of Catalysts
O
O
5
mol% catalyst
80 °C, 16 h, solvent
4
from allyl aryl ethers in a one-pot process. We describe
1
2
here our success in mediating this tandem process utiliz-
Catalyst
Solvent
Benzene
Toluene
Yield (%)a
69
ing PPh AuOTf, generated in situ, and report our studies
3
on the mechanism of this reaction.
AuCl /3AgOTf
3
AuCl /3AgOTf
(45)
3
O
OH
AuCl /3AgOTf
CCl4
(73)
Claisen
3
rearrangement
PPh AuCl/AgOTf
Toluene
>95 (82)
65
3
R
R
AuCl/AgOTf
AgOTf
Toluene
Toluene
Toluene
57
O
addition
reaction
HOTf
66 (53)
a
1
Yield based on H NMR, using an internal standard. Yields in
parentheses represent isolated yields.
R
Scheme 1
Having identified our best catalyst system, we applied
Our initial survey of reaction conditions focused upon these conditions to a number of aryl allyl ethers in order
AuCl /AgOTf as the catalyst, a system we have success- to investigate the scope of the reaction (Table 2). For less
3
5
fully applied in the past. Indeed, AuCl /3AgOTf (5 mol% activated systems than compound 1, it was found that
3
based on gold) was capable of catalyzing the transforma- slightly longer reaction times were required to afford
tion of compound 1 to 2 at 80 °C in a number of solvents complete conversion. The presence of electron-donating
(
Table 1). While the reaction proceeded at as low as room groups on the aromatic ring proved to increase the reac-
temperature, the reaction was too sluggish to be of prac- tion yield. Furthermore, the best yields were achieved
with donating groups para to the allyl group, though meta
electron-donating groups could also be beneficial to the
reaction. In addition, the reaction was also tolerant of
SYNLETT 2006, No. 8, pp 1278–1280
Advanced online publication: 10.03.2006
1
5.
0
5.
2
0
0
6
DOI: 10.1055/s-2006-932491; Art ID: W31305ST
©
Georg Thieme Verlag Stuttgart · New York

LETTER
Gold(I)-Catalyzed Synthesis of Dihydrobenzofurans from Aryl Allyl Ethers
1279
Table 2 Synthesis of Dihydrobenzofuransa
parison to the reaction starting from 5. These results sup-
port the proposed two-step mechanism we proposed.
Entry Substrate
Product
Yield (%)b
OH
O
O
5
mol% PPh3AuOTf
R1
O
34%
85 °C, 24 h, toluene
R1
3
4
1
1
2
R = H
82
81
Scheme 2
1
R = Br
R2
O
R2
O
O
O
R1
3
5 mol% PPh AuOTf
85 °C, 24 h, toluene
23%
R1
1
2
60c
69
68
62
3
4
5
6
R = H, R = H
5
6
1
2
R = OMe, R = H
OH
O
5
mol% PPh
3
AuOTf
1
2
R = t-Bu, R = H
85 °C, 24 h, toluene
74%
1
2
R = OMe, R = Me
7
6
MeO
O
Scheme 3
O
MeO
7
55
Finally, we attempted to compare the rates of the two
steps in the tandem reaction process (Scheme 4). Com-
plete conversion of compound 7 to product 6 was found to
occur after 10 hours, while the reaction of substrate 5 to
compound 6 proceeded to only about 50% conversion af-
ter even 24 hours, signifying that the Claisen rearrange-
ment is the slow step in the process. Interestingly,
gold(III) was able to catalyze the Claisen rearrangement
of compound 1 at 0 °C, without undergoing the second ad-
dition step to yield 2. Gold(I), at such a low temperature,
could not mediate the rearrangement step, indicating the
difference between the two oxidation states of gold. This
difference may be attributed to the increased oxophilicity
OMe
OMe
a
All reactions were run in toluene at 85 °C catalyzed by 5 mol%
PPh AuCl/AgOTf.
3
b
All yields are isolated, unless specified otherwise.
c
1
Yield based on H NMR using an internal standard.
electron-withdrawing groups on the naphthyl ring as seen
in entry 2, Table 2.
We next explored the mechanism of this transformation.
As part of demonstrating that the first step of the reaction
proceeded through a Claisen rearrangement, we synthe-
sized the 2,6-substituted aryl allyl ether 3. This compound
was subjected to our standard reaction conditions to afford
7
of gold(III) as compared to gold(I). Presumably, gold(III)
binds to the phenol oxygen to speed up the rearrangement
step. This observation appears to be general for the reac-
tions we tested.
4
in a 34% yield, in addition to recovery of most of the re-
maining starting material (Scheme 2). Unable to undergo
a tandem rearrangement and cyclization due to the pres-
ence of two ortho substituents, this substrate instead un-
derwent a [3,3] rearrangement to afford compound 4,
indicating that cationic gold(I) is capable of mediating the
rearrangement. We next conducted the reactions shown in
Scheme 3 in order to confirm the mechanism shown in
Scheme 1 for the one-pot reaction. Compound 5 under-
went the tandem reaction to give 6 in a low yield (24%) at
O
O
catalyst
5
6
3
+
Au fast,
Au slow
3+
OH
Au slow,
Au fast
1+
1+
8
5 °C after 24 hours. If the reaction was run for 12 hours,
7
an intermediate 7 could be isolated and confirmed by
NMR. Compound 7 can subsequently be converted to 6
with the same catalyst at much higher efficiency in com-
Scheme 4
Synlett 2006, No. 8, 1278–1280 © Thieme Stuttgart · New York

1
280
N. W. Reich et al.
LETTER
In conclusion, we have described a one-pot synthesis of 1 H, J = 8.74, 6.55 Hz, CH
), 4.90 (m, 1 H, CH), 6.67 (d, 1 H,
J = 8.36 Hz, ArH), 7.12 (d, 1 H, J = 8.41 Hz, ArH), 7.26 (s, 1 H,
2
dihydrobenzofurans from aryl allyl ethers by using a
gold(I) catalyst, further demonstrating the utility of gold
1
3
ArH). C NMR (125 MHz, CDCl ): d = 20.2, 31.9, 34.4, 37.5, 79.8,
3
1
08.6, 122.1, 124.80, 126.8, 143.3, 157.4. HRMS: m/z calcd for
8
,9
as an effective Lewis acid catalyst. We have probed the
mechanism of this reaction and revealed that the reaction
proceeds by a Claisen rearrangement followed by an
intramolecular addition of the resulting phenol to the allyl
group.
C H O: 190.1358; found: 190.1379.
1
3
18
Acknowledgment
N.W.R. thanks the Richter Foundation for a grant in support for un-
dergraduate research. This research is supported by the A. P. Sloan
Foundation and Research Corporation.
Representative Procedure for Synthesis of Aryl Allyl Ethers
2
-Naphthol (1.44 g, 10 mmol) and allylbromide (1.33 g, 11 mmol)
References and Notes
were mixed in 50 mL of acetone and refluxed for 3 h in the presence
of K CO (5.53 g, 40 mmol). The reaction mixture was filtered and
the solvent removed under vacuum. The crude product was purified
2
3
(1) Present address: College of Chemistry, Peking University,
Beijing 100871, P. R. of China.
by using flash column chromatography with 10:1 hexanes–Et O as
eluent. This yielded 1.74 g (95% yield) of pure 2-(allyloxy)naphtha-
(2) For a recent review: Castro, A. M. M. Chem. Rev. 2004, 104,
2939.
2
lene (1) as a yellow oil.
(3) Hiersemann, M.; Abraham, L. Eur. J. Org. Chem. 2002,
1461.
Representative Procedure for Synthesis of Dihydrobenzofurans
(4) (a) Kim, K. M.; Kim, H. R.; Ryu, E. K. Heterocycles 1993,
36, 497. (b) Grant, V. H.; Liu, B. Tetrahedron Lett. 2005, 46,
1237. (c) Zulfiqar, F.; Kitazume, T. Green Chem. 2000, 2,
296. (d) Bernard, A. M.; Cocco, M. T.; Onnis, V.; Piras, P.
P. Synthesis 1997, 41.
(5) (a) Shi, Z.; He, C. J. Am. Chem. Soc. 2004, 126, 5964.
(b) Shi, Z.; He, C. J. Org. Chem. 2004, 69, 3669. (c) Shi,
Z.; He, C. J. Am. Chem. Soc. 2004, 126, 13596.
2
-(Allyloxy)naphthalene (263 mg, 1 mmol), chlorotriphenylphos-
phinegold(I) (24.7 mg, 0.05 mmol) and silver(I) triflate (12.8 mg,
.05 mmol) were mixed in 3 mL of dry toluene in a sealed reaction
0
tube and wrapped with aluminum foil. The mixture was then heated
at 85 °C with stirring for 24 h. After removal of the solvent the
crude product was purified by using flash column chromatography
with 20:1 hexanes–Et O as eluent. This yielded 215 mg (82% yield)
2
of pure 1,2-dihydro-2-methylnaphtho[2,1-b]furan (2) as a yellow
oil.
(6) Yang, C.-G.; He, C. J. Am. Chem. Soc. 2005, 127, 6966.
(7) Sromek, A. K.; Rubina, M.; Gevorgyan, V. J. Am. Chem.
Soc. 2005, 127, 10500.
Spectral Data for Selected Compounds
(8) Recent reviews: (a) Hashmi, A. S. K. Angew. Chem. Int. Ed.
2005, 44, 6990. (b) Hoffmann-Röder, A.; Krause, N. Org.
Biomol. Chem. 2005, 3, 387. (c) Arcadi, A.; Di Giuseppe, S.
Curr. Org. Chem. 2004, 8, 795. (d) De Vos, D. E.; Sels, B.
F. Angew. Chem. Int. Ed. 2005, 44, 30.
7
-Bromo-1,2-dihydro-2-methylnaphtho[2,1-b]furan (Table 2,
Entry 2)
1
H NMR (500 MHz, CDCl ): d = 1.53 (d, 3 H, J = 6.3 Hz, CH ),
3
3
3
.01 (dd, 1 H, J = 7.46, 7.75 Hz, CH ), 3.53 (dd, 1 H, J = 9.24, 5.94
2
Hz, CH ), 5.11 (m, 1 H, CH), 7.07 (d, 1 H, J = 8.76, ArH), 7.37 (d,
(9) Selected recent examples: (a) Sherry, B. D.; Toste, F. D. J.
Am. Chem. Soc. 2004, 126, 15978. (b) Zhang, L.; Kozmin,
S. A. J. Am. Chem. Soc. 2005, 127, 6962. (c) Yao, Y.;
Zhang, X.; Larock, R. C. J. Am. Chem. Soc. 2004, 126,
11164. (d) Nieto-Oberhuber, C.; Paz Muñoz, M.; Buñuel,
E.; Nevado, C.; Cárdenas, D. J.; Echavarren, A. M. Angew.
Chem. Int. Ed. 2004, 43, 2402. (e) Mamane, V.; Gress, T.;
Krause, H.; Fürstner, A. J. Am. Chem. Soc. 2004, 126, 8654.
2
1
1
H, J = 8.76, ArH), 7.47 (dd, 1 H, J = 1.96, 6.82 Hz, ArH), 7.52 (d,
H, J = 8.71 Hz, ArH), 7.90 (d, 1 H, J = 1.91 Hz, ArH). C NMR
1
3
(
1
125 MHz, CDCl ): d = 22.2, 35.9, 80.5, 113.3, 116.2, 118.8, 124.5,
3
28.2, 129.5, 129.9, 130.3, 130.7, 157.4. HRMS: m/z calcd for
C H OBr: 261.9993; found: 261.9988.
1
3
11
5
-tert-Butyl-2,3-dihydro-2-methylbenzofuran (Table 2, Entry 5)
1
H NMR (500 MHz, CDCl ): d = 1.29 (s, 10 H, t-Bu), 1.46 (d, 3 H,
J = 6.31 Hz, CH ), 2.80 (dd, 1 H, J = 7.87, 7.42 Hz, CH ), 3.29 (dd,
3
3
2
Synlett 2006, No. 8, 1278–1280 © Thieme Stuttgart · New York