Quinolone analogues 7 [1‐6]. Synthesis of 3‐Heteroaryl‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones

The 3‐heteroaryl‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones 6a‐e were synthesized by the oxidative‐hydrolytic ring transformation of the 3‐heteroaryl‐1,2‐diazepino[3,4‐b]]quinoxaline‐5‐carbonitriles 9a‐c , which were obtained by the 1,3‐dipolar cycloaddition reaction of the 2‐(2‐heteroarylmethylene‐1‐methylhydrazino)quinoxaline 4‐oxides with 2‐chloroacrylonitrile. The assignment of the thiophene and furan ring protons was carried out through the data of the NOE, decoupling, and coupling constants.     

Synthesis of [3,3′(4H,4′H)‐Bi‐2H‐1,3‐oxazine]‐4,4′‐diones and Their Hydrolysis

The [3,3′(4H,4′H)‐bi‐2H‐1,3‐oxazine]‐4,4′‐diones 3a – 3i were obtained by [2+4] cycloaddition reactions of furan‐2,3‐diones 1a – 1c with aromatic aldazines 2a – 2d (Scheme 1). So, new derivatives of bi‐2H‐1,3‐oxazines and their hydrolysis products, 3,5‐diaryl‐1H‐pyrazoles 4a – 4c (Scheme 3), which are potential biologically active compounds, were synthesized for the first time.     

5‐Amido‐ and 5‐Amino‐Substituted Epoxyisoindolo[2,1‐a]tetrahydroquinolines and 10‐Carboxylic Acids: Their Synthesis and Reactivity

The interactions between 4‐R‐substituted 2‐furyl‐1,2,3,4‐tetrahydroquinolines (synthesized by the Povarov reaction) and a number of alkenes have been investigated. Maleic, dibromomaleic, dichloromaleic, and citraconic anhydrides, as well as acryloyl, methacryloyl, crotonyl, and cynnamoyl chlorides were used as alkene components. It was shown that the initial N‐acylation of the tetrahydroquinolines was followed by a spontaneous [4+2]‐cycloaddition of an N‐acryloyl substituent to the furan ring. It was established that the intramolecular Diels–Alder reaction of furans is reversible, occurs stereoselectively as exo‐addition, and led to target epoxyisoindolo[2,1‐a]tetrahydroquinolines with moderate yields. Oxidation and aromatization of the synthesized products were carried out.     

Total Synthesis of (−)‐Cephalotaxine and (−)‐Homoharringtonine via Furan Oxidation–Transannular Mannich Cyclization

Homoharringtonine and its congener cephalotaxine were synthesized. Oxidative ring‐opening of a furan unveils an amine‐tethered dicarbonyl, which undergoes spontaneous transannular Mannich cyclization. The cascade builds the full cephalotaxine substructure in a single operation in 60 % yield. A Noyori reduction enabled synthesis of the title compounds with excellent enantioselectivity (k_rel=278).     

On the Enantioselectivity of Transition Metal‐Catalyzed 1,3‐Cycloadditions of 2‐Diazocyclohexane‐1,3‐diones

The formal 1,3‐cycloaddition of 2‐diazocyclohexane‐1,3‐diones 1a –1 d to acyclic and cyclic enol ethers in the presence of Rh^II‐catalysts to afford dihydrofurans has been investigated. Reaction with a cis/trans mixture of 1‐ethoxyprop‐1‐ene ( 13a ) yielded the dihydrofuran 14a with a cis/trans ratio of 85 : 15, while that with (Z)‐1‐ethoxy‐3,3,3‐trifluoroprop‐1‐ene ( 13b ) gave the cis‐product 14b exclusively. The stereochemical outcome of the reaction is consistent with a concerted rather than stepwise mechanism for cycloaddition. The asymmetric cycloaddition of 2‐diazocyclohexane‐1,3‐dione ( 1a ) or 2‐diazodimedone (=2‐diazo‐5,5‐dimethylcyclohexane‐1,3‐dione; 1b ) to furan and dihydrofuran was investigated with a representative selection of chiral, nonracemic Rh^II catalysts, but no significant enantioselectivity was observed, and the reported enantioselective cycloadditions of these diazo compounds could not be reproduced. The absence of enantioselectivity in the cycloadditions of 2‐diazocyclohexane‐1,3‐diones is tentatively explained in terms of the Hammond postulate. The transition state for the cycloaddition occurs early on the reaction coordinate owing to the high reactivity of the intermediate metallocarbene. An early transition state is associated with low selectivity. In contrast, the transition state for transfer of stabilized metallocarbenes occurs later, and the reactions exhibit higher selectivity.     

Synthesis of New 3‐(Furan‐2‐yl)‐Substituted Dibenzo‐Diazepin‐1‐one Derivatives

A new series of 3‐(furan‐2‐yl) dibenzo‐diazepin‐1‐one derivatives were synthesized by condensation of 5‐(furan‐2‐yl)‐1,3‐cyclohexanedione, o‐phenylenediamine, and aromatic aldehydes, in which in some of them existed two very close isomer compounds. All the compounds were characterized by IR, MS, ¹H NMR, and elemental analysis. Also presented were the crystal structures of 3a , 3b and 3e , which were obtained and determined by X‐ray single‐crystal diffraction.     

Highly cis‐1,4 Selective Living Polymerization of Unmasked Polar 2‐(2‐Methylidenebut‐3‐enyl)Furan and Diels–Alder Addition

The polymerization of a new polar diene‐based monomer 2‐(2‐methylidenebut‐3‐enyl)furan (MBEF) without masking is achieved by using the bis(phosphino)carbazoleide‐ligated yttrium (Y) alkyl complex upon the activation of [Ph₃C][B(C₆F₅)₄]. Under mild conditions, the polymerizations under the monomer‐to‐Y ratios ranging from 100:1 to 500:1 perform fluently in high yields. The afforded polydienes bearing pendant terminal furan groups have high cis‐1,4‐regularity up to 98.6% and molecular weights close to the theoretic values and narrow polymer dispersity index(PDI) (1.13–1.17) suggesting a livingness polymerization mode. In addition, this novel polydiene is an excellent building block for preparing functional rubber materials. For example, via Diels–Alder addition of furan groups under mild conditions, hydroxyl groups are successfully introduced on the side chains efficiently in a 75% conversion. Furthermore, the copolymerization of polar MBEF and nonpolar isoprene is also successfully realized by the bis(phosphino) carbazoleide‐ligated scandium analog to access furan‐modified cis‐1,4 (>97%) polyisoprene with different MBEF contents (5.3%, 8.7%).     

Synthesis and Cytotoxic Activity of 1‐{3‐[1‐(5‐Organylsilylfuran‐2‐yl)silinan‐1‐yl]propyl}amines and Some Trimethylgermyl Analogues

New highly cytotoxic 1‐{3‐[1‐(5‐organylsilyl‐furan‐2‐yl)silinan‐1‐yl]propyl}amines and some trimethylgermyl analogues (IC₅₀ 1–7 μg mL^?1) have been synthesized by a hydrosilylation reaction of aliphatic and heterocyclic N‐allylamines in the presence of Speier’s catalyst. The effects of the silacycle, the element‐organic substituent in position 5 of the furan ring, and the structure of the amine on the cytotoxicity of the new compounds have been studied.     

Synthesis of Novel Pyrazole–sucrose Derivatives by 1,3‐dipolar Cycloaddition

The syntheses of an important class of enantiopure five‐membered glyconjucates containing furan unit are described. The regioselective synthesis of a series of sugar‐fused pyrazole heterocycles was achieved by the Huisgen cyclization of aryl diazomethanes with propargyl O‐glycoside derivatives in good yields. The cycloaddition regioselectivity was confirmed by NMR.     

Synthesis of Some Novel 4‐(Furan‐2‐yl)‐5,6‐dimethylpyridines

N‐2‐amino‐4‐(furan‐2‐yl)‐5,6‐dimethylnicotinonitrile ( 4 ) was utilized as key intermediate for the synthesis of some new, pyridopyrimidine, benzo[1,5][g]oxazocine, naphthoquinone, and isoindole derivatives. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, ¹H‐NMR, and mass spectral data.     

Synthesis of 1‐acyl‐2‐oxo‐3‐pyrrolidinecarbonitriles by the reaction of 2‐acylamino‐4,5‐dihydro‐3‐furancarbonitriles with sodium iodide

The reaction of 2‐acylamino‐4,5‐dihydro‐3‐furancarbonitriles 1 with sodium iodide in N,N‐dimethyl‐formamide gave the corresponding 1‐acyl‐2‐oxo‐3‐pyrrolidinecarbonitriles 2 in good yields. Successive treatment of 1 with titanium(IV) chloride and potassium carbonate resulted in the formation of N‐acyl‐1‐cyanocyclopropanecarboxamides 4 . The same compounds 2 were also obtained by treatment of 4 with sodium iodide. The starting compounds 1 were synthesized by the reaction of 2‐amino‐4,5‐dihydro‐3‐furan‐carbonitrile with acyl chlorides in pyridine.     

Synthesis of Two Natural Furan‐Cyclized Diarylheptanoids via 2‐Furaldehyde

Two natural diarylheptanoids, 2‐benzyl‐5‐(2‐phenylethyl)furan ( 1 ) and 2‐methoxy‐4‐{[5‐(2‐phenylethyl)furan‐2‐yl]methyl}phenol ( 2 ), were synthesized starting from 2‐furaldehyde. A Wittig reaction of 2‐furaldehyde with benzyltriphenylphosphonium bromide followed by reduction of the alkene C?C bond with Mg gave 2‐(2‐phenylethyl)furan ( 5 ). Lithiation of 5 with BuLi at ?78° followed by alkylation with benzyl bromide gave natural product 1 . In another approach, Friedel? Crafts acylation of compound 5 with benzoyl chloride followed by deoxygenation of the C?O group afforded 1 . The natural product 2 was also synthesized by acylation of 5 with 4‐acetoxy‐3‐methoxybenzoyl chloride ( 16 ) followed by deoxygenation and deacetylation.     

Studies on pyrazines. 36. A novel synthesis of 6‐(2‐hydroxyethyl)‐1,3‐dimethyllumazine

The titled compound was synthesized by cycloaddition of 5,6,7,8‐tetrahydro‐5,7‐dimethyl‐3,6,8‐trioxo‐3H‐pyrimido[5,4‐c][1,2,5]oxadiazine ( 1 ) with 2,3‐dihydrofuran ( 2a ).     

Synthesis and Bioactivity of Novel N,N′‐Diacylhydrazine Derivatives Containing Furan(I)

The furan ring system possesses electron‐rich properties and exhibits various biological activities, which was introduced into diacylhydrazine to create novel leading compounds that may serve as improved pesticides and pharmaceuticals. A series of novel diacylhydrazine derivatives containing a furan ring were synthesized by the reaction of 5‐fluorophenyl‐2‐furoyl chloride with substituted benzoylhydrazide in anhydrous dichloromethane under reflux. The structures of the resultant compounds were confirmed by IR, ¹H NMR, MS and elemental analysis. Insecticidal and anti‐tumor activities of these new compounds were evaluated.     

Eight‐Step Enantioselective Total Synthesis of (−)‐Cycloclavine

The first enantioselective total synthesis of (−)‐cycloclavine was accomplished in 8 steps and 7.1 % overall yield. Key features include the first catalytic asymmetric cyclopropanation of allene, mediated by the dirhodium catalyst Rh₂(S‐TBPTTL)₄, and the enone 1,2‐addition of a new TEMPO carbamate methyl carbanion. An intramolecular strain‐promoted Diels–Alder methylenecyclopropane (IMDAMC) reaction provided a pivotal tricyclic enone intermediate with more than 99 % ee after crystallization. The synthesis of (−)‐ 1 was completed by a late‐stage intramolecular Diels–Alder furan (IMDAF) cycloaddition to install the indole.     

Furan‐Based o‐Quinodimethanes by Gold‐Catalyzed Dehydrogenative Heterocyclization of 2‐(1‐Alkynyl)‐2‐alken‐1‐ones: A Modular Entry to 2,3‐Furan‐Fused Carbocycles

A strategy for in situ generation of furan‐based ortho‐quinodimethanes (o‐QDMs) by the gold(I)‐mediated dehydrogenative heterocyclization of 2‐(1‐alkynyl)‐2‐alken‐1‐ones in the presence of pyridine N‐oxide under mild reaction conditions was developed. These in situ furan‐based o‐QDMs were trapped by electron‐deficient olefins and alkynes, thus furnishing various 2,3‐furan‐fused carbocycles in good yields with high diastereo‐ and regioselectivities.     

Synthesis,structure and cytotoxicity of new 2‐[(3‐aminopropyl)dimethylsilyl]‐5‐furfural diethylacetals and 2‐[(3‐aminopropyl)dimethylsilyl]‐5‐phenylfurans

Novel 2‐[(3‐aminopropyl)dimethylsilyl]‐5‐furfural diethylacetals and 2‐[(3‐aminopropyl)di‐methylsilyl]‐5‐phenylfurans have been synthesized by a hydrosilylation reaction of aliphatic and heterocyclic N‐allylamines in the presence of the Speier's catalyst. The effects of the structure of the amine and nature of organic substituent at the furan ring on the cytotoxicity of the new compounds have been studied. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis,spectral, and antimicrobial studies of 1‐butyl‐3‐substituted‐4‐(2‐aryl‐1H‐indol‐3‐yl)‐2‐azetidinones

Ketene generated from acetyl chloride or chloroacetyl chloride adds on indolyl Schiff's base double bond to afford 1‐butyl‐3‐substituted‐4‐(2‐aryl‐1H‐indol‐3‐yl)‐2‐azetidinones in THF. The reaction proceeds stereospecifically via concerted trans [2+2] cycloaddition. The synthesized compounds have been characterized by elemental analyses and spectral data (IR, PMR, and mass). All synthesized compounds have been evaluated for antibacterial and antifungal activities, and 4g to 4l have shown promising results. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:494–501, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20052     

A new approach for the synthesis of some pyrazolo[5,1‐c]triazines and pyrazolo[1,5‐a]pyrimidines containing naphtofuran moiety

Naphtho[2,1‐b]furan‐2‐yl)(8‐phenylpyrazolo[5,1‐c][1,2,4]triazin‐3‐yl)methanone, ([1,2,4]triazolo[3,4‐c][1,2,4]triazin‐6‐yl)(naphtho[2,1‐b]furan‐2‐yl)methanone, benzo[4,5]imidazo[2,1‐c][1,2,4]triazin‐3‐yl‐naphtho[2,1‐b]furan‐2‐yl‐methanone, 5‐(naphtho[2,1‐b]furan‐2‐yl)pyrazolo[1,5‐a]pyrimidine, 7‐(naphtho[2,1‐b]furan‐2‐yl)‐[1,2,4]triazolo[4,3‐a]pyrimidine, 2‐naphtho[2,1‐b]furan‐2‐yl‐benzo[4,5]imidazo[1,2‐a]pyrimidine, pyridine, and pyrazole derivatives are synthesized from sodium salt of 5‐hydroxy‐1‐naphtho[2,1‐b]furan‐2‐ylpropenone and various reagents. The newly synthesized compounds were elucidated by elemental analysis, spectral data, chemical transformation, and alternative synthetic route whenever possible. J. Heterocyclic Chem., (2012).     

Multicomponent Reactions of Furan‐2,3‐diones: Synthesis and Characterizations of Furo[3,2‐c]pyran‐4‐ones

Furo[3,2‐c]pyran‐4‐ones, which possess a natural‐product skeleton, are synthesized via a simple, one‐pot, three‐component reaction of furan‐2,3‐diones with dialkyl acetylenedicarboxylates and Ph₃P.