Lewis Acid Catalyzed Reductive Cyclization of 2-Aryloxybenzaldehydes and 2-(Arylthio)benzaldehydes to Unsubstituted 9H-Xanthenes and Thioxanthenes in Diisopropyl Ether

Article abstract of DOI:10.1002/adsc.202000836

Readily accessible 2-aryloxybenzaldehydes and 2-(arylthio)benzaldehydes undergo a sequence of reactions leading to a wide variety of unsubstituted 9H-xanthenes and thioxanthenes in high yields when heated with a Lewis acid in diisopropyl ether. This reductive cyclization method is compatible with several important functional groups. The method is also applicable for the selective reductive cyclization of the more electron-rich aryl ring of a 2,6-bis(aryloxy)benzaldehyde. The key feature of this transformation is the chemoselective reduction of a transient xanthylium ion in the presence of aldehydic group via intermolecular hydride transfer from diisopropyl ether (solvent). (Figure presented.).

Full text of DOI:10.1002/adsc.202000836

Title: “Lewis Acid Catalyzed Reductive Cyclization of 2-
Aryloxybenzaldehydes and 2-(Arylthio)benzaldehydes to
Unsubstituted 9H-Xanthenes and Thioxanthenes in Diisopropyl
Ether”
Authors: Shashi Verma, Anamika Prajapati, Manoj Saini, and Ashok
Basak
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.202000836
Link to VoR: https://doi.org/10.1002/adsc.202000836

10.1002/adsc.202000836
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.202((will be filled in by the editorial staff))
Lewis Acid Catalyzed Reductive Cyclization of 2-
Aryloxybenzaldehydes and 2-(Arylthio)benzaldehydes to
Unsubstituted 9H-Xanthenes and Thioxanthenes in Diisopropyl
Ether
Shashi Kant Verma,a Anamika Prajapati,b Manoj Kumar Saini,a Ashok K Basak*a
aDepartment of Chemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India
bDepartment of Chemistry, University of Rajasthan, Jaipur 302004, India
E-mail ID: akbasak.chem@bhu.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. Readily accessible 2-aryloxybenzaldehydes and 2-
(arylthio)benzaldehydes undergo a sequence of reactions
leading to a wide variety of unsubstituted 9H-xanthenes and
thioxanthenes in high yields when heated with a Lewis acid
in diisopropyl ether. This reductive cyclization method is
compatible with several important functional groups. The
method is also applicable for the selective reductive
cyclization of the more electron-rich aryl ring of a 2,6-
bis(aryloxy)benzaldehyde. The key feature of this
transformation is the chemoselective reduction of a transient
xanthylium ion in the presence of aldehydic group via
intermolecular hydride transfer from diisopropyl ether
(solvent).
Keywords:
(arylthio)benzaldehyde; xanthylium ion; hydride transfer;
chemoselective reduction; 9H-xanthene; reductive
cyclization; redox-neutral conditions.
2-Aryloxybenzaldehyde;
2-
suitable reagent, unsubstituted 9H-xanthenes and
thioxanthenes can be converted into 9H-xanthylium
ion which is subsequently trapped by nucleophiles to
Introduction
Unsubstituted 9H-xanthenes and thioxanthenes
(Figure 1) are tricyclic aromatic structural motifs that
contain diaryl methylene group. Due to the moderate
pKa value (~35) of the methylene protons, relatively
stable (due to the presence of two aryl groups)
carbanions can be readily obtained by treating with a
strong base in suitable solvents. These carbanions
were utilized for nucleophilic arylation at C-9
position,[1] addition to styrenes and related olefins,[2]
and nucleophilic opening of oxetanes[3] to generate
synthetically useful novel molecular entities. In
addition, owing to the low C-H bond dissociation
energy[4] (76 Kcal/mol) of the methylene group, 9H-
xanthenes are often utilized as a choice of starting
materials for the development of benzylic C-H
functionalization reactions[5] such as radical C-H
Figure 1. Unsubstituted 9H-xanthene (A) and thioxanthene
(B)
generate useful compounds.[10] Despite these
synthetic importances, however, only a limited
number of methods are reported for the synthesis of
these extremely useful substrates. Scheme
1
represents the reported methods for the direct
synthesis of unsubstituted 9H-xanthene. Klussmann
and co-workers reported a Sc(OTf)3-catalyzed one-
pot condensation of 2-hydroxybenzaldehydes with
cyclohexenones under microwave as well as
conventional heating (PhCl reflux, 18-44 h, 12
functionalization,[6]
dehydrogenative
electrochemical
cross-
coupling,[7]
organocatalytic
asymmetric cross-dehydrogenative coupling,[8] and
Pd-catalyzed C(sp3)-H arylation reactions.[9] Using a
1
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10.1002/adsc.202000836
Advanced Synthesis & Catalysis
examples) to obtain unsubstituted 9H-xanthenes in
18-89% yields (Scheme 1a).[11] The efficiency of the
condensation reaction is dependent on the
nucleophilicity of the hydroxyl group of
salicylaldehydes and thus, provide poor yield (18%)
with 5-chlorosalicylaldehyde due to the presence of
the electronegative Cl-atom. Moreover, no example
fluorobenzaldehydes and phenols/thiophenols via
direct aromatic nucleophilic substitution reaction.[14]
These substrates were extensively utilized for the
synthesis of xanthene derivatives, particularly,
xanthones[15] and 9-(hetero)aryl xanthenes.[14,16] 2-
Aryloxybenzaldehydes yield xanthones when treated
with stoichiometric amount of a suitable oxidant in
the presence of a catalyst (Scheme 2a). These
xanthones can be reduced into unsubstituted 9H-
xanthenes under mild conditions.[17] Li et al. and later
on Panda et al. demonstrated that 2-
aryloxybenzaldehydes and 2-(arylthio)benzaldehydes
undergo domino reaction when treated with 2 equiv
of electron rich (hetero)arenes in the presence of
suitable Lewis acid catalyst (Scheme 2b).[16a,16b]
Despite these advances, to the best of our knowledge,
there is no report for the direct synthesis of
unsubstituted 9H-xanthenes and thioxanthenes from
the readily available 2-aryloxybenzaldehydes and 2-
(arylthio)benzaldehydes. Our hypothesis for a one-
pot transformation of 2-aryloxybenzaldehyde to
unsubstituted 9H-xanthene is outlined in Scheme 5.
Lewis acid/Bronsted acid (LA/BA) promoted
intramolecular Friedel-Crafts (FC) type cyclization
would lead to intermediate cyclic alcohol 2 which
would get converted into xanthylium ion under the
reaction conditions (LA/BA). This transient
xanthylium ion could be reduced in-situ to the
unsubstituted 9H-xanthene 3 by a suitable hydride
transfer reagent.[18]
Scheme 1. Reported methods for direct synthesis of
unsubstituted 9H-xanthenes
for the synthesis of 9H-thioxanthene was reported in
the paper. In a very recent report, Zhu, Wen and co-
workers demonstrated a Cu(OAc)2-catalysed base-
promoted
domino
reaction
of
cyclic
diphenyliodonium salts with water to access
unsubstituted 9H-xanthenes in 51-85% yields (8
o
examples, 100 C, 12 h) with limited substrate scope
(Scheme 1b).[12] Lastly, Harvey et al. showed that
simple polycyclic unsubstituted 9H-xanthenes can be
synthesized
via
ligand-free
Pd(II)-catalyzed
intramolecular cross-coupling reaction of polycyclic
aryltriflate esters at high temperature (3 examples,
145 C, 18 h, 22-57% yields) (Scheme 1c).[13] The
o
lack of a common method for the synthesis of
unsubstituted 9H-xanthenes as well as thioxanthenes
can be attributed to the non-identification of
competent starting materials for a common strategy.
Thus, in this context, the development of a common
method for the synthesis of unsubstituted 9H-
xanthenes as well as thioxanthenes with wide
substrate scope and functional group compatibility is
highly desired.
Scheme 3. Envision for direct synthesis of unsubstituted
9H-xanthene
However, finding
a
hydride transfer reagent
compatible with the reaction conditions and effective
for the chemoselective reduction of the xanthylium
ion in the presence of a highly reactive aryl aldehydic
group is the key challenge associated with this one-
pot multi-step catalytic conversion plan. For instance,
2-aryloxybenzaldehydes did not yield the anticipated
unsubstituted 9H-xanthenes and underwent reductive
etherification when treated with a Lewis acid in the
presence of triethylsilane as the reducing agent.[19]
Herein, we report the successful development of a
highly effective reductive cyclization of 2-
aryloxybenzaldehydes and 2-(arylthio)benzaldehydes
using In(OTf)3 as the Lewis acid in diisopropyl ether.
The method delivers a wide range of 9H-xanthenes
and thioxanthenes in excellent yields. In addition,
these conditions are also highly effective for the
Scheme
2.
Xanthene
derivatives
from
2-
selective
reductive
cyclization
of
2,6-
aryloxybenzaldehydes and 2-(arylthio)benzaldehydes
bis(aryloxy)benzaldehydes.
On the other hand, 2-aryloxybenzaldehydes and 2-
(arylthio)benzaldehydes are readily accessible in high
Results and Discussion
yields
from
commercially
available
2-
2
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10.1002/adsc.202000836
Advanced Synthesis & Catalysis
In recent literature, alkyl ethers, in the presence of
suitable Lewis acids/Bronsted acids, have been
utilized as traceless hydride transferring agents for
highly effective intramolecular[20] as well as
intermolecular[21] reduction of transient carbenium
ions. For instance, Gagosz, Chiba and co-workers
results of the reductive cyclization reactions are
presented in Scheme 4. Aryl ether derived from
electron-neutral
phenol
underwent
reductive
o
cyclization at 95 C to generate xanthene 3a in 86%
yield. However, 2-naphthol derived aryl ether showed
better reactivity and produced xanthene 3b at 80 oC in
90% yield. 2-Aryloxybenzaldehydes generated from
Table 1. Optimization studies
entry
deviation from standard conditionsa)
none
THF instead of DIPE
diethyl ether instead of DIPE
di-n-butyl ether instead of DIPE
50 oC instead of 80 oC
Sc(OTf)3 instead of In(OTf)3
Yb(OTf)3 instead of In(OTf)3
InCl3 instead of In(OTf)3
TfOH instead of In(OTf)3
HNTf2 instead of In(OTf)3
yield (%)
98
a
b
c
d
e
f
g
h
i
75
85
86
65b)
90
78c)
94
90d)
92d)
j
a)All reactions were carried out in 0.30 mmol scale using 10
mol% catalyst in appropriate solvent (0.2M concentration) in a
sealed tube. b)80% conversion after 24 h. c)80 oC, 36 h. d)80 oC, 24
h. DIPE = diisopropyl ether.
reported an elegant TsOH catalyzed intramolecular
hydrogenation of alkene using benzyl and isopropyl
ether as the traceless hydride transferring groups
under redox-neutral conditions.[20a] Similarly, Xiong,
Chen and co-workers demonstrated that diarylmethyl
carbenium ions, generated in situ from diarymethyl
alcohols by treating with stoichiometric amount (1.2
equiv) of BF3.OEt2, can be reduced via
intermolecular hydride transfer from the solvent (n-
butylether).[21] Inspired by these literature reports, we
tested the envisaged reductive cyclization reaction (as
shown in Scheme 3) in ethereal solvents in the
presence of LA/BA. As shown in Table 1, the
a)All reactions were carried out in 0.30 mmol scale in sealed tube
in anhydrous DIPE in 0.2 M concentration. b)reaction was carried
reductive
cyclization
reaction
of
2-
o
out at 95 C. c)mixture of regioisomers. d)reaction was carried out
o
at 90 C. e)reaction was carried out in DIPE-THF (4:1) mixture.
aryloxybenzaldehyde 1d furnished xanthene 3d in
nearly quantitative yield (98%) under the optimized
standard conditions: 10 mol% In(OTf)3, DIPE (0.2
f)reaction was carried out in DIPE-THF (4:1) mixture at rt. NR =
no reaction.
o
M), 80 C, 16 h. Reactions in other ethereal solvents
Scheme 4: Scope of the reductive cyclization reaction
(THF, diethyl ether, di-n-butyl ether) provided
inferior results (entries b-d, Table 1). The cyclization
o
2,5-dimethylphenol
and
3,5-dimethylphenol
reaction at lower temperature (50 C) was slow and
furnished xanthenes 3c and 3d in 94% and 98%
small amount (<10%) of intermediate cyclic alcohol
2d was observed at that temperature. While Sc(OTf)3
produced xanthene 3d in 90% yields, Yb(OTf)3 was
found to be less effective for this reductive
cyclization reaction. 10 mol% InCl3 as catalyst also
delivered xanthene 3d in excellent yield (94%). As
anticipated, Bronsted acids (TfOH, HNTf2) also
delivered xanthene 3d in very high yields (entries i-j,
Table 1).
yields, respectively. Aryl ether generated from 4-
isopropyl-3-methylphenol
produced
isomeric
xanthenes 3e and 3e´ in excellent yield (98%).
Similarly, aryl ether derived from 3-methyl-4-
(thiomethyl)phenol and 3-methoxyphenol also
resulted into xanthenes (3f, 3f´) and (3g, 3g´) as a
mixture of regiomers in high yields. The major
regiomer arising out of the cyclization of aryl ethers
derived from unsymmetrical phenols is predictable.
In general, p-position to an electron-donating group
(Me, OMe, NHAc) is the most preferred position for
cyclization leading to the formation of the major
Next, to probe the synthetic utility, a variety of 2-
aryloxybenzaldehydes,
generated
from
2-
fluorobenzaldehyde and readily available phenols,
were subjected to the standards conditions. The
3
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10.1002/adsc.202000836
Advanced Synthesis & Catalysis
regioisomer. The ratio of regioisomers in favour of
the major increases as the size of the electron
donating group increases (for example, Me group in
3e versus OMe group in 3g). While no reaction was
observed with aryl ether derived from 2-bromo-4,5-
dimethylphenol even after prolonged heating at 90 oC
(arylthio)benzaldehydes,
obtained
from
2-
fluorobenzaldehyde and commercially available
symmetrical thiophenol, were subjected to the
reductive cyclization reaction conditions. Aryl
thioether derived from electron-neutral naphthalene-
2-thiol underwent reductive cyclization to furnish
thioxanthene 3l in 74% yield. Aryl thioethers
generated from 2,5-dimethylbenzenethiol and 3,5-
dimethylbenzenethiol provided thioxanthenes 3m and
3n in 76% and 78% yields, respectively. Notably,
reductive cyclization at the ortho-position to a bulky
tert-butyl group was also successful generating
thioxanthene 3o in modest (48%) yield.
To evaluate the effect of substituents on the reductive
cyclization, a series of 2-aryloxybenzaldehydes
bearing various substituents on aryl ring containing
aldehyde group were subjected to the standard
reaction
conditions.
underwent
2-Aryloxy-6-
reductive
chlorobenzaldehydes
etherification to generate xanthenes 5a-5c in very
high yields (Scheme 5). Aryl ethers having Br-atom
at 4- and 5-position provided xanthenes 5d-5f in
excellent yields. Aryloxybenzaldehyde containing a
phenyl group at 4-position provided xanthene 5g in
90% yield. Similarly, aryl ether containing a phenyl-
2-carbonitrile group at 5-position gave corresponding
xanthene 5h in 66% yield. The In(OTf)3-catalyzed
reductive cyclization conditions were also compatible
with internal alkynes at 4- and 5-position providing
xanthenes 5i and 5j in 88% and 85% yields,
respectively. Aryl ethers having electron-deficient
olefin at 4- and 6-position furnished xanthenes 5k
and 5l in 98% and 94% yields, respectively.
Remarkably, the reductive cyclization of aryl ether
containing a strong electron-releasing piperidine
moiety at 4-position was also successful generating
xanthene 5m in moderate yield (50%). Gratifyingly,
aryl ether bearing strong electron-withdrawing NO2-
group at 5-position and Br-atom at 4-position
a)All reactions were carried out in 0.3 mmol scale in a sealed tube
using anhydrous DIPE in 0.2M concentration. b)Reaction was
carried out in DIPE-THF (4:1) mixture. dReaction was carried out
o
using 15 mol% In(OTf)3 at 120 C. d)Reaction was carried out at
90 oC.
Scheme 5: Scope of unsubstituted 9H-xanthene synthesis
a)All reaction were carried out in 0.30 mmol scale using 10 mol%
In(OTf)3 in DIPE (0.2M) at 80 oC.
due to the presence of electron-withdrawing Br-atom,
xanthene 3i could be obtained in 84% yield by
heating at 90 oC for 36 hours. 3,4,5-
Trimethoxyphenol derived aryl ether provided
xanthene 3j in high yield (85%). Aryl ether derived
from N-(3-hydroxyphenyl)acetamide underwent
Scheme 6: Selective reductive cyclization of 2,6-
bis(aryloxy)benzaldehydes.
provided xanthene 5n in 57% yield. Significantly
higher yield (70%) of xanthene 5o was obtained with
aryl ether having NO2-group at 5-position and a
second aryloxy group at 4-position.
o
reductive cyclization at ambient temperature (30 C)
to generate a mixture of isomeric xanthenes (3k, 3k´)
in moderate yield (58%). Next,
a
few 2-
4
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10.1002/adsc.202000836
Advanced Synthesis & Catalysis
As shown in Scheme 6, the In(OTf)3 catalyzed
reductive cyclization reaction could be exploited for
the selective cyclization of the more electron-rich aryl
ring in 2,6-bis(aryloxy)benzaldehydes obtained from
2-aryloxy-6-chlorobenzaldehydes via direct aromatic
nucleophilic substitution reaction (see page S11,
Supporting Information). While xanthenes 7a and 7b
were obtained via selective cyclization of electron-
condition for the synthesis of the typical compound 8
are in progress in our laboratory.
The mechanism of the reductive cyclization reaction
catalyzed by a Lewis acid (In(OTf)3) as well as a
Bronsted acid (HNTf2) is depicted in Scheme 7.
LA/BA promoted intramolecular Friedel-Crafts type
cyclization leads to intermediate cyclic alcohol 2d
Scheme 8: Supporting experiments and gram-scale
synthesis.
which then gets converted into xanthylium ion 12.
Chemoselective reduction of 12 via intermolecular
hydride transfer from diisopropyl ether (solvent)[21]
provides xanthene 3d and oxocarbenium ion 13.
Hydrolysis of 13 leads to hemiacetal 14 which
presumably decomposes under reaction conditions to
acetone and isopropanol. Hydride transfer from
isopropanol is likely to reduce xanthylium ion 12 to
generate acetone and xanthene 3d. The reductive
cyclization of 1d also occurs in dry isopropanol to
furnish xanthene 3d in good yield (Scheme 8b).
These results support the reduction of xanthylium ion
12 via hydride transfer from isopropanol and are in
complete agreement with literature report.[18b] The
cyclic alcohol 2d could be synthesized in two
steps[15d,22] and when subjected to the standard
conditions provided xanthene 3d within very short
time (10 min) in 79% yield (Scheme 8c). This
indicates that the formation of the intermediate
alcohol 2d is the slowest step and thus the rate
determining step. In the case of xanthylium ion 18
obtained from 2,6-bis(aryloxy)benzaldehyde 6c
(Scheme 7c), intermolecular hydride transfer precess
from the solvent (DIPE) outcompetes the
intramolecular Friedel-Crafts reaction providing 9H-
Scheme 7: Proposed reaction mechanism (a) In(OTf)3-
catalyzed cycle (b) HNTf2-catalyzed cycle (c) selective
reductive cyclization.
rich aryl ring versus electron-neutral aryl ring,
xanthene 7c was obtained via selective reduction of
the more electron-rich aryl ring between the two
electron-rich aryl rings. Compound 8, which would
arise when both the aryl rings undergo intramolecular
Friedel-Crafts type cyclization reaction with the
aldehydic group, was not observed in the above cases.
Further studies towards the development of efficient
5
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10.1002/adsc.202000836
Advanced Synthesis & Catalysis
xanthene 7c exclusively. This differential reactivity
can be attributed to the solvation of the xanthylium
ion by DIPE and the energy barrier associated with
intramolecular FC reaction forming a strained fused
deuteration reaction which is believed to proceed via
single-electron-transfer mechanism.[24] Deuterated
xanthenes of type 24 are useful for kinetic as well as
mechanistic studies.[25] The KOtBu-catalyzed addition
of xanthene 3d to diisopropyl azodicarboxylate
provides a novel method for the generation of C-N
bond at 9-position of unsubstituted 9H-xanthene
(Scheme 10b).[2a]
Conclusion
In conclusion, a highly efficient, robust and viable
reductive
cyclization
reaction
of
2-
aryloxybenzaldehydes and 2-(arythio)benzaldehydes
to the corresponding unsubstituted 9H-xanthenes and
thioxanthenes catalyzed by In(OTf)3 in diisopropyl
ether has been developed. This novel transformation
involves sequence of steps which include an
intramolecular Friedel-Crafts type cyclization,
xanthylium ion formation and the crucial
chemoselective reduction of xanthylium ion via
highly effective intermolecular hydride transfer from
diisopropyl ether (solvent). The method is compatible
with several important functional groups and can be
carried in gram-scale. Notably, this method can also
be utilized for the selective reductive cyclization of
the more electron-rich aryl ring in case of 2,6-
bis(aryloxy)benzaldehydes. Most of the reactions are
very clean and high yielding and thus the method is
poised for further development of one-pot
transformations of the resulting 9H-xanthenes and
thioxanthenes. Further applications of this novel
reductive cyclization method are in progress in our
laboratory.
Scheme 9: Synthesis 10-methyl-9,10-dihydroacridines
Scheme 10: KOtBu-catalyzed reactions of 3d
ring 8c. The formation of acetone was observed by
the real-time monitoring of a reaction in NMR tube
using CDCl3 as solvent and with added stoichiometric
amount of DIPE (see Scheme S1 & Figure S1, page
S3, SI). Due to volatile nature of the by-product
1
(acetone), H NMR of the crude reaction mixture of
1
1d appeared exceptionally clean (see crude H NMR,
Figure S5, page S7, SI). As shown in Scheme 8a,
acetone can be obtained quantitatively (82% yield) as
its N-phenylsulfonyl hydrazone derivative 19 by
treating the crude reaction mixture of 1d with N-
phenylsulfonyl hydrazide at rt for 24 h. The
xanthylium ion could be detected by HRMS analysis
of aliquot of crude reaction mixture of 1d at
intermediate time (~8 h) interval. Notably, the
deuterio-enriched aryl ether 20 prepared from
deuterio-enriched phenol[23] also provided xanthene
21 in high yield (86%). To probe the utility in large
scale synthesis, 2-aryloxybenzaldehyde 4f in 1.0 g
scale was subjected to the standard reaction
conditions. Gratifyingly, no loss in yield and/or
reactivity was observed thereby demonstrating the
robustness and practicality of this novel
transformation. As shown in Scheme 9, the method
can also be used for the reductive cyclization of 2-
(methyl(phenyl)amino)benzaldehydes[15c] to generate
Experimental Section
General experimental procedure for the synthesis of
9H-xanthenes (3a-3o and 5a-5o):
2-(3,5-dimethylphenoxy)benzaldehyde 1d (67.9 mg, 0.30
mmol), dry diisopropyl ether (1.5 mL, 0.2M) and In(OTf)3
(17 mg, 0.030 mmol) was charged into a 10 mL pressure
tube under nitrogen atmosphere. The pressure tube is then
sealed with a Teflon® screw cap and heated in a pre-
heated oil bath at 80 oC for 16 h. The reaction mixture was
the diluted with ethyl acetate (25 mL), washed with brine
(1 x 10 mL), dried over Na2SO4 and evaporated. The crude
product was purified by short silica gel column
chromatography using 100% hexanes as eluent to obtained
1,3-dimethyl-9H-xanthene 3d (61.8 mg, 98%) as a white
solid.
10-methyl-9,10-dihydroacridines (23a
&
23b).
However, these reactions are less efficient when
compared to the synthesis of unsubstituted 9H-
General experimental procedure for the synthesis of 8-
aryloxy-9H-xanthenes (7a-7c):
xanthenes.
KOtBu-catalyzed
selected
functionalization reactions presented in Scheme 10
showcase the synthetic utility of the unsubstituted
9H-xanthenes. For example, deuterated compound 24
was obtained in 78% yield via KOtBu catalysed
6
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10.1002/adsc.202000836
Advanced Synthesis & Catalysis
2,6-Bis(aryloxy)benzaldehyde
(0.30
mmol),
dry
B.-G. Sun, Green Chem. 2019, 21, 4412-4421; d) X.
Shao, L. Tian, Y. Wang. Eur. J. Org. Chem. 2019,
4089-4094; e) Y.-Z. Yang, Y.-C. Wu, R.-J. Song, J.-H.
Li, Chem. Commun. 2020, 56, 7585-7588.
diisopropyl ether (1.5 mL, 0.2M) and In(OTf)3 (17 mg,
0.030 mmol) were charged into a 10 mL pressure tube
under nitrogen atmosphere. The pressure tube is then
sealed with a Teflon® screw cap and heated in a pre-
heated oil bath at 80 oC for 16 h. The reaction mixture was
then diluted with ethyl acetate (25 mL), washed with brine
(1 x 10 mL), dried over Na2SO4 and evaporated. The crude
product was purified by short silica gel column
chromatography using 0 → 5% gradient mixture of ethyl
acetate in hexanes as eluent to obtain 8-aryloxy-9H-
xanthene 7.
[8] a) E. Larionov, M. M. Mastandrea, M. A. Pericás, ACS
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Acknowledgements
Research grant from Council of Scientific and Industrial
Research (Grant No. 02(0346)/19/EMR-II), India is gratefully
acknowledged. SKV thanks UGC, New Delhi for a research
fellowship. AP and MKS thank CSIR, New Delhi for research
fellowship
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8
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Advanced Synthesis & Catalysis
FULL PAPER
Lewis Acid Catalyzed Reductive Cyclization of 2-
Aryloxybenzaldehydes
and
2-
(Arylthio)benzaldehydes to Unsubstituted 9H-
Xanthenes and Thioxanthenes in Diisopropyl Ether
Adv. Synth. Catal. Year, Volume, Page – Page
Shashi Kant Verma, Anamika Prajapati, Manoj
Kumar Saini, Ashok K. Basak*
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