Gold-catalyzed oxidative cyclizations of 2-oxiranyl-1-alkynylbenzenes for diastereoselective synthesis of highly substituted 2-hydroxyindanones

Article abstract of DOI:10.1002/adsc.201100325

We report the gold-catalyzed oxidative cyclizations of 2-oxiranyl-1- alkynylbenzenes into highly substituted 2-hydroxyindanone frameworks bearing a tertiary alcohol. Such gold-catalyzed reactions comprise an initial internal redox reaction, sulfoxide oxidation of α-carbonyl gold-carbenoids, followed by gold-catalyzed formal ene reactions on the resulting diketone intermediates. Copyright

Full text of DOI:10.1002/adsc.201100325

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DOI: 10.1002/adsc.201100325
Gold-Catalyzed Oxidative Cyclizations of 2-Oxiranyl-1-alkynyl-
benzenes for Diastereoselective Synthesis of Highly Substituted
2-Hydroxyindanones
Rupsha Chaudhuria and Rai-Shung Liua,*
a
Department of Chemistry, National Tsing-Hua University, Hsinchu, Taiwan, Republic of China
Fax : (+886)-3-571-1082; e-mail: rsliu@mx.nthu.edu.tw
Received: April 27, 2011; Published online: October 10, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adcs.201100325.
Abstract: We report the gold-catalyzed oxidative
cyclizations of 2-oxiranyl-1-alkynylbenzenes into
highly substituted 2-hydroxyindanone frameworks
bearing a tertiary alcohol. Such gold-catalyzed reac-
tions comprise an initial internal redox reaction,
sulfoxide oxidation of a-carbonyl gold-carbenoids,
followed by gold-catalyzed formal ene reactions on
the resulting diketone intermediates.
Keywords: a-carbonyl gold-carbenoids; gold cataly-
sis; hydroxyindanones; oxidative cyclization; stereo-
controlled ene reaction
Scheme 1. Reported reactions of 2-oxiranyl-1- alkynylben-
zenes.
highly substituted 2-hydroxyindanones stereoselec-
tively; the resulting products 5 contain, notably, a ter-
The generation of reactive metal carbenoid intermedi- tiary alcohol that is not readily attainable otherwise.
ates from alkynes using gold catalysts represents one
Table 1 presents the tests of catalytic activity in the
important advent in modern catalysis.[1] a-Carbonyl oxidative cyclization of oxiranylalkyne 1a using vari-
carbenoids are readily accessible because of the avail- ous gold catalysts; herein, Ph2SO (4 equiv.) was used
ability of various redox reactions in both inter- and in- for the oxidative removal of hypothetical a-carbonyl
tramolecular fashions;[2–5] such reactions are safe be- carbenoid intermediate A.[2] In a typical operation, a
cause organic oxides replace hazardous diazocarbonyl mixture of compound 1a and Ph2SO (4 equiv.) was
reagents. Hashimi et al. and we independently report- treated with the catalyst (5 mol%) in dichlorome-
ed[6] the gold-catalyzed cycloisomerization of 2-oxir- thane (DCM, 258C) for 36 h, from which we obtained
anyl-1-alkynylbenznenes to give 3-1H-indenyl ketones the desired 2-hydroxy-indanone 5a as a single dia-
via a-carbonyl carbenoid intermediates (I), as depict-
ACHTUNGTRENNUNG
ed in Scheme 1.
In our subsequent work, we demonstrated the feasi- AgX bearing various silver sources (entries 1–3). We
bility of these intermediates to undergo tandem cyclo- found that X=SbF6 gave the best yield (82%) of
propanation or [3+2]cycloaddition with suitable al- product 5a. PACTHNUGTRNEUNG(t-Bu)2(o-biphenyl)AuCl/AgSbF6 main-
kenes, yielding cycloaddition products 3 and 4 effi- tained a satisfactory efficiency, but gave a mixture of
ciently.[6] 2,3-Disubstituted indanone II is closely relat- indanone 5a (21%) and diol 5a-OH (55%) that were
ed to the structures of several naturally occurring separable on a silica column (entry 4). AgSbF6 and
compounds[7] including pauciflorol F, quadrangularian HNTf2 alone give products in a complicated mixture
A and parthenocissin A (Scheme 2). Continuing our (entry 5). The proposed structure of compound 5a
1
interest in the catalytic cyclization of epoxy-alkyne was confirmed by the H NOE effect.[10] We envisage
functionalities,[5a,8,9] we report a new oxidative cycliza- that the 1a!5a transformation comprises an initial
tion of 2-oxiranyl-1-alkynylbenzenes 1 to produce redox reaction to form a-carbonyl carbenoid A,
Adv. Synth. Catal. 2011, 353, 2589 – 2592
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Rupsha Chaudhuri and Rai-Shung Liu
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Scheme 2. Natural products containing 2,3-disubstitued indanone(II).
Table 1. Activity screening over various Au(I) and Ag(I) thesis worked well for oxiranylalkynes 1b–1g contain-
catalysts.
ing methyl, n-propyl, cyclopropyl, cyclohexyl, tert-
butyl and phenyl at the alkynyl positions; their corre-
sponding products 5b–5g were obtained in 61–78%
yields. Here, we obtained excellent diastereoselectiv-
ity for 5b, c and 5e, f (dr>20:1), a useful dr ratio
(5:1) for 5g, and a limited dr=2:1 ratio for species 5d.
This catalysis is also compatible with alteration of the
oxiranyl substituents as exemplified by 1h–1k (en-
tries 7–10) that delivered the expected compounds
5h–5k with reasonable yields (56–76%). Excellent dr
ratios (dr>20:1) were obtained in most cases, except
compound 5k that existed in three diastereomers
(dr=2:1.3:1, entry 10). We employed the 1H-NOE
effect to confirm the structures of compounds 5c, 5h,
7a and 7c.[10]
We prepared additional oxiranylalkynes 6a–f to ex-
amine the effects of the phenyl substituents. As de-
picted in Table 3 (entries 1–4), this catalytic reaction
is directly applicable to substrates 6a–6d bearing elec-
tron-withdrawing chloro and fluoro moieties at the
phenyl C-4 and C-5 positions; the corresponding
products 7a–7d were obtained as a single diastereo-
mer with 70–76% yields. The effect of methoxy is no-
table in that we obtained a complicated mixture for
substrate 6e bearing this group at the C-4 position,
but a satisfactory yield of desired 7f with Y=OMe at
the C-5 position. This observation conforms to our ex-
pectation that the para-methoxy group enhances the
epoxy-ketone rearrangement in the presence of Lewis
acids.[6a]
[a]
L=(t-Bu)2P(o-biphenyl), [1a]=0.12M.
Product yields are reported after purification from silica
column.
[b]
which undergoes a subsequent Ph2SO oxidation/
Scheme 3 depicts our attempts to achieve a one-pot
formal ene reaction cascade to give observed 5a (see synthesis of 2-hydroxyindanone 5a from enyne 8.
Table 1). In this formal ene reaction, compound 5a is Compound 8 was treated with m-CPBA/NaHCO3
derived from the proton elimination of tertiary cation (1.1 equiv.) in dichloromethane (DCM, 158C, 8 h) to
intermediate C where 5a-OH is produced from water ensure the complete generation of oxiranylalkyne 1a
trapping of this cation.
in situ, that was subsequently treated with PPh3AuCl/
To assess the generality of this catalysis, we pre- AgSbF6 (5 mol%) and Ph2SO (4 equiv.) before stir-
pared various 2-oxiranyl-1-alkynylbenzenes 1b–1k, ring for 36 h in DCE at room temperature. However,
bearing varied substituents at the alkynyl and oxiranyl this reaction sequence only enabled the formation of
positions, as depicted in Table 2. The reactions were diketone 9 (82%)[11] due to the presence of m-chloro-
catalyzed with PPh3AuCl/AgSbF6 (5 mol%) in di- benzoic acid that impeded a final ene reaction. Fur-
chloromethane (DCM, 258C) in the presence of ther treatment of isolated diketone 9 with PPh3AuCl/
Ph2SO (4 equiv.). This new 2-hydroxyindanone syn- AgSbF6 in DCM effected the ene reaction to give de-
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Gold-Catalyzed Oxidative Cyclizations of 2-Oxiranyl-1-alkynylbenzenes
Table 2. Substrates bearing variable alkynyl and epoxy sub-
Table 3. Effects of the phenyl substituents.
stituents.
[a]
[b]
[substrate]=0.12M.
Product yields are reported after silica chromatography.
Scheme 3. Attempt for one-pot oxidative cyclization.
gold-catalyzed reactions comprise an initial internal
redox reaction, sulfoxide oxidation of a-carbonyl
gold-carbenoids, followed by gold-catalyzed formal
ene reactions on the resulting diketone intermediates.
This new catalysis proceeds with high stereocontrol
and efficiency, enabling a rapid access to complicated
2-hydroxyindanone frameworks bearing a tertiary al-
cohol.
[a]
PPh3AuCl/AgSbF6 (5 mol%), [substrate]=0.12M, di-
chloromethane, 258C, 36 h.
Product yields are reported after silica chromatography.
[b]
Experimental Section
General Procedure for Synthesis of 2-Hydroxy-2-
isopropyl-3-(prop-1-en-2-yl)-2,3-dihydro-1H-inden-1-
one (5a)
sired 5a in 91% yield, verifying our mechanistic hy-
pothesis (Table 1).
In summary, we have reported gold-catalyzed oxi-
dative cyclizations of 2-oxiranyl-1-alkynylbenzenes
To
a flask containing PPh3AuCl (11.5 mg, 0.02 mmol)/
into highly substituted 2-hydroxyindanones. Such AgSbF6 (8.0 mg, 0.02 mmol) was added dry dichloromethane
Adv. Synth. Catal. 2011, 353, 2589 – 2592
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Rupsha Chaudhuri and Rai-Shung Liu
COMMUNICATIONS
(2.0 mL), and the mixture was stirred for 10 min at room
temperature. To this solution was added a dichloromethane
solution (2.0 mL) of 2,2-dimethyl-3-[2-(3-methylbut-1-ynyl)-
phenyl]oxirane (1a, 100 mg, 0.46 mmol) and Ph2SO (377 mg,
1.86 mmol), the resulting suspension was stirred for 36 h at
room temperature. The solution was concentrated, and
eluted through a silica column to afford compound 5a as a
colorless liquid; yield: 88.1 mg (0.38 mmol, 82%).
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Acknowledgements
The authors wish to thank the National Science Council,
Taiwan for supporting this work.
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