Indane-Fused Spiropentadiene Chromanones: A Pd-Catalyzed Spiroannulation Followed by Cyclization via C-H Activation Strategy

Article abstract of DOI:10.1021/acs.joc.0c01475

Pd-catalyzed spiroannulation of 4-bromocoumarin with alkynes has been illustrated. The reaction highlights an interesting process for cascade formation of two five-membered rings through spiroannulation followed by cyclization via C-H activation. This method offers an attractive platform for the synthesis of a broad range of indane-fused spiropentadiene chromanones in good yields.

Full text of DOI:10.1021/acs.joc.0c01475

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Article
Indane-Fused Spiropentadiene Chromanones: A Pd-Catalyzed Spiro-
Annulation Followed by Cyclization via C-H Activation Strategy
Abhilash Sharma, Hemanta Hazarika, Manashi Sarmah, Babulal Das, and Pranjal Gogoi
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01475 • Publication Date (Web): 31 Jul 2020
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Indane-Fused Spiropentadiene Chromanones: A Pd-Catalyzed
Spiro-Annulation Followed by Cyclization via C-H Activation
Strategy
a,b
a,b
a
c
a,b
Abhilash Sharma , Hemanta Hazarika , Manashi Sarmah , Babulal Das and Pranjal Gogoi *
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aApplied Organic Chemistry Group, Chemical Science and Technology Division, CSIR-
North East Institute of Science and Technology, Jorhat 785006, India
bAcademy of Scientific and Innovative Research (AcSIR), CSIR-NEIST Campus, India
cDepartment of Chemistry, Indian Institute of Technology Guwahati, Guwahati-781039,
India
Email: gogoipranj@yahoo.co.uk
R
R
R
F
F
Pd(OAc)2, TFP
KOAc, 1,4-dioxane
Br
O
R
F
R1
85 oC, 8h
R1
R
O
R1
F
O
O
O O
1
R=H, Me, OMe
37 Examples
R =H, Me, OMe, F
5 Examples
R
ABSTRACT
Pd-catalyzed spiroannulation of 4-bromocoumarin with alkynes have been illustrated. The
reaction highlights an interesting process for cascade formation of two five-membered rings
through spiro-annulation followed by cyclization via C-H activation. This method offers an
attractive platform for the synthesis of a broad range of indane-fused spiropentadiene
chromanones in good yields.
INTRODUCTION
The synthetic reaction strategies of simplicity towards complexity are significantly
prevailing in the realm of polycyclic systems. Transition-metal catalyzed polycyclization has
become a popular tactic to access highly functionalized and structurally diverse complex
molecules. Particularly, spirocycles emerge as synthetically challenging and structurally
1
2
important frameworks of many bioactive molecules and optoelectronic materials. In general,
metal-catalyzed annulation has been recognized as an efficient and reliable synthetic route to
access 3D-spirocyclic scaffolds from simple planar arenes. Transition-metal catalyzed
annulative-dearomatization has been introduced by the pioneering and elegant works of
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7
Hamada, Buchwald, You, Feringa, and Tang using phenol, indole, or pyrrole-based
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9
precursors. Later, various Ru(II)/Rh(III) and Pd(0)/(II) catalyzed dearomatizing [3+2] and
[
2+2+1] spiroannulations have been demonstrated through C-H bond activation followed by
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oxidative annulation with alkynes. In particular, to achieve highly attractive chemo- and regio-
selective spiroannulated derivatives, transition-metal catalyzed annulations of alkynes with
haloarenes are considered as an attractive door with broad substrate compatibility.
Additionally, annulation of alkynes with readily available arenes such as phenol diazonium
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3b,14
salts, napthols, arylethers , arylhalides and heteroarenes
have been widely explored.
Scheme 1. Pd-Catalyzed Spiro-Annulation
(a) Luan and co-workers: Three-component [2+2+1] spiro-annulation
R
Ph
Ph
R
Br
Ph
Pd(OAc)2 (5 mol%)
Davephos, NBE
Cs2CO3, DMF, 100 o
I
OH
+
R'
+
O
C
H
R'
Ph
(
b) You and co-workers: [2+2+1] Spiro-annulation followed by Heck
R2
R1
Br
R1
R2
R1
Pd(OAc)2, P(p-anisyl)3
R
+
R
Cs2CO3, 1,4-dioxane
130 oC, N2, 12h
R2
(c) Wang and co-workers: [2+2+1] Spiro-annulation
Ph Ph
OH
Ph
O
Pd(OAc)2, Cu(OAc)2
Ph
Ph
+
R'
DMSO, 80 oC, 2d
R'
O
O
O
O
Ph
(d) Our Work: Spiro-annulation followed by cyclization via C-H activation
Ph
Ph
Br
Ph
Pd(OAc)2, TFP
Ph
1
+
R
KOAc, 1,4-dioxane,
85 oC, 8h
1
O
O
R
Ph
O
O
Nowadays, Pd-catalyzed processes gleam the synthetic world in a much effective
approach. In this regard, some noteworthy Pd-catalyzed spiro-annulation reactions could be
mentioned. Luan and co-workers described a three-component spiro-annulation of
bromonaphthols with aryl iodides and alkynes in the presence of Pd(0)/norbornene system
1
5
(
Scheme 1a). Whereas, You and co-workers reported the synthesis of a highly functionalized
spiropentadienes with an exocyclic C-C double bond using alkyl bromoarenes with alkynes.16
This reaction strategy discloses a Pd(0)-catalyzed dearomative [2+2+1] annulation reaction
with high chemo-, regio-, and E/Z-selectivity via a Heck-type pathway (Scheme 1b). In most
of the cases, simple aromatic precursors have been explored for the synthesis of sterically
congested fused spirocyclic compounds. On the other hand, Pd-catalyzed spiro-annulation of
heterocycle core unit with alkyne for the synthesis of spiro-annulated products is rare. In this
regard, introduction of alternative precursor having immense potential in synthetic chemistry
like coumarin or its derivatives could be an effective platform to access interesting spirocyclic
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targets. With this view, Wang and co-workers utilizes 4-hydroxycoumarin for the synthesis of
spiro cyclopentadiene-chroman derivatives employing Pd(II)-catalyzed cascade oxidative
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7
[
2+2+1] cycloaddition reaction (Scheme 1c). Although the reported methodologies have
gained significant progress, further improvement for the synthesis of complex polycyclic
systems is highly demanded in this field. Palladium catalyzed C-S bond activation of
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19
bromothiophenes and our research work on coumarin moiety encouraged us to design a new
Pd-catalyzed cascade strategy followed by C-H activation for the synthesis of indane-fused
spiropentadiene chromanones from 4-bromocoumarins and alkynes (Scheme 1d). This method
offers the privilege to form a sterically congested spirocyclic core via multiple bond formations
pathway providing a broad range of spirocyclic analogues. The present work in contrast, has
distinctively enhanced the scope and utility of our method by constructing an additional five
membered fused ring with spiropentadiene chromanone.
RESULTS AND DISCUSSION
At the onset, the envisioned reaction was optimized by considering 4-bromocoumarin
1a and 1,2-diphenylethyne 2a as model substrates for the synthesis of indane-fused
spiropentadiene chromanone 4aa (Table 1). In the initial study, we examine the reaction of 4-
bromocoumarin 1a (0.5 mmol) with 1,2-diphenylethyne 2a (1 mmol) in the presence of
Pd(OAc) (10 mol%) as catalyst, P(Cy) (20 mol%) as ligand and KOAc (1 mmol) as base in
2
3
DCE at room temperature for 24h (Table 1, entry 1). Under these conditions, the desired
product 4aa was obtained in 22% yield. To improve the yield of 4aa, we have investigated the
solvent effect by screening some of the commonly used solvents such as DMF, DMSO, toluene,
1,4-dioxane and t-AmOH. These investigations reveal that 1,4-dioxane is optimal to give the
desired product in 45% yield (Table 1, entries 1-6). To further improve the reaction efficiency,
we next examined the reaction temperature as well as reaction time and found that the yield of
o
the product 4aa was improved to 55% on increasing the temperature to 85 C for 8h (Table 1,
entry 7). Furthermore, screening of ligands revealed that tri(2-furyl)phosphine (TFP) promoted
the yield of the product 4aa upto 78%, whereas other phosphine ligands such as P(Ph) , X-
3
Phos, S-Phos, tri(p-tolyl)phosphine (TPTP), Ru-Phos and Dave-Phos were less effective (Table
1, entries 8-14). In addition to those, a series of Pd(II) catalysts were also screened, where
Pd(TFA) and PdCl provided our desired product in 45% and 32% yields respectively,
2
2
whereas Pd[(PPh ) ]Cl failed to afford our desired product 4aa (Table 1, entries 15-17).
3
2
2
Table 1. Optimization Studiesa
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Catalyst (mol %)
Ligand (20 mol%)
KOAc (2 equiv)
Br
O
Solvent, Temp,
Time
O
1
a
O
O
4aa
2a
entry
1.
catalyst
mol %)
ligand
solvent
time
(h)
temp
(ºC)
yield
(%)b
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(
(20 mol %)
Pd(OAc) (10)
P(Cy)
P(Cy)
P(Cy)
P(Cy)
P(Cy)
P(Cy)
3
3
3
3
3
3
DCE
24
24
4
4
4
4
rt
rt
22
ND
ND
trace
45
2
2
.
Pd(OAc) (10)
DMF
2
2
2
2
2
rt
rt
rt
rt
3.
Pd(OAc) (10)
DMSO
2
4
.
Pd(OAc) (10)
Toluene
2
5.
Pd(OAc) (10)
1,4-dioxane
t-AmOH
2
6
.
Pd(OAc) (10)
ND
55
2
7.
Pd(OAc) (10)
P(Cy)3
P(Ph)3
X-Phos
S-Phos
TPTP
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
8
85
85
85
85
85
85
85
2
8
9
1
1
1
1
.
Pd(OAc) (10)
8
8
8
8
8
8
41
2
.
Pd(OAc) (10)
trace
trace
40
2
0.
1.
2.
3.
Pd(OAc) (10)
2
Pd(OAc) (10)
2
Pd(OAc) (10)
TFP
78
2
Pd(OAc) (10)
Ru-Phos
ND
2
1
4.
Pd(OAc) (10) Dave-Phos 1,4-dioxane
8
8
8
8
85
85
85
85
ND
45
2
15.
Pd(TFA) (10)
TFP
TFP
TFP
1,4-dioxane
1,4-dioxane
1,4-dioxane
2
1
1
6.
7.
Pd(Cl) (10)
32
2
Pd[(PPh ) ]Cl (10)
ND
3
2
2
18.
9.
20.
1.
22.
Pd (dba) (10)
TFP
TFP
TFP
TFP
--
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
8
8
8
8
8
85
85
85
85
85
ND
56
2
3
1
Pd(OAc) (5)
2
Pd(OAc) (20)
60
2
2
--
ND
Pd(OAc) (10)
ND
2
aConditions: 1a (0.5 mmol), 2a (1 mmol), KOAc (1 mmol), solvent (3 mL) stirred at rt to 85
o
b
C; Isolated yield; ND: Not detected
On the other hand, Pd(0) catalyst Pd (dba) is unable to furnish our desired product 4aa (Table
2
3
1
, entry 18). In addition to these optimization studies, few more experiments were performed
by changing the amount of Pd(OAc) to 5 mol% and 20 mol% respectively, but no significant
2
improvement of yield was observed (Table 1, entries 19 & 20). In a control experiment, the
reaction was carried out in the absence of Pd-catalyst or ligand. However, the desired product
4aa was not obtained (Table 1, entries 21 & 22). Finally, the optimal reaction conditions can
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be summarized as follows: 4-bromocoumarin (0.5 mmol), 1,2-diphenylethyne (1 mmol),
o
Pd(OAc) (10 mol%), TFP (20 mol%) and KOAc (1 mmol) in 1,4-dioxane at 85 C for 8h
2
under argon atmosphere. The synthesized product 4aa was characterized by NMR and HRMS
analysis. In addition to basic spectroscopic analysis, the structure and configuration of the
product 4aa was confirmed unambiguously by single crystal X-ray diffraction analysis (See SI
for details).20
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With the optimized reaction parameters in hand, we explored the substrate scope for
the synthesis of indane-fused spiropentadiene chromanones 4. A wide variety of 4-
bromocoumarins 1 and alkynes 2 participated in our cascade process to afford 4 in good yields
(Table 2). Initially, three different alkynes 2a, 2b and 2c having -Me and -OMe functionalities
at the peripheral aryl ring were allowed to react with 4-bromocoumarin 1a under our optimized
reaction conditions leading to our desired indane-fused spiropentadiene chromanones 4aa, 4ab
and 4ac in good yields. On the other hand, 4-bromocoumarins with various substituents at the
aryl ring were also examined and a series of indane-fused spiropentadiene chromanones were
synthesized in good yields (Table 2, 4ba-4gc). The configuration of compound 4ba was also
2
1
established by X-ray crystallographic analysis (See SI for details). Notably, both electron-
donating and electron-withdrawing substituents at the aryl ring of 4-bromocoumarins were
equally participated in our cascade reaction. Interestingly 4,6-dibromocoumarin 1e undergoes
chemoselective coupling with the bromo- moiety prevailing in 4-position without effecting the
other bromo- group when treated with diaryl alkynes under our optimized conditions (Table 2,
4
ea-4ec). Additionally, other coupling prone chloro-functionality was also well tolerated
during our Pd-catalyzed process. As a result, several such halo-functionalized indane-fused
spiropentadiene chromanones were synthetized in good yields (Table 2, 4da-4dc).
Furthermore, the scope of our spiro-annulation strategy was explored by applying
unsymmetrically substituted alkynes as coupling partners. In this investigation, unsymmetrical
alkyne 1-methoxy-4-(phenylethynyl) benzene 2d was initially treated with 4-bromocoumarin
1
a under our optimized reaction conditions. Not surprisingly, the alkyne 2d gave mixture of
regio-isomers in 70% yield (Scheme 2a, 4ad -4ad ). The regio-isomers were difficult to
1
4
separate into individual isomers using column chromatography and they are represented as
mixture of regio-isomers.
Table 2. Synthesis of indane-fused spiropentadiene chromanones 4a
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R
R
R
Br
Pd(OAc) , TFP
KOAc, 1,4-dioxane
2
R
R1
o
O
O
85 C, 8h
R1
R
1
a-g
O
O
R
4
aa-gc
2
a-c
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Me
Me
MeO
OMe
Me
MeO
Me
Me
OMe
O
O
O
O
O
O
O
O
4
ba; 74%
4aa; 78%
4
ac; 82%
4
ab; 80%
Me
Me
MeO
OMe
Me
Me
Me
MeO
Me
F
Me
Me
F
Me
OMe
Me
O
O
O
O
O
O
O
O
4ca; 72%
4
bb; 76%
4bc; 77%
4cb; 75%
MeO
F
OMe
Me
Me
MeO
OMe
MeO
Me
MeO
Cl
Cl
Cl
OMe
Me
OMe
O
O
O
O
O
O
O
O
4
da; 73%
4
cc; 78%
4db; 76 %
4dc; 78%
Me
Me
MeO
OMe
Me
MeO
Br
Br
Br
Me
OMe
O
O
O
O
O
O
4
ea; 72%
4eb; 75%
4ec; 77%
Me
Me
MeO
OMe
Me
MeO
Me
OMe
MeO
O
O
MeO
Me
O
O
MeO
MeO
O
O
4
fa; 75%
4fb; 77%
4fc; 80%
Me
OMe
Me
MeO
Me
OMe
Me
O
O
Me
O
O
Me
O
O
4ga; 74%
4gb; 75%
4gc; 78%
a
Conditions: 1 (0.5 mmol), 2 (1.0 mmol), Pd(OAc) (10 mol%), TFP (20 mol%), KOAc (1.0
2
o
mmol), 1,4-dioxane (3 mL) stirred at 85 C for 8h
Under similar reaction conditions, two other bromocoumarins 1b and 1d effectively reacted
with 2d to afford the corresponding regio-isomers of indane-fused spiropentadiene
chromanones in 71% and 69% yields respectively (Scheme 2a, 4bd -4bd & 4dd -4dd ).
1
4
1
4
Similarly, another unsymmetrical alkyne having electron withdrawing group at aryl ring 1-
fluoro-4-(phenylethynyl) benzene 2e was also investigated as coupling partner with 4-
bromocoumarin 1a. Under our optimized reaction conditions, it furnishes two regio-isomers
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4
ae and 4ae The regio-isomers were separable under column chromatography and isolated
1
2.
into individual isomers with 15% and 16% yields respectively (Scheme 2b). Additionally,
significant amount of both the starting materials were also recovered after the reaction time of
8
h. This result indicates that C-H activation of the fluorophenyl group failed to occur, which
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
resulted in the formation of only two regio-isomers.
Scheme 2. Synthesis of indane-fused spiropentadiene chromanone from unsymmetrical
alkyne
a) Reaction with unsymmetrical alkyne bearing electron-donating group
MeO
OMe
MeO
OMe
Br
MeO
O
O
OMe
OMe MeO
1a
O
O
O
O
O
O
O
O
Mixture of 4ad , 4ad , 4ad & 4ad ; (70%)
1
2
3
4
OMe
MeO
OMe
MeO
MeO
Br
O
Me
2d
MeO
O
Pd(OAc)2, TFP, KOAc
1,4-dioxane, 85 oC, 8h
Me
Me
OMe
Me
MeO
Me
OMe
1b
O
O
O
O
O
O
O
O
Mixture of 4bd , 4bd , 4bd & 4bd ; (71%)
1
2
3
4
OMe
MeO
OMe
MeO
Br
O
Cl
MeO
O
Cl
1d
Cl
MeO
OMe
Cl
OMe
Cl
O
O
O
O
O
O
O
O
Mixture of 4dd , 4dd , 4dd & 4dd ; (69%)
1
2
3
4
b) Reaction with unsymmetrical alkyne bearing electron-withdrawing group
F
F
F
F
Br
O
Pd(OAc) , TFP
KOAc, 1,4-dioxane
85 oC, 8h
2
F
O
1a
O
O
O
O
2
e
4ae ; (15%)
1
4ae2; (16%)
In order to explore the alkyne reactivity for our cascade process, symmetrical alkynes
bearing electron withdrawing groups such as -F and -CF were considered. In this regard, the
3
alkyne 1,2-bis(4-fluorophenyl)ethyne 2f was treated with 4-bromocoumarin 1a under our
optimized conditions. Interestingly, a spiropentadiene chromanone 3af was isolated instead of
indane-fused spiropentadiene chromanone 4af, which was characterized by NMR and HRMS
analysis (Table 3). Similarly, alkyne 2f was further explored as reactive partner for the
synthesis of other spiropentadiene chromanones by considering various substituted
bromocoumarins. As a result, a series of spiropentadiene chromanones 3bf, 3cf, 3ff and 3gf
were synthetized in good yields (Table 3). Next, we considered another alkyne 1,2-bis[4-
(trifluoro-methyl)phenyl]ethyne 2g as reactive partner for our cascade process. Unfortunately,
the alkyne 2g neither gave 3ag nor the cyclized product 4ag under our optimized reaction
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2
2
2
2
2
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conditions even after prolong reaction time. However, we recovered both the starting materials
without significant loss. Under our experimental conditions, alkynes substituted with electron
withdrawing groups did not proceed for the penultimate C–H functionalization, which could
be due to weak interaction between carbopalladium intermediate and the C-H bond.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Table 3. Synthesis of spiropentadiene chromanones 3a
EWG
EWG
EWG
Br
Pd(OAc) , TFP
KOAc, 1,4-dioxane
2
EWG
R1
85 oC, 8h
O
O
R1
EWG
1
a-g
O
O
EWG
3af-gf
EWG: F=2f; CF =2g
3
F
F
F
F
F
F
F
F
F
Me
F
F
F
F
O
O
O
O
O
O
3af; 63%
3bf;
3cf; 62%
65%
F
F
F
F
CF3
CF3
F
F
CF3
F
F
CF3
MeO
O
O
Me
O
O
O
O
3
ff; 66%
3gf; 64%
3ag; Not Observed
a
Conditions: 1 (0.5 mmol), 2 (1.0 mmol), Pd(OAc) (10 mol%), TFP (20 mol%), KOAc (1.0
2
o
mmol), 1,4-dioxane (3 mL) stirred at 85 C for 8h.
Additionally, another interesting internal alkyne bearing a phenyl group and an alkyl
group was considered as reactive partner for our annulation process. As shown in Scheme 3,
alkyne 2h was treated with 4-bromocoumarin 1a under our optimized reaction conditions. This
alkyne 2h neither gave indane-fused spiropentadiene chromanone 4ah nor spiropentadiene
chromanone 3ah.
Scheme 3. Reaction Behavior of Internal Alkyne 2h
Br
Pd(OAc) , TFP
2
KOAc, 1,4-dioxane
O
O
o
8
5 C, 8h
1
a
O
O
O
O
2
h
4ah
3ah
Furthermore, we planned some competition reactions of 4-bromocoumarin 1a with two
different alkynes in a single reaction vessel as shown in Scheme 4. In an initial experiment, 4-
bromocoumarin 1a (0.5 mmol) was treated with a mixture of alkynes 2a (1 mmol) and 2g (1
mmol) under our optimized conditions. Interestingly, 4-bromocoumarin 1a predominantly
coupled with alkyne 2a instead of 2g to form 4aa in 73% yield (Scheme 4a). On the other hand,
when 1a (0.5 mmol) was treated with 2a (1 mmol) along with alkyne 2c (1 mmol), a mixture
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of hybrid products 4aac and 4aca were formed in 70% yield (Scheme 4b). This results reveal
that diaryl alkynes having electron neutral or electron rich substituents were more favourable
to form our desired indane-fused spiropentadiene chromanones. In addition to those, an
independent experiment was also performed to gain insight into the reaction mechanism. Here,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
the reaction of 1a with 2f was studied in the presence of D O as fourth component under our
2
optimized reaction conditions. To our delight, this experiment gives a deuterium incorporated
product at the C-3 position of 3af-D which could be due to the quenching of carbopalladium
intermediate with deuterium oxide (Scheme 4c). Reasonably, this observation reveals that C-
H activation failed to occur in presence of fluorophenyl group to give our desired indane-fused
spiropentadiene chromanone.
Scheme 4. Competition Experiments and Deuterium Labeling Experiment
CF3
Br
Pd(OAc)2, TFP
KOAc, 1,4-dioxane
a)
b)
c)
o
8
5 C, 8h
O
O
1
a (0.5 mmol)
O
O
2
a (1 mmol)
4aa (73%)
CF3
2g (1 mmol)
OMe
OMe
MeO
Br
Pd(OAc)2, TFP
KOAc, 1,4-dioxane
MeO
o
O
O
85 C, 8h
OMe
1a (0.5 mmol)
O
O
O
O
2
a (1 mmol)
2c (1 mmol)
OMe
Mixture of 4aac and 4aca (70%)
F
F
F
Br
Pd(OAc) , TFP
2
KOAc, 1,4-dioxane
F
F
o
85 C, 8 h
O
O
D
H
O
D2O
1a
O
F
3af-D (60%)
2f
To demonstrate the practical utility of our cascade annulation process, a scale-up
experiment was carried out under the optimized reaction conditions. As shown in Scheme 5a,
the reaction of 4-bromocoumarin 1a (3 mmol) with 1,2-diphenylethyne 2a (6 mmol) was
performed on a gram-scale to give our desired product 4aa (1.01 g) in 67% yield. In addition,
a control experiment with 1:1 ratio of 4-bromcoumarin 1a and 1,2-diphenylethyne 2a was
performed to elucidate the nature and amount of product formed. Interestingly, our cyclized
product 4aa was obtained in only 35% yield (Scheme 5b).
Scheme 5. Scale-Up Experiment and Control Experiment
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Br
O
Pd(OAc) , TFP
KOAc, 1,4-dioxane
2
a)
o
O
85 C, 8h
1a
(
3 mmol, 0.67 g)
O
O
2
a
4aa
1.01 g, 67%)
(
6 mmol, 1.07 g)
(
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Br
Pd(OAc) , TFP
2
KOAc, 1,4-dioxane
b)
o
O
a
O
85 C, 8h
1
(0.5 mmol)
O
O
2
a
4aa (35%)
(
0.5 mmol)
Based on our experiments and literature precedents, a plausible catalytic cycle for the
formation of 4aa was proposed and shown in Scheme 6. The catalytic cycle starts from Pd(0)L2
(
L=TFP), which was generated in situ from Pd(OAc) and TFP.
2
Scheme 6. Plausible Reaction Mechanism for the Synthesis of 4
Pd(OAc)2
2L
4
aa
2
OAc-
Br
Pd(0)L2
Ph
Ph
Ph
reductive
elemination
O
1a
O
oxidative
addition
Br
Pd(II)L2
Pd(II)L2
3af-D
O
F
O
O
A
O
D2O
Ph
HOAc
KOAc
Ph
Ph
Ph
Ph
2a
alkyne
insertion
Ph
Ph
Ph
H
C-H activation
Pd(II)L2
O
H
O
KBr
Pd(II)L2
O
O
Ph
CH3
Ph
O
O
OAc
E
Ph
Ph
Pd(II)L2
D
Ph
OAc
2a
Ph
Ph
Ph
Ph
O
O
Ph
O
Ph
Ph
Ph
Pd(II)L2
B
alkyne
insertion
unfavoured
product
Ph
unfavoured
product
O
O OAc
C
O
O
O
6aa
5
aa
Subsequently, the oxidative addition of Pd(0) into the C-Br bond of 1a takes place to form the
intermediate A. Then, insertion of 1,2-diphenylacetylene 2a into Pd-C bond would occur to
produce intermediate B, which subsequently undergoes second insertion of 1,2-
diphenylacetylene 2a to generate intermediate C. Next, a unique ring contraction phenomenon
takes place to generate a spiropentadiene chromanone intermediate D, which then undergoes
C-H activation to form the complex F. Finally, reductive elimination from F gave our desired
product 4aa and concomitantly regenerates Pd(0) to complete the catalytic cycle. However,
direct reductive elimination from intermediate B and C to form the unwanted product 5aa and
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aa was not observed. The deuterium labelling product 3af-D could be achieved by quenching
E with deuterium oxide.
In conclusion, we have developed a Pd(0)-catalyzed spiro-annulation reaction of 4-
bromocoumarin with alkynes to provide a wide range of indane-fused spiropentadiene
chromanone derivatives in good yields. In comparison to previous reports, our synthetic
protocol resulted in the formation of diverse sterically congested spirocyclic core bearing two-
fused five membered rings in a single operation.
1
1
1
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2
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EXPERIMENTAL SECTION:
General Information: All reactions involving oxygen- or moisture-sensitive compounds were
carried out under argon atmosphere using oven-dried or flame-dried glassware. All other
solvents and reagents were purified according to standard procedures or were used as received
from TCI, Aldrich, Merck and Spectrochem. Reactions were monitored by thin-layer
chromatography (TLC) using aluminium-backed silica gel plates (0.2 mm thickness); the
chromatograms were visualized with ultraviolet light (254 nm). Flash column chromatography
was performed with silica gel 60 (100-200 or 200-400 mesh). HRMS data were recorded by
electronspray ionization with a Q-TOF mass analyzer.
General procedure for the synthesis of 4-bromocoumarins:
An oven-dried round bottomed flask (50 mL capacity) equipped with a magnetic stir bar was
evacuated and purged with argon. 4-Hydroxycoumarin (1 equiv), TBAB (1.16 equiv), P O
2
5
o
(
2.4 equiv) and toluene (4 mL/mmol) was stirred at 94 C (preheated oil-bath) for 1.5 h. Upon
completion, the reaction mixture was washed with toluene (2x30 mL). The combined organic
phases were washed with saturated NaHCO and H O and dried over sodium sulfate. The
3
2
solvent was removed under reduced pressure to obtain 4-bromocoumarin 1a. Compounds 1b-
g was prepared using the same experimental procedure.
4
,6-Dibromo-2H-chromen-2-one; 1e
Using the general experimental procedure on 6-bromo-4-hydroxycoumarin (5 mmol, 1 equiv),
TBAB (5.8 mmol, 1.16 equiv), P O (12 mmol, 2.4 equiv) in toluene (20 mL), compound 1e
2
5
o
1
was obtained as light brown solid (1.033 g, 68% yield); mp: 166-168 C; H NMR (500 MHz,
CDCl ): δ 7.93 (d, J=2.3 Hz, 1H), 7.66 (dd, J =2.3 Hz, J =8.7 Hz, 1H), 7.20 (d, J=8.7 Hz, 1H),
3
1
2
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3
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4
4
4
5
5
5
5
5
5
5
5
5
5
6
13
1
6
.87 (s, 1H); C{ H} NMR (126 MHz, CDCl ): δ 157.8, 151.2, 139.7, 135.9, 130.3, 120.4,
3
-1
120.3, 118.7, 117.7; IR (CHCl ): 3425, 1756, 1649, 1546, 1329, 1266, 1187, 882, 772 cm ;
3
+
HRMS (+ESI) m/z: [M+H] Calcd for C H O Br 302.8656; found 302.8653.
9
5
2
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1
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3
4
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6
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1
2
3
4
5
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9
0
General procedure for the synthesis of indane-fused spiropentadiene chromanone 4:
An oven-dried round bottomed flask (50 mL capacity) equipped with a magnetic stir bar was
evacuated and purged with argon. 4-Bromocoumarin (0.5 mmol, 1 equiv), diaryl alkyne (1
mmol, 2 equiv), Pd(OAc) (10 mol%), TFP (20 mol%), KOAc (1 mmol, 2 equiv) and 1,4-
2
dioxane (3 mL) were added successively at room temperature. The reaction mixture was stirred
o
at 85 C (preheated oil-bath) for 8 h and then allowed to cool to room temperature. Saturated
NH Cl solution (10 mL) was added to the reaction mixture, and the organic layer was extracted
4
with EtOAc (2x30 mL). The combined organic phases were washed with brine and dried over
sodium sulfate. The solvent was removed and the residue was purified by column
chromatography on silica gel using hexane/ethyl acetate as eluent.
General procedure for gram scale experiment:
An oven-dried round bottomed flask (100 mL capacity) equipped with a magnetic stir bar was
evacuated and purged with argon. 4-Bromocoumarin 1a (3 mmol, 0.67 g), diaryl alkyne 2a (6
mmol, 1.07 g), Pd(OAc) (0.3 mmol, 67 mg), TFP (0.6 mmol, 140 mg), KOAc (6 mmol, 0.59
2
g) and 1,4-dioxane (20 mL) were added successively at room temperature. The reaction mixture
o
was stirred at 85 C (preheated oil-bath) for 8 h and then allowed to cool to room temperature.
Upon completion, saturated NH Cl solution (50 mL) was added to the reaction mixture, and
4
the organic layer was extracted with EtOAc (2x90 mL). The combined organic phases were
washed with brine and dried over sodium sulfate. The solvent was removed and the residue
was purified by column chromatography on silica gel to afford the corresponding indane-fused
spiropentadiene chromanone 4aa (1.01 g, 67%).
7
,8,9-Triphenylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; 4aa
Using the general experimental procedure on 4-bromocoumarin (0.112 g; 0.5 mmol, 1 equiv),
diphenylacetylene (0.178 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10 mol%), TFP
2
(0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-dioxane (3 mL),
compound 4aa was obtained as white solid (0.195 g, 78% yield) after purification by flash
o
1
column chromatography using hexane/EtOAc (19:1) as an eluent; mp: 218-220 C; H NMR
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(
500 MHz, CDCl ): δ 7.41 (d, J= 7.5 Hz, 1H), 7.29 (d, J= 7.6 Hz, 1H), 7.16-7.24 (m, 6H),
3
1
3
1
6.82-7.08 (m, 14H), 6.73 (dd, J = 1.2 Hz, J = 8.0 Hz, 1H), 4.52 (s, 1H); C{ H} NMR (126
1
2
MHz, CDCl ): δ 166.3, 154.4, 151.4, 148.8, 145.7, 145.6, 140.7, 135.1, 134.9, 134.4, 134.0,
3
1
1
29.9, 129.8, 128.8, 128.7, 128.6, 128.2, 128.0, 127.9, 127.8, 127.7, 127.4, 127.3, 125.6, 124.7,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
24.4, 122.3, 119.2, 117.7, 71.6, 48.8; IR (CHCl ): 3420, 2918, 2853, 1753, 1601, 1504, 1485,
3
-1
+
1443, 1219, 837, 772 cm ; HRMS (+ESI) m/z: [M+H] Calcd for C H O 501.1855; found
3
7
25
2
5
01.1859.
1
2-Methyl-7,8,9-tri-p-tolylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; 4ab
Using the general experimental procedure on 4-bromocoumarin (0.112 g; 0.5 mmol, 1 equiv),
1,2-di-p-tolylethyne (0.206 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10 mol%),
2
TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-dioxane (3
mL), compound 4ab was obtained as yellow solid (0.222 g, 80% yield) after purification by
o
1
flash column chromatography using hexane/EtOAc (19:1) as an eluent; mp: 253-255 C; H
NMR (500 MHz, CDCl ): δ 7.29 (d, J= 7.8 Hz, 1H), 7.15 (dd, J = 1.7 Hz, J = 7.8 Hz, 1H),
3
1
2
7
.09 (s, 1H), 7.03 (s, 4H), 6.90-6.93 (m, 1H), 6.84-6.87 (m, 3H), 6.78-6.81 (m, 5H), 6.70-6.73
13
1
(
m, 3H), 4.44 (s, 1H), 2.26 (s, 3H), 2.18 (s, 3H), 2.17 (s, 3H), 2.08 (s, 3H); C{ H} NMR (126
MHz, CDCl ): δ 166.7, 153.8, 151.4, 147.9, 145.6, 145.2, 139.9, 138.1, 137.3, 136.8, 136.7,
3
1
1
32.5, 131.8, 131.4, 129.8, 129.7, 129.3, 128.9, 128.6, 128.5, 128.4, 128.3, 125.8, 125.0, 124.5,
22.0, 119.9, 117.5, 71.6, 48.7, 21.4, 21.3, 21.2, 21.1 (One peak is missing due to overlap); IR
-1
(CHCl ): 3421, 2920, 2855, 1754, 1606, 1484, 1447, 1244, 1211, 820, 770 cm ; HRMS
3
+
(+ESI) m/z: [M+H] Calcd for C H O 557.2481; found 557.2486.
4
1
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1
4
2-Methoxy-7,8,9-tris(4-methoxyphenyl)cyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one;
ac
Using the general experimental procedure on 4-bromocoumarin (0.112 g; 0.5 mmol, 1 equiv),
1
1
,2-bis(4-methoxyphenyl)ethyne (0.238 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol,
2
0 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-
dioxane (3 mL), compound 4ac was obtained as brown solid (0.254 g, 82% yield) after
purification by flash column chromatography using hexane/EtOAc (4:1) as an eluent; mp: 170-
o
1
1
72 C; H NMR (500 MHz, CDCl ): δ 7.38 (d, J= 8.4 Hz, 1H), 7.21 (dd, J = 1.6 Hz, J = 7.8
3 1 2
Hz, 1H), 7.14 (d, J= 8.6 Hz, 2H), 7.01-7.04 (m, 1H), 6.91-6.97 (m, 4H), 6.82-6.86 (m, 5H),
6.69 (d, J= 8.8 Hz, 2H), 6.63-6.65 (m, 1H), 6.61 (d, J= 8.8 Hz, 2H), 4.52 (s, 1H), 3.82 (s, 3H),
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13
1
3
.75 (s, 3H), 3.74 (s, 3H), 3.69 (s, 3H); C{ H} NMR (126 MHz, CDCl ): δ 166.8, 159.8,
3
158.9, 158.5, 158.3, 152.7, 151.3, 147.0, 146.7, 144.6, 138.3, 131.2, 131.0, 129.8, 128.5, 128.1,
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5
5.5, 55.1, 55.0, 54.9, 49.0; IR (CHCl ): 3420, 2932, 2836, 1757, 1605, 1510, 1479, 1247,
3
0
1
2
3
4
5
6
7
8
9
0
1
2
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7
8
9
0
1
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7
8
9
0
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7
8
9
0
1
2
3
4
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7
8
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0
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+
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176, 1030, 834, 771 cm ; HRMS (+ESI) m/z: [M+H] Calcd for C H O 621.2277; found
41 33 6
621.2272.
5
-Methyl-7,8,9-triphenylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; 4ba
Using the general experimental procedure on 4-bromo-6-methylcoumarin (0.120 g; 0.5 mmol,
equiv), diphenylacetylene (0.178 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10
1
2
mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-
dioxane (3 mL), compound 4ba was obtained as light brown solid (0.190 g, 74% yield) after
purification by flash column chromatography using hexane/EtOAc (19:1) as an eluent; mp:
o
1
2
38-240 C; H NMR (500 MHz, CDCl ): δ 7.49 (d, J= 7.4 Hz, 1H), 7.36 (d, J= 7.5 Hz, 1H),
3
7.24-7.32 (m, 5H), 7.06-7.17 (m, 8H), 6.99-7.01 (m, 3H), 6.90-6.91 (m, 2H), 6.81 (dd, J = 1.7
1
1
3
1
Hz, J = 8.3 Hz, 1H), 6.71 (d, J= 8.3 Hz, 1H), 4.54 (s, 1H), 2.20 (s, 3H); C{ H} NMR (126
2
MHz, CDCl ): δ 166.6, 154.4, 149.4, 148.8, 145.7, 145.5, 140.6, 135.2, 135.0, 134.5, 134.2,
3
134.1, 130.0, 129.8, 129.6, 128.7, 128.6, 128.2, 128.0, 127.9, 127.8, 127.7, 127.3, 127.2, 125.5,
1
1
24.4, 122.4, 118.7, 117.3, 71.7, 48.9, 20.9; IR (CHCl ): 3423, 3055, 3023, 2920, 2853, 1751,
3
-1
+
607, 1494, 1444, 1247, 1209, 752, 697 cm ; HRMS (+ESI) m/z: [M+H] Calcd for
C H O 515.2011; found 515.2017.
3
8
27
2
5
,12-Dimethyl-7,8,9-tri-p-tolylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; 4bb
Using the general experimental procedure on 4-bromo-6-methylcoumarin (0.120 g; 0.5 mmol,
equiv), 1,2-di-p-tolylethyne (0.206 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10
1
2
mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-
dioxane (3 mL), compound 4bb was obtained as yellow solid (0.216 g, 76% yield) after
purification by flash column chromatography using hexane/EtOAc (19:1) as an eluent; mp:
o
1
2
1
54-256 C; H NMR (500 MHz, CDCl ): δ 7.39 (dd, J = 1.6 Hz, J = 7.7 Hz, 1H), 7.18 (s,
3 1 2
H), 7.13 (s, 4H), 6.95-6.98 (m, 3H), 6.88-6.92 (m, 5H), 6.80-6.82 (m, 3H), 6.72 (d, J= 8.3 Hz,
1
3
1
1H), 4.49 (s, 1H), 2.37 (s, 3H), 2.28 (s, 3H), 2.26 (s, 3H), 2.20 (s, 3H), 2.19 (s, 3H); C{ H}
NMR (126 MHz, CDCl ): δ 166.9, 153.8, 149.3, 147.9, 145.7, 145.0, 139.8, 138.0, 137.2,
3
1
36.7, 133.9, 132.5, 131.8, 131.4, 129.8, 129.7, 129.4, 129.3, 128.9, 128.6, 128.4, 128.3, 125.6,
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25.0, 122.0, 119.4, 117.2, 71.6, 48.8, 21.4, 21.3, 21.2, 21.1, 20.9 (Two peaks are missing due
-1
to overlap); IR (CHCl ): 3421, 3023, 2920, 1754, 1605, 1493, 1250, 1218, 818, 772 cm ;
3
+
HRMS (+ESI) m/z: [M+H] Calcd for C H O 571.2637; found 571.2639.
42 35
2
1
1
1
1
1
1
1
1
1
1
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0
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1
1
2-Methoxy-7,8,9-tris(4-methoxyphenyl)-5-methylcyclopenta[2,3]indeno[1,2-c]chromen-
(13bH)-one; 4bc
Using the general experimental procedure on 4-bromo-6-methylcoumarin (0.120 g; 0.5 mmol,
equiv), 1,2-bis(4-methoxyphenyl)ethyne (0.238 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05
1
2
mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv)
in 1,4-dioxane (3 mL), compound 4bc was obtained as brown solid (0.244 g, 77% yield) after
purification by flash column chromatography using hexane/EtOAc (4:1) as an eluent; mp: 155-
o
1
1
57 C; H NMR (500 MHz, CDCl ): 7.40 (d, J= 8.4 Hz, 1H), 7.16 (d, J= 8.7 Hz, 2H), 6.80-
3
6.97 (m, 9H), 6.61-6.73 (m, 6H), 4.49 (s, 1H), 3.81 (s, 3H), 3.74 (s, 3H), 3.73 (s, 3H), 3.68 (s,
1
3
1
3
1
1
H), 2.19 (s, 3H); C{ H} NMR (126 MHz, CDCl ): δ 166.9, 159.7, 158.8, 158.4, 158.2,
3
52.6, 149.2, 147.1, 146.7, 144.4, 138.2, 134.0, 131.2, 131.0, 129.7, 129.3, 128.1, 128.0, 127.2,
26.9, 125.5, 122.8, 119.7, 117.1, 114.9, 113.6, 113.3, 113.0, 109.5, 71.6, 55.4, 55.1, 55.0,
54.9, 49.0, 20.9; IR (CHCl ): 3421, 2931, 2836, 1741, 1605, 1509, 1288, 1247, 1175, 1030,
3
-1
+
8
35, 772 cm ; HRMS (+ESI) m/z: [M+H] Calcd for C H O 635.2434; found 635.2438.
42 35 6
5
-Fluoro-7,8,9-triphenylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; 4ca
Using the general experimental procedure on 4-bromo-6-fluorocoumarin (0.122 g; 0.5 mmol,
1 equiv), diphenylacetylene (0.178 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10
2
mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-
dioxane (3 mL), compound 4ca was obtained as white solid (0.187 g, 72% yield) after
purification by flash column chromatography using hexane/EtOAc (19:1) as an eluent; mp:
o
1
261-263 C; H NMR (500 MHz, CDCl ): δ 7.43 (d, J= 7.4 Hz, 1H), 7.29 (d, J= 7.5 Hz, 1H),
3
7
2
.24-7.26 (m, 3H), 7.16-7.18 (m, 2H), 7.00-7.11 (m, 8H), 6.91 (dd, J = 1.4 Hz, J = 8.0 Hz,
1
2
13
1
H), 6.84-6.87 (m, 3H), 6.69-6.72 (m, 1H), 6.62-6.67 (m, 1H), 4.52 (s, 1H); C{ H} NMR
(126 MHz, CDCl ): δ 166.0, 159.1 (d, J= 243.2 Hz), 154.0, 148.2, 147.5, 146.0, 145.2, 141.0,
3
1
1
34.8 (d, J= 7.5 Hz), 134.1, 133.8, 129.9, 129.8, 128.8, 128.6, 128.4, 128.2, 128.1, 128.0,
27.8, 127.5, 127.4, 124.4, 122.4, 121.4 (d, J= 7.5 Hz), 119.0 (d, J= 8.5 Hz), 116.0 (d, J= 23.9
Hz), 111.6 (d, J= 24.2 Hz), 71.6, 48.4 (One peak is missing due to overlap); IR (CHCl ): 3420,
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922, 2853, 1755, 1599, 1488, 1219, 1177, 817, 772 cm ; HRMS (+ESI) m/z: [M+H] Calcd
for C H O F 519.1760; found 519.1768.
3
7
24
2
5
-Fluoro-12-methyl-7,8,9-tri-p-tolylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; 4cb
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
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0
1
2
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9
0
Using the general experimental procedure on 4-bromo-6-fluorocoumarin (0.122 g; 0.5 mmol,
equiv), 1,2-di-p-tolylethyne (0.206 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10
1
2
mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-
dioxane (3 mL), compound 4cb was obtained as yellow solid (0.215 g, 75% yield) after
purification by flash column chromatography using hexane/EtOAc (19:1) as an eluent; mp:
o
1
2
65-267 C; H NMR (500 MHz, CDCl ): δ 7.40 (d, J= 7.8 Hz, 1H), 7.18 (s, 1H), 7.12 (s,
3
4H), 6.88-6.97 (m, 8H), 6.78-6.82 (m, 3H), 6.70-6.74 (m, 1H), 4.53 (s, 1H), 2.37 (s, 3H), 2.28
1
3
1
(
s, 3H), 2.27 (s, 3H), 2.20 (s, 3H); C{ H} NMR (126 MHz, CDCl ): δ 166.4, 159.1 (d, J=
3
2
1
42.7 Hz), 153.4, 147.4, 145.6, 145.3, 140.2, 138.3, 137.5, 136.9 (d, J=7.5 Hz), 132.3, 132.2,
31.5, 131.1, 129.8, 129.7, 129.5, 129.0, 128.7, 128.4, 125.0, 121.1, 122.0, 118.9 (d, J=8.3
Hz), 115.7 (d, J=23.9 Hz), 111.7 (d, J=24.1 Hz), 71.6, 48.3, 21.4, 21.3, 21.2, 21.1; IR (CHCl ):
3
-1
3
401, 3023, 2920, 2855, 1758, 1600, 1489, 1418, 1248, 1177, 817, 744 cm ; HRMS (+ESI)
+
m/z: [M+H] Calcd for C H O F 575.2386; found 575.2384.
4
1
32
2
5
1
-Fluoro-12-methoxy-7,8,9-tris(4-methoxyphenyl)cyclopenta[2,3]indeno[1,2-c]chromen-
(13bH)-one; 4cc
Using the general experimental procedure on 4-bromo-6-fluorocoumarin (0.122 g; 0.5 mmol,
1 equiv), 1,2-bis(4-methoxyphenyl)ethyne (0.238 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05
2
mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv)
in 1,4-dioxane (3 mL), compound 4cc was obtained as brown solid (0.249 g, 78% yield) after
purification by flash column chromatography using hexane/EtOAc (4:1) as an eluent; mp: 126-
o
1
128 C; H NMR (500 MHz, CDCl ): δ 7.41 (d, J= 8.4 Hz, 1H), 7.15 (d, J= 8.8 Hz, 2H), 6.78-
3
6
3
1
1
1
2
.94 (m, 9H), 6.62-6.74 (m, 6H), 4.54 (s, 1H), 3.81 (s, 3H), 3.75 (s, 3H), 3.74 (s, 3H), 3.69 (s,
13
1
H); C{ H} NMR (126 MHz, CDCl ): δ 166.4, 159.9, 159.2 (d, J=242.8 Hz), 158.9, 158.6,
3
58.4, 152.2, 147.3, 146.7, 146.2, 144.9, 138.6, 131.2, 131.0, 129.8, 127.9, 127.7, 126.9, 126.6,
22.9, 122.4 (d, J= 7.8 Hz), 118.9 (d, J=8.3 Hz), 115.7 (d, J=24.1 Hz), 115.1, 113.7, 113.4,
13.1, 111.6 (d, J=24.2 Hz), 109.6, 71.6, 55.4, 55.1, 55.0, 54.9, 48.6; IR (CHCl ): 3419, 2933,
3
-1
+
836, 1734, 1604, 1509, 1248, 1175, 1030, 837, 772 cm ; HRMS (+ESI) m/z: [M+H] Calcd
for C H O F 639.2183; found 639.2181.
4
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5-Chloro-7,8,9-triphenylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; 4da
Using the general experimental procedure on 4-bromo-6-chlorocoumarin (0.129 g; 0.5 mmol,
1 equiv), diphenylacetylene (0.178 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10
2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
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5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-
dioxane (3 mL), compound 4da was obtained as yellow solid (0.195 g, 73% yield) after
purification by flash column chromatography using hexane/EtOAc (19:1) as an eluent; mp:
o
1
246-248 C; H NMR (500 MHz, CDCl ): δ 7.52 (d, J= 7.1 Hz, 1H), 7.32-7.36 (m, 4H), 7.24-
3
7
6
.26 (m, 2H), 7.09-7.19 (m, 9H), 6.99-7.01 (m, 2H), 6.97 (dd, J = 2.5 Hz, J = 8.7 Hz, 1H),
1 2
13
1
.92-6.94 (m, 2H), 6.75 (d, J= 8.7 Hz, 1H), 4.59 (s, 1H); C{ H} NMR (126 MHz, CDCl ):
3
δ 165.8, 153.9, 150.0, 148.3, 146.0, 145.1, 141.1, 134.8, 134.7, 134.0, 133.0, 129.9, 129.8,
1
29.7, 129.0, 128.9, 128.5, 128.4, 128.2, 128.0, 127.7, 127.5, 127.4, 125.3, 124.3, 122.5, 121.3,
1
19.1, 71.4, 48.5 (One peak is missing due to overlap); IR (CHCl ): 3421, 2920, 2853, 1755,
3
-1
+
1
600, 1477, 1217, 1111, 933, 771 cm ; HRMS (+ESI) m/z: [M+H] Calcd for C H O Cl
37 24 2
535.1465; found 535.1467.
5
-Chloro-12-methyl-7,8,9-tri-p-tolylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; 4db
Using the general experimental procedure on 4-bromo-6-chlorocoumarin (0.129 g; 0.5 mmol,
equiv), 1,2-di-p-tolylethyne (0.206 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10
1
2
mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-
dioxane (3 mL), compound 4db was obtained as yellow solid (0.224 g, 76% yield) after
purification by flash column chromatography using hexane/EtOAc (19:1) as an eluent; mp:
o
1
2
42-244 C; H NMR (500 MHz, CDCl ): δ 7.41 (dd, J = 1.6 Hz, J = 7.8 Hz, 1H), 7.15-7.17
3 1 2
(m, 2H), 7.13 (d, J= 1.6 Hz, 4H), 6.89-6.98 (m, 8H), 6.81 (dd, J = 2.1 Hz, J = 8.1 Hz, 2H),
1
2
6
.76 (d, J= 8.7 Hz, 1H), 4.52 (s, 1H), 2.37 (s, 3H), 2.28 (s, 3H), 2.27 (s, 3H), 2.20 (s, 3H);
13
1
C{ H} NMR (126 MHz, CDCl ): δ 166.2, 153.2, 149.9, 147.5, 145.6, 145.2, 140.4, 138.3,
3
137.5, 137.0, 136.9, 132.3, 132.2, 131.4 131.1, 129.8, 129.7, 129.5, 129.1, 128.7, 128.6, 128.4,
1
25.4, 125.0, 122.1, 122.0, 118.9, 71.4, 48.5, 21.4, 21.3, 21.2, 21.1 (Two peaks are missing
-
due to overlap); IR (CHCl ): 3400, 2920, 2853, 1762, 1606, 1475, 1256, 1212, 816, 748 cm
3
1;
HRMS (+ESI) m/z: [M+H] Calcd for C H O Cl 591.2091; found 591.2098.
+
4
1
32
2
5-Chloro-12-methoxy-7,8,9-tris(4-methoxyphenyl)cyclopenta[2,3]indeno[1,2-c]chromen-
(13bH)-one; 4dc
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Using the general experimental procedure on 4-bromo-6-chlorocoumarin (0.129 g; 0.5 mmol,
1 equiv), 1,2-bis(4-methoxyphenyl)ethyne (0.238 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05
2
mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv)
in 1,4-dioxane (3 mL), compound 4dc was obtained as brown solid (0.256 g, 78% yield) after
purification by flash column chromatography using hexane/EtOAc (4:1) as an eluent; mp: 118-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
o
1
120 C; H NMR (500 MHz, CDCl ): δ 7.42 (d, J= 8.4 Hz, 1H), 7.13-7.16 (m, 3H), 6.96-6.99
3
(
(
(
m, 1H), 6.93-6.94 (m, 2H), 6.89-6.90 (m, 1H), 6.84-6.87 (m, 4H), 6.77 (d, J=8.7 Hz, 1H), 6.70
d, J=8.7 Hz, 2H), 6.64-6.68 (m, 1H), 6.64 (d, J=8.8 Hz, 2H), 4.52 (s, 1H), 3.82 (s, 3H), 3.75
1
3
1
s, 3H), 3.74 (s, 3H), 3.69 (s, 3H); C{ H} NMR (126 MHz, CDCl ): δ 166.1, 159.9, 159.0,
3
158.6, 158.4, 152.1, 149.9, 146.7, 146.3, 144.9, 138.8, 131.4, 131.3, 129.8, 129.6, 128.7, 127.9,
1
5
27.7, 126.9, 126.6, 125.3, 123.0, 122.4, 118.9, 115.1, 113.7, 113.4, 113.1, 109.6, 71.4, 55.5,
5.1, 55.0, 54.9, 48.7; IR (CHCl ): 3421, 2930, 2837, 1734, 1603, 1509, 1475, 1249, 1176,
3
-1
+
1029, 834, 770 cm ; HRMS (+ESI) m/z: [M+H] Calcd for C H O Cl 655.1887; found
4
1
32
6
6
55.1883.
5
-Bromo-7,8,9-triphenylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; 4ea
Using the general experimental procedure on 4,6-dibromocoumarin (0.152 g; 0.5 mmol, 1
equiv), diphenylacetylene (0.178 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10
2
mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-
dioxane (3 mL), compound 4ea was obtained as yellow solid (0.208 g, 72% yield) after
purification by flash column chromatography using hexane/EtOAc (19:1) as an eluent; mp:
o
1
264-266 C; H NMR (500 MHz, CDCl ): 7.45 (d, J= 7.2 Hz, 1H), 7.23-7.29 (m, 5H), 7.17-
3
7
1
1
.19 (m, 2H), 7.02-7.12 (m, 9H), 6.91-6.93 (m, 2H), 6.84-6.86 (m, 2H), 6.63 (d, J= 8.7 Hz,
1
3
1
H), 4.50 (s, 1H); C{ H} NMR (126 MHz, CDCl ): δ 165.7, 153.9, 150.5, 148.3, 146.0,
3
45.1, 141.2, 134.8, 134.7, 134.1, 133.7, 131.8, 130.0, 129.8, 128.9, 128.5, 128.4, 128.3, 128.2,
128.0, 127.8, 127.5, 127.4, 124.3, 122.5, 121.8, 119.4, 117.2, 71.4, 48.5 (One peak is missing
-1
due to overlap); IR (CHCl ): 3401, 2921, 2853, 1757, 1601, 1473, 1251, 854, 772, 699 cm ;
3
+
HRMS (+ESI) m/z: [M+H] Calcd for C H O Br 579.0960; found 579.0953.
3
7
24
2
5
-Bromo-12-methyl-7,8,9-tri-p-tolylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; 4eb
Using the general experimental procedure on 4,6-dibromocoumarin (0.152 g; 0.5 mmol, 1
equiv), 1,2-di-p-tolylethyne (0.206 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10
2
mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-
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dioxane (3 mL), compound 4eb was obtained as yellow solid (0.238 g, 75% yield) after
purification by flash column chromatography using hexane/EtOAc (19:1) as an eluent; mp:
o
1
2
7
4
58-260 C; H NMR (500 MHz, CDCl ): 7.40 (d, J= 7.8 Hz, 1H), 7.28 (d, J= 1.7 Hz, 1H),
3
.16 (s, 1H), 7.12 (s, 5H), 6.89-6.97 (m, 7H), 6.80 (d, J= 7.9 Hz, 2H), 6.70 (d, J= 8.7 Hz, 1H),
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
13
1
.51 (s, 1H), 2.36 (s, 3H), 2.28 (s, 3H), 2.27 (s, 3H), 2.20 (s, 3H); C{ H} NMR (126 MHz,
CDCl ): δ 166.1, 153.2, 150.5, 147.5, 145.6, 145.2, 140.4, 138.3, 137.5, 137.0, 136.9, 132.3,
3
1
1
32.1, 131.6, 131.4, 131.1, 129.8, 129.7, 129.5, 129.1, 128.7, 128.5, 128.4, 125.0, 122.5, 122.1,
19.3, 117.1, 71.4, 48.5, 21.4, 21.3, 21.2, 21.1 (One peak is missing due to overlap); IR
-1
(
CHCl ): 3420, 2920, 2854, 1763, 1604, 1473, 1213, 1110, 816, 771 cm ; HRMS (+ESI)
3
+
m/z: [M+H] Calcd for C H O Br 635.1586; found 635.1590.
4
1
32
2
5
1
-Bromo-12-methoxy-7,8,9-tris(4-methoxyphenyl)cyclopenta[2,3]indeno[1,2-c]chromen-
(13bH)-one; 4ec
Using the general experimental procedure on 4,6-dibromocoumarin (0.152 g; 0.5 mmol, 1
equiv), 1,2-bis(4-methoxyphenyl)ethyne (0.238 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05
2
mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv)
in 1,4-dioxane (3 mL), compound 4ec was obtained as brown solid (0.269 g, 77% yield) after
purification by flash column chromatography using hexane/EtOAc (4:1) as an eluent; mp: 109-
o
1
1
11 C; H NMR (500 MHz, CDCl ): 7.42 (d, J= 8.4 Hz, 1H), 7.27 (d, J= 2.2 Hz, 1H), 7.15
3
(d, J= 8.7 Hz, 2H), 7.10-7.13 (m, 1H), 6.93 (d, J= 8.8 Hz, 2H), 6.89-6.90 (m, 1H), 6.83-6.87
(m, 4H), 6.67-6.72 (m, 3H), 6.66-6.69 (m, 1H), 6.64 (d, J= 8.8 Hz, 2H), 4.51 (s, 1H), 3.82 (s,
1
3
1
3
H), 3.75 (s, 3H), 3.74 (s, 3H), 3.69 (s, 3H); C{ H} NMR (126 MHz, CDCl ): δ 166.1, 159.9,
3
1
59.0, 158.6, 158.4, 152.1, 150.4, 146.6, 146.3, 144.9, 138.9, 131.6, 131.3, 131.1, 129.8, 128.4,
127.9, 127.7, 126.9, 126.6, 123.0, 122.8, 119.3, 117.1, 115.1, 113.8, 113.4, 113.1, 109.7, 71.4,
5
5.2, 55.1, 55.0, 54.9, 48.8; IR (CHCl ): 3421, 2931, 2836, 1734, 1604, 1509, 1473, 1248,
3
-1
+
1
175, 1029, 834, 771 cm ; HRMS (+ESI) m/z: [M+H] Calcd for C H O Br 699.1382;
41 32 6
found 699.1379.
4
-Methoxy-7,8,9-triphenylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; 4fa
Using the general experimental procedure on 4-bromo-7-methoxycoumarin (0.127 g; 0.5
mmol, 1 equiv), diphenylacetylene (0.178 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol,
2
1
0 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-
dioxane (3 mL), compound 4fa was obtained as light brown solid (0.199 g, 75% yield) after
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2
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5
5
5
5
5
5
5
6
purification by flash column chromatography using hexane/EtOAc (9:1) as an eluent; mp: 210-
o
1
212 C; H NMR (500 MHz, CDCl ): δ 7.42 (d, J= 7.4 Hz, 1H), 7.29 (d, J= 7.4 Hz, 1H), 7.23-
3
7
.24 (m, 3H), 7.15-7.18 (m, 2H), 7.00-7.10 (m, 9H), 6.90-6.92 (m, 2H), 6.83-6.85 (m, 2H),
6
.47 (dd, J = 2.6 Hz, J = 8.7 Hz, 1H), 6.26 (d, J= 2.6 Hz, 1H), 4.48 (s, 1H), 3.55 (s, 3H);
1
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
13
1
C{ H} NMR (126 MHz, CDCl ): δ 166.5, 159.5, 154.3, 152.1, 148.8, 145.6, 145.3, 140.3,
3
135.2, 134.9, 134.5, 134.1, 130.0, 129.8, 128.7, 128.6, 128.2, 128.0, 127.9, 127.8, 127.7, 127.3,
1
2
5
27.2, 126.4, 124.3, 122.4, 112.1, 110.7, 101.9, 71.2, 55.2, 48.8; IR (CHCl ): 3417, 2918,
3
-1
+
850, 1754, 1623, 1219, 823, 772 cm ; HRMS (+ESI) m/z: [M+H] Calcd for C H O
3
3
8
27
31.1960; found 531.1964.
4
-Methoxy-12-methyl-7,8,9-tri-p-tolylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one;
4fb
Using the general experimental procedure on 4-bromo-7-methoxycoumarin (0.127 g; 0.5
mmol, 1 equiv), 1,2-di-p-tolylethyne (0.206 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05
2
mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv)
in 1,4-dioxane (3 mL), compound 4fb was obtained as yellow solid (0.226 g, 77% yield) after
purification by flash column chromatography using hexane/EtOAc (9:1) as an eluent; mp: 212-
o
1
2
7
2
14 C; H NMR (500 MHz, CDCl ): δ 7.39 (d, J= 7.8 Hz, 1H), 7.18 (s, 1H), 7.12 (s, 4H),
3
.10 (s, 1H), 6.95 (d, J= 7.9 Hz, 2H), 6.89 (dd, J = 2.1 Hz, J = 8.2 Hz, 5H), 6.81 (d, J= 8.1 Hz,
1
2
H), 6.53 (dd, J = 2.6 Hz, J = 8.7 Hz, 1H), 6.34 (d, J= 2.6 Hz, 1H), 4.50 (s, 1H), 3.62 (s, 3H),
1
2
1
3
1
2.36 (s, 3H), 2.28 (s, 3H), 2.27 (s, 3H), 2.19 (s, 3H); C{ H} NMR (126 MHz, CDCl ): δ
3
1
1
66.9, 159.3, 153.7, 152.1, 147.9, 145.7, 144.9, 139.6, 138.0, 137.2, 136.7, 132.6, 132.5, 131.8,
31.5, 129.8, 129.7, 129.3, 128.9, 128.6, 128.4, 128.3, 126.5, 125.0, 122.0, 111.9, 111.4, 101.8,
71.1, 55.1, 48.8, 21.4, 21.3, 21.2, 21.1 (One peak is missing due to overlap); IR (CHCl ): 3442,
3
-1
3
023, 2920, 2854, 1754, 1621, 1502, 1249, 1159, 1036, 824, 759 cm ; HRMS (+ESI) m/z:
+
[
M+H] Calcd for C H O 587.2586; found 587.2583.
4
2
35
3
4,12-Dimethoxy-7,8,9-tris(4-methoxyphenyl)cyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-
one; 4fc
Using the general experimental procedure on 4-bromo-7-methoxycoumarin (0.127 g; 0.5
mmol, 1 equiv), 1,2-bis(4-methoxyphenyl)ethyne (0.238 g; 1 mmol, 2 equiv), Pd(OAc) (0.012
2
g; 0.05 mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2
equiv) in 1,4-dioxane (3 mL), compound 4fc was obtained as light brown solid (0.260 g, 80%
yield) after purification by flash column chromatography using hexane/EtOAc (4:1) as an
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7
8
9
o
1
eluent; mp: 194-196 C; H NMR (500 MHz, CDCl ): δ 7.39 (d, J= 8.4 Hz, 1H), 7.13 (d, J=
3
8.8 Hz, 2H), 7.07 (d, J= 8.7 Hz, 1H), 6.82-6.92 (m, 7H), 6.51-6.69 (m, 5H), 6.52 (dd, J = 2.6
1
Hz, J = 8.7 Hz, 1H), 6.34 (d, J= 2.6 Hz, 1H), 4.92 (s, 1H), 3.81 (s, 3H), 3.74 (s, 3H), 3.73 (s,
2
1
3
1
3
1
H), 3.69 (s, 3H), 3.63 (s, 3H); C{ H} NMR (126 MHz, CDCl ): δ 166.9, 159.7, 159.3,
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
58.8, 158.4, 158.2, 152.5, 152.0, 147.1, 146.7, 144.2, 138.0, 131.2, 131.0, 129.8, 128.2, 128.1,
127.2, 126.9, 126.5, 122.9, 115.0, 113.6, 113.3, 113.0, 112.0, 111.7, 109.5, 101.7, 71.1, 55.4,
5
1
6
5.2, 55.1, 55.0, 54.9, 49.0; IR (CHCl ): 3440, 2933, 2835, 1753, 1606, 1502, 1247, 1176,
3
-
1
+
030, 835, 759 cm ; HRMS (+ESI) m/z: [M+H] Calcd for C H O 651.2383; found
4
2
35
7
51.2390.
4
-Methyl-7,8,9-triphenylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; 4ga
Using the general experimental procedure on 4-bromo-7-methylcoumarin (0.120 g; 0.5 mmol,
equiv), diphenylacetylene (0.178 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10
1
2
mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-
dioxane (3 mL), compound 4ga was obtained as yellow solid (0.191 g, 74% yield) after
purification by flash column chromatography using hexane/EtOAc (19:1) as an eluent; mp:
o
1
1
81-183 C; H NMR (500 MHz, CDCl ): δ 7.48 (d, J= 7.4 Hz, 1H), 7.36 (d, J= 7.5 Hz, 1H),
3
7.30-7.31 (m, 3H), 7.23-7.25 (m, 2H), 7.05-7.16 (m, 9H), 6.98-7.00 (m, 2H), 6.91-6.93 (m,
1
3
1
2
H), 6.76 (d, J= 8.0 Hz, 1H), 6.61 (s, 1H), 4.57 (s, 1H), 2.12 (s, 3H); C{ H} NMR (126 MHz,
CDCl ): δ 166.7, 154.5, 151.2, 148.7, 145.7, 145.5, 140.4, 138.9, 135.2, 134.9, 134.5, 134.1,
3
1
29.9, 129.8, 128.7, 128.6, 128.2, 128.0, 127.9, 127.8, 127.7, 127.2, 125.7, 125.3, 124.3, 122.3,
117.9, 115.9, 71.4, 48.9, 20.9 (One peak is missing due to overlap); IR (CHCl ): 3420, 2921,
3
-1
+
2
850, 1751, 1622, 1442, 1219, 1155, 822, 771 cm ; HRMS (+ESI) m/z: [M+H] Calcd for
C H O 515.2011; found 515.2007.
3
8
27
2
4,12-Dimethyl-7,8,9-tri-p-tolylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; 4gb
Using the general experimental procedure on 4-bromo-7-methylcoumarin (0.120 g; 0.5 mmol,
1
equiv), 1,2-di-p-tolylethyne (0.206 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10
2
mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-
dioxane (3 mL), compound 4gb was obtained as light brown solid (0.214 g, 75% yield) after
purification by flash column chromatography using hexane/EtOAc (19:1) as an eluent; mp:
o
1
2
1
05-207 C; H NMR (500 MHz, CDCl ): δ 7.26 (dd, J = 1.6 Hz, J = 7.7 Hz, 1H), 7.06 (s,
3 1 2
H), 6.97-7.00 (m, 5H), 6.69-6.82 (m, 9H), 6.60 (d, J= 7.8 Hz, 1H), 6.48 (s, 1H), 4.40 (s, 1H),
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2
2
2
2
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2
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3
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3
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3
3
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3
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4
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5
5
5
6
13
1
2
.21 (s, 3H), 2.13 (s, 3H), 2.11 (s, 3H), 2.02 (s, 3H), 1.96 (s, 3H); C{ H} NMR (126 MHz,
CDCl ): δ 167.0, 153.8, 151.1, 147.8, 145.7, 145.1, 139.7, 138.6, 137.9, 137.1, 136.6, 132.6,
3
1
1
32.5, 131.8, 131.4, 129.8, 129.7, 129.3, 128.9, 128.6, 128.4, 128.3, 125.6, 125.4, 124.9, 121.9,
17.7, 116.6, 71.3, 48.9, 21.3, 21.2, 21.1, 21.0, 20.8 (One peak is missing due to overlap); IR
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
-1
(
CHCl ): 3421, 3023, 2920, 2853, 1752, 1607, 1502, 1454, 1184, 1110, 823, 771 cm ; HRMS
3
+
(+ESI) m/z: [M+H] Calcd for C H O 571.2637; found 571.2635.
4
2
35
2
1
1
2-Methoxy-7,8,9-tris(4-methoxyphenyl)-4-methylcyclopenta[2,3]indeno[1,2-c]chromen-
(13bH)-one; 4gc
Using the general experimental procedure on 4-bromo-7-methylcoumarin (0.120 g; 0.5 mmol,
equiv), 1,2-bis(4-methoxyphenyl)ethyne (0.238 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05
1
2
mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv)
in 1,4-dioxane (3 mL), compound 4gc was obtained as light brown solid (0.247 g, 78% yield)
after purification by flash column chromatography using hexane/EtOAc (4:1) as an eluent;
o
1
mp: 161-163 C; H NMR (500 MHz, CDCl ): δ 7.39 (d, J= 8.4 Hz, 1H), 7.14 (d, J= 8.6 Hz,
3
2
H), 7.08 (d, J= 7.9 Hz, 1H), 6.93 (d, J= 8.7 Hz, 2H), 6.91-6.92 (m, 1H), 6.85 (d, J= 8.7 Hz,
4H), 6.74 (dd, J = 1.0 Hz, J = 8.0 Hz, 1H), 6.69 (d, J= 8.8 Hz, 2H), 6.60-6.64 (m, 4H), 4.51 (s,
1
2
1
3
1
1
H), 3.81 (s, 3H), 3.74 (s, 3H), 3.73 (s, 3H), 3.68 (s, 3H), 2.14 (s, 3H); C{ H} NMR (126
MHz, CDCl ): δ 167.0, 159.7, 158.8, 158.4, 158.2, 152.7, 151.1, 147.1, 146.6, 144.4, 138.7,
3
1
38.0, 131.2, 131.0, 129.8, 128.1, 127.3, 126.9, 125.7, 125.4, 122.8, 117.7, 117.0, 115.0, 113.6,
113.3, 113.0, 109.5, 71.3, 55.4, 55.1, 55.0, 54.9, 49.1, 20.9 (One peak is missing due to
-
overlap); IR (CHCl ): 3421, 2929, 2836, 1751, 1605, 1509, 1247, 1175, 1030, 834, 771 cm
3
1;
HRMS (+ESI) m/z: [M+H] Calcd for C H O 635.2434; found 635.2439.
+
4
2
35
6
1
2-Methoxy-7-(4-methoxyphenyl)-8,9-diphenylcyclopenta[2,3]indeno[1,2-c]chromen-
(13bH)-one; (4ad1) 8,9-bis(4-methoxyphenyl)-7-phenylcyclopenta[2,3]indeno[1,2-
(4ad2) 12-methoxy-8-(4-methoxyphenyl)-7,9-
diphenylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; (4ad ) 7-(3-methoxyphenyl)-9-
1
c]chromen-1(13bH)-one;
3
(
4-methoxyphenyl)-8-phenylcyclopenta[2,3]indeno [1,2-c]chromen-1(13bH)-one; (4ad4)
Using the general experimental procedure on 4-bromocoumarin (0.112 g; 0.5 mmol, 1 equiv),
-methoxy-4-(phenylethynyl)benzene (0.208 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05
1
2
mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv)
in 1,4-dioxane (3 mL), compounds 4ad , 4ad , 4ad & 4ad were obtained as light brown solid
1
2
3
4
(
0.197 g, 70% yield) after purification by flash column chromatography using hexane/EtOAc
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9
o
1
(
4:1) as an eluent; mp: 114-116 C; H NMR (500 MHz, CDCl ): δ 6.81-7.40 (m, 74H), 6.59-
3
6.69 (m, 10H), 4.56 (s, 4H), 3.82 (s, 3H), 3.80 (s, 3H), 3.74 (s, 6H), 3.73 (s, 6H), 3.68 (s, 3H),
1
3
1
3
1
1
.67 (s, 3H); C{ H} NMR (126 MHz, CDCl ): δ 166.7, 166.6 x 2, 166.5, 160.9, 160.1, 160.0,
3
59.1, 158.6, 158.5, 158.4, 154.2, 154.1, 153.7, 153.4, 152.9, 151.4, 151.3, 148.5, 148.4, 147.8,
47.6, 147.4, 147.3, 146.9, 145.3, 145.2, 145.0, 144.9, 141.9, 140.5, 138.5, 135.6, 135.5, 135.3,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
135.2, 134.8, 134.4, 134.3, 131.8, 131.3, 131.2 x 2, 131.1, 130.0, 129.9, 129.8 x 2, 129.7 x 2,
28.6 x 2, 128.2, 128.0, 127.9, 127.8 x 2, 127.7 x 2, 127.6 x 2, 127.5, 127.1 x 2, 127.0, 126.8
x 2, 126.5 x 2, 126.3, 125.7, 125.6 x 2, 124.7 x 2, 124.6 x 2, 124.3 x 2, 123.1, 123.0, 122.2,
22.1, 119.9, 119.8, 119.7, 119.5, 117.6, 117.5, 115.1, 114.4, 113.7, 113.3 x 2, 113.1 x 2, 112.3,
1
1
111.5, 109.6, 71.8, 71.6, 71.5, 71.4, 55.5, 55.1 x 2, 55.0, 54.9, 49.0, 48.9, 48.8 x 2 (Several
peaks are missing due to overlap); IR (CHCl ): 3436, 2922, 2852, 1756, 1606, 1508, 1485,
3
-1
+
1
247, 1219, 1029, 837, 771 cm ; HRMS (+ESI) m/z: [M+H] Calcd for C H O 561.2066;
39 29 4
found 561.2065.
1
2-Methoxy-7-(4-methoxyphenyl)-5-methyl-8,9-diphenylcyclopenta[2,3]indeno[1,2-
c]chromen-1(13bH)-one;
(4bd1)
8,9-bis(4-methoxyphenyl)-5-methyl-7-
(4bd2) 12-methoxy-8-(4-
methoxyphenyl)-5-methyl-7,9-diphenylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one;
phenylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one;
(
4bd ) 7-(3-methoxyphenyl)-9-(4-methoxyphenyl)-5-methyl-8-phenylcyclopenta[2,3]indeno
3
[
1,2-c]chromen-1(13bH)-one; (4bd4)
Using the general experimental procedure on 4-bromo-6-methylcoumarin (0.120 g; 0.5 mmol,
equiv), 1-methoxy-4-(phenylethynyl)benzene (0.208 g; 1 mmol, 2 equiv), Pd(OAc) (0.012
1
2
g; 0.05 mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2
equiv) in 1,4-dioxane (3 mL), compounds 4bd , 4bd , 4bd & 4bd were obtained as brown
1
2
3
4
solid (0.204 g, 71% yield) after purification by flash column chromatography using
o
1
hexane/EtOAc (4:1) as an eluent; mp: 115-117 C; H NMR (500 MHz, CDCl ): δ 7.41 (d, J=
3
7
.3 Hz, 2H), 7.32 (d, J= 8.4 Hz, 2H), 6.73-7.33 (m, 64H), 6.55-6.66 (m, 10H), 6.53 (d, J= 8.4
Hz, 2H), 4.44 (s, 4H), 3.74 (s, 3H), 3.73 (s, 3H), 3.66 (s, 6H), 3.65 (s, 6H), 3.60 (s, 3H), 3.59
1
3
1
(
s, 3H), 2.12 (s, 6H), 2.11 (s, 6H); C{ H} NMR (126 MHz, CDCl ): δ 166.9, 166.8, 166.7 x
3
2
, 161.1, 160.0 x 2, 159.0, 158.6, 158.4 x 2, 154.1, 153.7, 153.4, 152.9, 149.3, 149.2, 148.5,
147.8 x 2, 147.5, 147.4, 146.9, 145.4, 145.3, 145.2, 145.1 x 2, 144.8, 144.7, 141.9, 140.4, 138.4,
1
1
1
35.6, 135.5, 135.3 x 2, 134.9, 134.4 x 2, 134.1, 134.0 x 2, 133.9, 132.8, 131.3, 131.2 x 2,
31.1, 130.0 x 2, 129.8 x 2, 129.7 x 2, 129.4 x 2, 128.6 x 2, 128.2, 128.0, 127.9, 127.8 x 2,
27.7 x 2, 127.6 x 2, 127.4, 127.0, 126.9 x 2, 126.8, 126.6 x 2, 126.1, 125.6, 125.5 x 2, 125.4
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2
2
2
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3
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3
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3
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4
4
4
4
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5
5
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x 2, 123.1, 123.0, 122.2, 122.1, 119.4, 119.3, 119.2, 119.0, 117.3, 117.2, 115.1, 114.3, 113.6,
113.3 x 2, 113.1, 113.0, 112.3, 111.6, 109.5, 71.8, 71.6, 71.5, 71.4, 55.5, 55.1 x 2, 55.0, 54.9,
4
2
9.0 x 2, 48.9 x 2, 21.2, 20.9 x 2 (Several peaks are missing due to overlap); IR (CHCl ): 3421,
3
-1
920, 2853, 1754, 1605, 1506, 1487, 1247, 1217, 1177, 834, 771 cm ; HRMS (+ESI) m/z:
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
[
M+H] Calcd for C H O 575.2222; found 575.2221.
4
0
31
4
5
-Chloro-12-methoxy-7-(4-methoxyphenyl)-8,9-diphenylcyclopenta[2,3]indeno[1,2-
(4dd1) 5-chloro-8,9-bis(4-methoxyphenyl)-7-
c]chromen-1(13bH)-one;
phenylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; (4dd ) 5-Chloro-12-methoxy-8-
2
(4-methoxyphenyl)-7,9-diphenylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; (4dd3)
5
-chloro-7-(3-methoxyphenyl)-9-(4-methoxyphenyl)-8-phenylcyclopenta[2,3]indeno
c]chromen-1(13bH)-one; (4dd4)
Using the general experimental procedure on 4-bromo-6-chlorocoumarin (0.129 g; 0.5 mmol,
equiv), 1-methoxy-4-(phenylethynyl)benzene (0.208 g; 1 mmol, 2 equiv), Pd(OAc) (0.012
[1,2-
1
2
g; 0.05 mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2
equiv) in 1,4-dioxane (3 mL), compounds 4dd , 4dd , 4dd & 4dd were obtained as light
1
2
3
4
brown solid (0.204 g, 69% yield) after purification by flash column chromatography using
o
1
hexane/EtOAc (4:1) as an eluent; mp: 110-112 C; H NMR (500 MHz, CDCl ): δ 7.43 (d, J=
3
7
8
3
1
1
.0 Hz, 2H), 7.34 (d, J= 8.4 Hz, 2H), 6.75-7.26 (m, 62H), 6.64-6.70 (m, 4H), 6.58-6.61 (m,
H), 6.54 (d, J= 8.6 Hz, 2H), 4.47 (s, 4H), 3.73 (s, 3H), 3.71 (s, 3H), 3.64 (s, 6H), 3.63 (s, 6H),
1
3
1
.59 (s, 6H); C{ H} NMR (126 MHz, CDCl ): δ 166.1, 166.0, 165.9 x 2, 160.1 x 2, 159.2,
3
58.7, 158.6, 158.5, 153.6, 153.1, 152.8, 152.6, 152.3, 149.9, 149.8, 148.1, 147.9, 147.3, 147.2,
46.9, 146.8, 146.4, 145.7, 145.6, 145.3, 145.2, 144.9, 144.8, 141.0, 140.8, 138.9, 135.2, 135.1
x 2, 135.0, 134.5, 134.1, 134.0, 132.1, 131.7, 131.3, 131.2 x 2, 131.6, 130.0, 129.9, 129.8,
1
1
1
29.7 x 2, 129.6 x 2, 129.5 x 2, 128.8, 128.6, 128.5, 128.4, 128.0 x 2, 127.9, 127.8, 127.7 x 2,
27.6 x 2, 127.5, 127.3 x 2, 127.2 x 2, 126.4 x 2, 126.2 x 2, 126.0, 125.4, 125.3, 125.2, 124.2,
23.3, 123.2, 122.3, 122.8, 122.1, 121.9, 121.8, 121.7, 119.0, 118.9, 118.8, 115.1, 114.6, 113.7,
113.4, 113.3, 113.1 x 2, 112.5, 112.1, 109.6, 71.6, 71.5, 71.4, 71.2, 55.5, 55.1 x 2, 55.0, 54.9,
4
1
8.7 x 2, 48.5 x 2 (Several peaks are missing due to overlap); IR (CHCl ): 3421, 2927, 2835,
3
-1
+
761, 1605, 1508, 1476, 1248, 1217, 1175, 837, 770 cm ; HRMS (+ESI) m/z: [M+H] Calcd
for C H O Cl 595.1676; found 595.1672.
3
9
28
4
7
,9-Bis(4-fluorophenyl)-8-phenylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; (4ae1)
,9-bis(4-fluorophenyl)-7-phenylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; (4ae2)
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Using the general experimental procedure on 4-bromocoumarin (0.112 g; 0.5 mmol, 1 equiv)
1-fluoro-4-(phenylethynyl)benzene (0.196 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol,
2
1
0 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-
dioxane (3 mL), compound 4ae was obtained as white solid (0.041 g, 15% yield); mp: 171-
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
o
1
73 C and compound 4ae was obtained as off-white solid (0.044 g, 16% yield); mp: 172-174
2
oC; after purification by flash column chromatography using hexane/EtOAc (4:1) as an eluent;
1
For 4ae : H NMR (500 MHz, CDCl ): δ 7.44 (d, J= 7.4 Hz, 1H), 7.38 (d, J= 7.5 Hz, 1H),
1
3
1
3
1
6
.96-7.22 (m, 14H), 6.84-7.88 (m, 3H), 6.78 (t, J= 8.7 Hz, 2H), 4.56 (s, 1H); C{ H} NMR
(
126 MHz, CDCl ): δ 166.2, 162.3 (d, J=247.9 Hz), 161.8 (d, J=247.9 Hz), 154.5, 151.4, 147.8,
3
145.8, 145.4, 139.4, 134.8, 134.0, 131.5 (d, J=8.1 Hz), 131.1 (d, J=3.1 Hz), 130.3 (d, J=8.0
Hz), 130.0 (d, J=3.2 Hz), 129.9, 128.9, 128.8, 128.3, 128.2, 127.6, 125.4, 124.8, 124.5, 122.3,
1
19.0, 117.8, 115.4 (d, J=21.6 Hz), 114.9 (d, J=21.8 Hz), 71.7, 48.7; IR (CHCl ): 3422, 2932,
3
-1
+
2835, 1751, 1603, 1505, 1245, 1173, 831, 771 cm ; HRMS (+ESI) m/z: [M+H] Calcd for
C H F O 537.1666; found 537.1671.
37 23
2
2
1
For 4ae : H NMR (500 MHz, CDCl ): δ 7.43 (d, J= 7.5 Hz, 1H), 7.39 (d, J= 7.6 Hz, 1H),
2
3
7.17-7.23 (m, 4H), 7.09-7.14 (m, 4H), 7.02-7.06 (m, 3H), 6.94-6.99 (m, 3H), 6.82-6.90 (m,
1
3
1
5
H), 4.57 (s, 1H); C{ H} NMR (126 MHz, CDCl ): δ 166.2, 162.3 (d, J=248.0 Hz), 162.0
3
(d, J=247.7 Hz), 154.7, 151.4, 149.0, 145.5, 145.3, 139.2, 134.8, 134.7, 131.7 (d, J=8.0 Hz),
1
1
7
31.5 (d, J=8.1 Hz), 130.2 (d, J=3.4 Hz), 129.9 (d, J=3.1 Hz), 128.9, 128.8, 128.5, 128.4, 128.2,
27.6, 125.4, 124.7, 124.5, 122.2, 118.9, 117.8, 115.2 (d, J=26.8 Hz), 115.0 (d, J=27.0 Hz),
-1
1.7, 48.8; IR (CHCl ): 3425, 2928, 2830, 1751, 1602, 1512, 1252, 1172, 832, 770 cm ;
3
+
HRMS (+ESI) m/z: [M+H] Calcd for C H F O 537.1666; found 537.1670.
3
7
23
2
2
General procedure for the synthesis of spiropentadiene chromanone 3:
',3',4',5'-Tetrakis(4-fluorophenyl)spiro[chromane-4,1'-cyclopentane]-2',4'-dien-2-one; 3af
2
Using the general experimental procedure on 4-bromocoumarin (0.112 g; 0.5 mmol, 1 equiv),
1,2-bis(4-fluorophenyl)ethyne (0.214 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10
2
mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-
dioxane (3 mL), compound 3af was obtained as yellow solid (0.181 g, 63% yield) after
purification by flash column chromatography using hexane/EtOAc (19:1) as an eluent; mp:
o
1
100-102 C; H NMR (500 MHz, CDCl ): δ 7.46 (dd, J = 1.6 Hz, J = 7.7 Hz, 1H), 7.29-7.32
3
1
2
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2
2
2
2
2
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3
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3
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(
m, 1H), 7.21 (td, J = 1.2 Hz, J = 7.5 Hz, 1H), 6.88-6.92 (m, 5H), 6.74-6.82 (m, 12H), 2.96 (s,
1
2
1
3
1
2H); C{ H} NMR (126 MHz, CDCl ): δ 166.7, 162.5 (d, J=248.3 Hz), 161.8 (d, J=247.7
3
Hz), 152.7, 147.3, 142.7, 131.5 (d, J=11.5 Hz), 131.4 (d, J=11.6 Hz), 130.1 (d, J=3.4 Hz),
1
29.6, 129.5 (d, J=3.4 Hz), 125.4, 125.2, 120.0, 118.0, 115.3 (d, J=38.4 Hz), 115.1 (d, J=38.7
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
-1
Hz), 60.8, 34.6; IR (CHCl ): 3400, 2918, 2850, 1768, 1600, 1503, 1220, 1158, 834, 772 cm ;
3
+
HRMS (+ESI) m/z: [M+H] Calcd for C H O F 575.1634; found 575.1642.
3
7
23
2 4
2
',3',4',5'-Tetrakis(4-fluorophenyl)-6-methylspiro[chromane-4,1'-cyclopentane]-2',4'-dien-2-
one; 3bf
Using the general experimental procedure on 4-bromo-6-methylcoumarin (0.120 g; 0.5 mmol,
1
equiv), 1,2-bis(4-fluorophenyl)ethyne (0.214 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05
2
mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv)
in 1,4-dioxane (3 mL), compound 3bf was obtained as white solid (0.191 g, 65% yield) after
purification by flash column chromatography using hexane/EtOAc (19:1) as an eluent; mp:
o
1
2
6
29-231 C; H NMR (500 MHz, CDCl ): δ 7.17 (d, J= 1.4 Hz, 1H), 7.09-7.11 (m, 1H), 6.89-
3
.92 (m, 4H), 6.75-6.83 (m, 13H), 2.92 (s, 2H), 2.38 (s, 3H); 13C{ H} NMR (126 MHz,
1
CDCl ): δ 166.9, 162.1 (d, J=248.4 Hz), 161.8 (d, J=247.7 Hz), 150.7, 147.3, 142.6, 134.8,
3
1
1
3
31.5 (d, J=11.4 Hz), 131.4 (d, J=11.5 Hz), 130.3, 130.1 (d, J=3.3 Hz), 129.6 (d, J=3.4 Hz),
25.3, 119.6, 117.7, 115.2 (d, J=35.7 Hz), 115.1 (d, J=35.8 Hz), 60.8, 34.8, 21.0; IR (CHCl ):
3
-1
+
420, 2921, 2850, 1768, 1600, 1502, 1221, 1158, 832, 771 cm ; HRMS (+ESI) m/z: [M+H]
Calcd for C H O F 589.1791; found 589.1787.
3
8
25
2 4
6
-Fluoro-2',3',4',5'-tetrakis(4-fluorophenyl)spiro[chromane-4,1'-cyclopentane]-2',4'-dien-2-
one; 3cf
Using the general experimental procedure on 4-bromo-6-fluorocoumarin (0.122 g; 0.5 mmol,
equiv), 1,2-bis(4-fluorophenyl)ethyne (0.214 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05
1
2
mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv)
in 1,4-dioxane (3 mL), compound 3cf was obtained as white solid (0.183 g, 62% yield) after
purification by flash column chromatography using hexane/EtOAc (19:1) as an eluent; mp:
o
1
1
73-175 C; H NMR (500 MHz, CDCl ): δ 7.11 (dd, J = 2.9 Hz, J = 8.5 Hz, 1H), 6.99-7.03
3 1 2
m, 1H), 6.87-6.91 (m, 4H), 6.76-6.85 (m, 13H), 2.96 (s, 2H); 13C{ H} NMR (126 MHz,
1
(
CDCl ): δ 166.2, 162.2 (d, J=248.8 Hz), 161.9 (d, J=247.9 Hz), 159.5 (d, J=244.5 Hz), 148.8
3
(d, J=2.2 Hz), 149.6, 143.1, 131.4 (d, J=15.3 Hz), 131.4 (d, J=15.4 Hz), 129.8 (d, J=3.3 Hz),
1
29.3 (d, J=3.4 Hz), 122.0 (d, J=7.3 Hz), 119.5 (d, J=8.3 Hz), 116.7 (d, J=23.7 Hz), 115.4 (d,
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J=47.8 Hz), 115.2 (d, J=47.7 Hz), 111.4 (d, J=24.2 Hz), 60.7, 34.1; IR (CHCl ): 3420, 2923,
3
-1
+
2853, 1773, 1600, 1503, 1221, 1158, 833, 771 cm ; HRMS (+ESI) m/z: [M+H] Calcd for
C H O F 593.1540; found 593.1536.
37 22
2 5
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
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4
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5
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5
5
5
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0
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0
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0
2
',3',4',5'-Tetrakis(4-fluorophenyl)-7-methoxyspiro[chromane-4,1'-cyclopentane]-2',4'-dien-2-
one; 3ff
Using the general experimental procedure on 4-bromo-7-methoxycoumarin (0.127 g; 0.5
mmol, 1 equiv), 1,2-bis(4-fluorophenyl)ethyne (0.214 g; 1 mmol, 2 equiv), Pd(OAc) (0.012
2
g; 0.05 mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2
equiv) in 1,4-dioxane (3 mL), compound 3ff was obtained as yellow solid (0.200 g, 66% yield)
after purification by flash column chromatography using hexane/EtOAc (19:1) as an eluent;
o
1
mp: 170-172 C; H NMR (500 MHz, CDCl ): δ 7.29 (d, J= 8.6 Hz, 1H), 6.86-6.89 (m, 4H),
3
1
3
1
6.76-6.83 (m, 13H), 6.44 (d, J= 2.6 Hz, 1H), 3.80 (s, 3H), 2.92 (s, 2H); C{ H} NMR (126
MHz, CDCl ): δ 166.8, 162.1 (d, J=248.2 Hz), 161.8 (d, J=247.5 Hz), 160.3, 153.6, 147.5,
3
1
1
42.4, 131.5 (d, J=11.1 Hz), 131.4 (d, J=11.2 Hz), 130.1 (d, J=3.3 Hz), 129.7 (d, J=3.5 Hz),
26.2, 115.2 (d, J=41.3 Hz), 115.1 (d, J=41.3 Hz), 112.2, 111.2, 102.4, 60.3, 55.5, 34.7; IR
-1
(CHCl ): 3414, 2920, 2850, 1767, 1601, 1503, 1220, 1158, 834, 772 cm ; HRMS (+ESI)
3
+
m/z: [M+H] Calcd for C H O F 605.1740; found 605.1748.
3
8
25
3 4
2
',3',4',5'-Tetrakis(4-fluorophenyl)-7-methylspiro[chromane-4,1'-cyclopentane]-2',4'-dien-2-
one; 3gf
Using the general experimental procedure on 4-bromo-7-methylcoumarin (0.120 g; 0.5 mmol,
1
equiv), 1,2-bis(4-fluorophenyl)ethyne (0.214 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05
2
mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv)
in 1,4-dioxane (3 mL), compound 3gf was obtained as yellow solid (0.188 g, 64% yield) after
purification by flash column chromatography using hexane/EtOAc (19:1) as an eluent; mp:
o
1
1
01-103 C; H NMR (500 MHz, CDCl ): δ 7.30 (d, J= 8.6 Hz, 1H), 7.01 (dd, J = 0.9 Hz, J =
3 1 2
7.8 Hz, 1H), 6.88-6.91 (m, 4H), 6.76-6.82 (m, 12H), 6.72 (s, 1H), 2.92 (s, 2H), 2.35 (s, 3H);
1
3
1
C{ H} NMR (126 MHz, CDCl ): δ 166.9, 162.1 (d, J=248.3 Hz), 161.7 (d, J=247.6 Hz),
3
1
52.6, 147.4, 142.6, 140.0, 131.4 (d, J=10.1 Hz), 131.4 (d, J=10.0 Hz), 130.1 (d, J=3.2 Hz),
29.7 (d, J=3.4 Hz), 126.1, 125.1, 120.0, 118.2, 116.7, 115.2 (d, J=37.5 Hz), 115.0 (d, J=37.7
1
Hz), 60.6, 34.7, 21.1; IR (CHCl ): 3421, 2920, 2853, 1773, 1600, 1502, 1222, 1158, 833, 770
3
-1
+
cm ; HRMS (+ESI) m/z: [M+H] Calcd for C H O F 589.1791; found 589.1788.
3
8
25
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,8,9-Triphenylcyclopenta[2,3]indeno[1,2-c]chromen-1(13bH)-one; 4aa
Using the general experimental procedure on 4-bromocoumarin (0.112 g; 0.5 mmol, 1 equiv),
diphenylacetylene (0.178 g; 1 mmol, 2 equiv), 1,2-bis(4-(trifluoromethyl)phenyl)ethyne (0.314
g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-dioxane (3 mL), compound 4aa was
obtained as white solid (0.182 g, 73% yield) after purification by flash column chromatography
o
1
using hexane/EtOAc (19:1) as an eluent; mp: 218-220 C; H NMR (500 MHz, CDCl ): δ
3
7.45 (d, J= 7.4 Hz, 1H), 7.37 (d, J= 7.7 Hz, 1H), 7.24-7.32 (m, 6H), 6.90-7.16 (m, 14H), 6.81
1
3
1
(dd, J = 1.2 Hz, J = 8.0 Hz, 1H), 4.60 (s, 1H); C{ H} NMR (126 MHz, CDCl ): δ 166.4,
1
2
3
1
54.4, 151.4, 148.8, 145.7, 145.6, 140.7, 135.1, 134.9, 134.4, 130.4, 129.9, 129.8, 128.8, 128.7,
128.6, 128.2, 128.0, 127.9, 127.8, 127.7, 127.4, 127.3, 125.6, 124.7, 124.4, 122.3, 119.2, 117.7,
-
1
7
1.6, 48.8; IR (CHCl ): 3421, 2928, 2852, 1757, 1605, 1508, 1487, 1219, 836, 771 cm ;
3
+
HRMS (+ESI) m/z: [M+H] Calcd for C H O 501.1855; found 501.1854.
3
7
25
2
12-Methoxy-9-(4-methoxyphenyl)-7,8-diphenylcyclopenta[2,3]indeno[1,2-c]chromen-
(13bH)-one; (4aac) 7,8-bis(4-methoxyphenyl)-9-phenylcyclopenta[2,3]indeno[1,2-
c]chromen-1(13bH)-one; (4aca)
1
Using the general experimental procedure on 4-bromocoumarin (0.112 g; 0.5 mmol, 1 equiv),
diphenylacetylene (0.178 g; 1 mmol, 2 equiv), 1,2-bis(4-methoxyphenyl)ethyne (0.238 g; 1
mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10 mol%), TFP (0.023 g; 0.1 mmol, 20 mol%),
2
and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-dioxane (3 mL), compounds 4aac & 4aca were
obtained as light brown solid (0.196 g, 70% yield) after purification by flash column
o
1
chromatography using hexane/EtOAc (4:1) as an eluent; mp: 126-128 C; H NMR (500 MHz,
CDCl ): δ 7.47 (d, J= 7.4 Hz, 1H), 7.41 (d, J= 8.4 Hz, 1H), 7.25-7.36 (m, 8H), 7.21 (dd, J =
3
1
1
.4 Hz, J = 7.8 Hz, 1H), 7.12-7.16 (m, 5H), 7.00-7.09 (m, 8H), 6.80-6.98 (m, 13H), 6.61-6.68
2
1
3
1
(m, 5H), 4.57 (s, 1H), 4.55 (s, 1H), 3.80 (s, 3H), 3.74 (s, 3H), 3.73 (s, 3H), 3.68 (s, 3H); C{ H}
NMR (126 MHz, CDCl ): δ 166.6, 166.5, 159.9, 158.9, 158.5, 158.4, 153.8, 153.3, 151.4,
3
1
51.3, 147.8, 147.7, 147.3, 145.9, 145.3, 144.3, 140.9, 138.0, 135.3, 135.1, 134.7, 134.3, 131.2,
131.0, 130.0, 129.9, 129.8, 128.7, 128.6, 128.5, 128.2, 127.9, 127.8 x 2, 127.7, 127.1 x 2, 126.9,
1
1
26.6, 125.7, 125.6, 124.3, 123.0, 122.2, 119.8, 119.7, 117.6, 117.5, 115.1, 113.7, 113.4, 113.1,
09.6, 71.6, 71.5, 55.5, 55.1, 55.0, 54.9, 48.9, 48.8 (Several peaks are missing due to overlap);
IR (CHCl ): 3427, 2924, 2853, 1757, 1606, 1511, 1483, 1247, 1210, 1175, 1029, 837, 769 cm-
3
1
+
; HRMS (+ESI) m/z: [M+H] Calcd for C H O 561.2066; found 561.2068.
3
9
29
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2',3',4',5'-Tetrakis(4-fluorophenyl)spiro[chromane-4,1'-cyclopentane]-2',4'-dien-2-one-3-d;
3
af-(D)
Using the general experimental procedure on 4-bromocoumarin (0.112 g; 0.5 mmol, 1 equiv),
,2-bis(4-fluorophenyl)ethyne (0.214 g; 1 mmol, 2 equiv), Pd(OAc) (0.012 g; 0.05 mmol, 10
1
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1
1
1
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1
1
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0
1
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0
1
2
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8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
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8
9
0
1
2
3
4
5
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7
8
9
0
1
2
mol%), TFP (0.023 g; 0.1 mmol, 20 mol%), and KOAc (0.098 g; 1 mmol, 2 equiv) in 1,4-
dioxane (3 mL) and D O (10.0 µL, 0.5 mmol), compound 3af-(D) was obtained as yellow
2
solid (0.173 g, 60% yield) after purification by flash column chromatography using
o
1
hexane/EtOAc (19:1) as an eluent; mp: 108-110 C; H NMR (500 MHz, CDCl ): δ 7.43 (dd,
3
J = 1.5 Hz, J = 7.7 Hz, 1H), 7.29-7.32 (m, 1H), 7.20 (td, J = 1.2 Hz, J = 7.5 Hz, 1H), 6.88-
1
2
1
2
1
3
1
6
.92 (m, 5H), 6.74-6.83 (m, 12H), 2.95 (d, J=6.4 Hz, 1H); C{ H} NMR (126 MHz, CDCl ):
3
δ 166.7, 162.1 (d, J=248.4 Hz), 161.9 (d, J=247.6 Hz), 152.7, 147.3 (m), 142.7 (t, J=6.5 Hz),
131.5 (d, J=11.9 Hz), 131.4 (d, J=11.9 Hz), 130.0 (d, J=4.7 Hz), 129.7, 129.6 (d, J=3.2 Hz),
1
3
25.4, 125.2, 120.0, 118.0, 115.3 (d, J=38.8 Hz), 115.1 (d, J=38.6 Hz), 60.7 (t, J=7.9 Hz),
-1
4.6; IR (CHCl ): 3407, 2922, 2853, 1767, 1604, 1507, 1218, 1159, 832, 771 cm ; HRMS
3
+
(
+ESI) m/z: [M+H] Calcd for C H DO F 576.1697; found 576.1696.
3
7
22
2 4
ASSOCIATED CONTENT
Supporting Information
1
13
Copies of NMR ( H and C), HRMS spectra and X-ray data for compound 4aa and 4ba (CIF).
This material is available free of charge via the internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
gogoipranj@yahoo.co.uk
ACKNOWLEDGMENT
We are grateful to the Director, CSIR-NEIST, Jorhat, India, for his interest in this work and
facilities. A.S. and H.H. acknowledge the DST, New Delhi, for DST-Inspire Fellowship
Grants. M.S. acknowledges the DST-SERB for financial assistance in the form of NPDF.
REFERENCES
(
1) (a) Zhang, Y. L.; Ge, H. M.; Zhao, W.; Dong, H.; Xu, Q.; Li, S. H.; Li, J.; Zhang, J.; Song,
Y. C.; Tan, R. X. Unprecedented Immunosuppressive Polyketides from Daldinia
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