Ca(II)-Mediated Regioselective One-pot Sequential Annulation of Acyclic compounds to Polycyclic Fluorenopyrans

Article abstract of DOI:10.1002/adsc.201801030

Herein we report a facile synthesis of tetracyclic fluorenopyrans from simple acyclic reactants, propargyl alcohols and 3-methylpentane-2,4-dione under calcium catalysis. This one-pot, 3-component reaction proceeds through a sequential allene formation, F

Full text of DOI:10.1002/adsc.201801030

Title: Ca(II)-Mediated Regioselective One-pot Sequential Annulation of
Acyclic compounds to Polycyclic Fluorenopyrans
Authors: SRINIVASARAO YARAGORLA, Rajesh P, Abhishek pareek,
and Ankit Kumar
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801030
Link to VoR: http://dx.doi.org/10.1002/adsc.201801030

10.1002/adsc.201801030
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.2017((will be filled in by the editorial staff))
Ca(II)-Mediated Regioselective One-pot Sequential Annulation
of Acyclic compounds to Polycyclic Fluorenopyrans
Srinivasarao Yaragorla,* P. Rajesh, Abhishek Pareek and Ankit Kumar
School of Chemistry, University of Hyderabad, Prof. C. R. Rao Road, Gachibowli, Hyderabad, 500046, India.
Email: srinivas.yaragorla@uohyd.ac.in
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. Herein we report a facile synthesis of Noticeably, this highly practical, atom and the step-
tetracyclic fluorenopyrans from simple acyclic economic procedure is catalyzed by a sustainable
reactants, propargyl alcohols and 3-methylpentane-2,4- (alkaline earth) metal salt and tolerates the broad
dione under calcium catalysis. This one-pot, 3- substrate scope, allowing the further transformations
component reaction proceeds through a sequential and synthetic utilities of these complex polycyclic
allene
formation,
Friedel-Crafts
cyclization/ moieties.
Keywords: Fluorenopyran; calcium catalysis;
iodocyclization; 6-endo-dig-cycization; allene;
tetracyclic, Friedel-Crafts annulation.
cycloisomerization, intramolecular aldol reaction,
Claisen rearrangement, and 6-endo dig cyclization to
result in the formation of fluorenopyrans (indeno[2,1-
g]chromenes). This strategy was further used in the
synthesis of 3-iodo-fluorenopyrans, by iodocyclization
to the above sequence of reactions (4-CR).
patent, these compounds exhibited excellent
photochromic properties and used in many types of
plastics and especially for ophthalmic purposes.[10]
Introduction
Synthesis of complex polycyclic molecules from
simple acyclic starting materials is always
challenging and demanding owing to their
widespread nature in natural products, and
importance in chemical biology and material science.
For example, chromenes represent an important class
of heterocyclic compounds from both pharmaceutical
and biological point of view.[1] As a result, the
synthesis of chromenes has been attracted the
attention of many synthetic chemists.[2] Similarly,
fluorene is another privileged carbocyclic moiety that
is presented in many of the bioactive natural and
synthetic molecules.[3] This moiety is extensively
used in material science, in light emitting diodes
(OLEDs), and dyes sensitized solar cells due to their
unique properties such as good charge transporters
with high chemical stability.[4] Interestingly, nature
created some of these tetracyclic frameworks from
the combination of fluorenyl and pyran scaffolds
(Figure 1), such as gnetuhainins S,[7] and parvifolol
A.[8,9] When it comes to the laboratory synthesis, very
few reports are available for indeno[1,2-
c]chromenes,[5,6] but none for the indeno[1,2-
g]chromenes, except a patent.[10] According to this
Figure 1. Representative structures of natural polycyclic
frameworks embedded with chromene, indene, and
fluorene.
However, the reported synthesis of these polycyclic
moieties is often hampered by limitations like multi-
step process, several protection and deprotection
strategies, low yield, longer reaction times etc. In the
modern synthetic chemistry, there is a high demand
1
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10.1002/adsc.201801030
Advanced Synthesis & Catalysis
Assuming that a higher reaction temperature would
for green (sustainable) synthetic procedures, and
hence many protocols have been developed and being
help in increasing the yield of 4a, the reaction was
o
followed.[11] One of them is
a
one-pot,
refluxed in a high boiling solvent, toluene (120 C)
but the yield was only 40% (entry 3). The reaction
could not initiate in the protic solvent like ethanol at
reflux, and a solvent-free condition gave a moderate
multicomponent reaction (MCR) approach.[12] Owing
to the potential usefulness of fluorenopyrans, and
lack of synthetic procedures, herein we disclose the
first report of one-pot, multicomponent annulation of
acyclic propargyl alcohols and 2-methyl-1,3-
diketones into tetracyclic fluorenopyrans under
calcium catalysis.[13]
o
yield of 48% at 110 C (entries 4, 5). Among the
solvent systems studied, DCE found to be better at
reflux conditions, hence considering DCE as the best
solvent, few more experiments were performed to
minimize the catalyst loadings and found that 10
mol% Ca(OTf)2/5 mol% Bu4NPF6 gave 70% of 4a in
4 h (entry 6). To examine the importance of the
catalyst, we performed the reaction without
catalyst/additive (entry 10), without Ca(II) (entry 9)
and without additive (entry 8). These results inferred
us that the combination of both is mandated as the
mixture undergo a ligand metathesis to yield more
soluble and more acidic Ca(II) salt.[16] KPF6 was
proved as a bad choice of additive along with a Ca
(II) (entry 11). Other acid catalysts such as Mg(OTf)2,
FeCl3 and p-TSA were found to be less effective
(entries 12-14). Finally, entry 6 turned out to be the
optimum condition for the formation of 4a.
Results and Discussion
Table 1. Optimization of reaction conditions.a
En Catalyst (mol%)
try
Reaction
Yield
(%)[b]
25
conditions[a]
DCE, rt, 15 h
1
2
3
4
5
Ca(OTf)2/ Bu4NPF6 (10/10)
DCE, 90 oC, 4 h
Toluene, 120 oC, 8 h
EtOH, 90 oC, 8 h
Neat, 110 oC, 8 h
DCE, 90 oC, 4 h
DCE, 90 oC, 4 h
DCE, 90 oC, 12 h
DCE, 90 oC, 12 h
DCE, 90 oC, 12 h
DCE, 90 oC, 4 h
DCE, 90 oC, 12 h
DCE, 90 oC, 4.5 h
DCE, 90 oC, 12 h
Ca(OTf)2/ Bu4NPF6 (10/10)
Ca(OTf)2/ Bu4NPF6 (10/5)
Ca(OTf)2/ Bu4NPF6 (10/5)
Ca(OTf)2/ Bu4NPF6 (10/5)
67
40
nr
After discovering the best reaction conditions for the
regioselective, one-pot, annulation of propargyl
alcohol 1a and 2-methyl acetylacetone to form
fluorenopyran 4a, we planned to investigate the
generality of this method (Table 2). Accordingly, 1a
and 2 were refluxed in 1,2-DCE along with 10 mol%
Ca(II)/5 mol% Bu4NPF6 until the consumption of
starting materials (monitored by TLC) then propargyl
alcohol 3b was added to the reaction pot and
continued the reaction till completion to isolate the
fluorenopyran 4b in 67% yield. Similarly, other
propargyl alcohols 3c-3f were treated with 1a and 2
under standard reaction conditions to show the
diversity at the quaternary-C2-center and synthesized
the flurenopyran 4a-4e in good yields. Compared to
4a, the yields of 4b, 4c, and 4d were slightly lower,
and this maybe due to the presence of halogen
substitution on the phenyl ring at C2 center. The yield
of 4a was comparable with that of 4e (diphenyl
verses dimethyl at C2). The reaction with other
diketones was not successful (complex mixture
formed), it suggested that the methyl ketones are
essential to perform aldol reaction. The scope of
substitutions at C4 was demonstrated, by adding 3h
& 3i (bearing p-tolyl, and cyclopropyl groups) as the
second alcoholic partners to synthesize the
corresponding products 4f-4h in good yields. Next,
we examined the scope of 1,1-diphenyl-3-(p-
tolyl)prop-2-yn-1-ol (1b), 2 with various propargylic
48
70
53
nr
6[c] Ca(OTf)2/ Bu4NPF6 (10/5)
7
8
9
Ca(OTf)2/ Bu4NPF6 (5/10)
Ca(OTf)2, (10)
Bu4NPF6, (10)
nr
10 No catalyst, no additive
11 Ca(OTf)2/ KPF6 (10/5)
12 Mg(OTf)2/Bu4NPF6 (10/5)
13 PTSA (10)
nr
10
26
60
15
14 FeCl3 (10)
[a]1a (1 equiv., 1.2 equiv.), 2 (1.3 equiv.), were used; [b]Isolated
yields; [c]Optimum conditions; DCE: 1,2-dichloroethane; rt:
room temperature; nr
trifluoromethanesulfonate
=
no reaction; OTf
=
To implement our hypothesis, we commenced the
synthesis of fluorenopyrans by stirring a mixture of
propargyl alcohol (1a, 1 equiv.), 3-methylpentane-
2,4-dione (2, 1.3 equiv.) and 10 mol%
Ca(OTf)2/Bu4NPF6 in 1,2-DCE at room temperature
for 15 h and found that the desired flurenopyran (4a)
was formed in <10% along with other inseparable
mixture. To increase the yield of the 4a, the second
portion of 1a was added to the same flask after the
formation of fluorenol intermediate, (VIII)
(monitored by TLC). As expected, the yield of the
product was increased to 25% (entry 1, Table 1). [14,15]
This encouraged us to seek different conditions to
improve the reaction yield, hence we refluxed the
partners
3
and made the corresponding
fluorenopyrans 4j-4n in moderate to good yields.
Encouraged by these results, next, we intended to
build a spirocyclic quaternary center at C2 position
(of compound 4) by replacing the acyclic propargyl
alcohols with cyclic propargyl alcohols in the second
addition.
o
reaction in DCE at 90 C and found that the yield of
4a was increased to 67% (entry 2).
2
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10.1002/adsc.201801030
Advanced Synthesis & Catalysis
Table 2. Substrate scope of the Ca(II)-catalyzed synthesis of fluorenopyrans[a]
[a]Reaction conditions: A mixture of 1 equiv. 1, 1.3 equiv. 2, 10 mol% Ca(OTf)2/ 5 mol% Bu4NPF6 were refluxed in 1,2-
dichloroethane for 1.5-2.5 h then 1.2 equiv. of 3 was added
Accordingly, 1a and diketone 2 were subjected to
annulation under standard conditions and then
fluorenyl propargyl alcohol was added after the
formation of flurenol and continued the reaction to
isolate indeno[2,1-g]chromene 4o in 70% yield.
Similarly, we prepared the other fluorenopyrans 4p &
4q bearing a spirocyclic 9-fluorenyl moiety at C2
center in good yields as described in Table 2. When
1-(phenylethynyl)cyclohexan-1-ol was used as the
second propargylic partner, the reaction could not
proceed beyond the formation of fluorenol, as the 1-
(phenylethynyl)cyclohexan-1-ol undergone Rupe
elimination.[17]
To understand the reaction mechanism, we have
performed control experiments as depicted in the
Scheme 1. Initially, a mixture of 1a, 2 and Ca(II) was
refluxed in DCE for 1.5 h to obtain the fluorenol
intermediate (VIII) in 85% yield (eq-i). Next, VIII
was subjected to standard reaction conditions with 1a
and the target compound 4a was obtained (eq-ii).
3
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10.1002/adsc.201801030
Advanced Synthesis & Catalysis
Experiments iii and iv confirmed that the fluorenol
was obtained from allene intermediate (I). When
cyclopropyl acetylene was treated with 2, the reaction
stopped after the formation of allene; this confirmed
the importance of phenyl group bonded to the alkyne
to take part in the intramolecular Friedel-Crafts
annulation (eq-v, vi).
Scheme 2. Plausible Reaction Mechanism
After realizing the formation of propargylic ether
(IX) in reaction (Scheme 2), we decided to activate
the alkyne with molecular iodine so that an
intramolecular-iodocyclization can be achieved
(Table 3) to get iodo-fluorenopyrans.[21] Based on this
assumption we have designed our experiment; 1a and
2 were subjected to standard reaction condition to
obtain the fluorenol (VIII), then brought the reaction
to room temperature and 1a was added as a second
alcoholic partner along with molecular iodine and 2
mL of toluene.[22] Presumably, the iodocyclization
proceeded well to yield 3-iodo flurenopyran 5a in
80% yield (Table 3). This result motivated us to see
the generality of this protocol, by employing a
various type of propargyl alcohols 1 and 3 with
diketone 2. Thus we obtained the respective 3-iodo-
fluorenopyrans 5b-5f in good to excellent yields as
depicted in Table 3.
Scheme 1. Control experiments
Based on the observations made during the control
experiments (Scheme 1), we have proposed the
reaction mechanism in the Scheme 2. Initially, the
enol form of diketone 2 reacts with the activated
propargyl alcohol (1) through the SN2I mechanism
and yields the tetra-substituted allene intermediate
(I)[18] (isolated and confirmed), which then proceeded
to
an
intra-molecular
Allene-Friedel-Crafts
annulation to give the tricarbocyclic compound (II)
and further cycloisomerizes to the indene (III) in the
presence of Ca(II). A Ca(II)-catalyzed intramolecular
aldol condensation of V gave the annulated product-
VI.[19a,19b] Aromatization of VII provides fluorenol
VIII[19c] (isolated and characterized), which formed
ether IX with the second propargyl alcohol partner
(3). Finally, Claisen or [3,3]-rearrangement[20] of
ether IX yields allene intermediate (X), which further
cyclizes through a 6-endo dig fashion to provide the
fluorenopyran 4.
4
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10.1002/adsc.201801030
Advanced Synthesis & Catalysis
Table 3. Ca(II)-catalyzed, one-pot, 4-component Iodo-cycloisomerization reaction[a]
[a]Reaction conditions: A mixture of 1 equiv. 1, 1.3 equiv. 2, 10 mol% Ca(OTf)2/5 mol% Bu4NPF6 were refluxed in 1,2-
dichloroethane for 2 h then the reaction was brought to rt and added 1.2 equiv. of 3 and 2 equiv. of iodine in toluene and
continued the reaction at rt until completion
After the development of a highly facile 4-component
synthesis of 3-iodo-fluorenopyrans, we were
interested in demonstrating the synthetic utility of
these iodo compounds in cross-coupling reactions
(Scheme 3).
achieved with ethyl acrylate under Heck conditions[24]
[Pd(OAc)2, Bu4NBr, Na2CO3, DMF, 80 oC] to furnish
the acrylate compound 7 in 75% yield. The third
reaction was performed with phenylacetylene under
Sonogashira conditions[25] [(Pd(OAc)2, DABCO,
CH3CN, r.t.] and furnished the alkyne 8 in 70% yield
(Scheme 3).
Conclusion
In summary, we have demonstrated an operationally
simple method for the synthesis of complex
polycyclic molecules, fluorenopyrans, and 3-iodo-
fluorenopyrans, starting from simple acyclic
propargyl alcohols and 3-methylpentane-2,4-dione
using calcium(II) catalyst in one-pot. The proposed
reaction mechanism was authenticated, by the
isolation and characterization of key intermediates.
Broad substrate scope, the formation of seven new
bonds (3-contiguous C-C bonds) in one-pot, via the
Scheme 3. Synthetic transformations of 5a
Therefore, the first cross-coupling was executed with
phenylboronic acid and iodide 5a under Suzuki
conditions[23] [5 mol% Pd(OAc)2, Na2CO3, DMF:H2O
(1:1), 100 C] to yield the cross-coupled product 6 in
73% yield. Another transformation of 5a was
sequential
Allene-Friedel-Crafts
cyclization/
cycloisomerization, intramolecular aldol reaction,
Claisen rearrangement, iodocyclization and 6-endo
dig cyclization to get the desired products are some of
the highlights of the synthesis. Acidochromic
o
5
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10.1002/adsc.201801030
Advanced Synthesis & Catalysis
properties of selected compounds suggested that
these compounds can be useful candidates in material
applications.
Typical experimental procedure for the Heck
cross-coupling (7) : Ethyl acrylate (47.9 mg, 0.47
mmol), was added to a solution of 5a (173 mg, 0.23
mmol) in DMF (1.8 mL) containing K2CO3 (2.5
equiv.) and Bu4NBr (1 equiv.) and stirred at room
temperature for 5 min. Pd(OAc)2 (5 mol %) was then
added, and the flask was flushed with N2, sealed and
allowed to stir at 80 °C for 22 h. The resulting
mixture was filtered off, washed and the filtrate was
extracted with diethyl ether. The combined organic
layers were washed with brine and dried over
anhydrous Na2SO4. The solvent was evaporated
under reduced pressure, and the residue was purified
by column chromatography (4-6%, EtOAc in pet
ether) with silica gel to give product 7 in 75% yield.
Experimental Section
Typical experimental procedure for the synthesis
of indeno[2,1-g]chromene (4a): A mixture of 1,1,3-
triphenylprop-2-yn-1-ol 1a (0.35 mmol, 100 mg) and
3-methylpentane-2,4-dione 2a (0.45 mmol, 52 mg)
o
were refluxed in 1,2-DCE at 90 C in presence of
Ca(OTf)2/Bu4NPF6 (10/5 mol%) for 2 h. Then 0.42
mmol (119 mg) of 1,1,3-triphenylprop-2-yn-1-ol 1a
was added to the reaction mixture and continue till
completion of the reaction (monitored by TLC). After
completion of the reaction, the crude product was
purified by silica gel column chromatography (3-5 %,
EtOAc in pet ether) to obtain the desired product 4a
in 70% yield.
Typical experimental procedure for Sonogashira
cross-coupling (8): Pd(OAc)2 (2 mol%) was
dissolved in MeCN (1 mL), and was added to a
mixture of phenylacetylene (45 mg, 0.45 mmol), 5a
(168 mg, 0.22 mmol), DABCO (3 equiv.), and MeCN
(4 mL). Then the mixture was stirred under N2 at
room temperature for 12 h. The resulting mixture
was filtered off, washed and the filtrate was extracted
with diethyl ether. The combined organic layers were
washed with brine and dried over anhydrous Na2SO4.
The solvent was evaporated under reduced pressure
and the residue was purified by column
chromatography (4-6%, EtOAc in pet ether) with
silica gel to give product 8 in 70% yield.
Typical experimental procedure for the synthesis
of 3-iodo-indeno[2,1-g]chromene (5a): A mixture of
1,1,3-triphenylprop-2-yn-1-ol 1a (0.35 mmol, 100
mg) and dione 2a (0.45 mmol, 42.15 mg ) was
refluxed in 1,2-DCE at 90 oC in presence of
Ca(OTf)2/Bu4NPF6 (10/5 mol%) for 2 h. Then the
reaction was brought to rt, and was added 0.42 mmol
(119 mg) of 1a along with 1.42 mmol (180 mg) of I2
and 1 mL of toluene to the reaction mixture and
continue at rt till completion of the reaction
(monitored by TLC). After completion of the reaction,
the reaction mixture was diluted with a saturated
Na2S2O8 solution, extracted with EtOAc (thrice), the
combined organic layers were washed with brine
solution and dried over anhydrous Na2SO4. The
solvent was filtered and removed under reduced
pressure, and the crude product was purified by silica
gel column chromatography (3-5 %, EtOAc in pet
ether) to obtain the desired product 5a in 80% yield.
Acknowledgement
This work is partially supported by SERB India, grant
No-EMR/2016/4812 and CSIR no-02(333)/18/EMR-
II. Authors thankful to the school of chemistry, UoH
for the infrastructure. PR and AP thankful to CSIR
for the fellowships. PR, AP and AK contributed
equally.
References
Typical experimental procedure for the Suzuki
cross-coupling reaction (6): PhB(OH)2 (41.1 mg,
0.33 mmol) was added to a solution of 5a (203 mg,
0.27 mmol) in 3.0 mL of DMF/H2O (1:1) containing
Na2CO3 (1 equiv.) and stirred at room temperature for
5 min. Then Pd(OAc)2 (5 mol %) was added, and the
flask was flushed with N2, sealed and allowed to stir
at 100 °C for 4 h. The resulting mixture was filtered
off, washed and the filtrate was extracted with diethyl
ether. The combined organic layers were washed with
brine and dried over anhydrous Na2SO4. The solvent
was evaporated under reduced pressure, and the
residue was purified by column chromatography (4-
6%, EtOAc in pet ether) with silica gel to give the
product in 6 in 73% yield.
[1] a) D. Kumar, P. Sharma, H. Singh, K. Nepali, G.
K. Gupta, S. K. Jaina, F. N. Kang, RSC Adv.
2017, 7, 36977; b) A. Goel, A. Kumar, A.
Raghuvanshi, Chem. Rev. 2013, 113, 1614.
[2] a) N. Majumdar, N. D. Paul, S. Mandal, B. De-
Bruin, W. D. Wulff, ACS Catal. 2015, 5, 2329; b)
R. Pratap, V. J. Ram, Chem. Rev. 2014, 114,
10476.
[3] a) M. Zeng, T. E. Ballard, A. Tkachenko, V.
Burns, D. Feldheim, C. Melander, Bioorg. Med.
Chem. Lett. 2006, 16, 5148; b) Y. Han, A. Bisello,
C. Nakamoto, M. Rosenblatt, M. Chorev, J. Pept.
Res. 2000, 55, 230; c) P. Perry, M. Read, R.
Davies, S. Gowan, A. Reszka, A. Wood, L.
Kelland, S. Neidle, J. Med. Chem. 1999, 42, 2679.
6
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10.1002/adsc.201801030
Advanced Synthesis & Catalysis
[4] a) L. Xiao, Z. Chen, B. Qu, J. Luo, S. Kong, Q.
Gong, Q. Kido, Adv. Mater. 2011, 23, 926; b) S.
Beaupré, P.-L. T. Boudreault, M. Leclerc, Adv.
Mater. 2010, 22, E6; c) A. C. Grimsdale, K. L.
Chan, R. E. Martin, P. G. Jokisz, A. B. Holmes,
Chem. Rev. 2009, 109, 897; d) U. Scherf, E. J. W.
List, Adv. Mater. 2002, 14, 477.
[5] a) Y. M. Zhai, K. Jiang, S. J. Qu, H. F. Luo, J. J.
Tan, C. H. Tan, RSC Adv. 2016, 6, 50083; b) S.
Saisin, S. Tip-pyang, P. Phuwapraisirisan, Nat.
Prod. Res. 2009, 23, 1472.
[6] T. Tanaka, I. Iliya, T. Ito, M. Furusawa, K.
Nakaya, M. Iinuma, Y. Shirataki, N. Matsuura, M.
Ubukata, J. Murata, F. Simozono, K. Hirai, Chem.
Pharm. Bull. 2001, 49, 858.
[7] H. Jiang, J. Ferrara, X. Zhang, K. Oniwa, A.
Islam, L. Han, Y.-J. Sun, M. Bao, N. Asao, Y.
Yamamoto, T. Jin, Chem. Eur. J. 2015, 21, 4065
and references cited for JH dyes.
[13] a) S. Yaragorla, R. Dada, A. Pareek,
ChemistrySelect 2018, 3, 435; b) C. Qi, F.
Hasenmaile, V. Gandon, D. Lebœuf, ACS Catal.
2018, 8, 1734; c) S. Yaragorla, A. Pareek, R.
Dada, Adv. Synth. Catal. 2017, 359, 3068; d) S.
Yaragorla, R. Dada, A. Pareek, G. Singh, RSC
Adv. 2016, 6, 28865; e) S. Yaragorla, R. Dada,
ACS Omega, 2017, 2, 4859; f) S. P. Morcillo, D.
Leboeuf, C. Bour, V. Gandon, Chem. Eur. J.
2016, 22, 16974; g) M. Presset, B. Michelet, R.
Guillot, C. Bour, S. B. Lafollée, V. Gandon, Chem.
Commun. 2015, 51, 5318; h) h) S. P. Morcillo, M.
Presset, S. Floquet, V. Coeffard, C. Greck, C. Bour,
V. Gandon, Eur. J. Org. Chem. 2016, 2688
[14] Even though an excess of 1a was used, the yield
of 4a did not increase, but the second addition of
1a after the formation of fluorenol helped in
increasing the yield of 4a.
[15] See
the
supporting
information
for
[8] a) X. Pan, Y. Luo, Y. Ding, X. Fan, J. Wu, Adv.
Synth. Catal. 2014, 356, 1072; b) M. Furusawa,
K. Arita, T. Imahori, K. Igawa, K. Tomooka, R.
Irie, Tetrahedron Lett. 2013, 54, 7107; c) Y. Luo,
L. Hong, J. Wu, Chem. Commun. 2011, 47, 5298;
d) Z.-Q. Wang, Y. Lei, M.-B. Zhou, G.-X. Chen,
R.-J. Song, Y.-X. Xie, J.-H. Li, Org. Lett. 2011,
13, 14.
characterization of 4a using single crystal XRD
(CCDC 1842703), experimental procedures,
copies of 1H NMR, 13C NMR, and HRMS data is
available in supporting information as PDF file.
Details of acidochromism are also available.
[16] a) J.-M. Begouin, M. Niggemann, Chem. Eur. J.
2013, 19, 8030; b) D. Leboeuf, V. Gandon,
Synthesis, 2017, 49, 1500.
[9] a) S. Akbar, K. Srinivasan, J. Org. Chem. 2016,
81, 1229; b) H. Zhu, Z. Chen, Org. Lett. 2016, 18,
488; c) Z. Chen, M. Zeng, J. Yuan, Q. Yang, Y.
Peng, Org. Lett. 2012, 14, 3588; d) D. Rodríguez,
M. Martínez, A. Navarro, L. Castedo, D.
Domínguez, C. Saꢀ, J. Org. Chem. 2004, 69,
3842; e) D. Rodríguez, A. Navarro, L. Castedo,
D. Domínguez, C. Saꢀ, Org. Lett. 2000, 2, 1497.
[10] a) K. Fukashi, H. Hideki, S. Shinichi, S. Jpn.
Patent, JP 2017036248 A, 2017; b) O. G.
Petrovskaia, A. Kumar, Patent, PCT Int. Appl.
WO 2002053553, 2002; c) A. Mukhopadhyay, M.
[17] a) H. Rupe, K. Glenz, Justus Liebigs Ann. Chem.
1924, 436, 195; b) S. Swaminathan, K. V.
Narayanan, Chem. Rev. 1971, 71, 429.
[18] a) R. Sanz, D. Miguel, A. Martinez, J. M. A.
Gutierrez, F. Rodriguez, Org. Lett. 2007, 9, 727;
b) P. N. Chatterjee, S. Roy, Tetrahedron Lett.
2011, 67, 4569.
[19] a) A. Izumiseki, H. Yamamoto, J. Am. Chem.
Soc. 2014, 136, 1308; b) D. F. Cauble, J. D.
Gipson, M. J. Krische, J. Am. Chem. Soc. 2003,
125, 1110; c) P. N. Chatterjee, S. Roy, J. Org.
Chem. 2010, 75, 4413.
V. Kumar, J. N. Moorthy, J. Org. Chem. 2016, 81, [20] a) K. Tanaka, H. Aoki, H. Hosomi, S. Ohba, Org.
7741.
Lett. 2000, 2, 2133; S. Yaragorla, A. Pareek, R.
Dada, Tetrahedron Lett. 2017, 58, 4642.
[21] a) S. Yaragorla, A. Pareek, Eur. J. Org. Chem.
2018, 1863; b) S. Yaragorla, A. Pareek, R. Dada,
P. L. Saini, Eur. J. Org. Chem. 2017, 4600; c) Y.
M. Ren, C. Cai, R. C. Yanga, RSC Adv. 2013, 3,
7182; d) M. J. Mphahlele, Molecules 2009, 14,
4814.
[22] Addition of toluene along with iodine gave the
best result, when compared to the DCE alone and
with other solvent combinations
[23] A. Suzuki, J. Organomet. Chem. 1999, 576, 147.
[24] R. F. Heck, J. P. Nolley, J. Org. Chem. 1972, 37,
2320.
[11] a) A. Sarkar, S. Santra, S. K. Kundu, A. Hajra, G.
V. Zyryanov, O. N. Chupakhin, V. N. Charushin,
A. Majee, Green Chem. 2016, 18, 4475; b) R. A.
Sheldona, Chem. Soc. Rev. 2012, 41, 1437; c) M.
O. Simona, C. J. Li, Chem. Soc. Rev. 2012, 41,
1415; d) K. Tanaka, F. Toda, Chem. Rev. 2000,
100, 1025; e) S. Yaragorla, A. Pareek, R. dada,
P.L.Saini. Eur. J. Org. Chem. 2017,4600
[12] a) T. Z. Tzitzikas, A. L. Chandgude, A. Dömling,
Chem. Rec. 2015, 15, 981; b) M. M. Khan, R.
Yousuf, S. Khan, Shafiullah, RSC Adv. 2015, 5,
57883; c) B. H. Rotstein, S. Zaretsky, V. Rai, A.
K. Yudin, A. Chem. Rev. 2014, 114, 8323; d) A.
Dꢁmling, W. Wang, K. Wang, Chem. Rev. 2012,
112, 3083.
[25] K. Sonogashira, Y. Tohda, N. Hagihara,
Tetrahedron Lett. 1975, 16, 4467
7
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10.1002/adsc.201801030
Advanced Synthesis & Catalysis
FULL PAPER
Ca(II)-Mediated Regioselective One-Pot
Sequential Annulation of Acyclic compounds
to Polycyclic Fluorenopyrans
Adv. Synth. Catal.Year, Volume, Page – Page
Srinivasarao Yaragorla,* P. Rajesh, Abhishek
Pareek and Ankit Kumar
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