Platinum- and gold-catalyzed hydrative carbocyclization of oxo diynes for one-pot synthesis of benzopyrones and bicyclic spiro ketones

Article abstract of DOI:10.1021/ol801601q

(Chemical Equation Presented) We report a one-pot synthesis of benzopyrones and tricyclic spiroketones from hydrative carbocyclization of oxodiyne substrates catalyzed by PtCl₂ and PPh₃AuCl/AgOTf, respectively. The distinct carbocyclizations with R and Au catalysts stem from their altered regioselectivity in the oxo-assisted hydration of the neighboring alkyne carbons.

Full text of DOI:10.1021/ol801601q

ORGANIC
LETTERS
2008
Vol. 10, No. 18
4061-4064
Platinum- and Gold-Catalyzed Hydrative
Carbocyclization of Oxo Diynes for
One-Pot Synthesis of Benzopyrones and
Bicyclic Spiro Ketones
Arindam Das, Hsu-Kai Chang, Cheng-Hua Yang, and Rai-Shung Liu*
Department of Chemistry, National Tsing-Hua UniVersity, Hsinchu, Taiwan, ROC
rsliu@mx.nthu.edu.tw
Received July 14, 2008
ABSTRACT
We report a one-pot synthesis of benzopyrones and tricyclic spiroketones from hydrative carbocyclization of oxodiyne substrates catalyzed
by PtCl2 and PPh3AuCl/AgOTf, respectively. The distinct carbocyclizations with Pt and Au catalysts stem from their altered regioselectivity in
the oxo-assisted hydration of the neighboring alkyne carbons.
Regiocontrolled metal-catalyzed hydrative coupling of an
alkyne with another functionality is synthetically useful as
this procedure provides oxygenated carbocyclic frameworks
from readily available alkynes.1-5 Known examples are
reported for 1,n-diynes,1 1-yne-5-enones,2 1-en-5-ynes,3
1-allen-n-ynes4 (n ) 5-7), and triynes.5 With PtCl2 catalyst,
we found that the neighboring ketone of 2-ketonyl-1-
alkynylbenzenes selectively controlled the hydration regi-
oselectivity of its tethered alkyne via formation of benzopy-
rilium species (eq 1).6 We applied this ketone-assisted alkyne
hydration to the one-pot synthesis of bicyclic spiro ketones
using suitable triynes;5 the reaction protocol is depicted in
Scheme 1. In this hydrative carbocyclization, the ketone
Scheme 1
(1) (a) Trost, B. M.; Rudd, M. T. J. Am. Chem. Soc. 2003, 125, 11516.
(b) Trost, B. M.; Rudd, M. T. J. Am. Chem. Soc. 2005, 127, 4763. (c)
Odedra, A.; Wu, C.-J.; Pratap, T. B.; Huang, C.-W.; Ran, Y. F.; Liu, R.-S.
J. Am. Chem. Soc. 2005, 127, 3406
.
(2) Trost, B. M.; Brown, R. E.; Toste, F. D. J. Am. Chem. Soc. 2000,
122, 5877
.
(3) (a) Chen, Y.; Ho, D. M.; Lee, C. J. Am. Chem. Soc. 2005, 127,
12184. (b) Kennedy-Smith, J. J.; Staben, S. T.; Toste, F. D. J. Am. Chem.
Soc. 2004, 126, 4526. (c) Qian, H.; Widenhoefer, R. A. J. Am. Chem. Soc.
2003, 125, 2056
(4) Yang, C.-Y.; Lin, G.-Y.; Liao, H.-Y.; Datta, S.; Liu, R.-S. J. Org.
Chem. 2008, 73, 4907
(5) Chang, H.-K.; Datta, S.; Das, A.; Odedra, A.; Liu, R.-S. Angew.
Chem. 2007, 46, 4744
.
group of initial intermediate I controls a selective hydration
of the neighboring propynyl C(2) carbon, whereas its
.
.
(6) Das, A.; Liao, H.-H.; Liu, R.-S. J. Org. Chem. 2007, 72, 9214.
10.1021/ol801601q CCC: $40.75
Published on Web 08/23/2008
2008 American Chemical Society

platinum acyl group undergoes an addition of its enolate form
to the remaining π-propyne to form intermediate II.
Table 1. Chemoselectivity with Gold and Platinum Catalysts
Benzopyrone frameworks are commonly found in naturally
occurring compounds including amottin I, givocarcin V, and
defucogilvocarcin V, M.7 On the basis of oxo-assisted alkyne
hydration depicted in eq 1,8,9 we sought a facile synthesis
of benzopyrone derivatives via platinum-catalyzed hydrative
carbocyclization of readily available oxodiynes that undergo
two consecutive selective alkyne hydrations to give key
triketone intermediates IV (Scheme 2); the ketone of species
Scheme 2
a 5 mol % for gold catalyst, 8 mol % for PtCl2, 1,4-dioxane, [substrate]
) 0.15 M. b 10 mol % of 2,6-lutidine. c Yields are reported after separation
from silica column.
III is presumed to be equally active and selective in the
second alkyne hydration. Here, we found surprisingly that
PPh3AuCl/AgOTf gave bicyclic spiro ketones selectively
using the same diynone substrates.
lutidine (10 mol %) to PtCl2/CO allowed the isolation of
key triketone intermediate 6a (47%), which was convertible
to compound 5a by PtCl2/CO catalyst (entries 9 and 10). In
the absence of CO, we obtained a messy mixture of products,
from which ketal 5a′ was isolated in a 23% yield. Conversion
of ketal 5a′ to its hydrogenated form 5a was achieved in
83% yield by this PtCl2/CO/water system. The role of CO
is 2-fold: (1) to increase the electrophilicity of platinum(II)
Table 1 shows the results for active gold and platinum
catalysts, which exhibit distinct chemoselectivities for hy-
drative carbocyclization of diynone 1a. The use of AuCl (5
mol %) in wet 1,4-dioxane at 25 °C (12 h) led to a 65%
yield of diketone product 2a (entry 1), of which the
neighboring alkynyl C(1) carbon was selectively hydrated.
At 100 °C (12 h), we obtained satisfactory yields (63-74%)
of 1H-inden-1-one 3a from AuCl and AuCl3. Notably, the
use of PPh3AuCl/AgOTf afforded spiro ketone 4a with a
yield up to 78% (dr ) 2:1). Species 2a was confirmed to be
an intermediate for spiro ketone 4a because it was convertible
to 4a efficiently with PPh3AuCl/AgOTf (5 mol %) in both
wet and dry dioxane (entries 5 and 6). In contrast, 1H-inden-
1-one 3a was unrelated to ketone 4a because it remained
unreacted in the presence of gold catalyst. PtCl2/CO catalyst10
(8 mol %) showed a distinct chemoselectivity to give
benzoisochromene 5a in a 61% yield. The addition of 2,6-
10
via formation of PtCl2(CO)n and (2) to hydrogenate
unstable ketal product 5a′ to give stable benzoisochromene
using H2O/CO reactant; the latter process was verified by a
D2O-labeling experiment (vide infra).
Table 2 shows the applicability of this hydrative carbocy-
clization to diynones 1b-h. We obtained benzoisochromene
species 5b-h rather than original ketals because H2O/CO
caused their secondary hydrogenation. Entries 1-3 show the
variation of R4 and R5 substituents of substrates 1b-d, which
produced desired isochromenes 5b-d in moderate yields
(48-59%). For diynones 1e-h bearing fluoro and methoxy
at substituents R1, R2, and R3 of the two benzenes, the
corresponding carbocyclization products 5e-h were obtained
in 52-61% yields.
We extended this hydrative carbocyclization to various
diynals 7a-g using the same PtCl2/CO catalyst. Unlike their
ketone analogues 1a-h, we obtained the primary lactol
products 8a-g in good yields (72-88%) without a secondary
hydrogenation. Entries 1-3 show the applicability of this
hydrative carbocyclization to substrates 7a-c bearing R3 )
methyl, butyl, and 4-methoxyphenyl, which gave cyclized
(7) (a) Konno, F.; Ishikawa, T.; Kawahata, M.; Yamaguchi, K. J. Org.
Chem. 2006, 71, 9818. (b) Madan, S.; Cheng, C.-H. J. Org. Chem. 2006,
71, 8312.
(8) (a) Asao, N.; Takahashi, K.; Lee, S.; Kasahara, T.; Yamamoto, Y.
J. Am. Chem. Soc. 2002, 124, 12650. (b) Iwasawa, N.; Shido, M.; Kusama,
H. J. Am. Chem. Soc. 2001, 123, 5814
.
(9) Oxo-assisted alkyne hydration was recently reported by Pd(II)
catalyst, see: Momiyama, N.; Kanan, M. W.; Liu, D. R. J. Am. Chem. Soc.
2007, 129, 2230
.
(10) (a) Fu¨rstner, A.; Davies, P. W.; Gress, T. J. Am. Chem. Soc. 2005,
127, 8244. (b) Fu¨rstner, A.; Davies, P. W. J. Am. Chem. Soc. 2005, 127,
15024. (c) Zhang, G; Catalano, V. J; Zhang, L. J. Am. Chem. Soc. 2007,
129, 11358. (d) Taduri, B. P.; Ran, Y.-F.; Huang, C.-W.; Liu, R.-S. Org.
Lett. 2006, 8, 883. (e) Lo, C.-Y.; Lin, C.-C.; Cheng, H.-M.; Liu, R.-S. Org.
Lett. 2006, 8, 3153.
4062
Org. Lett., Vol. 10, No. 18, 2008

Table 2. Platinum-Catalyzed Synthesis of Benzoisochromenes
time
(h)
product
(yield, %)b
entry
diynonea
R1
R2
R3
R4
R5
1
2
3
4
5
6
7
1b
1c
1d
1e
1f
H
H
H
H
H
H
F
H
H
H
H
OCH3
F
H
H
H
OCH3
H
CH2CH3
CH2Ph
CH3
CH3
CH3
CH3
CH3
6
5
9
6
5.5
4.5
4.5
5b (59)
5c (56)
5d (48)
5e (52)
5f (53)
5g (61)
5h (60)
C3H7
C3H7
C3H7
C3H7
C3H7
1g
1h
H
H
CH3
CH3
H
a [Substrate] ) 0.15 M. b Yields are reported after separation from a silica column.
products 8a-c in good yields (75-82%). The same reaction
is also extendible to diynones 7d-g bearing methoxy and
fluoro at substituents R1 and R2 of the two benzenes; the
resulting acetals 8d-g were obtained with yields exceeding
63%.
6a. We envisage that a Brønsted acid11 or PtCl2 catalyzes
aldol condensation of triketone 6a via enol intermediate B
to produce 1-naphtanol C, which ultimately provides tetra-
cyclic ketal 5a′. The deuterium-labeling result confirms that
D2O serves as the hydrogen source for the reduction of ketal
5a′, which likely forms oxonium intermediate E to undergo
We performed deuterium-labeling experiments to under-
stand the mechanism of formation of benzoisochromene 5a.
With D2O, we obtained species 5a with deuterium labeling
exclusive at its methyl, OCH-, and -MeCdCH- positions
(eq 2). This deuterium-labeling experiment confirms the
source of hydrogen given from the water-gas shift reaction.
-
-
hydride addition by DPtCl2 . Formation of DPtCl2 from
CO and HOPtCl2 has been reported in the literature.12,13
-
This model also rationalizes that ketal products 5a-h are
more prone to secondary hydrogenation than their acetal
analogues 8a-g. The proton enhances reversible addition
of H2O to species D to produce lactol 5a′; this effect also
contributes to complete deuteration of the methyl group of
benzoisochromenes. Formation of enol ether D is responsible
for the low yield (23%) of tetracyclic ketal 5a′ because of
its facile cycloaddition with benzopyriliums.14
In contrast with PtCl2, PPh3AuCl/AgOTf produced bicyclic
spiro ketone 4a using the same diynone 1a (Table 1, entry
4). Table 4 shows the generality of this spiro ketone
synthesis. Diynones 1b-d and 1i are suitable for this
carbocyclization to give desired spiro ketones 4b-d and 4i
in satisfactory yields (63-82%,). Relative to spiro ketone
4a, the diasteromeric ratios of products 4b,c and 4i were
significantly enhanced (dr ) 4.5-15:1) with an increasing
size of ketone substituent R4 (R4 ) n-C3H7, CH2Ph, n-C6H13).
Scheme 3 shows a plausible mechanism including the
secondary hydrogenation of primary ketal product 5a′. With
isolation of triketone 6a by 2,6-lutidine (Table 1, entry 9),
we propose that diynone 1a likely undergoes repeated
formation of benzopyriliums A to give observed triketone
(11) In the PtCl2/CO/H2O system, aldol reactions between two ketones
can be catalyzed by either Brønsted acid or PtCl2; see control experiments
described in ref 5.
Scheme 3
(12) Treatment of styrene or 1-phenylpropyne with PtCl2/CO in wet 1,4-
dioxane (100 °C, 10 h) led to their exclusively recovery (>95%) without
any hydrogenation product, and we did not detect hydrogen with GC
analysis. This information indicates that a PtCl2-catalyzed water-gas shift
reaction did not occur in this system
(13) For platinum-catalyzed water-gas shift reaction, see: Yoshida, T.;
Ueda, Y.; Otsuka, S. J. Am. Chem. Soc. 1978, 100, 3941
.
.
(14) We reported a facile synthesis of chrysenes from PtCl2-catalyzed
dimerization of diketone via [4 + 2]-cycloaddition of its benzopyrilium
with enol intermediate; see ref 6.
Org. Lett., Vol. 10, No. 18, 2008
4063

likely undergoes Conia-ene reaction3b,16 via attack of the
enol group of its enol form G at the π-alkyne group to form
indenyl ketone H. A subsequent gold- or proton-catalyzed
aldol reaction of species H produces the desired spiro ketone
4a.
Table 3. Platinum-Catalyzed Carbocyclization of Diynals
In summary, we report a one-pot synthesis of benzopyrone
derivatives from PtCl2-catalyzed18 hydrative carbocyclization
of oxodiynes. This hydrative carbocyclization proceeds
through a sequential oxo-assisted hydration of two tethered
alkynes to give oxo dione intermediates, followed by
intramolecular aldol reactions. With the same diynones, we
obtained tricyclic spiro ketones using PPh3AuOTf catalyst
in wet dioxane. This gold species alters regioselectivity in
the hydration of the neighboring alkyne to give ynedione
intermediate, followed by Conia-ene and aldol condensation
to complete a distinct hydrative carbocyclization.
time
(h)
product
(yield, %)
entry diynal
R1
R2
R3
1
2
3
4
5
6
7
7a
7b
7c
7d
7e
7f
H
H
H
H
OMe
F
F
H
H
H
Me
2
2
4
4
1.5
2
4
8a (75)
8b (78)
8c (82)
8d (88)
8e (63)
8f (86)
8g (72)
n-Bu
4-MeOC6H4
OMe Me
H
H
Me
Me
7g
OMe Me
a [Substrate] ) 0.15 M. b Yields are reported after separation froma
silica column.
Table 4. Au(I)-Catalyzed Synthesis of Spiro Ketones
For diynones 1g and 1h bearing fluoro at the phenyl R1 and
R2 positions, the desired ketones 4g and 4h were obtained
in 73-78% yields (dr ) 2.1-2.2:1). This spiro ketone
synthesis is applicable to substrate 1k bearing a naphthalene
group, which gave ketone 4k in a 78% yield (dr ) 2.4:1).
Its analogue 1l gave ketone 4l in great dr ratio (>15:1),
reflecting the influence of a long R4 substituent (R4 )
n-C6H13). This spiro ketone synthesis, however, failed to
work with diynal 7a and other aldehyde analogues (entry
10). The structures of spiro ketones 4c, 4d(A), 4d(B), and
1
4h(A) were determined by H NOE, and the molecular
structure of 4h(A) was confirmed by an X-ray diffraction
study.15
On the basis of control experiments,16 we proposed that
the ketone group of diynone 1a facilitates the hydration of
the proximate C(1)-carbon of the neighboring alkyne via
intermediate F (Scheme 4). As we observed that diketone
a 5 mol % of PPh3AuCl and AgOTf, [substrate] ) 0.15 M. b Yields
were reported after separation from silica column.
Scheme 4
Acknowledgment. We thank the National Science Coun-
cil, Taiwan, for supporting this work
Supporting Information Available: Experimental pro-
cedures including detailed synthesis, X-ray data of compound
4h(A), spectral data and NMR spectra of new compounds
is available free of charge via the Internet at http://pubs.acs.org.
2a was convertible to spiro ketone 4a with PPh3AuOTf in
dry dioxane (Table 1, entry 6), we envisage that species 2a
OL801601Q
(15) The 1H-NOE spectra of key compounds and X-ray structure of
ketone 4h(A) are provided in the Supporting Information.
(17) (a) Staben, S. T.; Kennedy-Smith, J. J.; Toste, F. D. Angew. Chem.,
Int. Ed. 2004, 43, 5350. (b) Corkey, B. K.; Toste, F. D. J. Am. Chem. Soc.
2005, 127, 17168.
(16) Upon treatment of the triyne substrate (Scheme 1, R ) Me) with
PPh3AuCl/AgOTf (5 mol %) in wet dioxane (80 °C, 8 h), we recovered
the triyne substrate with a 95% recovery yield. This observation was
described in the Supporting Information of ref 5. With this control
experiment, the ketone of substrate facilitates the hydration of the
neighboring alkynyl C(1) carbon catalyzed by this gold catalyst.
(18) (a) For divergent reactivities between platinum and gold catalysts,
see: Zhang, G.; Catalano, V.; Zhang, L. J. Am. Chem. Soc. 2007, 129, 11358.
(b) Hashimi, A. S. K.; Kurpejovic, E.; Frey, W.; Bats, J. W. Tetrahedron
2007, 63, 5879. (c) Godet, T.; Vaxelaire, C.; Michel, C.; Milet, A.; Belmont,
P. Chem.sEur. J. 2007, 13, 5632.
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Org. Lett., Vol. 10, No. 18, 2008