Cationic Au(I)-catalyzed cycloisomerization of aromatic enynes for the synthesis of substituted naphthalenes

Article abstract of DOI:10.1055/s-2006-926261

A cationic Au(I) complex catalyzed the cycloisomerization of aromatic enynes that possess a substituent on their alkyne terminus. Cyclization of the 6-endo-dig type proceeded dominantly to give 1,3-di- and 1,2,3-trisubstituted naphthalenes. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-926261

LETTER
411
Cationic Au(I)-Catalyzed Cycloisomerization of Aromatic Enynes for the
Synthesis of Substituted Naphthalenes
Cationic
Au(I)-
a
C
atalyzedC
k
ycloisomeri
a
zationof
A
n
romatic
E
nyn
o
es ri Shibata,* Yasunori Ueno, Kazumasa Kanda
Department of Chemistry, School of Science and Engineering, Waseda University, Shinjuku, Tokyo, 169-8555, Japan
E-mail: tshibata@waseda.jp
Received 10 November 2005
substituent on their alkyne terminus, electron-donating
ene components, such as a silyl enol ether, were submitted
to the cycloisomerization.4
Abstract: A cationic Au(I) complex catalyzed the cycloisomeriza-
tion of aromatic enynes that possess a substituent on their alkyne
terminus. Cyclization of the 6-endo-dig type proceeded dominantly
to give 1,3-di- and 1,2,3-trisubstituted naphthalenes.
We here examined Au(I)-catalyzed cycloisomerization of
Key words: cycloisomerization, catalysis, enynes, gold, indenes, aromatic enynes. When alkyne moiety of aromatic enyne
naphthalenes
1 is activated by a cationic Au(I) catalyst, 6-endo-dig- or
5-exo-dig-type cyclization proceeds and the following
deprotonation gives substituted naphthalene 2 or 1-meth-
ylene-1H-indene derivative 3 (Scheme 1).
Recently, activation of alkyne moiety by a metal complex
has been an attractive strategy for the development of new
catalytic carbon–carbon bond forming reactions and gold-
catalyzed cyclization has been intensively studied, which
gives various types of carbo- and heterocyclic skele-
tons.1,2 In particular, Au(I)-catalyzed cycloisomerization
of enynes draws much attention in these days.3 We here
disclose Au(I)-catalyzed cycloisomerization of aromatic
enynes, which have a substituent on their alkyne terminus,
under mild reaction conditions.
We chose 1-(1-hexynyl)-2-isopropenylbenzene (1a) as a
model aromatic enyne and examined a Au(I)-catalyzed
cycloisomerization under various reaction conditions
(Table 1). No reaction proceeded at room temperature us-
ing AuCl(PPh3) (entry 1); however, the addition of Ag
salts increased the catalytic activity of Au(I) complex and
aromatic enyne 1a was consumed within one hour. Cy-
clization proceeded exclusively in a 6-endo-dig-type
manner regardless of counter anions of Ag salts and 3-bu-
tyl-1-methylnaphthalene (2a) was obtained in high yield
(entries 2–4). Ag salt itself did not work at all as a catalyst
even at 40 °C (entry 5). High yield was achieved using
only 1 mol% catalyst (entry 6) and it is noteworthy that the
cyclization efficiently proceeded even under an atmo-
sphere of air (entry 7). In the presence of 10 mol% of
TsOH·H2O as a protic acid catalyst, naphthalene 2a could
not be detected, which means that the cationic Au(I) com-
plex worked as an effective catalyst in the present cyclo-
isomerization.9,10
Catalytic benzannulation of aromatic enynes is a well-
known protocol for the synthesis of naphthalene deriva-
tives and various metal complexes, including Ru(II),4–6
Pt(II),4,5 Pd(II),4 Rh(I),4 Au(III),4,5 Ag(I),4 W(0),7 and
In(III),8 have already been reported as efficient catalysts.
In the Ru(II)- and W(0)-catalyzed reactions, however,
aromatic enynes with no substituent on their alkyne termi-
nus were used. The authors explained the reason that the
formation of vinylidene complexes, prepared from unsub-
stituted alkynes and metal catalysts, triggers the following
cycloisomerization.6,7a In the reactions of enynes with a
Au
R1
R3
R1
R3
6-endo-dig
Au+
R1
R3
H
R1
R3
R2
R2
Au
Au+
2
R1
R1
R3
R2
R2
1
5-exo-dig
R3
H
R2
R2
3
Scheme 1
SYNLETT 2006, No. 3, pp 0411–0414
1
5.
0
2.
2
0
0
6
Advanced online publication: 06.02.2006
DOI: 10.1055/s-2006-926261; Art ID: U30105ST
© Georg Thieme Verlag Stuttgart · New York

412
T. Shibata et al.
LETTER
Table 1 Screening of Reaction Conditions Using Cationic Au(I)
Catalysts
3c was detected (entry 2). AgSbF6 induced a more active
catalyst and cyclized products 2c/3c were obtained in
higher yield at the lower temperature (entry 3). Protective
groups of hydroxyl substituent controlled the reaction
pathway and almost no 5-exo-dig-type product 3 was de-
tected in the case of TIPS-protected propargyl alcohol 1e
(entries 4 and 5). Moreover, the protection of a hydroxyl
substituent was unnecessary and (2-naphthyl)methanol
(2f) was exclusively obtained from propargyl alcohol 1f
(entry 6).12 The cyclization of nitrogen-functionalized
enyne 1g also proceeded, however, a significant amount
of 5-exo-dig-type product 3g13 was obtained (entry 7). An
aryl group on the alkene moiety was acceptable (entry 8).
Aromatic enyne 1i possessing trisubstituted alkene
moiety was also a good substrate and 1,2,3-trisubstituted
naphthalene 2i was obtained (entry 9).
n-Bu
n-Bu
AuCl (PPh3) (X mol%)
Ag salt (1.2 x X mol%)
CH2Cl2
Me
Me
Entry
Ag salt
X (mol%)
Time (h)
Yield (%)
NRc
93
1
None
5
5
5
5
5
1
1
1
2
AgBF4
AgSbF6
AgOTf
AgOTf
AgOTf
AgOTf
1
3
1
92
4
1
92
5a
6
1
NRc
94
An o-alkynyl biphenyl, with an aryl group as ene moiety
in aromatic enyne, was also a good substrate: Au(I)-cata-
lyzed cyclization of 2-(1-hexynyl)biphenyl (1j) pro-
ceeded at higher reaction temperature and 9-butyl-
phenanthrene (2j) was a major product (Equation 1). Dif-
ferent from the previous examples,5,8 electron-donating
substituents, such as a methoxy or methyl group, were not
needed.14
1.5
1.5
7b
96
a The reaction was examined without AuCl(PPh3) at 40 °C.
b The reaction was examined under an atmosphere of air.
c NR = no reaction.
Under the above reaction conditions (Table 1, entry 6),
various aromatic enynes were examined (Table 2).11 An
aryl group was tolerable as a substituent of the alkyne
terminus and enyne 1b was transformed into the biaryl
compound 2b exclusively (entry 1). When oxygen-func-
tionalized enyne 1c was subjected to the present cyclo-
isomerization, a small amount of 5-exo-dig-type product
Double cyclization of dienediyne 1k efficiently proceed-
ed under the typical reaction conditions and 2,2¢-binaph-
thyl compound 2k was obtained in good yield
(Equation 2).
When aromatic enyne 1l, having no substituent on its
alkyne terminus, was examined, 5-exo-dig-type cycliza-
Table 2 Au(I)-Catalyzed Cycloisomerization of Various Aromatic Enynes 1
R1
R1
R3
AuCl (PPh3) (1 mol%)
R1
AgOTf (1.2 mol%)
+
CH2Cl2, r.t.
R3
R3
R2
R2
R2
1
2
3
Entry
R1
R2
R3
H
Enyne
1b
1c
Time (h)
Yield (%)
Product ratio 2/3
1
2
3a
4
5
6
7
8
9
Ph
Me
Me
Me
Me
Me
Me
Me
Ph
2
1
2
1
1
1
2
1
1
87
71
87
78b
73b
93
84
86
97
>20:1
7:1
CH2OMe
CH2OMe
CH2OTBS
CH2OTIPS
CH2OH
CH2NMeTs
n-Bu
H
H
1c
7:1
H
1d
1e
20:1
>20:1
>20:1
2:1
H
H
1f
H
1g
H
1h
1i
>20:1
5:1
n-Bu
Me
Mec
a AgSbF6 was used in place of AgOTf and the reaction was examined at 0 °C.
b Some product (ca. 20%) was obtained as desilylated alcohol 2f.
c E/Z ratio was ca. 1:1.
Synlett 2006, No. 3, 411–414 © Thieme Stuttgart · New York

LETTER
Cationic Au(I)-Catalyzed Cycloisomerization of Aromatic Enynes
413
n-Bu
n-Bu
n-Bu
AuCl (PPh3) (10 mol%)
AgSbF6 (12 mol%)
+
ClCH2CH2Cl, 40 °C, 90 h
1j
2j
3j
57% (2j/3j = 5/1)
Equation 1
tion proceeded and 1-methylene-1H-indene (3l) was a
major product. In the case of iodo-substituted enyne 1m,
vinyl iodide 3m was dominantly obtained15,16 and only a
small amount of naphthalene derivative 2m was detected
(Equation 3). These results strikingly contrast with the re-
ported examples, where enyne 1l gave naphthalene 2l6,7a
and iodo migration occurred from iodoalkynes.7b
References and Notes
(1) Pioneering works of cyclization triggered by alkyne
activation using Au catalyst: (a) Hashmi, A. S. K.; Frost, T.
M.; Bats, J. W. J. Am. Chem. Soc. 2000, 122, 11553.
(b) Asao, N.; Takahashi, K.; Lee, S.; Kasahara, T.;
Yamamoto, Y. J. Am. Chem. Soc. 2002, 124, 12650.
(2) A short review: Hoffmann-Röder, A.; Krause, N. Org.
Biomol. Chem. 2005, 3, 387.
(3) (a) Nieto-Oberhuber, C.; Muñoz, M. P.; Buñuel, E.; Nevado,
C.; Cárdenas, D. J.; Echavarren, A. M. Angew. Chem. Int.
Ed. 2004, 43, 2402. (b) Mamane, V.; Gress, T.; Krause, H.;
Fürstner, A. J. Am. Chem. Soc. 2004, 126, 8654.
(c) Luzung, M. R.; Markham, J. P.; Toste, F. D. J. Am. Chem.
Soc. 2004, 126, 10858. (d) Zhang, L.; Kozmin, S. A. J. Am.
Chem. Soc. 2004, 126, 11806. (e) Shi, X.; Gorin, D. J.;
Toste, F. D. J. Am. Chem. Soc. 2005, 127, 5802. (f) Nieto-
Oberhuber, C.; Lopez, S.; Echavarren, A. M. J. Am. Chem.
Soc. 2005, 127, 6178. (g) Zhang, L.; Kozmin, S. A. J. Am.
Chem. Soc. 2005, 127, 6962. (h) Suhre, M. H.; Reif, M.;
Kirsch, S. F. Org. Lett. 2005, 7, 3925. (i) Gagosz, F. Org.
Lett. 2005, 7, 4129. (j) Mézailles, N.; Ricard, L.; Gagosz, F.
Org. Lett. 2005, 7, 4133. (k) Muñoz, M. P.; Adrio, J.;
Carretero, J. C.; Echavarren, A. M. Organometallics 2005,
24, 1293. (l) Shibata, T.; Fujiwara, R.; Takano, D. Synlett
2005, 2062.
(4) Dankwardt, J. W. Tetrahedron Lett. 2001, 42, 5809.
(5) (a) Fürstner, A.; Mamane, V. J. Org. Chem. 2002, 67, 6264.
(b) Mamane, V.; Hannen, P.; Fürstner, A. Chem. Eur. J.
2004, 10, 4556.
(6) Shen, H.-C.; Pal, S.; Lian, J.-J.; Liu, R.-S. J. Am. Chem. Soc.
2003, 125, 15762.
(7) (a) Maeyama, K.; Iwasawa, N. J. Org. Chem. 1999, 64,
1344. (b) Miura, T.; Iwasawa, N. J. Am. Chem. Soc. 2002,
124, 518.
Me
Me
AuCl (PPh3) (2 mol%)
AgOTf (2.4 mol%)
CH2Cl2, r.t., 1 h
Me
1k
2k 83%
Me
Equation 2
R
R
AuCl (PPh3) (1 mol%)
R
AgOTf (1.2 mol%)
CH2Cl2, r.t.
+
Me
1l (R = H)
1m (R = I)
Me
Me
2l, m
3l, m
80% (R = H) (2l/3l = 1:4)
86% (R = I) (2m/3m = 1:13)
Equation 3
(8) Fürstner, A.; Mamane, V. Chem. Commun. 2003, 2112.
(9) Using AuCl3 (1 mol%) as a catalyst in toluene (see ref. 4),
the cycloisomerization of 1a did not proceed at r.t. and it did
at 100 °C for 24 h to give 2a yet in ca. 30% yield. Moreover,
AuCl(PPh3) is more stable and easy to handle than
hygroscopic AuCl3.
(10) Cationic platinum, which was prepared from PtCl2 (1 mol%)
and AgOTf (2.5 mol%), did not work as a catalyst even in
refluxed CH2Cl2.
(11) Typical Experimental Procedure (Table 2).
AuCl(PPh3) (1.2 mg, 0.0024 mmol) was placed in a flask and
a CH2Cl2 solution (2.5 mL) of aromatic enyne (0.25 mmol)
was added. To the resulting mixture was added AgOTf (0.8
mg, 0.0030 mmol) and the mixture was stirred at r.t. for 1–2
h. After completion of the reaction, the mixture was
quenched with H2O and extracted with CH2Cl2 three times.
The combined extracts were washed with brine and dried
over MgSO4. The solvent was removed under reduced
pressure and the crude products were purified by thin-layer
chromatography.
In summary, we disclosed a cationic Au(I) complex-cata-
lyzed cycloisomerization of aromatic enynes. Enynes
with an alkyl- or aryl-substituted alkyne terminus under-
went 6-endo-dig-type cyclization to give various 1,3-di-,
and 1,2,3-trisubstituted naphthalenes. The enyne with an
iodo-substituted alkyne terminus underwent 5-exo-dig-
type cyclization, which provides a new protocol for the
construction of an indene skeleton.
Acknowledgment
This research was supported by a Waseda University Grant for
Special Research Projects.
Synlett 2006, No. 3, 411–414 © Thieme Stuttgart · New York

414
T. Shibata et al.
LETTER
(12) (1-Methylnaphthalen-3-yl)methanol (2f): yellow oil. IR
(neat): 3350, 872, 773, 748 cm–1. 1H NMR (600 MHz,
CDCl3): d = 1.92 (br s, 1 H), 2.68 (s, 3 H), 4.79 (s, 2 H), 7.31
(s, 1 H), 7.47–7.52 (m, 2 H), 7.64 (s, 1 H), 7.81–7.82 (m, 1
H), 7.96–7.97 (m, 1 H). 13C NMR (100 MHz, CDCl3):
d = 19.4, 65.4, 123.7, 123.9, 125.6, 125.7, 125.8, 128.4,
132.0, 133.4, 134.7, 137.8. HRMS (FAB): m/z calcd for
C12H12O [M+]: 172.0888; found: 172.0891.
(14) In the presence of AuCl3 (5 mol%) as a catalyst, almost no
cycloisomerization of 1j proceeded even at 80 °C in toluene
(see ref. 5).
(15) (1E)-1-(Iodomethylene)-3-methyl-1H-indene (3m): yellow
oil. IR (neat): 1110, 1079, 1019 cm–1. 1H NMR (400 MHz,
CDCl3): d = 2.16 (s, 3 H), 6.35 (s, 1 H), 7.14–7.29 (m, 4 H),
7.39 (d, 1 H, J = 7.2 Hz). 13C NMR (100 MHz, CDCl3):
d = 13.5, 79.1, 119.1, 125.1, 125.7, 126.5, 127.8, 135.6,
144.3, 145.9, 150.0. HRMS (FAB): m/z calcd for C11H9I
[M+]: 267.9749; found: 267.9747.
(13) The stereochemistry of alkene moiety was determined by
NOE observation (Figure 1).
(16) During the purification of the products, some vinyl iodide
(E)-3m was isomerized to (Z)-3m.
NOE
H
H
NMeTs
3g
Me
Figure 1
Synlett 2006, No. 3, 411–414 © Thieme Stuttgart · New York