synthetic methodologies of furan derivatives

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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

2 Recent synthetic methodologies for furan derivatives

Anil Kumar1 and Srinivas Rao Meneni2 1Chemistry Group, Birla Institute of Technology and Science, Pilani, Rajasthan 333031, India. E-mail: [email protected] 2Department 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: [email protected]

Anil Kumar & Srinivas Rao Meneni 2

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


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


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


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


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


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


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


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


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.


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


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


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


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].

NH

OR1

+O

Cl O

OR2 N

OR1

O

OO

N

R2

N

N

R1

O

OOR2

R3 R4

N O

OR3

R4O

O R2O

R4R3

R1O

OR2

Scheme 34


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].

IHOOC

OAc

OH

+1. DEAD, PPh3

2. 6 % NH3 I

OAc

O

OHOOC

OR

RPdCl2(Ph3P)2, CuI,TMG, DMF

1.

2. NaOH/iPrOH

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


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


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).


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. 5. References 1. Boykin, D. W. J. Braz. Chem. Soc. 2002, 13, 763. 2. a) Bauer, K. and Garbe, D. “Common fragrance and flavor materials”. VCH,

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