Diversity-Oriented Synthesis of Spirocyclohexene Indane-1,3-diones and Coumarin-Fused Cyclopentanes via an Organobase-Controlled Cascade Reaction

Article abstract of DOI:10.1002/adsc.202000597

An organobase-controlled, divergent cascade reaction to construct spirocyclohexene indane-1,3-diones and coumarin-fused cyclopentanes is reported. The cascade reaction is triggered by the 1,6-addition of 3-homoacylcoumarins to the indanedione-derived acce

Full text of DOI:10.1002/adsc.202000597

Title: Diversity-Oriented Synthesis of Spirocyclohexene Indane-1,3-
diones and Coumarin-Fused Cyclopentanes via an Organobase-
Controlled Cascade Reaction
Authors: Min Wang, Ping-Yao Tseng, Woei-Jye Chi, Sundaram
Suresh, Athukuri Edukondalu, Yi-Ru Chen, and Wenwei Lin
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content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.202000597
Link to VoR: https://doi.org/10.1002/adsc.202000597

10.1002/adsc.202000597
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.202((will be filled in by the editorial staff))
Diversity-Oriented Synthesis of Spirocyclohexene Indane-1,3-
diones and Coumarin-Fused Cyclopentanes via an Organobase-
Controlled Cascade Reaction
Min Wang,a,† Ping-Yao Tseng,a,† Woei-Jye Chi,a,† Sundaram Suresh,a Athukuri
Edukondalu,a Yi-Ru Chena and Wenwei Lina,*
a
Department of Chemistry, National Taiwan Normal University, 88, Sec. 4, Tingchow Road, Taipei 11677, Taiwan,
R.O.C. Fax: (+886)-2-2932-4249; Email: wenweilin@ntnu.edu.tw
†
These authors contributed equally.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. An organobase-controlled, divergent cascade
reaction to construct spirocyclohexene indane-1,3-diones and
coumarin-fused cyclopentanes is reported. The cascade
reaction is triggered by the 1,6-addition of 3-
homoacylcoumarins to the indanedione-derived acceptors
and further regio/chemoselective reaction that preferentially
resulted in spiro systems and fused cyclopentanes in a
diversity-oriented manner. The 1,6-addition/aldol and 1,6-
addition/vinylogous Michael addition cascade processes
were controlled by different base/solvent systems to the
predominant formation of one of the two carbocyclic
compounds.
Keywords: Diversity-oriented synthesis; 1,6-addition; aldol
reaction; vinylogous Michael addition; spiro and fused
systems
potential to construct a C-C bond at remote γ-
position.[8] The difficult control of regioselectivity is
a major challenge in vinylogous Michael addition and
1,6-addition reactions. Comprising both of these two
reactions in a single cascade is the most challenging
task and the development of those cascade reactions
has attracted great interest.
Introduction
Diversity-oriented synthesis via an organocatalytic
approach offers a cost-effective strategy to access
vast libraries of bioactive molecules.[1] The
generation of molecular diversity and complexity
plays a crucial role in drug discovery to ascertain a
variety of structurally diverse compounds.[2]
Synthesis of spiro/fused systems is a topic of recent
interest because of their numerous applications in
medicinal chemistry.[3] In recent years, elegant
methods were reported for cascade reactions initiated
by 1,6-addition to generate complex structural
motifs.[4] Competing from the 1,4-addition reaction,
facilitation of 1,6-addition and further cascade
reaction is a great challenge in synthetic chemistry
due to the presence of more reactive β-position in
extended conjugation.[5] A few strategies have been
adopted to overcome such complications, such as
increasing steric crowding at the β-position or by
activating δ-position with a suitable catalyst.[6] The
LUMO-lowering strategy has also been one of the
most frequently employed activation modes to realize
1,6-addition reactions.[7] On the other hand,
vinylogous Michael addition reaction has long
attracted the attention of synthetic chemists due to the
Indanedione-derived
spiro
six-membered
carbocycles were found in many natural products and
bioactive molecules, most of those are generated via
1,4-addition reactions of 1,3-indanedione systems.[9]
Several conjugated systems were found as acceptors
in the 1,6-addition reaction to activate a remote δ-
position.[10] However, 1,3-indanedione bearing an
extended conjugation was rarely explored as an
acceptor in 1,6-addition initiated cascade reactions.[11]
On the other hand, coumarin and its derivatives are
privileged heterocyclic scaffolds, and their numerous
applications have been found in medicinal and
materials
chemistry.[12]
Furthermore,
these
compounds tend to show diverse reactivity, which
can be tuned by proper functionalization.[13] Owing to
their immense biological activities and their
applications in medicinal chemistry (Figure 1),[14] the
development of an efficient method that could
1
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10.1002/adsc.202000597
Advanced Synthesis & Catalysis
provide both of the spiro and fused systems is highly
desirable.
homoacylcoumarin as an all-carbon 1,3-dipole
precursor with 2-arylidene-1,3-indanedione (Scheme
1).[15] In continuation of our efforts for the
development of novel cascade reactions,[16] we
envisioned that complex structural motifs could be
synthesized via an organocatalytic cascade strategy
initiated by 1,6-addition, and that could turn into a
divergent synthesis of spiro and fused carbocycles. In
this context, we report
a
diversity-oriented
construction of spirocyclohexene indane-1,3-diones
and coumarin-fused cyclopentanes in good yields
Figure 1. Natural products with spirocyclic 1,3-
indanedione and coumarin-fused cyclopentane moieties
with
high
diastereoselectivities
from
3-
homoacylcoumarin and 1,3-indanedione-derived 1,6-
acceptor as reacting partners via an organobase-
controlled cascade reaction.
Recently, we have reported a (3+2) cycloaddition
reaction for the generation of coumarin/indanedione-
fused spirocyclopentane derivatives by employing 3-
Scheme 1. (a) Synthesis of coumarin/indandione-fused spirocyclopentanes (b) Our design for the synthesis
of spiro and fused systems.
reaction. Thus, the substrate 2a has been designed as
a model 1,6-acceptor for our studies.
Initially, we have examined the reaction with 3-
Results and Discussion
homoacylcoumarin 1a and 2-(3-phenylallylidene)-
1,3-indanedione
5
in the presence of 1,4-
diazabicyclo[2.2.2]octane (DABCO) at 30 °C. It was
found that a double Michael cascade reaction took
place to generate compound 6 in 36% yield (Scheme
2). To realize our objective, we envisioned that if we
could incorporate a group at the more reactive β-
position, the nucleophile would be possible to attack
at δ-position and that would further lead to a cascade
Scheme 2. Double Michael addition reaction of 3-
homoacylcoumarin 1a with 5.
2
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10.1002/adsc.202000597
Advanced Synthesis & Catalysis
Accordingly, we have carried out the reaction with
conditions were screened with different bases, we
have found the formation of two types of products in
a few cases. These results opened up the possibility
of diversity-oriented synthesis by altering the reaction
conditions. Further optimization of the reaction using
Et3N as a base furnished the products 3aa and 4aa in
27% and 5% yields in EtOAc (entry 14). To our
surprise, the reaction in acetone solvent afforded the
products 3aa and 4aa in 20% and 50% yields,
respectively (entry 15). The screening of solvents,
temperature and utilizing dry solvents revealed that
the reaction in CH3CN at 40 °C furnished the fused
ring systems in good yields (entries 16–21). Finally,
the optimal conditions for the selective synthesis of
products 3aa and 4aa were determined as listed in
entries 12 and 17, respectively. Therefore, the
3-homoacylcoumarin derivative 1a and 1,3-
indanedione-derived 1,6-acceptor 2a in the presence
of DABCO in CHCl3 at 30 °C. The products 3aa and
4aa were observed in 24% yield and a trace amount
of yield, respectively (Table 1, entry 1). To optimize
the reaction conditions, different bases and various
solvents were screened (entries 2–10). Notably, the
strong bases such as 1,8-diazabicyclo[5.4.0]undec-7-
ene (DBU) and 1,1,3,3-tetramethylguanidine (TMG)
employed in the reaction conditions for the efficient
deprotonation of 3-homoacylcoumarin, but only trace
amount of desired products 3aa and 4aa were found
after 48–60 h (entries 3 and 4). Delightfully, product
3aa was obtained in 61% yield along with a trace
amount of product 4aa using 4-dimethylamino
pyridine (DMAP) as a base in chlorobenzene or
EtOAc as solvent (entries 7 and 8). The yield of the
product 3aa was further increased to 73% by using
dry EtOAc as solvent under anhydrous conditions
(entry 11). Significantly, by employing the 1.2 equiv
of 2a was found to furnish the desired product 3aa in
84% yield in a 1,6-addition/aldol cascade reaction
(entry 12). We have also found that raising the
reaction temperature to 50 °C did not improve the
yield of the product (entry 13). When the reaction
outcome
of
1,6-addition/aldol
and
1,6-
addition/vinylogous Michael addition cascade
reactions can be tuned by appropriate selection of the
reaction conditions from one of the DMAP/EtOAc
and Et3N/CH3CN systems. The structures of the
compounds 3aa and 4aa were further confirmed by
X-ray diffraction analysis (see Supporting
Information for detailed optimization and crystal
data).[17]
Table 1. Optimization of the reaction conditions.[a]
Entry
Base
Solvent
T (°C)
t (h)
3aa/4aa (%)[b]
1
2
3
4
5
6
7
8
DABCO
DIPEA
DBU
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
toluene
PhCl
30
30
30
30
30
30
30
30
30
30
30
30
50
30
30
30
40
40
40
40
40
60
60
48
60
60
60
60
60
60
60
84
84
48
60
60
84
60
60
60
72
60
24/trace
23/trace
trace/trace
trace/6
38/trace
40/trace
61/trace
61/trace
53/trace
39/trace
73/trace
84[e]/trace
70/8
27/5
20/50
10/53
10/65
13/trace
16/trace
16/50
TMG
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
EtOAc
THF
9
10
11[c]
12[c,d]
13[c,d]
14
15
16
17
18
19
20
21[f]
CH3CN
EtOAc
EtOAc
EtOAc
EtOAc
acetone
CH3CN
CH3CN
CHCl3
EtOAc
acetone
CH3CN
14/47
3
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10.1002/adsc.202000597
Advanced Synthesis & Catalysis
[a]Unless otherwise specified, all reactions were carried out using 1a (0.1 mmol), 2a (1.0 equiv), and
1
base (20 mol%) in the given solvent (0.5 mL). [b]Yield was determined by H NMR analysis of the
crude reaction mixture using Ph3CH as an internal standard. [c]The reaction was carried out using dry
EtOAc as solvent under argon. [d] 1.2 equiv of 2a was used. [e]Isolated yield of 3aa. [f]The reaction was
carried out using dry CH3CN as a solvent.
Table 2. Substrate scope of 1,6-addition/aldol cascade reaction.[a,b]
Entry
R1/R2
R3
t (h)
3 (%)[c]
1
2
3
4
5
6
7
8
H/Ph (1a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
84
72
252
168
240
48
96
84
240
72
240
72
84 (3aa)
60 (3ba)
59 (3ca)
66 (3da)
43 (3ea)
trace (3fa)
34 (3ga)
45 (3ha)
20 (3ia)
66 (3ja)
58 (3ab)
76 (3ac)
85 (3ad)
79 (3ae)
74 (3af)
20 (3ag)
6-Cl/Ph (1b)
6-Br/Ph (1c)
6-OMe/Ph (1d)
7-OMe/Ph (1e)
8-OMe/Ph (1f)
6,8-Cl2/Ph (1g)
H/4-Cl-Ph (1h)
H/4-OMe-Ph (1i)
H/CH3 (1j)
H/Ph (1a)
H/Ph (1a)
H/Ph (1a)
H/Ph (1a)
9
Ph (2a)
Ph (2a)
10
11
12
13
14
15
16
2-Cl-Ph (2b)
3-Cl-Ph (2c)
4-Cl-Ph (2d)
4-Br-Ph (2e)
4-NO2-Ph (2f)
4-OMe-Ph (2g)
84
72
60
240
H/Ph (1a)
H/Ph (1a)
[a]Unless otherwise specified, all reactions were carried out using 1 (0.2 mmol), 2 (1.2 equiv), and
DMAP (20 mol%) in dry EtOAc (1.0 mL) under argon and stirred at 30 °C. [b]Trace amount of product
1
4 was determined by H NMR analysis of the crude reaction mixture using Ph3CH as an internal
standard in all the cases. [c]Isolated yield of the product 3.
Having established the optimal conditions, the
substrate scope of spirocyclohexene indane-1,3-
diones 3 was further investigated (Table 2).
Examination of different substituents (R1 and R2) of
3-homoacylcoumarin 1 for the reaction with 2a
afforded the desired products 3 in moderate to good
yields with high diastereoselectivities. The electronic
properties of R1 substituents on the coumarin ring did
not follow any trend. For example, 6-Cl, 6-Br, and 6-
OMe groups on the coumarin ring provided desired
products up to 59–66% yields, albeit with different
rates of the reaction (entries 2–4). However, the
position of substituent on the coumarin ring has a
significant impact on the reaction outcome. The
coumarin derivatives bearing 7-OMe, 8-OMe, and
6,8-Cl2 substituents on the coumarin ring reacted with
2a to afford the corresponding products in low to
moderate yields (entries 5–7). Furthermore, we have
carried out the reactions of different R2 substitutions
of the coumarin 1 with 2a under the optimized
conditions. A substrate 1h with chloro group at para-
position of the aryl ring is more efficient than the
substrate 1i bearing methoxy group (entries 8 and 9).
The coumarin derivative with methyl (R2) group 1j
also well-tolerated, and the desired product 3ja was
obtained in 66% yield (entry 10).
Furthermore, indanedione-derived acceptors 2
bearing different R3 substitutions were also examined
with 1a in 1,6-addition/aldol cascade reaction.
Substrates 2c–2f with electron-withdrawing R3
groups provided the products 3ac–3af in good yields
as compared with the substrate 2g bearing 4-OMe
(R3) group, irrespective of their position (entries 11–
15). Interestingly, substrate 2b with chloro group at
the ortho-position of the aryl ring also afforded the
corresponding product 3ab in 58% yield under the
reaction conditions (entry 11). Along with the desired
products 3 in DMAP/EtOAc system, the formation of
a trace amount of product 4 was observed in all the
reactions.
Next, we investigated the substrate scope of 1,6-
addition/vinylogous Michael addition adducts under
the optimal conditions (Table 1, entry 17). A series of
coumarin-fused cyclopentanes 4 was generated, and
4
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10.1002/adsc.202000597
Advanced Synthesis & Catalysis
the results are shown in Table 3. Substrates with
electron-withdrawing R1 groups at coumarin ring 1b
and 1c efficiently facilitated the reaction to afford the
desired fused adducts in good yields when compared
with substrates bearing electron-donating groups 1d–
1f, regardless of their position (entries 2–6). Again
substrate having 8-OMe on coumarin ring shows a
poor reactivity under the optimized conditions (entry
6). The substrates bearing an electron-donating group
as R1 substituent would prevent the intramolecular
Michael addition reaction by enhancing the electron
density at the reactive site. As a result, the lower
yield of the product 4 and lower 4/3 ratios were
observed when substrates with electron-releasing
groups were employed (entries 4 and 5). The reaction
of coumarin with different acyl R2 substitutions also
reacted well with 2a and furnished the corresponding
products 4ha–4ja in up to 60% yields (entries 8–10).
The substrate bearing R2 as an electron-withdrawing
group would enhance the reactivity of the carbonyl
group, which may facilitate the intramolecular aldol
reaction to give the product 3. This could contribute
to the observed lower 4/3 ratios (entry 8).
addition/vinylogous Michael addition cascade
reaction. Substrates with electron-withdrawing
groups at the ortho, meta, and para positions were
well-tolerated and afforded the corresponding
products 4ab–4af in up to 65% yields. Based on our
observation, the sterically hindered R3 substituent
may favour the formation of product 4. In the cases of
para-substituted R3 substrates, less steric hindrance
observed in the reacting model and that favours the
formation of products 3, which results in the lower
4/3 ratios (entries 13-15). However, the electron-
donating 4-OMe substituent 2g did not provide the
desired product under the optimal reaction conditions.
Besides the desired products 4, 4% to 25% yields of
the spiro compounds 3 were observed as minor
products in all the cases. The cascade reactions under
Et3N catalysis gave the corresponding mixture of
products (3 and 4) in good yields. However, the
selective formation of fused products 4 was moderate
due to the aromatic-like character of the coumarin
ring, which would prevent the addition of
nucleophilic vinylogous enolate to the coumarin ring
in an 1,4-addition manner.
Furthermore,
different
indanedione
R3
substitutions were also tested with 1a for the 1,6-
Table 3. Substrate scope of 1,6-addition/vinylogous Michael addition cascade reaction.[a]
Entry
R1/R2
R3
t (h)
4[b] (%)
3[c] (%)
1
2
3
4
5
6
7
8
H/Ph (1a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
60
52
48
56
56
72
52
56
56
60
60
96
56
48
48
48
63 (4aa)
75 (4ba)
77 (4ca)
42 (4da)
34 (4ea)
trace (4fa)
45 (4ga)
44 (4ha)
60 (4ia)
47 (4ja)
49 (4ab)
65 (4ac)
45 (4ad)
54 (4ae)
41 (4af)
nr
11 (3aa)
4 (3ba)
9 (3ca)
15 (3da)
20 (3ea)
trace (3fa)
12 (3ga)
23 (3ha)
7 (3ia)
16 (3ja)
7 (3ab)
11 (3ac)
24 (3ad)
25 (3ae)
19 (3af)
nr
6-Cl/Ph (1b)
6-Br/Ph (1c)
6-OMe/Ph (1d)
7-OMe/Ph (1e)
8-OMe/Ph (1f)
6,8-Cl2/Ph (1g)
H/4-Cl-Ph (1h)
H/4-OMe-Ph (1i)
H/CH3 (1j)
H/Ph (1a)
H/Ph (1a)
H/Ph (1a)
H/Ph (1a)
9
Ph (2a)
Ph (2a)
10
11
12
13
14
15
16
2-Cl-Ph (2b)
3-Cl-Ph (2c)
4-Cl-Ph (2d)
4-Br-Ph (2e)
4-NO2-Ph (2f)
4-OMe-Ph (2g)
H/Ph (1a)
H/Ph (1a)
[a]Unless otherwise specified, all reactions were carried out using 1 (0.2 mmol), 2 (1.0 equiv), and Et3N
(20 mol%) in CH3CN (1.0 mL) and stirred at 40 °C (Some of the reactions were scaled up to 0.8 mmol
due to the moderate yields of 4). [b]Isolated yield of the product 4. [c]Yield of the product 3 was
determined by 1H NMR analysis of the crude reaction mixture using Ph3CH as an internal standard. nr:
no reaction.
5
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10.1002/adsc.202000597
Advanced Synthesis & Catalysis
Furthermore, the indane-1,3-dione derivative
would provide a common intermediate A for both the
bearing a phenyl group at β-position 7 was tested for
its reactivity towards the construction of the
corresponding spiro and fused compounds. Although
the reaction under DMAP catalysis did not furnish
the expected spiro product, the corresponding fused
product 8 was obtained in only 20% yield in the
presence of Et3N when increasing the catalyst loading
to 40 mol% (Scheme 3). It indicates that the strong
electron-withdrawing group at β-position would
facilitate the reaction more efficiently to afford the
desired products in good yields.
1,6-addition/aldol
and
1,6-addition/vinylogous
Michael addition cascade reactions. On the one hand,
deprotonation of intermediate by DMAP,
A
corresponding conjugate acid would engage with
dienolate which is resulted from A, to provide an
intermediate B. Further, a regio and chemoselective
intramolecular aldol reaction of intermediate B leads
to a desired spirocyclic product 3. On the other hand,
in the presence of Et3N, the intermediate A would
form dienolate, and that would associate with
respective conjugate acid to generate intermediate C.
An intramolecular vinylogous Michael addition upon
intermediate C results in the desired product 4 in
regio and chemoselective manner under the reaction
conditions. Although the regio-selectivity observed in
the second step is not clear, it could be attributed to
the use of different base and solvent systems. The
respective conjugate acids of DMAP and Et3N would
have different hydrogen-bonding interactions
accompanied by steric hindrance with a key dienolate
intermediate, which would lead to two different
transition states and result in the formation of
Scheme 3. Reactions of indane-1,3-dione 7 bearing phenyl
group at β-position with 1a.
products in
a
divergent manner. However,
chemoselectivity would be controlled by the active α
and γ positions of dienolate intermediate to provide
favoured ring systems over unfavoured ones (6
membered over 7 and 5 membered over 4).
On the basis of the results, a plausible reaction
mechanism is illustrated in Scheme 4. The reaction
initiated by 1,6-addition of 3-homoacylcoumarin 1 to
the indanedione derivative 2 in the presence of a base
Scheme 4. Plausible mechanism.
6
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10.1002/adsc.202000597
Advanced Synthesis & Catalysis
Scheme 5. Gram-scale synthesis of 3aa, 4aa, and 4ca.
To demonstrate the feasibility of the cascade
or controlled by the substrate or the catalyst.[18,19]
Therefore, the diversity-oriented cascade reactions
described here could have good potential to generate
molecular diversity and complex structures in organic
synthesis.
reactions, we also carried out the gram-scale
reactions for the synthesis of spiro and fused
carbocyclic systems. The desired products 3aa, 4aa,
and 4ca were obtained in more substantial quantities
with similar efficiency and selectivity as shown in
Scheme 5. Furthermore, we tested our protocol in an
asymmetric version under cinchona-alkaloid derived
hydrogen-bonding catalyst reaction conditions.
Unfortunately, the efforts to optimize the reaction
under various conditions gave the inferior results in
our hand (see SI for the experimental details). The
cascade reaction of 1a with 2a in CHCl3 has been
examined in the presence of HQN-catalyst [(R)-
((1S,2S,4S,5R)-5-ethylquinuclidin-2-yl)(6-methoxy
quincolin-4-yl)methanol]. The corresponding product
3aa was obtained in 55% yield with 32% ee in 72 h
(Scheme 6).
Experimental Section
General procedure for
the preparation of
spirocyclohexene indane-1,3-diones 3: A dry and argon-
flushed two-neck reaction tube equipped with a magnetic
stir bar was charged with 1 (0.2 mmol), 2 (1.2 equiv),
DMAP (4.9 mg, 20 mol%), and dry EtOAc (1.0 mL) and
stirred at 30 °C. The progress of the reaction was
1
monitored by TLC and H NMR data analysis. After the
completion of the reaction, the reaction mixture was
quenched with 2N HCl (0.25 mL) and extracted with
CH2Cl2 (3x2 mL). The combined organic layers were dried
over anhydrous MgSO4, filtered, then concentrated in
vacuo, and the residue was purified by silica gel flash
chromatography to afford the pure spiro compound 3.
General procedure for the preparation of coumarin-
fused cyclopentanes 4: A capped glass vial equipped with
a magnetic stir bar was charged with 1 (0.1 mmol), 2 (1
equiv), Et3N (2.8 µL, 20 mol%), and CH3CN (0.5 mL) and
stirred at 40 °C. The progress of the reaction was
Scheme 6. Attempt to prepare the chiral 3aa.
1
monitored by TLC and H NMR data analysis. After the
Conclusions
completion of the reaction, the reaction mixture was
quenched with 2N HCl (0.25 mL) and extracted with
CH2Cl2 (3x2 mL). The combined organic layers were dried
over anhydrous MgSO4, filtered, then concentrated in
vacuo, and the residue was purified by silica gel flash
chromatography to afford the pure fused compound 4.
In summary, a novel switchable organocatalytic
reaction has been developed for the synthesis of spiro
and fused carbocyclic systems in moderate to good
yields. The tunable reactivity of the key 1,6-addition
intermediate resulted from 3-homoacylcoumarin and
indanedione derivative has been utilized as an
advantage to realize diversity-oriented synthesis. In
the presence of DMAP, 1,6-addition/aldol cascade
reaction furnished the spirocyclic systems, whereas
the 1,6-addition/vinylogous Michael addition
sequence resulted in fused ring systems by using
Et3N as a base. Besides, the diversity-oriented
switchable reactions have been reported in recent
years by choosing appropriate base/solvent systems
Acknowledgements
The authors thank the Ministry of Science and Technology of the
Republic of China (MOST 107-2628-M-003-001-MY3) for
financial support.
References
7
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10.1002/adsc.202000597
Advanced Synthesis & Catalysis
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10.1002/adsc.202000597
Advanced Synthesis & Catalysis
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[17] See Supporting Information for detailed optimization
Tables, reactions of 1a with 2h and crystal data of
compounds 3aa (CCDC 1840057), 4aa (CCDC
1840058), and 6 (CCDC 1840052).
9
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10.1002/adsc.202000597
Advanced Synthesis & Catalysis
FULL PAPER
Diversity-Oriented Synthesis of Spirocyclohexene
Indane-1,3-diones
and
Coumarin-Fused
Cyclopentanes via an Organobase-Controlled
Cascade Reaction
Adv. Synth. Catal. Year, Volume, Page – Page
Min Wang,a,† Ping-Yao Tseng,a,† Woei-Jye Chi,a,†
Sundaram Suresh,a, Athukuri Edukondalu,a, Yi-Ru
Chena, and Wenwei Lina,*
10
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