Palladium-catalyzed annulation of alkynes with ortho -halide-containing benzyl alcohols in aqueous medium

Article abstract of DOI:10.1021/jo501444g

The Pd-catalyzed annulations of ortho-halide-containing benzyl alcohols with alkynes for the synthesis of indenones were achieved in aqueous Triton X-100 micelles with good yields and wide substrate scopes. Moreover, the indenones obtained in this procedure can be further functionalized to form some more synthetic useful derivatives via an environmental-friendly way.

Full text of DOI:10.1021/jo501444g

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Note
Palladium-catalyzed annulation of alkynes with ortho-
halide-containing benzyl alcohols in aqueous medium
Jie Feng, Guoping Lu, Meifang Lv, and Chun Cai
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo501444g • Publication Date (Web): 13 Oct 2014
Downloaded from http://pubs.acs.org on October 15, 2014
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Palladiumꢀcatalyzed annulation of alkynes with
orthoꢀhalideꢀcontaining benzyl alcohols in
aqueous medium
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Jie Feng, Guoping Lu, Meifang Lv, Chun Cai*
College of Chemical Engineering, Nanjing University of Science & Technology 200
Xiaolingwei, Nanjing 210094, P. R. China
Eꢀmail: c.cai@njust.edu.cn
O
O2
Pd,H2O, Triton X-100, 70 oC
Ph
Green solvents,
mild conditions
OH
Ph
+
Ph
Ph
X
X=I, Br etc.
indenone derivatives:indenol,
2,3-dihydro-indenol, indene etc
water
nature compound: pauciflorol F
Abstract:
The Pdꢀcatalyzed annulations of orthoꢀhalideꢀcontaining benzyl alcohols with alkynes
for the synthesis of indenones were achieved in aqueous Triton Xꢀ100 micelles with
good yields and wide substrate scopes. Moreover, the indenones obtained in this
procedure can be further functionalized to form some more synthetic useful
derivatives via an environmentalꢀfriendly way.
Indenones are a class of important compounds since they are ubiquitous in
synthetic chemistry, biology, pharmacology and material chemistry.1 Consequently,
preparation of indenones and their derivatives has aroused great interest among
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synthetic chemists over the past decades.2 Typically, indenones have been synthesized
by transition metal (Pd3, Co4, Ru5 etc.)ꢀcatalyzed annulations of alkynes with
orthoꢀbifunctionalized arenes (Scheme 1).6 In recent years, guided by powerful C−H
activation technologies, Rhꢀcatalyzed direct annulations of aldehydes with alkynes
have appeared.7 In addition, other approaches such as trimerization, cross couplings
and amino transfer reactions have also been developed for the formation of
indenones.8
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Scheme 1 Preparation of indeones via annulation of alkynes.
Despite all these advances, development of greener methods for preparation of
indenones is in high demand as the existing methods usually require high reaction
temperature, expensive reagents and the use of potential toxic organic solvents.
Water is an ideal green medium for organic synthesis.9 Meanwhile, nonionic
surfactants develop well that enable transitionꢀmetal catalyzed crossꢀcouplings to be
performed in water. The surfactants may spontaneously selfꢀaggregate to form
nanomicelles that serve as nanoreactors for many valued types of couplings.10
Alone this line, we herein wish to explore a novel approach to synthesize indenones
via Pdꢀcatalyzed annulation in water under relatively mild conditions. We originally
planned to furnish the Pdꢀcatalyzed annulations with orthoꢀhalogenated
benzaldehydes and alkynes in water. In the course of exploring this reaction, it was
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found that orthoꢀhalideꢀcontaining benzyl achohols could also efficiently convert to
indenones. To date, there is no report describing the synthesis of indenones from
orthoꢀhalideꢀcontaining benzyl achohols. In addition, the usage of benzyl achohols
may broaden the scope of substrates to prepare indenones. In this regard, the
Pdꢀcatalyzed annulations using cheaper benzyl alcohols instead of corresponding
aldehydes (for example, 2ꢀiodobenzaldehyde 20 $/g vs 2ꢀiodobenzyl alcohol 1 $/g in
aldrich) deserved further investigation.
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As a representative example, the annulation of 2ꢀiodobenzyl alcohol and
diphenylethyne was selected to optimize the reaction (Table 1). The present reaction
could not occur in the absence of a palladium catalyst (entry 1). The use of surfactant
is crucial for the reaction, and the yield increased from 5% to 69% in the presence of a
surfactant (entries 2, 3). Screening ionic and nonionic surfactants revealed that Triton
Xꢀ100 was still the best choice (entries 3ꢀ6). Next, the reaction temperature was
examined in a quest to improve the yield. There was a sharply decrease of the
reactivity at lower temperature (entries 3, 7ꢀ9), but side reactions could be inhibited at
the same time. Avoiding the nasty byꢀproducts, the reaction was finally conducted at
70 °C. To our delight, satisfactory yield could be obtained when the reaction was
extended to 24 hours (entry 10). Considering that the annulation of 2ꢀiodobenzyl
alcohol with diphenylethyne may need consumption of molecular oxygen, an oxygen
balloon was introduced. As expected, oxygen promoted the reaction with the yield
increased to 86% (entry 11). Then some other commercial available palladium
complexes were tested (entries 12ꢀ14). However, palladium complexes, such as
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Pd(dppf)Cl2, Pd(PPh3)2Cl2 and Pd(Xphos)Cl2 did not give any improvement. Finally,
an examination of the bases demonstrated that K2CO3 was the most effective base for
this transformation, and other bases were not suitable for this reaction (entries 11,
15ꢀ17).
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Table 1 Optimizations for the preparation of indenone.a
Entry
Catalysts
Additives
Bases Temp Time
Yield %b
oC
K2CO3 110
K2CO3
h
2
1
2
ꢀ
TXꢀ100c
ꢀ
0
5
Pd(Amphosd)Cl2
Pd(Amphos)Cl2
Pd(Amphos)Cl2
Pd(Amphos)Cl2
Pd(Amphos)Cl2
Pd(Amphos)Cl2
Pd(Amphos)Cl2
Pd(Amphos)Cl2
Pd(Amphos)Cl2
Pd(Amphos)Cl2
Pd(dppf)Cl2
2
3
TXꢀ100
TBAC
K2CO3 110
K2CO3 110
K2CO3 110
K2CO3 110
2
69 (15e,10f)
23
4
2
5
SDS
2
50
6
Brij L23
TXꢀ100
TXꢀ100
TXꢀ100
TXꢀ100
TXꢀ100
TXꢀ100
TXꢀ100
TXꢀ100
TXꢀ100
TXꢀ100
TXꢀ100
2
55
7
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
NaOAc
90
25
70
70
70
70
70
70
70
2
53 (13e)
0
8
2
9
2
31 (2e)
80 (9e)
86 (6e)
70 (17e)
17 (10e, 23f)
44 (15e)
16 (62e)
7 (41e)
40f
10
11h
12h
13h
14h
15h
16h
17h
24
24
24
24
24
24
24
24
Pd(PPh3)2Cl2
Pd(Xphos)Cl2
Pd(Amphos)Cl2
Pd(Amphos)Cl2
Pd(Amphos)Cl2
KHCO3 70
tꢀBuOK 70
a
reaction conditions: (2ꢀiodobenzyl alcohol 0.5 mmol, 1,2ꢀdiphenylethyne 0.55
mmol, palladium complex 0.01 mmol, base 0.5 mmol, 2 wt.% surfactants/H2O,
2 mL, in air, 24 h. b determined by GC. c Txꢀ100 was Triton Xꢀ100. d Amphos=
diꢀtertꢀbutyl(4ꢀdimethylaminophenyl)phosphine. e the yield of 5a. f the yield of 4a.
h with O2 balloon.
With the optimized conditions in hand, a series of internal alkynes and
2ꢀhalobenzyl alcohols were chosen to establish the scope and generality of the method
(Table 2). Symmetric diarylethynes bearing methyl substituent at different positions
coupled with 2ꢀiodobenzyl alcohol to afford the indenones in good yields (3b, 3c).
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Notably, alkylꢀsubstituted internal alkyne was also tolerated (3e), but propargyl
chloride failed to provide the desired product (3d).
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Table 2 Scope of substrates.a,b
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a reaction conditions: 2ꢀhalobenzyl alcohol 0.5 mmol, alkyne 0.55 mmol, palladium complex 0.01 mmol, base, 0.5
mmol, 2wt.% Triton Xꢀ100/H2O 2 mL, with O2 balloon, 70oC, 24 h.; b isolated yields; c the reaction was conducted
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at 110 C; d the reaction was conducted at 80 C; e 2wt.% Triton Xꢀ100/H2O 2 mL was replaced by 2 wt.% Brij
L23/H2O; f yield of all the isomers; g the two isomers were separated, and the ratio of two isomers(3/3’) was
determined by isolated yield; h the two isomers were unꢀseparated, the ratio of two isomers (3/3’) was determined
by 1H NMR, and the regioselectivty was not determined.
As for asymmetric diarylacetylenes, most of them underwent smooth coupling with
two isomers obtained (3g, 3nꢀ3p). The electronic effect seems to have little influence
on the regioselectivity except for 3q, while the steric effect plays an important role on
the regioselectivity. For example, the usage of butꢀ1ꢀynꢀ1ꢀylbenzene only afforded
sole product (3h). Similarly, regioselective product was obtained when 1ꢀpentylꢀ
4ꢀ(phenylethynyl)benzene was used (3r). After that, substituted 2ꢀiodobenzyl alcohols
were examined. Variation of substituents showed obvious effects on the reaction
efficiency. Chloro or fluoro substituted 2ꢀiodobenzyl alcohols survived the reaction
with satisfactory yields (3iꢀ3k). However, 2ꢀiodobenzyl alcohol substituted with an
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electronꢀdonating group afforded the corresponding product in only 68% yield even at
a higher temperature (3f). Gratefully, higher yield could be obtained when Triton
Xꢀ100 was replaced by Brij L23. 2ꢀIodoꢀ4ꢀnitrobenzyl alcohol was also subjected to
the reaction. But unfortunately, the deꢀiodination product instead of the desired
indenone was observed in this case (3l). We further used 2ꢀbromobenzyl alcohol and
2ꢀchlorobenzyl alcohol to replace 2ꢀiodobenzyl alcohol. 2ꢀBromobenzyl alcohol
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survived this reaction with moderate to good yields at a higher temperature (110 C)
(3a, 3b, 3f, 3i, 3j). As for 2ꢀchlorobenzyl alcohol, only trace amount of product could
be observed at 110 oC for 24 h (3a).
Next, we performed several experiments to explore the sequence reactions of the
aboveꢀmentioned annulation (Scheme 2). 2,3ꢀDiphenylꢀ1Hꢀindenꢀ1ꢀone (3a) could
easily convert to 2,3ꢀdiphenylꢀ1Hꢀindene (3s) with hydrazine in the presence of KOH.
When 3a was treated with NaBH4, the corresponding indenol (3t) was obtained,
whereas in Pd/C hydrogenation conditions, 2,3ꢀdiphenylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀol
(3u) was produced. All the reactions were conducted in Triton Xꢀ100/water system
(methanol need to be added in some cases) which doesn’t need separation of
indenones from the original reaction system. Thus these synthetic useful structures
(indenol, 2,3ꢀdihydroꢀindenol, indene etc.) can be achieved in one pot via an
environmentalꢀfriendly way.
To further highlight the potential advantage of our methodology, the developed
method was utilized for preparation of 2ꢀ(3,5ꢀdimethoxyphenyl)ꢀ5,7ꢀdimethoxyꢀ3ꢀ
(4ꢀmethoxyphenyl)ꢀ1Hꢀindenꢀ1ꢀone (3v), a key intermediate which can eventually
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convert to Pauciflorol F (a kind of polyphenolic natural products1e) (Scheme 3).
1,3ꢀDimethoxyꢀ5ꢀ((4ꢀmethoxyphenyl)ethynyl)benzene was firstly synthesized via
iodidation and Sonogashira couplings using 3,5ꢀdimethoxyaniline as the starting
material.11 Next, 1,3ꢀDimethoxyꢀ5ꢀ((4ꢀmethoxyphenyl)ethynyl)benzene reacted with
(2ꢀiodoꢀ3,5ꢀdimethoxyphenyl)methanol under the developed conditions to obtain two
isomers in moderate yields (64% total yields). Indenone 3v was separated by
preparative HPLC. According to the literature1e, further hydrogenation and
demethylation of 3v can finally yield the Pauciflorol F.
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Scheme 2 Sequence reactions with indenones in aqueous medium.
Scheme 3 A potential application of the protocol in total synthesis
Finally, we tried to go through the mechanism of the developed reaction. The
reaction could not proceed under argon atmosphere which means oxygen is necessary
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for this reaction. To clarify when benzyl alcohol was oxidized, 2ꢀiodobenzyl alcohol
was stirred under the optimal conditions. It failed to convert to 2ꢀiodobenzaldehyde
under the optimal conditions without adding alkyne. However, the oxidative addition
of 2ꢀiodobenzyl alcohol to the active Pd(0) complex occurred with selfꢀcoupling
product obtained. It indicates that the insertion of alkyne may occur before the
oxidation. Although details about the mechanism remain to be ascertained, based on
the results above and the well documented annulation of orthoꢀhalobenzaldehyde with
an alkyne3a, 6b, a proposed mechanism was outlined in Scheme 4. The palladium
complex Pd(Amphos)Cl2 was a precursors for the active Pd(0) complex. The
oxidative addition of 2ꢀiodobenzyl alcohol to the Pd(0) complex firstly took place.
Then the alkyne was inserted to the C–Pd bond to form the intermediate A. After
dehydrohalogenation, intermediate B was formed. The intermediate B can directly
lead to byproduct 5a via the reductive elimination of palladium. Also, intermediate B
can convert to intermediate C through hydrogen transfer. The formation of
intermediate C provided a good explanation for the formation of byproduct 4a.
According to the paper reported by Uemura14, a palladium hydroperoxide
intermediate D may further formed. Then there may exist two ways to close the ring.
Intermediate D could transfer to the intermediate E via the insertion of the C=O
double bond. Then βꢀH elimination of intermediate E would give the indenone and
HPdOOH species. The HPdOOH species could further decompose to the Pd(0)
complex and H2O2 which finished the catalytic cycle. On the other hand, intermediate
F was produced via the intramolecular oxidative addition along with the detachment
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of H2O2. Intermediate F could also form the desired indenone 3a and Pd(0) species.
The H2O2 formed in the two paths may produce H2O and O2 in situ. In this procedure,
ligands and Triton Xꢀ100 may help to stabilize and improve the reactivity of the Pd(0)
species in water (it is possible to form nanomicelles), avoiding the formation of
palladium black.
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Scheme 4 Proposed mechanism of the Pdꢀcatalyzed annulation
In summary, we have described a novel synthesis of indenones via Pdꢀcatalyzed
annulation of orthoꢀhalobenzyl alcohol with internal alkynes in aqueous system. This
new procedure is environmentalꢀfriendly because no toxic solvent is required in the
coupling step. In addition, the indenones formed in the procedure can undergo some
sequence reactions without any separation process which can decrease the
consumption of energy and reagents. The protocol also exhibits good yields and broad
substrate scopes, thereby offering considerable potential applications to complex
targets (Pauciflorol F intermediate) in water.
Experimental Section
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Melting points are uncorrected. All commercial materials were used without further
purification. Asymmetric diarylacetylenes was synthesized according to the
literature12; 2ꢀiodoꢀ4,6ꢀdimethoxybenyl alcohol was synthesized according to the
literature13. The proton (1H) and carbon (13C) NMR spectra were obtained in CDCl3
using a 500 MHz spectrometer referenced to TMS and are reported in δ units.
Coupling constants (J values) are reported in Hz. Mass spectra was obtained using EI
technique. Elemental analysis was performed on a C/H mode. Preparative high
performance liquid chromatography was performed on the Column: XDBꢀC18
9.6×250 mm with methanol/water (70:30) as eluent.
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General procedure for synthesis of indenones
A mixture of 2ꢀiodobenzyl alcohol (0.5 mmol), alkyne (0.55 mmol), Pd(Amphos)Cl2
(0.01 mmol), K2CO3 (0.50 mmol) were stirred in 2wt.% Triton Xꢀ100 /H2O (2 mL) in
o
a 5 ml vial with oxygen balloon at 70 C for 24 h. The reaction mixture was then
cooled, extracted with ethyl acetate (3 × 15 mL). The combined organic layers were
dried over Na2SO4 and concentrated in vacuo to give a crude mixture which was
purified by silica gel column chromatography to afford the desired product.
2,3ꢀDiphenylꢀ1Hꢀindenꢀ1ꢀone (3a). Starting material: 2ꢀiodobenzyl alcohol 117 mg
(0.5 mmol), 1,2ꢀdiphenylethyne 97.9 mg (0.55 mmol). The crude material was
purified by column chromatography (ethyl acetate: petroleum ether, 1:100) to give
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121 mg of product as a red solid (86% yield); mp. 152ꢀ153 C; H NMR (500 MHz,
CDCl3) δ 7.52 (d, J = 7.0 Hz, 1H), 7.36 – 7.28 (m, 6H), 7.20 (dt, J = 6.5, 5.3 Hz, 6H),
7.08 (d, J = 7.2 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 195.6, 154.4, 144.3, 132.5,
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131.8, 131.4, 129.8, 129.0, 128.4, 128.0, 127.8, 127.6, 127.1, 126.8, 122.0, 120.3.
GC/MS, m/z: 282 [M+]; Anal. Calcd for C21H14O: C, 89.34; H, 5.00. Found: C, 89.65;
H, 5.15.
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2,3ꢀDiꢀpꢀtolylꢀ1Hꢀindenꢀ1ꢀone (3b). Starting material: 2ꢀiodobenzyl alcohol 117 mg
(0.5 mmol), 1,2ꢀdiꢀpꢀtolylethyne 113 mg (0.55 mmol). The crude material was
purified by column chromatography (ethyl acetate: petroleum ether, 1:100) to give
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135 mg of product as a red solid (87% yield); mp. 143ꢀ145 C; H NMR (500 MHz,
CDCl3) δ 7.58 (d, J = 7.0 Hz, 1H), 7.36 (s, 1H), 7.28 (d, J = 8.4 Hz, 2H), 7.22 (m, 2H),
7.20 – 7.10 (m, 4H), 7.07 (d, J = 12.0 Hz, 2H), 2.36 (s, 3H), 2.30 (s, 3H); 13C NMR
(126 MHz, CDCl3) δ 195.7, 154.5, 144.5, 137.4, 136.5, 132.5, 131.8, 129.7, 129.1,
127.9, 127.7, 127.6, 126.9, 126.1, 124.8, 121.9, 120.3, 20.5. GC/MS, m/z: 310 [M+];
Anal. Calcd for C23H18O: C, 89.00; H, 5.85. Found: C, 88.79; H, 5.69.
2,3ꢀDiꢀmꢀtolylꢀ1Hꢀindenꢀ1ꢀone (3c). Starting material: 2ꢀiodobenzyl alcohol 117 mg
(0.5 mmol), 1,2ꢀdiꢀmꢀtolylethyne 113 mg (0.55 mmol). The crude material was
purified by column chromatography (ethyl acetate: petroleum ether, 1:100) to give
o
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125 mg of product as a red solid (81% yield); mp 141ꢀ143 C; H NMR (500 MHz,
CDCl3) δ 7.55 (d, J = 7.0 Hz, 1H), 7.34 (t, J = 7.4 Hz, 1H), 7.30 – 7.23 (m, 3H), 7.21
(d, J = 7.8 Hz, 2H), 7.15 (dd, J = 13.7, 7.6 Hz, 3H), 7.07 (d, J = 7.8 Hz, 2H), 2.39 (s,
3H), 2.31 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 195.8, 153.8, 144.5, 138.4, 136.6,
132.3, 131.1, 130.0, 128.9, 128.5, 127.9, 127.7, 127.5, 127.0, 121.8, 120.2, 20.5, 20.4.
GC/MS, m/z: 310 [M+]; Anal. Calcd for C23H18O: C, 89.00; H, 5.85. Found: C, 88.63;
H, 5.71.
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2,3ꢀDipropylꢀ1Hꢀindenꢀ1ꢀone(3e). Starting material: 2ꢀiodobenzyl alcohol 117 mg
(0.5 mmol), decꢀ5ꢀyne 76 mg (0.55 mmol). The crude material was purified by
column chromatography (ethyl acetate: petroleum ether, 1:20) to give 82 mg of
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product as a red oil (77% yield); H NMR (500 MHz, CDCl3) δ 7.35 (d, J = 7.0 Hz,
1H), 7.29 (t, J = 7.4 Hz, 1H), 7.13 (t, J = 7.4 Hz, 1H), 7.01 (d, J = 7.2 Hz, 1H), 2.57 –
2.48 (m, 2H), 2.27 – 2.20 (m, 2H), 1.61 – 1.54 (m, 2H), 1.48 – 1.38 (m, 4H), 1.33 (dd,
J = 14.9, 7.2 Hz, 2H), 0.96 (dd, J = 13.8, 6.5 Hz, 3H), 0.90 (t, J = 7.2 Hz, 3H); 13C
NMR (126 MHz, CDCl3) δ 197.5, 156.7, 144.7, 133.9, 132.1, 130.2, 126.9, 120.7,
118.0, 30.5, 29.0, 25.0, 22.1, 21.8, 21.7, 12.9. GC/MS, m/z: 214 [M+]; Anal. Calcd for
C15H18O: C, 84.07; H, 8.47. Found: C, 84.39; H, 8.38.
5,7ꢀDimethoxyꢀ2,3ꢀdiphenylꢀ1Hꢀindenꢀ1ꢀone(3f). Starting material: 2ꢀiodoꢀ4,6ꢀ
dimethoxy benzyl alcohol 147 mg (0.5 mmol), 1,2ꢀdiphenylethyne 97.9 mg (0.55
mmol). The crude material was purified by column chromatography (ethyl acetate:
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petroleum ether, 1:20) to give 116 mg of product as a red oil (68% yield). H NMR
(500 MHz, CDCl3) δ 7.30 (m, 5H), 7.17 (d, J = 7.4 Hz, 3H), 7.11 (d, J = 6.9 Hz, 2H),
6.87 (s, 1H), 6.42 (s, 1H), 3.86 (s, 3H), 3.56 (s, 3H); 13C NMR (126 MHz, CDCl3) δ
195.2, 161.8, 157.3, 154.0, 134.0, 133.3, 130.2, 130.1, 128.9, 127.7, 127.4, 126.8,
126.5, 126.0, 121.6, 106.2, 103.1, 101.9, 54.9, 54.7. GCꢀMS, m/z: 342 [M+]; Anal.
Calcd for C23H18O3: C, 80.68; H, 5.30. Found: C, 80.29; H, 5.45.
2ꢀ(4ꢀChlorophenyl)ꢀ3ꢀphenylꢀ1Hꢀindenꢀ1ꢀone (3g) and 3ꢀ(4ꢀchlorophenyl)ꢀ2ꢀphenylꢀ
1Hꢀindenꢀ1ꢀone (3g’). Starting material: 2ꢀiodobenzyl alcohol 117 mg (0.5 mmol),
1ꢀchloroꢀ4ꢀ(phenylethynyl)benzene 117 mg (0.55 mmol). The crude material was
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mg of product (mixture of 3g, 3g’, the ratio is 1:1 which is determined by H NMR)
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as a red oil (84% yield). 3g and 3g’ was separated by preparative HPLC
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(methonol:water, 70:30).
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2ꢀ(4ꢀChlorophenyl)ꢀ3ꢀphenylꢀ1Hꢀindenꢀ1ꢀone (3g): H NMR (500 MHz, CDCl3) δ
7.61 (d, J = 7.0 Hz, 1H), 7.41 (d, J = 8.3 Hz, 3H), 7.35 (d, J = 8.5 Hz, 2H), 7.33 –
13
7.24 (m, 7H), 7.14 (d, J = 7.3 Hz, 1H); C NMR (126 MHz, CDCl3) δ 195.2, 154.8,
144.1, 132.8, 132.6, 131.5, 129.7, 128.6, 128.2, 128.0, 127.4, 122.1, 120.4; GCꢀMS,
m/z: 316 [M+]; Anal. Calcd for C21H13ClO: C, 79.62; H, 4.14. Found: C, 80.01; H,
4.28.
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3ꢀ(4ꢀChlorophenyl)ꢀ2ꢀphenylꢀ1Hꢀindenꢀ1ꢀone (3g’): H NMR (500 MHz, CDCl3) δ
7.60 (d, J = 7.0 Hz, 1H), 7.49 – 7.43 (m, 3H), 7.42 – 7.36 (m, 3H), 7.32 (t, J = 7.3 Hz,
1H), 7.24 (q, J = 8.7 Hz, 4H), 7.16 (d, J = 7.2 Hz, 1H);13C NMR (126 MHz, CDCl3) δ
195.2, 152.9, 143.9, 134.3, 132.6, 131.9, 130.2, 129.6, 129.4, 129.0, 128.2, 127.2,
127.0, 122.2, 120.0. GCꢀMS, m/z: 316 [M+]; Anal. Calcd for C21H13ClO: C, 79.62; H,
4.14. Found: C, 79.97; H, 4.31;
2ꢀEthylꢀ3ꢀphenylꢀ1Hꢀindenꢀ1ꢀone (3h). Starting material: 2ꢀiodobenzyl alcohol 117
mg (0.5 mmol), butꢀ1ꢀynꢀ1ꢀylbenzene 71.5 mg (0.55 mmol). The crude material was
purified by column chromatography (ethyl acetate: petroleum ether, 1:50) to give 94
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mg of product as an orange oil (80% yield). H NMR (500 MHz, CDCl3) δ 7.50 (d, J
= 7.0 Hz, 2H), 7.45 (t, J = 8.6 Hz, 4H), 7.28 (s, 1H), 7.19 (s, 1H), 7.00 (d, J = 7.2 Hz,
1H), 2.35 (q, J = 7.5 Hz, 2H), 1.10 (t, J = 7.5 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ
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197.2, 153.7, 144.9, 135.7, 132.2, 131.8, 130.1, 128.1, 127.8, 127.2, 126.8, 121.4,
119.6, 76.3, 76.0, 75.8, 15.7, 13.0; GCꢀMS, m/z: 234 [M+]; Anal. Calcd for C17H14O:
C, 87.15; H, 6.02. Found: C, 87.39; H, 5.84.
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6ꢀChloroꢀ2,3ꢀdiphenylꢀ1Hꢀindenꢀ1ꢀone (3i). Starting material: 5ꢀchloroꢀ2ꢀiodo benzyl
alcohol 134 mg (0.5 mmol), 1,2ꢀdiphenylethyne 97.9 mg (0.55 mmol). The crude
material was purified by column chromatography (ethyl acetate: petroleum ether,
1:100) to give 137 mg of product as an orangeꢀred solid (87% yield). mp: 183ꢀ184 oC ;
1H NMR (500 MHz, CDCl3) δ 7.54 (d, J = 1.6 Hz, 1H), 7.44 – 7.41 (m, 3H), 7.39 –
7.32 (m, 3H), 7.25 (d, J = 7.6 Hz, 5H), 7.09 (d, J = 7.8 Hz, 1H); 13C NMR (126 MHz,
CDCl3) δ 194.1, 154.1, 142.3, 134.1, 131.7, 131.4, 131.3, 129.4, 129.0, 128.6, 127.9,
127.4, 127.2, 127.0, 122.6, 121.2. GCꢀMS, m/z: 316 [M+]; Anal. Calcd for C21H13ClO:
C, 79.62; H, 4.14. Found: C, 79.89; H, 3.97.
6ꢀFluoroꢀ2,3ꢀdiphenylꢀ1Hꢀindenꢀ1ꢀone (3j). Starting material: 5ꢀfluoroꢀ2ꢀiodo benzyl
alcohol 126 mg (0.5 mmol), 1,2ꢀdiphenylethyne 97.9 mg (0.55 mmol). The crude
material was purified by column chromatography (ethyl acetate: petroleum ether,
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1:100) to give 135 mg of product as an orangeꢀred oil (90% yield). H NMR (500
MHz, CDCl3) δ 7.39 (ddd, J = 7.0, 5.8, 3.4 Hz, 4H), 7.33 – 7.15 (m, 7H), 7.11 (dd, J =
8.0, 4.5 Hz, 1H), 7.03 (td, J = 8.7, 2.4 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 193.9,
166.5, 152.2, 147.6, 132.7, 131.3, 129.4, 129.0, 128.5, 128.0, 127.4, 127.2, 127.1,
125.6, 123.8, 123.8, 113.5, 113.4, 109.3, 109.1; 19F NMR (470 MHz, CDCl3) δ
ꢀ111.53. GCꢀMS, m/z: 300[M+]; Anal. Calcd for C21H13FO: C, 83.98; H, 4.36. Found:
C, 83.79; H, 4.53.
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5ꢀFluoroꢀ2,3ꢀdiphenylꢀ1Hꢀindenꢀ1ꢀone (3k). Starting material: 4ꢀfluoroꢀ2ꢀiodo benzyl
alcohol 126 mg (0.5 mmol), 1,2ꢀdiphenylethyne 97.9 mg (0.55 mmol). The crude
material was purified by column chromatography (ethyl acetate: petroleum ether,
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1:100) to give 128 mg of product as an orange oil (85% yield). H NMR (500 MHz,
CDCl3) δ 7.58 (dd, J = 7.9, 5.2 Hz, 1H), 7.47 – 7.41 (m, 3H), 7.37 (dd, J = 6.6, 3.0 Hz,
2H), 7.27 (d, J = 3.9 Hz, 5H), 6.94 (td, J = 9.0, 2.1 Hz, 1H), 6.87 (dd, J = 8.5, 2.0 Hz,
1H);13C NMR (126 MHz, CDCl3) δ 193.7, 166.5, 152.2, 147.6, 132.7, 131.3, 129.4,
129.0, 128.5, 128.0, 127.4, 127.2, 127.1, 125.6, 123.8,123.8, 113.5, 113.4, 109.3,
109.1. 19F NMR (470 MHz, CDCl3) δ ꢀ104.02; GCꢀMS, m/z: 300 [M+]; Anal. Calcd
for C21H13FO: C, 83.98; H, 4.36. Found: C, 83.76; H, 4.47.
2ꢀ(2,4ꢀDimethoxyphenyl)ꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ1Hꢀindenꢀ1ꢀone
3ꢀ(2,4ꢀdimethoxyphenyl)ꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ1Hꢀindenꢀ1ꢀone
(3m)
(3m’).
and
Starting
material: 2ꢀiodobenzyl alcohol 117 mg (0.5 mmol), 1,3ꢀdimethoxyꢀ
5ꢀ((4ꢀmethoxyphenyl)ethynyl)benzene 147 mg (0.55 mmol). The crude material was
purified by column chromatography (ethyl acetate: petroleum ether, from 1:200 to
1:20) to give 126 mg of product (mixture of 3m, 3m’, the ratio is 56:44 which is
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determined by H NMR) as a red oil (68% yield). 3m and 3m’ was separated by
preparative HPLC (methonol:water, 70:30).
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2ꢀ(2,4ꢀDimethoxyphenyl)ꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ1Hꢀindenꢀ1ꢀone (3m). H NMR (500
MHz, CDCl3) δ 7.53 (d, J = 6.8 Hz, 1H), 7.33 (dd, J = 14.5, 7.8 Hz, 3H), 7.23 (s, 2H),
7.05 (d, J = 8.3 Hz, 1H), 6.87 (d, J = 8.2 Hz, 2H), 6.47 (d, J = 8.3 Hz, 1H), 6.39 (s,
13
1H), 3.80 (m, 6H), 3.43 (s, 3H); C NMR (126 MHz, CDCl3) δ 196.2, 160.9, 158.0,
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157.4, 150.9, 145.1, 132.3, 131.4, 129.8, 129.6, 129.5, 127.2, 123.6, 121.3, 120.1,
114.0, 112.5, 104.0, 98.3, 54.4, 54.3, 54.2; MS, m/z: 372 [M+]; Anal. Calcd for
C24H20O4: C, 77.40; H, 5.41. Found: C, 77.67; H, 5.49.
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3ꢀ(2,4ꢀDimethoxyphenyl)ꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ1Hꢀindenꢀ1ꢀone (3m’). 1H NMR (500
MHz, CDCl3) δ 7.50 (d, J = 7.1 Hz, 1H), 7.29 (d, J = 7.4 Hz, 1H), 7.24 (m, 2H), 7.20
(s, 1H), 7.15 (d, J = 9.0 Hz, 1H), 6.91 (d, J = 7.2 Hz, 1H), 6.78 (d, J = 8.4 Hz, 2H),
6.51 (s, 2H), 3.85 (s, 3H), 3.77 (s, 3H), 3.55 (s, 3H); 13C NMR (126 MHz, CDCl3) δ
195.6, 160.0, 159.2, 157.7, 154.3, 144.4, 131.9, 131.3, 130.7, 129.1, 128.5, 127.4,
125.3, 121.6, 120.0, 112.8, 103.7, 98.1, 54.3, 54.3, 54.2; MS, m/z: 372 [M+]; Anal.
Calcd for C24H20O4: C, 77.40; H, 5.41. Found: C, 77.73; H, 5.54.
2ꢀ(4ꢀFluorophenyl)ꢀ3ꢀphenylꢀ1Hꢀindenꢀ1ꢀone
(3n)
and
3ꢀ(4ꢀFluorophenyl)ꢀ
2ꢀphenylꢀ1Hꢀ indenꢀ1ꢀone (3n’). Starting material: 2ꢀiodobenzyl alcohol 117 mg (0.5
mmol), 1ꢀfluoroꢀ4ꢀ(phenylethynyl)benzene 108 mg (0.55 mmol). The crude material
was purified by column chromatography (ethyl acetate: petroleum ether, 1:100) to
give 139.5 mg of product (mixture of 3n, 3n’, the ratio is 1:1 which is determined by
1H NMR) as a red oil (93% yield). 3n and 3n’ could hardly be separated.
Mixture of 3n, 3n’, the ratio is 1:1. 1H NMR (500 MHz, CDCl3) δ 7.60 – 7.54 (m, 1H),
7.45 – 7.32 (m, 4H), 7.32 – 7.20 (m, 4H), 7.16 – 7.05 (m, 2H), 6.94 (t, J = 8.7 Hz, 1H);
13C NMR (126 MHz, CDCl3) δ 195.4, 195.2, 170.1, 163.1, 162.3, 161.1, 160.4, 154.3,
153.2, 144.2, 144.0, 132.5, 132.5, 131.6, 130.8, 130.8, 130.4, 129.6, 129.0, 128.8,
128.4, 128.1, 127.9, 127.7, 127.5, 127.2, 126.9, 125.8, 122.1, 120.3, 120.1, 115.2,
115.0, 114.3, 114.1; GCꢀMS, m/z: 300 [M+]. Anal.Calcd for C21H13FO: C, 83.98; H,
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4.36. Found: C, 84.18; H, 4.53.
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2ꢀ(3ꢀMethylphenyl)ꢀ3ꢀphenylꢀ1Hꢀindenꢀ1ꢀone (3o) and 3ꢀ(3ꢀmethylphenyl)ꢀ2ꢀphenylꢀ
1Hꢀindenꢀ1ꢀone (3o’). Starting material: 2ꢀiodobenzyl alcohol 117 mg (0.5 mmol),
1ꢀmethylꢀ4ꢀ(phenylethynyl)benzene 106 mg (0.55 mmol). The crude material was
purified by column chromatography (ethyl acetate: petroleum ether, 1:100) to give
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121 mg of product (mixture of 3o, 3o’, the ratio is 1:1 which is determined by H
NMR) as a red oil (82% yield). 3o and 3o’ could hardly be separated.
Mixture of 3o and 3o’ (50:50)；1H NMR (500 MHz, CDCl3) δ 7.57 (d, 1H), 7.41 –
7.35 (m, 3H), 7.24 (m, 6H), 7.12 (dd, J = 13.7, 6.9 Hz, 2H), 7.04 (d, J = 7.5 Hz,
0.5×1H), 6.99 (d, J = 7.6 Hz, 0.5×1H), 2.34 (s, 0.5×3H), 2.26 (s, 0.5×3H); 13C NMR
(126 MHz, CDCl3) δ 206.2, 195.6, 154.2, 144.4, 136.6, 132.4, 131.3, 129.8, 129.6,
129.1, 129.0, 128.2, 127.9, 127.7, 127.6, 127.5, 127.0, 126.9, 126.7, 126.1, 124.7,
121.9, 120.3, 20.5. GCꢀMS, m/z: 296 [M+]; Anal. Calcd for C22H16O: C, 89.16; H,
5.44. Found: C, 88.98; H, 5.52.
3ꢀ(4ꢀChlorophenyl)ꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ1Hꢀindenꢀ1ꢀone (3p) and 2ꢀ(4ꢀchlorophenyl)
ꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ1Hꢀindenꢀ1ꢀone (3p’). Starting material: 2ꢀiodobenzyl alcohol
117 mg (0.5 mmol), 1ꢀchloroꢀ4ꢀ((4ꢀmethoxyphenyl)ethynyl)benzene 133 mg (0.55
mmol). The crude material was purified by column chromatography (ethyl acetate:
petroleum ether, from 1:200 to 1:20) to give 140 mg of product (mixture of 3p, 3p’,
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the ratio is 51:49 which is determined by H NMR) as a red oil (81% yield). 3p and
3p’ was separated by preparative HPLC (methanol: water, 70:30).
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3ꢀ(4ꢀChlorophenyl)ꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ1Hꢀindenꢀ1ꢀone (3p). H NMR (500 MHz,
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CDCl3) δ 7.56 (d, J = 7.0 Hz, 1H), 7.39 (d, J = 8.3 Hz, 2H), 7.34 (t, J = 8.6 Hz, 2H),
7.27 (d, J = 7.3 Hz, 1H), 7.20 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 7.3 Hz, 1H), 6.81 (d, J
= 8.7 Hz, 2H), 3.79 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 195.6, 158.5, 151.3, 144.2,
134.1, 132.5, 131.4, 130.5, 130.3, 129.6, 129.0, 128.2, 127.8, 122.1, 121.8, 119.7,
112.8, 54.2; GCꢀMS, m/z:346 [M+]; Anal. Calcd for C22H15ClO2: C, 76.19; H, 4.36.
Found: C, 76.38; H, 4.47.
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2ꢀ(4ꢀChlorophenyl)ꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ1Hꢀindenꢀ1ꢀone (3p’) H NMR (500 MHz,
CDCl3) δ 7.56 (d, J = 7.0 Hz, 1H), 7.37 (t, J = 7.4 Hz, 1H), 7.34 – 7.27 (m, 3H), 7.21
(dd, J = 15.8, 7.3 Hz, 4H), 6.93 (d, J = 8.6 Hz, 2H), 3.85 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 195.2, 159.7, 154.7, 144.0, 132.6, 132.4, 130.3, 130.0, 129.2, 128.6, 128.1,
127.4, 123.6, 121.9, 120.4, 113.4, 54.4; GCꢀMS, m/z:346 [M+]; Anal. Calcd for
C22H15ClO2: C, 76.19; H, 4.36. Found: C, 76.39; H, 4.45.
2ꢀ(4ꢀNitrophenyl)ꢀ3ꢀphenylꢀ1Hꢀindenꢀ1ꢀone (3q) and 3ꢀ(4ꢀnitrophenyl)ꢀ2ꢀphenylꢀ
1Hꢀindenꢀ1ꢀone (3q’). Starting material: 2ꢀiodobenzyl alcohol 117 mg (0.5 mmol),
1ꢀnitroꢀ4ꢀ((4ꢀmethoxyphenyl)ethynyl)benzene 123 mg (0.55 mmol). The crude
material was purified by column chromatography (ethyl acetate: petroleum ether,
from 1:20 to 1:10) to give 135 mg of product (mixture of 3q, 3q’, the ratio is 75:25
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which is determined by H NMR, but the regioselectivity is not determined.) as a red
oil (total yield 83%). 3q and 3q’ could hardly be separated.
Mixture of 3q and 3q’ (75:25). 1H NMR (500 MHz, CDCl3) δ 9.83 (s, 1H), 8.27 (d, J
= 8.6 Hz, 1H), 8.10 (d, J = 8.7 Hz, 0.75×1H), 8.08 (d, J = 8.7Hz, 0.25×1H), 8.06 (m,
1H), 7.62 (m, 1H), 7.56 (m, 1H), 7.50 – 7.38 (m, 3H), 7.34 (m, 2H), 7.28 (m, 1H),
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7.19 (t, J = 6.5 Hz, 0.75×2H), 7.07 (d, J = 7.2 Hz, 0.25×2H); 13C NMR (126 MHz,
CDCl3) δ 194.3, 157.4, 145.8, 143.5, 136.8, 132.9, 130.9, 129.7, 129.6, 129.1, 128.9,
128.2, 127.3, 125.2, 122.4, 122.3, 121.1, 111.3; GCꢀMS, m/z: 327 [M+]. Anal.Calcd
for C21H13NO3: C, 77.05; H, 4.00. Found: C, 76.77; H, 4.25.
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2ꢀ(4ꢀPentylphenyl)ꢀ3ꢀphenylꢀ1Hꢀindenꢀ1ꢀone (3r) and 3ꢀ(4ꢀpentylphenyl)ꢀ2ꢀphenylꢀ
1Hꢀindenꢀ1ꢀone (3r’) (77:23). Starting material: 2ꢀiodobenzyl alcohol 117 mg (0.5
mmol), 1ꢀpentylꢀ4ꢀ(phenylethynyl)benzene 136 mg (0.55 mmol). The crude material
was purified by column chromatography (ethyl acetate: petroleum ether, from 1:200
to 1:10) to give 135 mg of product (mixture of 3r, 3r’, the ratio is 77:23 which is
determined by 1H NMR, but the regioselectivity is not determined.) as a red oil (73%
yield). 3r and 3r’ could hardly be separated.
Mixture of 3r and 3r’. 1H NMR (500 MHz, CDCl3) δ 7.57 (d, J = 7.0 Hz, 1H), 7.43 –
7.34 (m, 2H), 7.27 (dd, J = 16.1, 6.7 Hz, 7H), 7.19 (dd, J = 10.8, 8.1 Hz, 3H), 7.09
(dd, J = 24.2, 7.6 Hz, 1H), 2.59 (dt, J = 42.1, 7.8 Hz, 2H), 1.69 – 1.59 (m, 2H), 1.39 –
13
1.28 (m, 4H), 0.90 (dd, J = 13.7, 6.7 Hz, 3H); C NMR (126 MHz, CDCl3) δ 195.6,
154.6, 144.3, 143.6, 132.3, 131.1, 130.0, 130.0, 129.0, 128.9, 128.8, 128.2, 127.9,
127.8, 127.5, 127.2, 127.1, 126.6, 121.9, 120.4, 120.1, 34.9, 34.8, 30.6, 29.9, 21.6,
13.1. MS, m/z: 352 [M+]; Anal. Calcd for C26H24O: C, 88.60; H, 6.86. Found: C,
88.27; H, 6.51.
The synthesis of 2, 3-diphenyl-1H-indene 3s
A mixture of 2ꢀiodobenzyl alcohol 117 mg (0.5 mmol), 1,2ꢀdiphenylethyne 97.9 mg
(0.55 mmol), Pd(Amphos)Cl2 8 mg (0.01 mmol), K2CO3 69 mg (0.50 mmol) were
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stirred in 2 wt.% Triton Xꢀ100/H2O (2 ml) in a 5 ml vial with oxygen balloon at 60 oC
for 24 h. Then the resulting indenone mixture was transferred to a sealed tube. Then
KOH, 31 mg (0.55 mmol), hydrazine 28 mg (0.55 mmol) and H2O 1 mL was added.
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The resulting mixture was stirred at 150 C for 24 h. Upon competition, the mixture
was cooled, extracted with ethyl acetate (15 mL) and washed with diluted
hydrochloric acid (3 × 15 mL), sat. aq. NaHCO3 (3 × 15 mL), and dried over
anhydrous Na2SO4. After filtration, the organic layer was concentrated in vacuo and
the residue was purified by column chromatography on silica gel (pure petroleum
ether) to give 95 mg 3s (71% total yield) as a colorless oil. 1H NMR (500 MHz,
CDCl3) δ 7.56 (d, J = 7.1 Hz, 1H), 7.44 (d, J = 6.7 Hz, 2H), 7.41 – 7.36 (m, 3H), 7.32
– 7.19 (m, 8H), 3.95 (s, 2H); 13C NMR (126 MHz, CDCl3) δ 146.0, 141.4, 140.1,
139.0, 135.6, 135.1, 128.4, 127.8, 127.3, 127.2, 126.4, 125.9, 125.5, 124.1, 122.6,
119.4, 40.2. GCꢀMS, m/z: 268 [M+] Anal. Calcd for C21H16: C, 93.99; H, 6.01. Found:
C, 93.79; H, 5.89.
The synthesis of 2, 3-diphenyl-1H-indenol 3t
A mixture of 2ꢀiodobenzyl alcohol 117 mg (0.5 mmol), 1,2ꢀdiphenylethyne 97.9 mg
(0.55 mmol), Pd(Amphos)Cl2 8 mg (0.01 mmol), K2CO3 69 mg (0.50 mmol) were
stirred in 2wt.% Triton Xꢀ100/H2O (2 mL) in a 5 mL vial with oxygen balloon at 60
oC for 24 h. Then the resulting indenone mixture was added 3 mL methanol and
cooled to 0 oC, NaBH4 (3 mmol) was then added in portion over 30 min. The resulting
o
mixture was stirred at 0 C for another 3 h. After that the mixture was treated with
diluted hydrochloric acid, extracted with ethyl acetate (15 mL), washed with sat. aq.
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NaHCO3 (3 × 15 mL), and dried over anhydrous Na2SO4. After filtration, the organic
layer was concentrated in vacuo and the residue was purified by column
chromatography on silica gel (ethyl acetate: petroleum ether, 1:10) to give 121 mg 3t
(85% total yield) as a colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.60 (d, J = 6.7 Hz,
1H), 7.35 (d, J = 6.9 Hz, 2H), 7.30 (dd, J = 17.2, 9.0 Hz, 5H), 7.24 (t, J = 6.6 Hz, 2H),
7.21 (s, 1H), 7.18 (s, 1H), 7.16 (d, J = 7.0 Hz, 1H), 7.11 (d, J = 6.8 Hz, 1H), 5.65 (s,
1H); 13C NMR (126 MHz, CDCl3) δ 143.3, 142.9, 142.8, 138.8, 133.8, 133.1, 128.3,
128.1, 127.8, 127.7, 127.3, 127.1, 126.8, 126.4, 125.4, 122.7, 119.7, 76.3; GCꢀMS,
m/z: 284 [M+] Anal. Calcd for C21H16O: C, 88.70; H, 5.67. Found: C, 88.57; H, 5.74.
The synthesis of 2,3-diphenyl-2,3-dihydro-1H-inden-1-ol 3u
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A mixture of 2ꢀiodobenzyl alcohol 117 mg (0.5 mmol), 1,2ꢀdiphenylethyne 97.9 mg
(0.55 mmol), Pd(Amphos)Cl2 8 mg (0.01 mmol), K2CO3 69 mg (0.50 mmol) were
stirred in 2 wt.% Triton Xꢀ100/H2O (2 mL) in a 5 mL vial with oxygen balloon at 60
oC for 24 h. Then the resulting indenone mixture was added 10% Pd/C (50 mg), 3 mL
methanol and introduced to a pressure reactor. The suspension was stirred at room
temperature for 6 h under 5 atm of hydrogen. After the reaction, the pressure was
released. The reaction mixture was then extracted with ethyl acetate (15 mL) and
filtered through a pad of Celite®. After filtration, the organic layer was concentrated in
vacuo and the residue was purified by column chromatography on silica gel (ethyl
acetate: petroleum ether, 1:4) to give 109 mg 3u (78% total yield) as a colorless oil.
1H NMR (500 MHz, CDCl3) δ 7.56 (d, J = 7.4 Hz, 1H), 7.35 (t, J = 7.4 Hz, 1H), 7.28
(t, J = 7.4 Hz, 1H), 7.15 (d, J = 7.4 Hz, 1H), 7.08 – 7.00 (m, 4H), 6.97 (t, J = 7.4 Hz,
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2H), 6.85 (dd, J = 6.2, 3.0 Hz, 2H), 6.65 (d, J = 7.3 Hz, 2H), 5.45 (t, J = 7.0 Hz, 1H),
4.68 (d, J = 7.4 Hz, 1H), 4.02 (t, J = 6.9 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ
144.8, 142.6, 139.1, 135.5, 129.2, 128.6, 127.3, 127.0, 126.7, 126.5, 126.0, 125.4,
124.5, 122.9, 76.3, 76.0, 75.8, 58.5, 53.2. GCꢀMS, m/z: 286 [M+] Anal. Calcd for
C21H18O: C, 88.08; H, 6.34. Found: C, 88.27; H, 6.19.
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The synthesis of Pauciflorol F intermediate 3v
A
mixture of (2ꢀiodoꢀ3,5ꢀdimethoxyphenyl)methanol 147 mg (0.5 mmol),
1,3ꢀdimethoxyꢀ5ꢀ((4ꢀmethoxyphenyl)phenylethyne 147 mg (0.55 mmol),
Pd(Amphos)Cl2 8 mg (0.01 mmol), K2CO3 69 mg (0.50 mmol) were stirred in 2 wt.%
Triton Xꢀ100/H2O (2 mL) in a 5 mL vial with oxygen balloon at 100 oC for 24 h. The
reaction mixture was then cooled to room temperature, extracted with EtOAc (15 mL),
washed with sat. aq. NaHCO3 (3 × 15 mL) and dried over anhydrous Na2SO4. After
filtration, the organic layer was concentrated in vacuo affording a mixture of indenone
isomers 138 mg (64% yield). 3v and 3v’ was separated by preparative HPLC
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(methanol: water, 70:30). H NMR (500 MHz, CDCl3) δ 7.12 (d, J = 8.7 Hz, 2H),
6.86 (d, J= 1.9 Hz, 1H), 6.75 (d, J= 8.7 Hz, 2H), 6.49 (d, J = 2.1 Hz, 2H), 6.43 (d, J =
2.0 Hz, 2H), 3.86 (s, 3H), 3.76 (s, 3H), 3.70 (s, 6H), 3.60 (s, 3H); 13C NMR (126
MHz, CDCl3) δ 195.6, 161.5, 159.2, 157.8, 155.6, 153.7, 136.0, 133.1, 130.0, 129.7,
122.6, 121.8, 112.5, 105.6, 103.2, 101.8, 100.0, 54.9, 54.8, 54.4, 54.2. Anal.Calcd for
C26H24O6: C, 72.21; H, 5.59. Found: C, 72.37; H, 5.44.
Acknowledgments
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We gratefully acknowledge National Natural Science Foundation of Jiangsu Province
(BK 20131346) for financial support.
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Supporting information
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Copies of H NMR spectra and 13C NMR spectra. This material is available free of
charge via the Internet athttp://pubs.acs.org
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(9) LindstrÖm, U. M. Organic Reactions in Water: Principles, Strategies and
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