Gold-catalyzed cyclo-isomerization of 1,6-diyne-4-en-3-ols to form naphthyl ketone derivatives

Article abstract of DOI:10.1039/b618291g

We report a new efficient gold-catalyzed cyclization of 1,6-diyne-4-en-3-ols to give naphthyl ketone derivatives under ambient conditions. The value of this cyclization is reflected by its applicability to a wide range of alcohol substrates. The Royal Society of Chemistry.

Full text of DOI:10.1039/b618291g

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Gold-catalyzed cyclo-isomerization of 1,6-diyne-4-en-3-ols to form
naphthyl ketone derivatives{
Jian-Jou Lian and Rai-Shung Liu*
Received (in Cambridge, UK) 14th December 2006, Accepted 8th January 2007
First published as an Advance Article on the web 18th January 2007
DOI: 10.1039/b618291g
no activity with catalysts such as AuCl, AuCl3, AuClPPh3,
AgSbF6 and AuPPh3SbF6 in CH2Cl2 (2%, 23 uC). In contrast, the
use of AuPPh3OTf (2 mol%) in CH2Cl2 (23 uC) gave naphthyl
ketone 2 with yield up to 85% (entry 6).{ The presence of external
water (2 equiv.) greatly decreased the yield of ketone 2 (21%). This
result is expected as water can inhibit catalytic activity through
coordination to the gold species. The structure of compound 2§
was identified by X-ray diffraction.13 PtCl2 and PtCl2/CO catalysts
with a 2% loading are less efficient for this cyclization and gave
ketone 2 in 45% and 56% yields respectively in hot toluene (100 uC,
entries 8–9).
We report a new efficient gold-catalyzed cyclization of 1,6-
diyne-4-en-3-ols to give naphthyl ketone derivatives under
ambient conditions. The value of this cyclization is reflected by
its applicability to a wide range of alcohol substrates.
Metal-catalyzed cyclo-isomerization of acyclic molecules to various
cyclic frameworks is very useful in organic synthesis.1–4 Despite
intensive studies of the metal-catalyzed cyclo-isomerization of
1-en-6-ynes,1–4 3,5-dien-1-ynes5,6 and endiynes7,8 functionalities,
little attention has been focused on other molecules. Saa´ reported
that 1,6-diyne-3-ols undergo thermal intramolecular [4 + 2]
cycloaddition to give benzo[b]fluorene derivatives;9 this process
involves initial formation of a 1,4-vinyl biradical, which then
undergoes rapid intramolecular coupling to form strained cyclic
allene intermediate (eqn 1). Toste and coworkers reported10 the use
of Au(I) catalysts to implement a tandem [3,3]-sigmatropic
rearrangement11/formal Myers–Saito12 cyclization of propargyl
acetates to produce naphthyl ketones via generation of 2-allenyl-1-
alkynylbenzene intermediates (eqn 2). We report here gold-
catalyzed cyclization of 1,6-diyne-4-en-3-ols to give different
naphthyl ketones via a new mechanism. In contrast with Toste’s
pathway,10 this cyclization is presumably initiated by a OH-
chelating Au(I)–p-alkyne species, which controls the regioselective
hydration of the other alkyne group to complete the aromatization
(eqn 3).
We prepared various 1,6-diyne-4-en-3-ols 3–17 to examine the
generality and the scope of this cyclization; the results are
depicted in Table 2. The catalytic reactions were performed using
2 mol% AuPPh3OTf in CH2Cl2 at 23 uC without external water.
Entries 1–5 show the compatibility of this cyclization with
variation of the alkynol groups of substrates 3–7 bearing R =
p-tolyl, p-fluorophenyl, p-methoxyphenyl, methyl and butyl
groups; the resulting naphthyl ketones 18–22 were obtained in
78–86% yields. The structures of compounds 19 and 20 were
confirmed by 1H-NOE effects.13 A high efficiency was maintained
for the gold-catalyzed cyclization of 1,6-diyne-4-en-3-ol derivatives
8–10 bearing a 4-methoxyphenyl group on their alkynes, giving
expected phenyl naphthyl ketones 23A–25 in 73–81% yields with a
small proportion of debenzylated products 23B and 24B (8–14%,
entries 6–8). Furthermore, we obtained p-methoxybenzoic acid in
11% and 5% yields during the cyclization of alcohols 8–9 (entries
6–7). The gold-catalyzed cyclization of substrates 11–15 bearing a
ð1Þ
Table 1 Catalytic cycloaddition over various catalysts
ð2Þ
ð3Þ
Catalysta
Solvent (conditions)
Yieldsb
(1) AuCl
(2) AuCl3
(3) AuClPPh3
(4) AgSbF6
(5) AuClPPh3/AgSbF6
(6) AuClPPh3/AgOTf
(7) AuClPPh3/AgOTf
(8) PtCl2
CH2Cl2 (23 uC, 12 h)
CH2Cl2 (23 uC, 12 h)
CH2Cl2 (23 uC, 12 h)
CH2Cl2 (23 uC, 12 h)
CH2Cl2 (23 uC, 12 h)
CH2Cl2 (23 uC, 3 h)
wet CH2Cl2 (23 uC, 3 h)
toluene (100 uC, 12 h)
toluene (100 uC, 12 h)
b
N.R.c
N.R.c
N.R.c
traced
dec.d
85%
Table 1 shows a screening of the catalytic activity to cyclize 1,6-
diyne-4-en-3-ol 1 using various p-alkyne activators; we observed
21%e
45%
Department of Chemistry, National Tsing-Hua University, Hsinchu,
Taiwan 300, ROC. E-mail: rsliu@mx.nthu.edu.tw; Fax: +886 3-5711082;
Tel: +886 3-5721424
{ Electronic supplementary information (ESI) available: NMR spectra,
spectral data of compounds 1–32, and X-ray structural data of compound
2. See DOI: 10.1039/b618291g
(9) PtCl2/CO
a
56%
2 mol% catalyst, [diyne] = 0.20 M. Products were separated using
c
a silica column. Starting 1 was recovered in 90%, 89% and 93%
d
e
respectively. No starting substrates were recovered. External
water (2 equiv.) was added.
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Table 2 Gold-catalyzed intramolecular cyclization of 1,6-diyne-4-en-3-ol derivatives
Substrates
Products (yields)b
Substrates
Products (yields)b
18 (84%)
19 (86%)
20 (82%)
21 (78%)
22 (81%)
(9) R = Ph (11)
26 (90%)
27 (88%)
28 (87%)
29 (91%)
30 (88%)
(4) R = CH3 (6)
(5) R = n-Bu (7)
(13) R = CH3 (15)
(6) R = Ph (8)c
23 A 73%
24 A (80%)
23 B (14%)
24 B (8%)
(14) R = CH3 (16)
(15) R = n-Bu (17)
31 A (80%)
32 (85%)
31 B (2%)
(8) R = CH3 (10)
a
25 (81%)
The reaction was performed using 1,6-diyne-4-en-3-ols 1 (1 equiv., 0.20 M) in the presence of PPh3AuCl/AgOTf (2 mol%) in dichloromethane
at room temperature for 3 h. Product yields are given after separation from a silica column. p-Methoxybenzoic acid was obtained in 11%
and 5% yields respectively in entries 6 and 7.
b
c
+
p-tolylalkynyl group produced only p-tolyl naphthyl ketones 26–30
without formation of by-products. This cyclo-isomerization works
well with alcohol 16 bearing two propynyl groups, such that
methyl naphthyl ketone 31A was obtained with yield up to 80%. In
a separate experiment, naphthyl ketone 23A was treated with
AuPPh3OTf in CH2Cl2 (23 uC, 120 h), from which we did not
obtain its debenzylated product 23B in the presence or absence of
water. Formation of naphthalene 23B is evidently not caused by
debenzylation of species 23A.
cationic AuPPh3 species to form p-alkyne species A, which
preferably generates a cationic charge on the alkyne carbon
adjacent to the phenyl group. This cationic charge induces a
6-endo-dig attack of the other alkyne group to generate highly
electrophilic cationic vinylgold(I) intermediate B,14 which was
captured by water to form enol species C. An enol–ketone
tautomerization of species C, followed by hydrodeauration and
dehydroxylation, generates the observed naphthyl ketone pro-
ducts. According to this mechanism, a trace amount of water is
sufficient for this catalytic sequence because a final step involves
the release of one water. This allylic intermediate C enables us to
propose the formation mechanism of naphthalene by-products.
We envisage that this species will form oxonium species D, which is
decomposed irreversibly by water to form naphthalene and
organic acids. Yamamoto et al. demonstrate the feasibility of this
step in a gold-catalyzed cyclization of 2-en-4-yn-1-als with
alkynes.15 Although formation of naphthalene products requires
a stoichiometric amount of water, addition of excess water to this
system fails to increase their yields because of its catalytic
inhibition by water.
Scheme 1 shows our mechanistic speculation to rationalize the
chemoselectivity of this gold-based catalysis. We envisage that
the hydroxyl group of the alcohol substrate is to coordinate the
In summary, we report an efficient gold-catalyzed cyclization of
1,6-diyne-4-en-3-ols to give naphthyl ketone derivatives under
ambient conditions. The cyclization is proposed16,17 to proceed via
a OH-chelated Au(I)–p-alkyne species, which subsequently triggers
the cyclization via a 6-endo-dig attack of the second alkyne group.
The value of this cyclization is reflected by its applicability to
diverse alcohol substrates. The application of this reaction
mechanism to construct larger aromatic ketones is under
investigation.
Scheme 1 Proposed mechanism.
1338 | Chem. Commun., 2007, 1337–1339
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We wish to thank the National Science Council, Taiwan for
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Notes and references
{ Synthesis of phenyl(2-phenylnaphthalen-1-yl)methanone (2): A solution
of PPh3AuOTf (2 mol%) was prepared by mixing PPh3AuCl (3.2 mg,
0.006 mmol) and AgOTf (1.7 mg, 0.006 mmol) in dichloromethane
(1.0 mL). To this solution was added compound 1 (100 mg, 0.32 mmol) at
25 uC, the mixture was stirred for 3 h. The resulting solution was filtered
through a celite bed, and eluted through a silica gel column (ethyl acetate/
hexane = 1/15) to give compound 2 (85.0 mg, 0.28 mmol, 85%) as yellow
solid.
10 J. Zhao, C. O. Hughes and F. D. Toste, J. Am. Chem. Soc., 2006, 128,
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§ Crystallographic data for compound 2: C23H16O (M.W. = 308.36),
˚
triclinic, space group P-1, a = 9.3540(17) A, b = 9.4771(18) A, c =
˚
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3
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˚
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This observation suggests that the gold catalyst will not cause
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which may give the same products according
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15
to the Yamamoto’s mechanism
.
17 As suggested by one reviewer, we cannot exclude an alternative
mechanism as depicted below. In this mechanism, gold activates a
6-endo-dig addition of the alcohol of species E at its p-alkyne group to
form oxacyclic species F, which undergoes cleavage of an ether ring to
form enol G. A subsequent aldol-condensation of species H is expected
to give the observed naphthyl ketones. For related references,
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Chem. Commun., 2007, 1337–1339 | 1339