Gold-catalyzed consecutive [1,2] alkyl migration-oxygen transfer reaction of 2-alkynyl-1-tetralones

Article abstract of DOI:10.1016/j.tetlet.2008.10.129

Gold-catalyzed isomerization of 2-alkynyl-1-tetralones afforded the corresponding 2-naphthylmethyl ketones in good to high yields. For example, the reaction of 2-{4-(methoxyphenyl)methyl}-2-(phenylethynyl)-3,4-dihydronaphthalen-1(2H)-one and 2-benzyl-2-(p

Full text of DOI:10.1016/j.tetlet.2008.10.129

Tetrahedron Letters 50 (2009) 216–218
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Gold-catalyzed consecutive [1,2] alkyl migration-oxygen
transfer reaction of 2-alkynyl-1-tetralones
*
Ching Siew Chan, Toshiharu Araki, Itaru Nakamura , Masahiro Terada
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Gold-catalyzed isomerization of 2-alkynyl-1-tetralones afforded the corresponding 2-naphthylmethyl
ketones in good to high yields. For example, the reaction of 2-{4-(methoxyphenyl)methyl}-2-(phenylethy-
nyl)-3,4-dihydronaphthalen-1(2H)-one and 2-benzyl-2-(phenylethynyl)-3,4-dihydronaphthalen-1(2H)-
one in the presence of 5 mol % of (Ph3P)AuCl and 5 mol % of AgOTf in THF at 50 °C gave 2-{1-(4-methoxy-
phenylmethyl)naphthalen-2-yl}-1-(4-methoxyphenyl)ethanone and 2-(1-benzylnaphthalen-2-yl)-1-
phenylethanone in 85% and 96% yields, respectively. The present reaction proceeds through [1,2] alkyl
migration followed by oxygen transfer.
Received 25 September 2008
Revised 21 October 2008
Accepted 27 October 2008
Available online 31 October 2008
Ó 2008 Elsevier Ltd. All rights reserved.
M
The employment of domino reaction in rearrangement is espe-
cially important for the access of complex frameworks.1 Several
groups, including ours, have recently reported domino reactions
proceeding through consecutive nucleophilic attack of an alkoxy
sp3-oxygen atom to a C–C triple bond, which were activated by
M
M
n
n
or
n
O
O
O
A
exo
A'
endo
p-acidic transition metal complex, followed by [1,3] alkyl migra-
tion (Scheme 1).2 We envisioned that the use of carbonyl sp2-oxy-
gen nucleophile instead of ether sp3-oxygen nucleophiles would
lead us to new domino reactions incorporating carbon–oxygen
bond formation and carbon group migration (Scheme 2). It has
been revealed that the resulting oxonium-containing vinylmetal
intermediate A and A0 undergoes various transformations, such
as isomerization to vinyl carbenoids,3 [3,3] rearrangement,4 proton
shift involving protodemetalation,5 trapping with external nucleo-
philes,6 ring expansion,7 oxygen transfer (hetero-enyne meta-
Scheme 2. Intramolecular nucleophilic attack of a carbonyl oxygen atom catalyzed
by -acidic transition metal (M).
p
thesis),8 and cycloaddition.9 Recently, Kirsch et al. reported gold-
and platinum-catalyzed domino reactions consisting of hetero-
cyclization and [1,2] alkyl migration (Eq. 1).10,11 In their reaction,
the oxygen lone pair of the hydroxy group provides the critical
driving force in the reaction allowing this kind of acyloin rear-
rangements to take place under mild conditions. Herein, we report
that the gold-catalyzed reaction of 2-alkynyl-1-tetralones 1 pro-
ceeds through consecutive [1,2] alkyl migration-oxygen transfer
producing 1,2-disubstituted naphthalenes 2 in good to excellent
yields (Eq. 2).12
M
M
M
nucleophilic
attack
or
O
O
O E
n
E
E
n
n
O
R
R
cat. AuCl3 or PtCl2
O
-M
[1,3] alkyl migration
E
ð1Þ
OH
toluene, 80 °C
E
O
O
Ph
5 mol % (Ph3P)AuCl
5 mol % AgOTf
or
O
n
O
R1
n
THF, 50 °C
R2
ð2Þ
Scheme 1. Intramolecular nucleophilic attack of an alkoxy oxygen atom followed
by [1,3] alkyl migration catalyzed by -acidic transition metal (M).
R1
p
O
* Corresponding author. Tel.: +81 22 795 6754; fax: +81 22 795 6602.
E-mail address: itaru-n@mail.tains.tohoku.ac.jp (I. Nakamura).
Ph
R2
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.10.129

C. S. Chan et al. / Tetrahedron Letters 50 (2009) 216–218
217
Table 1
Table 2
Catalytic activity for isomerization of 1a
Gold-catalyzed consecutive [1,2] alkyl migration-oxygen transfer reaction of 1a
R1
Ph
O
Ph
5 mol % (Ph3P)AuCl
5 mol % AgOTf
Ar
O
O
conditions
50
O
Ar
R1
THF, 50 °C
Ph
°
C
Ph
R1
benzyl
(p-Tolyl)CH2
(p-Anisyl)CH2
Time
2
Yield/%b
MeO
Entry
1
MeO
1
2
3
4
5
6
7c
1b
1c
1d
1e
1f
20 min
20 min
20 min
21 h
12 h
1 h
2b
2c
2d
2e
—
96
1a (Ar =
p
-anisyl)
2a (Ar = p-anisyl)
Quant
Entry
Catalyst (mol %)
Solvent
Yield/%a
85
59
{2,5-(MeO)2C6H3}CH2
1
2b
3
(Ph3P)AuCl (5) + AgOTf (5)
(Ph3P)AuCl (5) + AgOTf (5)
(tBu2PhP)AuCl (5) + AgOTf (5)
THF
THF
THF
THF
THF
THF
THF
THF
Toluene
CH2Cl2
MeCN
MeNO2
Toluene
Toluene
Toluene
89
73
63
57
69
57
16c
11d
80
18e
5f
Me
Et
i-Pr
No reaction
1g
1h
2g
2h
12
21
14.5 h
4
5
6
7
8
9
{(p-Anisyl)Ph2P}AuCl (5) + AgOTf (5)
{(p-F3CC6H4)Ph2P}AuCl (5) + AgOTf (5)
(Ph3P)AuCl (5) + AgBF4 (5)
(Ph3P)AuCl (5) + AgSbF6 (5)
(Ph3P)AuCl (5) + AgNTf2 (5)
(Ph3P)AuCl (5) + AgOTf (5)
(Ph3P)AuCl (5) + AgOTf (5)
(Ph3P)AuCl (5) + AgOTf (5)
(Ph3P)AuCl (5) + AgOTf (5)
(Ph3P)AuCl (10)
a
The reaction of 1 (0.2 mmol) was carried out in the presence of 5 mol % of
(Ph3P)AuCl and 5 mol % of AgOTf in THF (0.4 mL) at 50 °C.
b
Isolated yield.
c
The reaction of 1h was carried out in the presence of 5 mol % of AuCl at 70 °C.
10b
11b
12b
13
14b
15
8).15 The reaction of 1a using toluene instead of THF gave 2a in
80% yield, whereas CH2Cl2, acetonitrile, and nitromethane were
less effective (entries 9–12). The reaction in the absence of silver
salts did not proceed at all (entry 13). The reaction using AgOTf
as catalyst afforded 2a in a lower yield, although TfOH led to
decomposition of the starting material 1a (entries 14 and 15).
5g
Nrh
43
AgOTf (10)
TfOH (20)
i
—
1H NMR yield using dibromomethane as an internal standard.
At 35 °C.
a
b
c
d
e
f
42% of 3 was obtained.
53% of 3 was obtained.
48% of 1a was recovered.
16% of 1a was recovered.
57% of 1a was recovered.
Nr: no reaction.
Ph
O
g
h
i
H
Decomposition of 1a was observed.
3
First, we optimized the reaction conditions using 1a as the sub-
We applied the optimal conditions (Table 1, entry 1) to various
substrates (Eq. 2). The results are summarized in Table 2. The reac-
tion of 1b and 1c, which had a benzyl and p-tolylmethyl group,
respectively, as a migrating group, completed within 20 min, giving
2b and 2c in good to excellent yields (entries 1 and 2). The reaction
of 1d bearing a (p-methoxyphenyl)methyl group at R1 proceeded
smoothly, while that of 1e having a (2,4-dimethoxyphenyl)methyl
group took 21 h due to steric hindrance of the migration group
(R1) (entries 3 and 4). As expected, methyl and ethyl groups proved
to be poor migrators; formation of gold mirror was observed
(entries 5 and 6). The substrate 1h having an isopropyl group at
strate. The results are summarized in Table 1. The reaction of 1a in
the presence of 5 mol % of (Ph3P)AuCl and 5 mol % of AgOTf in THF
at 50 °C gave 2a in 89% yield (entry 1).13 The reaction at 35 °C affor-
ded 2a in 73% yield (entry 2). The use of other gold-phosphine
complexes, such as (tBu2PhP)AuCl, {(p-anisyl)Ph2P}AuCl,14 and
{(p-F3CC6H4)Ph2P}AuCl14 instead of (Ph3P)AuCl, afforded 2a in low-
er yields (entries 3–5). The present reaction was significantly
affected by the counteranion of the silver salt; when silver salts
having weakly coordinating anions, such as bis(trifluorosulfo-
nyl)amide and hexafluoroantimonate, were used, the yield of 2a
decreased, forming a large amount of byproduct 3 (entries 7 and
O
Ph
R1
Ph
O
Au
R1
1
Ph
O
R1
O
Ph
8
Au
Au
R1
4
R1
7
H
O
Ph
Ph
Ph
O
O
R1
Au
2
Au
R1
5
6
Scheme 3. Plausible mechanism.

218
C. S. Chan et al. / Tetrahedron Letters 50 (2009) 216–218
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R1 was instead converted to 2h by the use of AuCl as catalyst and by
elevating the reaction temperature to 70 °C, though the chemical
yield was low (entry 7).
A plausible mechanism of the reaction of 1 is illustrated in
Scheme 3. The cationic gold catalyst first coordinates to the alkynyl
moiety of 1. The then triggered intramolecular nucleophilic attack
of the carbonyl group to the electron-deficient triple bond leads to
the formation of cyclic intermediate 6. [1,2] Alkyl migration would
be followed by C–O bond cleavage, forming the gold carbenoid
intermediate 7.16,17 Finally, hydrogen transfer leads to elimination
of the gold catalyst, and aromatization of 8 would give 2. Forma-
tion of 3 as a byproduct clearly suggests intermediacy of the furyl-
gold species 5.18
In conclusion, we are now in the position to synthesize 2-naph-
thylmethyl aryl ketones by using cationic gold catalysts. This
present reaction, which proceeds via carbon functional group
migration on an oxonium ion, is a useful methodology to synthe-
size complex compounds in an efficient and atom-economic
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Supplementary data
Experimental procedures and characterization of the products 2
and 3. This material is available. Supplementary data associated
with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2008.10.129.
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References and notes
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mixing stoichiometric amounts of (Ph3P)AuCl and AgOTf in THF under argon at
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gravitational sedimentation to take place. To a 1 dram vial with a threaded cap
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50 °C under argon was added 0.2 mL of the pre-generated solution of
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(Ph3P)AuOTf by
a microsyringe. The mixture was stirred at 50 °C and
monitored by TLC analysis. Upon completion, the mixture was filtered
through a short silica plug and eluted with ethyl acetate. The solvent was
removed under reduced pressure, and the crude product was
chromatographed with hexanes–EtOAc (20:1 v/v) to afford 2b as pale yellow
solid.
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18. Presumably,
a trace amount of water would capture 5 to form the
byproduct 3.