Tetrahedron Letters
FeCl3ꢀ6H2O-catalyzed facile and efficient synthesis of pyrano[4,3-b]
quinolines and isochromenes
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Mrityunjaya Asthana, Jay Bahadur Singh, Radhey M. Singh
Department of Chemistry, Centre of Advanced Study, Institute of Science, Banaras Hindu University, Varanasi 221005, U.P., India
a r t i c l e i n f o
a b s t r a c t
Article history:
An inexpensive 1 mol % FeCl3ꢀ6H2O reagent has been developed for the synthesis of 1,3-disubstituted 1H-
pyrano[4,3-b]quinolines from o-arylethnylquinonylmethanol via 6-endo-dig cyclization of alcoholic –OH
onto alkynes in good to excellent yields. The reaction conditions were successfully exploited on primary
and tertiary alcohol analogs. The reagent was further generalized with the aromatic alcohol analogs pro-
viding the synthesis of isochromenes in good yields. The enhancement in the reaction rates and yields
from primary to secondary to tertiary alcohols could be attributed to inductive effect of alkyl groups
which enhanced the nucleophilicity of hydroxyl group and accelerated the cyclization mode.
Ó 2015 Elsevier Ltd. All rights reserved.
Received 17 November 2015
Revised 26 December 2015
Accepted 26 December 2015
Available online 28 December 2015
Keywords:
FeCl3ꢀ6H2O
Catalyzed
Pyrano[4,3-b]quinoline
Isochromene
o-Arylethnylquinonylmethanol
The development of transition metal-catalyzed cyclization reac-
tions for the synthesis of carbocycles and heterocycles has emerged
as one of the most significant advances in recent years.1 Among
them, iron salts and complexes which are inexpensive, easily
available, and environmentally benign have been explored as an
alternative over many expensive and less abundant transition
metal-catalysts in various organic transformations.2 Recently,
FeCl3-catalyzed/promoted intramolecular cyclizations of vinyl-/
arylalkynes with pre-existing nucleophilic functional groups at
ortho position have been reported to the synthesis of oxazoles,3a
pyrroles,3b indoles,3c benzofurans,3d and isochromeneones3e
(Scheme 1).
However, on the contrary, examples of the cyclization of the cor-
responding alcoholic group at ortho position have been less studied.
However, very recently, Fe(OTf)3-catalyzed cyclization reaction of
20-alkynylbiphenyl-2-carbinols have been reported to the synthesis
of phenanthrenes.4 The product was shown via formation of the car-
bocation at hydroxyl carbon atom. In contrast, PdI2,5a Ir-hydride5b
and gold-catalyzed5c cyclizations of 2-arylethynylphenylmethanol
(Scheme 2a) have been recently reported to isochromenes, phtha-
lans, and isochromenes respectively. These reactions demonstrated
the nucleophilic attack of alcoholic –OH on carbon–carbon triple
bond. However, these transition metal reagents have certain draw-
backs such as being expensive5d–h, non-aerobic conditions, longer
reaction times, and moderate yields. Therefore, the development
of a new and efficient reagent for similar synthesis is still highly
desirable. We introduced here a new and inexpensive reagent
FeCl3ꢀ6H2O for the cyclization of ortho alcoholic OH to alkynes. We
have been engaged in exploring the metal-catalyzed, electrophile,
and base promoted cyclization reactions of o-chroquinolnyl6-/
o-arylalkynylquinolinyl aldehydes7/nitriles7/esters8 for the synthe-
sis of quinoline-fused carbocycles9 and oxygen,10 nitrogen,11 and
sulfur12 heterocycles with different structural features. In continua-
tion of thesecyclization studies, wenow reportherein1% FeCl3ꢀ6H2O-
catalyzed cyclization of 2-arylalkynylquinolin-3-ylmethanol by
alcoholic –OH on carbon–carbon triple bond in acetonitrile under
an aerobic condition providing the facile synthesis of 1,3-disubsti-
tuted-1H-pyrano[4,3-b]quinolines via 6-endo-dig cyclization in
good to excellentyields (Scheme 2b). Thereaction was foundto have
a wide substrate scope including aromatic, heteroaromatic alkynes
along with primary, secondary, and tertiary alcohols.
The pyranoquinoline moieties are present in a number of alka-
loids such as flindersine, oricine, and verprisine. The derivatives of
these alkaloids are used as pharmaceuticals and agrochemicals and
exhibit
inflammatory, anti-allergic, psychotropic, and estrogenic effects.13
The required allyl,3-(2-arylethynylquinolinyl) methanols,
a wide range of biological activities including anti-
3
were prepared in two steps from 2-chloroquinoline-3-carbaldehy-
des 1, firstly copper-free Sonogashira coupling7 with terminal
alkynes to 2 followed by Barbier reaction9 with allylbromide and
indium in DMF at rt to 314 in good yields (Scheme 3, Table S1,
Supporting information).
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0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.