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Modern Approaches to the Synthesis of O- and N-Heterocycles, 2007:

ISBN: 81-308-0165-5 Editors: Teodoro S. Kaufman and Enrique L. Larghi

Recent synthetic
2 methodologies for furan
derivatives
Anil Kumar1 and Srinivas Rao Meneni2
1
Chemistry Group, Birla Institute of Technology and Science, Pilani, Rajasthan
333031, India. E-mail: anilkumar@bits-pilani.ac.in
2
Department of Biomedical and Pharmaceutical Sciences, University of Rhode
Island, Kingston, RI 02881, USA

Abstract
Furan is a central five membered O-heterocycle.
This unit is found in a variety of pharmacologically
relevant natural products and due to their remarkable
properties many synthetic furans are used as
pharmaceutical agents. Furans are also versatile
building blocks for the synthesis of natural and non
natural compounds. In recent years, a considerable
interest in the development of efficient methods for the
synthesis of furan derivatives has been observed. This
Chapter describes recent developments in synthetic
methodologies for the preparation of furans and
compounds containing furan ring system.
Dedicated to Prof. Karsten Krohn on the occasion of his 63rd birthday

Correspondence/Reprint request: Dr. Srinivas Rao Meneni, Department of Biomedical and Pharmaceutical
Sciences, University of Rhode Island, Kingston, RI 02881, USA. E-mail: srmeneni@uri.edu
2 Anil Kumar & Srinivas Rao Meneni

1. Introduction
Furan is an important five membered O-heterocycle. The furan system is a
very familiar motif in many biologically active substances and natural products,
occurring widely in secondary plant metabolites, variety of commercially
important compounds and synthetic materials, including industrial intermediates,
pharmaceuticals, flavour and fragrance enhancers [1,2]. Furans are also versatile
building blocks for the synthesis of natural and non natural compounds.
In recent years, given furans well documented uses and the considerable
synthetic challenge of many furan-containing natural products, there has been
considerable interest in the development of efficient synthetic routes that allow
the facile assembly of substituted furans under mild conditions from simple,
readily available starting materials.
Hence, various simple and convenient methodologies have been developed
for the synthesis of furans and its derivatives [3-5]. Substituted furans are
accessed by modification of commercially available furans [6,7], by
cyclodehydration of saturated open chain 1,4-diketones [8], Diels-Alder-retro-
Diels-Alder strategies with 4-phenyloxazoles and acetylenes [9], cyclization of
radicals and carbenes [10], heteroannulation reactions including transition-
metal catalyzed cyclizations [11,12] base induced cyclization of allenyl
alcohols and epoxides [13], as well as many others [14-16]. This Chapter gives
a brief overview of the recent developments in synthetic methodologies for the
preparation of furan ring and congeners containing the furan ring via
cyclization of acyclic precursors.

2. Synthetic methodologies
2.1. From 1,4-dicarbonyl compounds
The most widely used approach to furans is the cyclizing dehydration of
1,4-dicarbonyl compounds. This approach is known as the Paal-Knorr synthesis
of furans. Generally, furan derivatives are prepared from 1,4-dicarbonyl
compounds using acid catalysts (Scheme 1). Strong acids such as conc.
H2SO4, P2O5, p-TSA and montmorillonite KSF and basic reagents including
TsCl/DBU, alumina, zirconium phosphate/zirconium sulfophenyl phosphate
under classical as well as microwave irradiation have been employed for their
synthesis from 1,4-dicarbonyl compounds [17].

Scheme 1
Methodologies for furan derivatives 3

Siedem and co-workers [18] reported synthesis of substituted 2-

silylfurans from acylsilane dicarbonyl compounds that introduces synthetic
flexibility to the more traditional 1,4-dicarbonyl entry to furans (Scheme 2).
The acylsilane reacts under milder conditions and, in general, gives more
acceptable yields than simple alkyl-substituted 1,4-diketones. Furthermore,
the silyl substituent facilitates the subsequent regiospecific C2-elaboration of
the furan ring.

Scheme 2

Furan derivatives can also be synthesized under mild conditions from 1,4-
diketones using 5 mol% Bi(OTf)3 immobilized in the air and moisture stable
ionic liquid [bmim]BF4 [19]. The reaction of 1-phenyl-3-(2-thienyl)-1,4-
octanedione with 5 mol% of Bi(OTf)3 in [bmim]BF4 at 90 °C afforded 2-butyl-
5-phenyl-3-(2-thienyl)furan in 85% yield (Scheme 3).

Scheme 3

2.2. From α-halocarbonyl and 1,3-dicarbonyl compounds

α-Halocarbonyl compounds react with 1,3-dicarbonyl compounds in the
presence of a base (not ammonia) to give furans and this is one of the classical
methods for synthesis of furans, known as the Feist-Benary synthesis (Scheme 4).

Scheme 4
4 Anil Kumar & Srinivas Rao Meneni

2.3. From alkynes

A modern approach to the furan skeleton is the interaction of allenylsulfonium
salts with 1,3-dicarbonyl compounds where alkynes are utilized as carbonyl
equivalents (Scheme 5).

Scheme 5

Exposure of γ-acyloxy butynoates to stoichiometric quantities of triaryl-

phosphine results in reductive condensation to afford substituted furans, by
way of allenic ester intermediates [20].
Synthesis of furans from epoxyalkynes is also a convenient and useful
route [21]. Epoxyalkynes can be easily prepared by epoxidation of the
corresponding enyne. KH or KOtBu-catalyzed transformation via a cumulene
anion [22] and Mo(CO)5-Et3N-catalyzed cyclization via molybdenum
vinylidene species [23] are two important methods for this transformation. The
former is useful for internal alkynes, whereas the latter is suitable for terminal
alkynes. Recently, Liu and co-workers have reported the efficient ruthenium-
catalyzed synthesis of furan derivatives from various epoxyalkynes with
suitable oxygen and nitrogen functionalities (Scheme 6) [21].

Scheme 6

A variety of 3-substituted furans, are obtained via reductive annulation of

1,1,1-trichloroethyl propargyl ethers using catalytic CrCl2 in good yield
(Scheme 7) [24]. The natural products perillene and dendrolasin were also
synthesized by this methodology.

Scheme 7
Methodologies for furan derivatives 5

2.4. Via electrophilic cyclization

Electrophilic cyclization of unsaturated compounds has proven to be an
efficient method for the one-step construction and functionalization of furan
units [25]. Electrophilic cyclization of but-3-yn-1-ones with various electrophilic
halogen sources such as NBS and NIS yields halofurans under mild conditions
(Scheme 8), and this gives excellent regiocontrol in the preparation of
unsymmetrically 2,5-disubstituted 3-halofurans [26].

Scheme 8

Iodine-induced 5-endo-dig cyclization followed by dehydration of the 3-

alkyne-1,2-diols, readily prepared by highly regioselective bis-hydroxylations
of the corresponding enynes gave excellent yield of β-iodofuran (Scheme 9) [25c].

Scheme 9

Palladium-catalyzed sequential cyclization/coupling of alkynes and allenes

containing proximal oxygen based nucleophilic functionality with organic halides
or triflates has attracted much attention in the field of regioselective synthesis of
polysubstituted furan and related derivatives from acyclic precursors [27, 28].
Recently, samarium alkoxides of α-hydroxy-[3]-cumulenes, generated in
situ by SmI2-promoted reduction of appropriate epoxypropargyl esters, were
reported to participate in a novel Pd-catalyzed cyclization/allylation sequences
in the presence of allylic bromides to give efficient regioselective formation of
polysubstituted furans incorporating the allyl unit (Scheme 10) [29].

Scheme 10
6 Anil Kumar & Srinivas Rao Meneni

2,5-Disubstituted furan derivatives have been synthesized from α,β-

acetylenic ketones having nearby methylene unit in the presence of ZnBr2 and
DIPEA in acetonitrile. The α,β-acetylenic ketones can be synthesized from the
reaction of acid chlorides and acetylenic compounds under the same conditions
(scheme 11) [30].

Scheme 11

There are many other more recent methods for the formation of the furan
ring by cyclization, e.g. intramolecular cyclization of (Z)-3-methyl-2-en-4-yn-
1-ol catalyzed by ruthenium(II) complexes give 2,3-dimethylfuran (Scheme
12) [31].

Scheme 12

Furan derivatives have been synthesized by the coupling of Fischer

carbene complexes with conjugated enyne-carbonyl compounds (Scheme 13)
[32]. A variety of enyne-carbonyl derivatives were prepared by conversion of
ketones into their α-bromo enal derivatives [33], followed by palladium-
catalyzed alkynylation. Related methods have also been reported for the
synthesis of furan derivatives by coupling alkynes and Fischer carbene
complexes [34].

Scheme 13
Methodologies for furan derivatives 7

According to the proposed mechanism regioselective and stereoselective

alkyne insertion affords vinylcarbene complex. Nucleophilic attack by oxygen
affords carbonyl ylide intermediate which then loses chromium to afford the
furan derivative (Scheme 14).

Scheme 14

2.4.1. Synthesis of substituted furanopyrimidine nucleosides

Electrophilic cyclization of unsaturated compounds has proven to be an
efficient method for the one-step construction and functionalization of furan
units [25, 35]. Halobenzofurans and related furan derivatives have been
synthesized by electrophilic cyclization of o-alkynyl phenols and acetoxy or
benzyloxypyridines [35]. Iodocyclization of alk-3-yn-1,2-diols followed by
dehydration in the presence of base yielded 3-iodofurans derivatives.
Furanopyrimidine have been reported to show important potency and
exclusive selectivity against varicella zoster virus (VZV) [35]. Robins and co-
workers [36] reported base and copper-catalyzed 5-endo-dig cyclization of
alkynyluridines with CuI in triethylamine/methanol at reflux, between the C-4
pyrimidine oxygen and acetylenic bond to give the target substituted
furanopyrimidine (Scheme 15).

Scheme 15
8 Anil Kumar & Srinivas Rao Meneni

Electrophilic heteroannulation of 5-alkynyl-2c-deoxyuridines leads to

formation of furanopyrimidine nucleosides [37]. 2,3-Disubstituted furo[3,2-
b]pyridines, 2,3-disubstituted furo[2,3-b]pyridines, and 2,3-disubstituted
furo[2,3-c]pyridines can be synthesized via electrophilic cyclization of o-
acetoxy- and o-benzyloxyalkynylpyridines [25c]. The palladium-catalyzed
cross-coupling of 1-alkynes with o-iodoacetoxy- or o-iodobenzyloxypyridines,
followed by electrophilic cyclization promoted by I2 or PdCl2 in presence of
carbon monoxide, gives 2,3-disubstituted furopyrimidines (Scheme 16).

Scheme 16

Agrofoglio and co-workers reported a 5-endo-dig electrophilic cyclization

of α-alkynyl carbonyl compounds catalyzed by AgNO3 as a clean, efficient and
improved method for the synthesis of alkyl furanopyrimidine nucleosides [38].
The reaction proceeds at room temperature and gives furanopyrimidine
nucleosides in quantitative yield. This electrophilic 5-endo-dig cyclization with
AgNO3 is believed to proceed through a catalytic mechanism involving a
cationic intermediate (Scheme 17).

Scheme 17

2.5 Via ring closing metathesis (RCM)

The olefin metathesis reaction has recently emerged as one of the most
powerful methodologies for alkene formation and works particularly well in
intramolecular coupling reactions to form cyclic olefins. The ring closing
metathesis (RCM) reaction has been used to prepare substituted furans by
Methodologies for furan derivatives 9

utilizing a Pd catalyzed coupling reaction with methoxyallene, allylic alcohols

and sulfonamides which can be converted into substrates that are ideal
precursors for ring closing metathesis (Scheme 18) [39]. A range of different
substitution patterns and functional groups are compatible with this sequence.

Scheme 18

The 3-carboxy-2,5-furan system is featured in several structurally and

biologically interesting natural compounds. The Pd(0) or base-catalyzed ring
closure of an α-propargylic β-keto ester is used to prepare 2-isopropyl-3-
carboxy-5-vinyl furans (Scheme 19) [40].

Scheme 19

Marshall and co-workers have developed a new method for the synthesis
of 3-carboxy-2,5-disubstituted furans and their conversion into 5-vinyl
derivatives (Scheme 20) [41]. The key transformation involves treatment of a
2-(4-keto-2-alkynyl)-3-ketobutanoate with silica gel or Et3N to effect ring
closure, generating the furan motif.

Scheme 20
10 Anil Kumar & Srinivas Rao Meneni

2,3-Disubstituted furans can be synthesized from α,β-unsaturated

enones. Paquette and co-workers [42] have shown that the conjugate addition
of organocopper reagents to α,β-unsaturated enones results in the
regiospecific generation of enolate anions, which undergo aldol reaction with
(tetrahydropyranyloxy)acetaldehyde under zinc chloride catalysis (Scheme
21). Treatment of the resulting product with p-toluenesulfonic acid in THF
affords the targeted 2,3-disubstituted furan.

Scheme 21

An efficient synthetic route to polysubstituted furans using dibenzoylacetylene

and an enol system such as acetylacetone, 5,5-dimethylcyclohexane-1,3-dione,
1-naphthol, 2-naphthol, 2,7-dihydroxynaphthalene, or 8-hydroxyquinoline in
the presence of triphenylphosphine in DCM has been reported (Scheme 22)
[43].

Scheme 22

The synthesis of 2-monosubstituted and 2,5-disubstituted furans can be

accompanied via the CuI-catalyzed cycloisomerization of alkynyl ketones.
Furans containing both acid- and base-labile groups could be easily synthesized
using this methodology (Scheme 23) [44].

Scheme 23
Methodologies for furan derivatives 11

A wide variety of polysubstituted furans can be achieved upon reaction of

various 2-(1-alkynyl)-2-alken-1-ones with an unprecedented set of nucleophiles
in presence of gold catalyst [45]. Alcohols and 1,3-diketones, as well as various
electron-rich aromatics, serve as efficient nucleophiles in this new process. The
reaction was also catalyzed with other transition metal catalysts in dichloromethane
e.g. CF3CO2Ag, (CF3SO3)2Cu and (CF3SO3)2Hg afforded good yields of furan
derivatives. However, AuCl3 is the most efficient catalyst based on reaction time.
The cyclization of 3-alkyn-1-ones to furans is also achieved in the presence of
Pd(OAc)2, but only in low yield, mainly due to the facile reduction of Pd(II) to
Pd(0) in the presence of the alcohol. The addition of 2 equivalents of PPh3 to
Pd(OAc)2 did stabilize the Pd(II) salt, but slowed the reaction. Thus, AuCl3 was
chosen as the catalyst for the cyclization of a number of other substrates.
A convenient and efficient approach was described by Liu and co-workers
[46] for the synthesis of 3-iodofuran derivatives by electrophilic cyclization of
2-(1-alkynyl)-2-alken-1-ones using I2/K3PO4 system (Scheme 24).

Scheme 24

A plausible reaction mechanism for this cyclization is shown in Scheme

25, which involve: (i) cyclic iodonium ion formation through coordination to
the triple bond with iodine; (ii) the anti attack of the oxygen onto the iodonium
ion led to the formation of intermediate; (iii) 1,4-addition of a nucleophile to
the C-C double bond to afford furan derivative.

Scheme 25

The convergent three-component construction of substituted furans based

on ethyl propiolate, aldehydes and acyl halide has been described (Scheme 26)
[20]. Triphenylphosphine mediated reductive condensation of γ-acyloxy
butynoates afford substituted furans, by way of allenic ester intermediates. The
γ-acyloxy butynoates are readily obtained through condensation of ethyl
propiolate with aldehydes followed by acylation.
12 Anil Kumar & Srinivas Rao Meneni

Scheme 26

2.6. Synthesis of benzo[b]furans

Palladium catalyzed coupling reactions are important processes leading to
the construction of functionalized benzo[b]furan and furan rings [47]. The
palladium-catalyzed sequential cyclization/coupling of alkynes and allenes
containing a proximal O-based nucleophile with organic halides or triflates (R–
X) has led to the efficient preparation of a variety of substituted furan derivatives.
The most common approach for the synthesis of benzo[b]furans consists
of the palladium-catalyzed cyclization of the corresponding 2-(1-
alkynyl)phenols [48]. The palladium-catalyzed carbonylative cyclization of
arylacetylenes bearing hydroxyl groups in the ortho position is a useful
method for the synthesis of benzo[b]furan-3-carboxylates [49]. However,
low yields of the benzo[b]furan-3-carboxylates were found when electron-
deficient o-hydroxylarylacetylenes are used and reaction conditions are
incompatible with silyl protecting groups. Yang and co-workers [50] have
reported palladium catalyzed carbonylative heteroannulation of both electron-
rich and electron-deficient O-hydroxylarylacetylenes with PdI2-thiourea, CBr4,
and Cs2CO3 as the base, in methanol and this approach tolerates silyl-
protecting groups (Scheme 27).

Scheme 27
Methodologies for furan derivatives 13

Synthesis of benzo[b]furans has been accomplished through a tandem

Sonogashira coupling/5-endo-dig cyclization starting from o-iodophenols
catalyzed by Pd/C–PPh3-CuI in water in the presence of prolinol [51].
Benzo[b]furan derivatives have been synthesized from 1,1-dibromo-1-alkenes
using a tandem Pd-assisted cyclization–coupling reaction (Scheme 28) [52].
This is a one-pot procedure involving a tandem cyclization–coupling. Some
other one-pot procedures catalyzed by palladium-based [53] and copper-based
[54] catalysts are also available for the preparation of furan derivatives which
involves alkynes instead of dibromoalkenes.

Scheme 28

Recently, the copper-catalyzed synthesis of benzo[b]furan derivatives

from 2-bromo-arylketones has been reported; this reaction was carried out in
organic solvents as well as in water (Scheme 29) [55]. The combination of CuI
and TMEDA was the most efficient systems, providing the benzofuran in 91%
yield in neat water.

Scheme 29

A new synthetic transformations using Baylis–Hillman chemistry has been

reported for the synthesis of functionalized fused furans via the reaction
between aryl 1,2-diones and alkyl vinyl ketones, promoted by titanium
tetrachloride (Scheme 30) [56].

Scheme 30
14 Anil Kumar & Srinivas Rao Meneni

2-Arylbenzo[b]furans have been synthesized via copper(I)-catalyzed

coupling of o-iodophenols and aryl acetylenes (Scheme 31) [57]. This method
can be used to construct a variety of 2-arylbenzo[b]furans in good to excellent
yields, being the process tolerant of a variety of functional groups.

Scheme 31

Benzo[b]furans have been synthesized via O-alkylation of ortho-

hydroxylated aromatic carbonyl compounds with α-haloesters, followed by
intramolecular cyclization by solid-liquid phase-transfer catalysis (PTC), under
microwave irradiation (Scheme 32) [58]. Varma and co-workers have also
reported the preparation of 2-aroylbenzo[b]furans using microwave irradiation
to drive the condensation of α-tosyloxyketones with salicylaldehyde
derivatives on potassium fluoride doped alumina.

Scheme 32

Cyclization of various 2-alkynylphenols is facilitated by different bases

such as NaOEt, [59] CuOtBu, [60] or Et3N [61] to form 3-benzo[b]furans. The
synthesis of 4-, 5-, and 6-nitrobenzo[b]furans has been achieved via the
Sonogashira cross-coupling reaction of 2-iodonitrophenol acetates, prepared
from commercially available and inexpensive 2-aminonitrophenols. The 2-
alkynylnitrophenol acetates were then subjected to a KOtBu-promoted
cyclization at room temperature to form nitrobenzo[b]furans (Scheme 33) [62].

Scheme 33
Methodologies for furan derivatives 15

Highly substituted 1H-isochromenes, isobenzofurans, and pyranopyridines

can be prepared by allowing O-(1-alkynyl)arenecarboxaldehydes and ketones
to react with I2, ICl, NIS, Br2, NBS, p-O2NC6H4SCl, or PhSeBr and various
alcohols or carbon-based nucleophiles at room temperature. [63] Naphthyl
ketones and iodides are also readily prepared by the reaction of 2-(1-
alkynyl)arenecarboxaldehydes with I2 and simple olefins or alkynes.

2.7. Solid phase synthesis of furan derivatives

Gallop and co-workers [64] and Austin and co-workers [65, 66] have
described the solid-phase synthesis of furan libraries (Scheme 34). Both
strategies employed rhodium(II) mediated 1,3-dipolar cycloaddition reactions
on solid-phase, using either TentaGel or polystyrene resins, respectively. A
polymer-bound amide served as the first point of diversity. The anchored
compound was converted into the corresponding amide derivative by reaction
with the appropriate chloro-ketopropionic acid derivatives. Then, the
intermediate was subjected to diazo transfer conditions which in presence of
dirhodium tetra-acetate or tetra-perfluorobutyramidate catalyst gave
isomünchnones in variable yields. The isomünchnones were treated with an
array of acetylenes to furnish the desired furan products. This approach for
furan synthesis is advantageous because it eliminates the need for purification
of the furan since the unreacted starting materials are removed by filtration
after each step. Only pure product is obtained, regardless of cycloaddition
yield, since the isocyanate and unreacted synthesis intermediates remain
attached to the solid-phase resin. Various other methods have been reported for
solid phase synthesis of substituted furans [67-69].

N
R1 O R1 O R1
N
Cl O
NH R2 N O N O
+ R2 R2
O O
O O O O

R3 R4

R3 R4 R4
R O
O3
O
R1 O R2 O R2
O N O

Scheme 34
16 Anil Kumar & Srinivas Rao Meneni

Nicolaou and co-workers [70] have reported the solid-phase synthesis of

benzofurans in a split pool fashion resulting in the production of libraries of
significant complexity and diversity. Liao and co-workers developed a general
cross metathesis strategy for the synthesis of substituted benzo[b]furans [71].
A wide range of structurally diverse dimeric benzofuranoid congeners
suitable for biological screening were also synthesized with this technology.
The immobilized aromatic building blocks, available from the corresponding
iodides via a Sonogashira coupling, were converted into their respective
benzofuran monomers through a carbonylative annulation process. The
immobilized monomers were then subjected to olefin cross metathesis using
Grubbs’ first-generation catalyst, to afford the corresponding cross linked
polystyrene beads. The homo-dimers were then cleaved from the resin,
affording the benzofurans.
2-Substituted benzofurans have been synthesized on solid phase using
Sonogashira coupling followed by cyclization of the resulting ortho-hydroxy
alkynes (Scheme 35) [72].
HOOC I 1. R
PdCl2(Ph3P)2, CuI,
TMG, DMF
OAc
1. DEAD, PPh3 2. NaOH/iPrOH HOOC
+ O R
2. 6 % NH3
I O
OH O

OAc

Scheme 35

2.8. Miscellaneous
2,5-Disubstituted furans were obtained by a gold-catalyzed cycloisomerization/
dimerization pathway, involving terminal allenyl ketones and α,β-unsaturated
ketones (Scheme 36) [73].

Scheme 36

An intermolecular version of a [4+2] cycloaddition-retrofragmentation of

alkyne-oxazoles could be adapted to the synthesis of 2,3,4-trisubstituted furan
Methodologies for furan derivatives 17

in high regioselectivity, if acetylene aldehydes were used as starting materials

(Scheme 37) [74]. Methyl-substituted oxazoles reacted in a hetero [4+2]
cycloaddition reaction, with subsequent thermal extrusion of acetonitrile by a
retro-Diels-Alder process, giving substituted furan derivatives. This strategy
was applied in an elegant synthesis of norsecurinine [75].

Scheme 37

2-Aryl-3,4-fused furans were synthesized through the reaction of

propargyl nucleophiles and α-sulfonyl α,β-unsaturated ketones under
palladium catalysis conditions (Scheme 38) [76].

Scheme 38

Polysubstituted furans can be obtained in good to excellent yields via the

reactions of properly substituted 1,2-allenylketones with organic halides, under
catalysis with Pd(0) and Ag2CO3 (Scheme 39) [77].

Scheme 39

Furan-2-acetic esters were synthesized by palladium-catalysed oxidative

cyclization-alkoxycarbonylation of (Z)-2-en-4-yn-l-ols. [78] 2,3-Dimethylfurans
18 Anil Kumar & Srinivas Rao Meneni

are also formed as by-products due to a competitive cycloisomerization reaction.

The formation of furans is viewed as occurring through endo-exo-dig
intramolecular nucleophilic attack of the hydroxy group on the triple bond,
coordinated to palladium, followed by alkoxycarbonylation and aromatization
(Scheme 40).

Scheme 40

α-Cyanoketones react with ethyl glycolate under Mitsunobu conditions to

produce vinyl ethers, which on treatment with sodium hydride give rise to 3-
aminofuran-2-carboxylate esters in good yields (Scheme 41) [79]. A one-pot
procedure using the Mitsunobu reaction followed by cyclization afforded the
3-aminofuran in comparable yield. Electron-withdrawing substituents other
than carboxylic esters were also capable of stabilizing the carbanion necessary
for cyclization to the furan.

Scheme 41

The reaction of 1,1,1-trifluoro-4-arylbutan-2,4-diones with tert-butyl

isocyanide leads to fluorinated aminoketenimines, which were converted
quantitatively to trifluoromethylated furan derivatives (Scheme 42) [80].

Scheme 42

The one-pot reaction of propargyl alcohols with Grignard reagents

followed by treatment with electrophiles producing polysubstituted furans, has
been described by Fallis [81] (Scheme 43).
Methodologies for furan derivatives 19

Scheme 43

On dehydration, γ-hydroxy-α,β-unsaturated carbonyl compounds form

furans (Scheme 44). This transformation can be achieved using mineral or
Lewis acids.

Scheme 44

Functionalized furans have been synthesized employing a [3+2]

cyclization/oxidation strategy [82]. By [3+2] annulation with aldehydes,
several monohetero-substituted acetylenic or allenic derivatives have been
transformed into furans. 3-Phenylthio and 3-methoxy functionalized furans
have been obtained from 3-methoxy-l-phenylthio-1-propyne, by a sequence of
hydroxyalkylation/alkylation and cyclization [83].

3. Conclusion
This review clearly shows how different methodologies for furan
derivatives have played an important role in the development of strategies for
the preparation of mono and multi-substituted furan rings.

4. Acknowledgements
The authors wish to thank the University of Rhode Island, USA for
providing financial assistance.

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