Synthesis Of Furans Research Articles

Hexafluoroisopropanol as solvent and promotor in the Paal-Knorr synthesis of N-substituted diaryl pyrroles

Abstract An additive-free synthesis of challenging N-substituted aryl pyrroles from the often poorly soluble corresponding 1,4-diketones by means of the Paal-Knorr pyrrole synthesis is reported, which makes use of the unique properties of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a solvent and reaction promotor. Our procedure offers simple execution and purification as well as easy scale-up and can be applied in the Paal-Knorr synthesis of a large number of structurally diverse pyrroles including the synthetically challenging tetra- and penta-substituted pyrroles in moderate to excellent yields. HFIP can also be used as solvent in the Paal-Knorr synthesis of furans and thiophenes; however, the solvent effect is more pronounced in synthesis of pyrroles.

Recent Advances in the Silver Catalysed Synthesis of Furan and Its Applications

Furan and its derivatives find wide-spread application as pharmaceuticals, pigments, dyes, brighteners, flavour & fragrance compounds and insecticides. They also exhibit antihyperglycemic, analgesic, anti-inflammatory, anti-bacterial, anti-fungal and anti-tumour activities. Silver catalysts are nowadays commonly used in organic synthesis due to the high oxidation potential and versatile nature of silver complexes. In this review, we summarise the recent advances in the synthesis and applications of furan moiety using silver catalysis and covers literature from 2015-2020.

Rapid Assembly of Tetrasubstituted Furans via Pummerer-Type Rearrangement.

Despite the many methods available for the synthesis of furans, few methods remain that allow for the custom-made assembly of fully substituted furans. Here we report a powerful protocol to rapidly construct tetrasubstituted, orthogonally functionalized furans under mild reaction conditions. The developed method involves the regioselective ring-opening of readily available 2,5-dihydrothiophenes followed by an oxidative cyclization to provide the heterocycle. The selective oxidation at sulfur is promoted by N-chlorosuccinimide as an inexpensive reagent and proceeds at ambient temperature in high yield within 30 min. The obtained furans serve as exceptionally versatile intermediates and were shown to participate in a series of valuable postmodifications. The fate of the initial sulfonium intermediate was investigated by mechanistic experiments, and computational studies revealed the existence of an unprecedented Pummerer-type rearrangement. The potential for organic synthesis is highlighted by the total synthesis of bisabolene sesquiterpenoids (pleurotins A, B, and D).

Tetra-substituted furans by a gold-catalysed tandem C(sp3)–H alkynylation/oxy-alkynylation reaction

A gold-catalysed cascade C(sp3)–H alkynylation/oxy-alkynylation of acceptor-substituted carbonyl compounds with hypervalent iodine(iii) reagents for the synthesis of tetra-substituted furans, offering distinct advantages over previous methods.

Rhodium(iii)-catalyzed synthesis of trisubstituted furans via vinylic C-H bond activation.

We report an Rh(iii)-catalyzed one-pot synthesis of trisubstituted furan derivatives through Cvinyl-H activation of α,β-unsaturated ketones with acrylates. The control study revealed that the Heck-type product obtained undergoes Paal-Knorr type cyclization in the presence of an Ag salt. Hence, the Ag salt plays a dual role of a halide scavenger and a Lewis acid catalyst for Paal-Knorr type cyclization. The furan product can be transferred into the respective alcohol and acid derivatives which are useful intermediates in synthesizing biologically active molecules.

Multicomponent formation route to a new class of oxygen-based 1,3-dipoles and the modular synthesis of furans.

A new class of phosphorus-containing 1,3-dipoles can be generated by the multicomponent reaction of aldehydes, acid chlorides and the phosphonite PhP(catechyl). These 1,3-dipoles are formally cyclic tautomers of simple Wittig-type ylides, where the angle strain and moderate nucleophilicity in the catechyl-phosphonite favor their cyclization and also direct 1,3-dipolar cycloaddition to afford single regioisomers of substituted products. Coupling the generation of the dipoles with 1,3-dipolar cycloaddition offers a unique, modular route to furans from combinations of available aldehydes, acid chlorides and alkynes with independent control of all four substituents.

Merging radical-polar crossover/cycloisomerization processes: access to polyfunctional furans enabled by metallaphotoredox catalysis

Metallaphotoredox catalysis for furan synthesis: The cyclisation of yne-enones proceeds smoothly via consecutive reductive radical-polar crossover and cycloisomerization processes enabled by cooperative photoredox-neutral and copper catalysis.

Gold Catalysis and Furans: A Powerful Match for Synthetic Connections

AbstractThis review summarizes the advances made on the synthesis and functionalization of furans via gold catalysis during the period between 2016 and 2020. A separate section is dedicated to the tandem gold-catalyzed synthesis and functionalization of furans.1 Introduction2 Gold-Catalyzed Synthesis of Furans2.1 Cycloisomerizations of Alkynyl and Cumulenyl Alcohols2.2 Cycloisomerizations of Alkynyl and Allenyl Ketones2.3 Reactions with External Oxidants2.4 Miscellaneous3 Gold-Catalyzed Functionalization of Furans3.1 Cycloadditions3.2 Furan Ring Decorations3.3 Reactions Involving Furan Ring Opening4 Gold-Catalyzed Tandem Synthesis and Functionalization of Furans­4.1 Cycloisomerizations Followed by Gold-Catalyzed Cycloaddition4.2 Cycloisomerizations to a Gold 1,3- or 1,4-Dipole and Intermolecular Annulation4.3 Cycloisomerizations to a Gold Carbene and Intermolecular Trapping5 Conclusion

Lipase-catalyzed synthesis of polyhydroxyalkyl furans from unprotected sugars and malononitrile

BackgroundPolyhydroxyalkyl furans are important bioactive compounds that have been extensively studied in organic chemistry. In this work, a green and chemoselective process for the synthesis of polyhydroxyalkyl furans from unprotected sugars and malononitrile was developed. ResultsUnder optimal conditions (sugar (1 mmol), malononitrile (1 mmol), water (1 mL), Novozym 435 (200 U,13.2 mg), 60 °C, 6 h), high isolated yields of polyhydroxyalkyl furans (79 %–92 %) could be obtained when Novozym 435 was used as the catalyst, and no by-product was found in this system. Moreover, 76 % yield of polyhydroxyalkyl furan could be obtained even after six cycles. Thus, Novozym 435 exhibits satisfactory chemoselectivity and good reusability in this reaction. ConclusionThis enzymatic method demonstrates the great potential for the synthesis of polyhydroxyalkyl furans and extends the application of enzyme catalytic promiscuity in organic synthesis.

Synthesis of β-acylamino furans from glucosamine

A facile method for the synthesis of a series of novel β-acylamino furans stating from renewable monosaccharide was achieved. Glucosamine hydrochloride was selectively N-acylated with acyl chlorides in methanol/triethylamine to yield N-acyl-d -glucosamines, which were subsequently converted into β-acylamino furans through dehydration and cyclization under microwave irradiation.

Synthesis of Heterobiaryl 4-Aryl Furans through a Base-Promoted Decarboxylative Propargylation/Cycloisomerization Annulation

A transition-metal-free synthesis of heterobiaryl 4-aryl furans through a base-promoted decarboxylative propargylation/cycloisomerization annulation of ethynyl benzoxazinanones and readily accessible β-keto esters or 1,3-diketones has been developed. A series of novel heterobiaryl 4-aryl furans were accessed efficiently in the presence of base under mild reaction conditions. This protocol is significant for probing the reaction mechanism of ethynyl benzoxazinanones and even other propargylic compounds.

Synthesis of Polycyclic Furan and Chromene Derivatives via Cascade Reactions Enabled by Cleavage of Multiple C(sp3)−F Bonds

AbstractThe strong and unreactive C−F bond makes polyfluorocarbons extremely long‐lived and potentially toxic. A successive selective and controllable C(sp3)−F functionalization of polyfluoroalkylated ketones with S‐ and O‐nucleophiles to enable efficient synthesis of pharmaceutically important fluorine‐ and sulfur‐containing polycyclic furan and chromene derivatives under transition metal‐free conditions is demonstrated here. The combination of C−S/C−O coupling, aromatization, and cyclization cascade contribute to the accurate four/five C(sp3)−F bond cleavage at two different sites of perfluoroalkyl chain. The formation of reactive quinoid intermediates and the necessity of using TBAB (tetrabutylammonium bromide) as additive and Cs2CO3 as base were identified by detailed mechanistic studies.magnified image

Design, Synthesis and Biological Evaluation of Novel Furan & Thiophene Containing Pyrazolyl Pyrazolines as Antimalarial Agents

In search for novel compounds targeting Malaria, based on the in silico molecular docking binding affinity data, the novel furans containing pyrazolyl chalcones (3a-d) and pyrazoline derivatives (4a-d) were synthesized. The formation of the synthesized compound were confirmed by spectral analysis like IR, 1H NMR, 13C NMR and mass spectrometry. Compounds with thiophene and pyrazoline ring 4b (0.47 μM), 4c (0.47 μM) and 4d (0.21 μM) exhibited excellent anti-malarial activity against Plasmodium falciparum compared with standard antimalarial drug Quinine (0.83 μM). To check the selectivity furthermore, compounds were tested for antimicrobial activity and none of the synthesized compound exhibited significant potency compared with the standard antibacterial drug Chloramphenicol and antifungal drug Nystatin respectively. So, it can be resolved that the produced compounds show selectively toward antimalarial activity and have the potential to be explored further.

Transition-Metal-Free Synthesis of Trifluoromethylated Furans via a Bu3P-Mediated Tandem Acylation–Wittig Reaction

AbstractA highly efficient nucleophilic addition–O-acylation–intramolecular Wittig reaction of β-trifluoromethyl α,β-enones is disclosed. This strategy features mild reaction conditions and provides a practical transition-metal-free method to a set of biologically significant trifluoromethylated furans in high yields with diverse functional groups.

Brønsted Acid Ionic Liquid-Catalyzed Ring Opening of 3,3-Disubstituted Oxetanes in Water: Efficient Access to Furans and Benzofurans

By using water as a solvent, an eco-friendly and practical protocol for the synthesis of furans and benzofurans through a Bronsted acid ionic liquid-catalyzed ring opening of 3,3-disubstituted oxet...

Progress in Cyclizations of 4‐Acetylenic Ketones: Synthesis of Furans and Pyrroles

Abstract4‐Acetylenic ketones are a class of useful and important synthons with functionalized alkynes and carbonyl groups in one molecular skeleton. They displayed unique reactivity via cyclizations that provided access to multi‐functional furans and pyrroles. This minireview offers a comprehensive coverage of the development of their multifaceted reactivity for synthetic applications in furans and pyrroles.

Modular Synthesis of Furans with up to Four Different Substituents by a trans‐Carboboration Strategy

AbstractPropargyl alcohols, on treatment with MHMDS (M=Na, K), B2(pin)2, an acid chloride and a palladium/copper co‐catalyst system, undergo a reaction cascade comprised of trans‐diboration, regioselective acylation, cyclization and dehydration to give trisubstituted furylboronic acid pinacol ester derivatives in good yields; subsequent Suzuki coupling allows a fourth substituent of choice to be introduced and hence tetrasubstituted (arylated) furans to be formed. In terms of modularity, the method seems unrivaled, not least because each product can be attained by two orthogonal but convergent ways (“diagonal split”). This asset is illustrated by the “serial” formation of a “library” of all twelve possible furan isomers that result from systematic permutation of four different substituents about the heterocyclic core.

Modular Synthesis of Furans with up to Four Different Substituents by a trans-Carboboration Strategy.

Propargyl alcohols, on treatment with MHMDS (M=Na, K), B2(pin)2, an acid chloride and a palladium/copper co‐catalyst system, undergo a reaction cascade comprised of trans‐diboration, regioselective acylation, cyclization and dehydration to give trisubstituted furylboronic acid pinacol ester derivatives in good yields; subsequent Suzuki coupling allows a fourth substituent of choice to be introduced and hence tetrasubstituted (arylated) furans to be formed. In terms of modularity, the method seems unrivaled, not least because each product can be attained by two orthogonal but convergent ways (“diagonal split”). This asset is illustrated by the “serial” formation of a “library” of all twelve possible furan isomers that result from systematic permutation of four different substituents about the heterocyclic core.

Aryltellurium Trihalides in the Synthesis of Heterocyclic Compounds (Microreview)

The review is devoted to the methods of synthesis of furan, pyran, and thiazole derivatives employing aryltellurium trihalides published in 1983–2019.

Synthesis of Tetrasubstituted Furans through One-Pot Formal [3 + 2] Cycloaddition Utilizing [1,2]-Phospha-Brook Rearrangement.

An efficient method for the synthesis of tetrasubstituted furans was developed by utilizing the [1,2]-phospha-Brook rearrangement under Brønsted base catalysis. The two-step one-pot formal [3 + 2] cycloaddition involves the nucleophilic addition of a propargyl anion, which is catalytically generated through the [1,2]-phospha-Brook rearrangement, to an aldehyde and the subsequent intramolecular cyclization mediated by N-iodosuccinimide to provide 2,4,5-trisubstituted-3-iodofurans. The present method with readily available substrates provides new access to a wide range of well-organized tetrasubstituted furans.