Tetrahedron Letters
A green synthesis of unsymmetrical 9-arylxanthenes in a one-pot
cascade benzylation/annulation/dehydration strategy
a
a
b
Srinivasarao Yaragorla a, , Pyare L. Saini , P. Vijaya Babu , Abdulrahman I. Almansour ,
⇑
Natarajan Arumugam b
a SY-Organic & Medicinal Chemistry Laboratory, Department of Chemistry, Central University of Rajasthan, Bandarsindri, NH-8, Ajmer, Rajasthan 305817, India
b Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
a r t i c l e i n f o
a b s t r a c t
Article history:
A green synthesis of unsymmetrical 9-arylxanthenones is described using Ca(OTf)2 in one-pot cascade
Received 15 March 2016
Revised 4 April 2016
Accepted 7 April 2016
Available online 23 April 2016
benzylation, annulation and dehydration strategy starting from readily accessible p-activated carbinols.
4-Hydroxycoumarin/cyclohexane-1,3-dione required to be refluxed in water with 2-(hydroxy(phenyl)
methyl)phenol derivatives in the presence of 5 mol% of Ca(OTf)2 to yield the unsymmetrical 9H-xan-
thenes, whereas a/b-naphthols reacted under solvent free-microwave irradiation conditions. Use of eco-
friendly alkaline earth catalyst, water as the solvent, mw-irradiation, substrate scope and high yields
make this methodology more amenable.
Keywords:
Unsymmetrical xanthenes
Microwave reaction
Green synthesis
Ó 2016 Elsevier Ltd. All rights reserved.
Tandem process
Heterocyclic compounds
Calcium catalysis
Pyran (a six membered oxygen heterocycle) is known to be the
potential ‘privileged structure’ in the drug discovery and medicinal
chemistry fields.1 Amongst the several subclasses of pyrans, 9-aryl-
xanthenes and 4-aryl-chromenes are widely distributed in nature
and used as building blocks in the synthesis of molecules.2,1a In
addition they are best known about their biological profiles. For
example, 9-aryl-xanthenes possess antiviral,3a anti-inflamma-
tory3b and antibacterial activities.3c They are also useful in
photodynamic therapy,4 used as fluorescent materials and dyes5
(e.g., rhodamine B and rhodamine 6G). Xanthene derivatives are
extremely useful in laser technology due to their interesting spec-
troscopic properties.6 As a consequence of their importance, sev-
eral synthetic methodologies have been developed for the
synthesis of xanthenes (i) the most established method is the con-
densation of aldehydes with naphthols or 1,3-diones;7 (ii) the
cyclization of polycyclic aryl triflate esters;8 (iii) condensation of
aryloxy-magnesium halides with triethyl orthoformates;9 (iv)
reaction of xanthones with arylmagnesium halides or aryllithiums
followed by subsequent conversion of the resulting carbinols;10
and (v) coupling of arynes with aromatic aldehydes.11 Nevertheless
only method (iv) would provide the unsymmetrical 9-aryl-xan-
thene derivatives. But this method involves the xanthone as
starting material which needs to be accessed in multistep process.
Another attractive method was reported by Panda et al.12a using
12b
FeCl3
catalyzed intramolecular cyclization to access
unsymmetrical 9-arylxanthenes from arenoxy carbinols, but the
method is limited to dibenzoxanthenes. Hence it is still desirable
to develop
a
general synthetic procedure to access
unsymmetrical 9-aryl dibenzoxanthenes as well as 9-
aryltetrahydrobenzoxanthenes using easily available reagents,
environmentally benign catalyst and water as the solvent.
Since the past decade the chemists are more concern about the
environment and health. Hence the focused research is being con-
ducted in the area of green chemistry. One-Pot reactions, MCRs,
Cascade/tandem processes with step economy & atom economy,
microwave reactions, ‘on-water’ reactions and solvent-free reac-
tions are part of the exploration towards the green chemistry for
the sustainability.13 In the recent years we have reported sustain-
able catalysis using environmentally benign alkaline earth catalyst
which is more abundant, stable towards, moisture and air under
solvent free reactions, water as the solvent (On-Water synthesis),
microwave reactions and cascade MCRs with step & atom econ-
omy.14 In continuation of our research aimed towards the develop-
ment of sustainable synthetic protocols towards the biologically
relevant molecules probably privileged structural motifs here in
we report a benzopyran synthesis from the easily available ben-
zylic alcohols with 1,3-diones and naphthols using Ca(OTf)2.
⇑
Corresponding author. Tel.: +91 463 238535; fax: +91 463 238722.
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.