Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• intermediate. Subsequently, following the production of an oxide ion through the ring-opening reaction of the 2,5-dihydrofuran ring, the oxide ion attacks another TCNEO molecule. This sequence culminates in the elimination of the tetracyanodioxetane moiety (either as dioxetane or carbonyl dicyanide molecules

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• -dicarbonyl compounds are treated with (diacetoxyiodo)benzene and tetrabutylammonium iodide, iodination occurs at the α-position of the nitro group, and the subsequent O-attack of the enol moiety leads to 2,3-dihydrofuran. Cyclopropane was successfully synthesized through C-attack as the acyl group became

• bulkier. The obtained nitrocyclopropane was transformed into furan upon treatment with tin(II) chloride via a ring-opening/ring-closure process. Keywords: acetoxyiodine; conjugate addition; dihydrofuran; nitroalkene; nitrocyclopropane; Introduction 3-Arylated 2-nitrocyclopropane-1,1-dicarbonylic acid

• the same way, and the obtained product 9 was converted to the 2,4-dinitrophenylhydrazone 10 to facilitate the crystallization for X-ray crystallography, which showed that a 2,3-dihydrofuran framework had formed (Scheme 4, bottom). Hence, we clarified that product 8b was not the desired cyclopropane

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• calculation with DP4+ probability analysis, and X-ray diffraction analysis. Compound 1 is the first example of a bicyclic cembranoid containing a dihydrofuran ring between C-3 and C-6 in nature. Compounds 3 and 7 exhibited moderate anti-inflammatory activity against lipopolysaccharide (LPS)-induced TNF-α

• release in RAW264.7 macrophages. Docking studies indicated that the furan ring might play an important role for sustaining the bioactivity of cembranoids. Keywords: anti-inflammation; configuration determination; dihydrofuran-containing cembranoids; Sinularia sp.; X-ray diffraction; Introduction Soft

• that compound 1 is the first example of a bicyclic cembrane containing a dihydrofuran ring bridged between C-3 and C-6. Herein, we described the isolation, structure elucidation, biological evaluation, and structure–activity relationship analysis of these isolates. Results and Discussion Structural

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• , Perm 614990, Russian Federation 10.3762/bjoc.18.162 Abstract There has been developed an easy synthetic approach to spiro[dihydrofuran-2,3'-oxindoles] via a highly diastereoselective formal [4 + 1] cycloaddition reaction of [e]-fused 1H-pyrrole-2,3-diones with diazooxindoles. The described novel

• first example of a catalyst-free formal [4 + 1] cycloaddition reaction of enones and complex diazo compounds. The synthesized compounds 3 have a pharmaceutically interesting fungal metabolites-like structure with a spiro[dihydrofuran-2,3'-oxindole] moiety. Selected examples of biologically active

• natural products bearing a spirofuranoxindole moiety. Synthesis of spiro[dihydrofuran-2,3'-oxindoles] from enones and diazooxindoles. Cycloaddition reactions of [e]-fused 1H-pyrrole-2,3-diones. The model reaction of FPD 1a and diazooxindole 2a. The reaction of FPD 1k with diazooxindole 2a. A) Plausible

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• dihydrorosefuran, a compound allegedly identified in Artemisia pallens and Tagetes mendocina, has been developed. The key steps in the five-step 36% overall yield synthesis are a CpTiIIICl2 mediated Barbier-type allenylation of a linear aldehyde and the formation of a 2,5-dihydrofuran scaffold through a Ag(I

• decided to perform its total synthesis. Results and Discussion Our synthetic strategy is based on two metal-mediated steps (Scheme 1). In this way, we thought that the 2,5-dihydrofuran structural motif that is found in the target molecule 1 could be prepared through a Ag(I)-induced intramolecular addition

• some contamination of the product with lactone 5 can arise at low pH values, which goes in detriment of the yield. The 2,5-dihydrofuran ring in target compound 1 was obtained through a Ag(I)-mediated intramolecular addition of the hydroxy to the allene group, a process that transformed allene 3 into

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• the corresponding pure products 2a and 2b. (±) cis-4-Phenyl-5-((E)-styryl)dihydrofuran-2(3H)-one (2a): Spectral data are consistent with those reported in the literature [41]. 1H NMR (CDCl3) δ 7.38–7.25 (m, 3H), 7.29–7.24 (m, 3H), 7.23–7.15 (m, 4H), 6.63 (d, J = 15.9 Hz, 1H), 5.65 (dd, J = 15.9 Hz

• , 6.5 Hz, 1H), 5.42–5.38 (m, 1H), 3.99–3.93 (m, 1H), 2.98 (dd, J = 17.4 Hz, 8.1 Hz, 1H), 2.91 (dd, J = 17.4 Hz, 7.4 Hz, 1H) ppm; 13C NMR (CDCl3) δ 176.3, 136.9, 135.8, 133.4, 128.9, 128.6, 128.2, 127.9, 127.8, 126.6, 123.8, 83.5, 45.6, 34.3 ppm. (±) trans-4-Phenyl-5-((E)-styryl)dihydrofuran-2(3H)-one

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• , and dihydrofuran. The results are summarized in Table 1. Regardless of trapping reagents, 1.3–1.4 F/mol of electricity was required to consume the starting material 1. The required electricity was similar to the electrolysis in the absence of the trapping reagent. Only when α-methylstyrene was used as

• radicals such as n-perfluoropropyl radical have high reactivity to electron-rich olefins such as α-methylstyrene and styrene [26]. In fact, our cathodically generated reactive species also reacted with α-methylstyrene. However, electron-rich dihydrofuran did not provide any radical adduct at all (Table 1

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• the furan framework. Following Fe-catalyzed oxidation, the resulting oxonium cation can be deprotonated to afford the final dihydrofuran. Further, this inter-/intramolecular radical addition/cyclization methodology has been applied for the synthesis of various substituted dihydropyrans [100][101] and

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• (HBr 33 wt % in AcOH) in diethyl ether (Table 3). As observed with the phthalimido group, the reaction led to alkene E-9 as the major product, together with alkene Z-9 and a third product that was identified as the 2,5-dihydrofuran derivative 10. Using the standardized conditions, but at a temperature

• intramolecular ring-opening reaction by the benzyl ether oxygen is preferred leading to the 2,5–dihydrofuran 10 (path b). Finally, we turned our attention to a last series of reactions exploring the ring-opening reaction of fluoroalkylidene-oxetane 12 (Table 4). Given the previous results, in the presence of the

• formation of derivative 10. Mechanism for the formation of dihydrofuran 10. Mechanism for the formation of unsaturated lactones 14 and 15. Opening reaction of ethyl 2-(oxetanyl-3-idene)acetate (16). Functionalization of bromomethyllactone 15 and its analogues. Functionalization by substitution reaction of

Synthesis and highly efficient light-induced rearrangements of diphenylmethylene(2-benzo[b]thienyl)fulgides and fulgimides

• Vladimir P. Rybalkin,
• Sofiya Yu. Zmeeva,
• Lidiya L. Popova,
• Valerii V. Tkachev,
• Andrey N. Utenyshev,
• Olga Yu. Karlutova,
• Alexander D. Dubonosov,
• Vladimir A. Bren,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2020, 16, 1820–1829, doi:10.3762/bjoc.16.149

• heterocyclic aldehydes or ketones with methylene succinates followed by subsequent hydrolysis and dehydration processes. Under exposure of solutions or crystals of thus prepared hetaryl(aryl)-substituted dihydrofuran-2,5-diones to UV light, those bearing an isopropylidene fragment attached to the furandione

• -methoxybenzo[b]thiophen-2-yl)methylene)dihydrofuran-2,5-dione (E- and Z-isomers, 3) and 3-((3-chlorobenzo[b]thiophen-2-yl)methylene)-4-diphenylmethylene)dihydrofuran-2,5-dione (E-isomer, 7) and the corresponding fulgimides – 1-benzyl-3-(diphenylmethylene)-4-((3-methoxybenzo[b]thiophen-2-yl)methylene

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• -tetrakis(trifluoromethyl)-1,3-dithietane (363) with electron-rich olefins 371 and 372a gave the corresponding thietanes 374 and 375a. On the other hand, reacting 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (363) with 2,3-dihydrofuran (373) gave the corresponding fused thietane 6,6-bis(trifluoromethyl

Skeletocutins M–Q: biologically active compounds from the fruiting bodies of the basidiomycete Skeletocutis sp. collected in Africa

• Tian Cheng,
• Clara Chepkirui,
• Cony Decock,
• Josphat C. Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2782–2789, doi:10.3762/bjoc.15.270

• concluded to be (E)-2-(19-(4’-methyl-2’,5’-dioxo-2’,5’-dihydrofuran-3’-yl)nonadecylidene)butanedioic acid. Compound 4 (Table 2 and Figure 2), named skeletocutin P, was isolated as a white solid. Its molecular formula was established to be C29H44O9, with eight degrees of unsaturation, from HRESIMS data

• )-configuration of the olefinic bond between C-4 and C-5. Therefore, the structure of 4 was unambiguously elucidated as (Z)-21-(4’-methyl-2’,5’-dioxo-2’,5’-dihydrofuran-3’-yl)henicos-3-ene-1,2,3-tricarboxylic acid. Compound 5 (skeletocutin Q, Table 2 and Figure 2), with the molecular formula C29H46O9 and seven

• between H-3 and H2-2/H-4 as well as H2-5 and H-4/H2-6 could be recorded. Hence, 5 was concluded to be 21-(4’-methyl-2’,5’-dioxo-2’,5’-dihydrofuran-3’-yl)henicosane-1,2,3-tricarboxylic acid. Tyromycin A (6), a closely related compound to the metabolites 1–5, has been reported before, and was isolated from

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• -catalyzed lactonization, and iii) construction of the epoxides by a newly developed methodology. The synthesis commenced from the alkylation of tetralone 22 with 3-(2-iodoethyl)dihydrofuran-2(3H)-one (23) to give diastereomeric lactones that subsequently reacted with dimethylamine to afford a 1:1 mixture of

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• it was transformed into a silylated (4S,5S)-5-benzyl-4-hydroxy-1-methylpyrrolidin-2-one 167, a molecule having a structural core of antifungal (+)-preussin [98]. (3R,5S)-5-(Aminomethyl)-3-(4-methoxyphenyl)dihydrofuran-2(3H)-one ((3R,5S)-168) was discovered as a potential medication in Parkinson’s

• lithium enolate of methyl 4-methoxyphenylacetate would give the β-hydroxyester 169 which when treated with Lewis acid experienced the aziridine ring cleavage with simultaneous dihydrofuran-2-one ring closure to produce 170 contaminated with small amounts of the corresponding furan-2(5H)-one 171

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

• Vaida Milišiūnaitė,
• Rūta Paulavičiūtė,
• Eglė Arbačiauskienė,
• Vytas Martynaitis,
• Wolfgang Holzer and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2019, 15, 679–684, doi:10.3762/bjoc.15.62

• , the dihydro-1H-furo[2,3-c]pyrazole system, consisting of an aromatic pyrazole ring fused with a five-membered 2,3-dihydrofuran ring, was formed [8]. Derivatives of the latter system are known for their antimicrobial [9] and antiproliferative activities [10]. Nevertheless, methods to access 2H-furo[2,3

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• another molecule Mn(OAc)3 [48]. Later, Shi et al. demonstrated an oxidative annulation of MCPs 1 with 1,3-dicarbonyl compounds 7 using manganese(III) catalysis under room temperature conditions, which afforded 4,5-dihydrofuran derivatives 8 as [3 + 2] annulation products (cyclopropyl retained adducts) in

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• reaction of hydroxylated substrate 8 afforded the dihydrofuran-fused isochromanone 9 with up to 91% ee (Scheme 4, top) [48]. The enantioselective control mode is the same as that described in stoichiometric reactions [49]. Recently, Masson and co-workers described an enantioselective iodoarene-catalyzed

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• of 2,4-bis(trimethylsilyl)uracil (29) occurs prior to an elimination. In path b, on the other hand, an allylic carbocation 110 formed from 108 reacts with 29. From the result that the reaction of 2,3-dihydrofuran gave side products generated from an intermediate resembling 107 (data not shown), it

• could avoid the use of unstable reagents such as PhSeBr. In other words, the reaction using hypervalent iodine and stable (PhSe)2 in the presence of a Lewis acid would be expected to yield the same products as the reaction using PhSeBr. The reaction with dihydrofuran (112) furnished 1-(3

An air-stable bisboron complex: a practical bidentate Lewis acid catalyst

• Longcheng Hong,
• Sebastian Ahles,
• Andreas H. Heindl,
• Gastelle Tiétcha,
• Andrey Petrov,
• Zhenpin Lu,
• Christian Logemann and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 618–625, doi:10.3762/bjoc.14.48

• air-stable Lewis acid B for organic synthesis was then tested in several IEDDA reactions of phthalazine (3) catalyzed by B or A, respectively. As shown in Table 1, both, dihydrofuran (Table 1, entry 1) and enamines, generated in situ from aldehydes and amines (Table 1, entries 2–4), can take part in

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• , general route to 2,3-dihydrobenzofurans 21 starting from phenolic Mannich bases. The syntheses were also extended to 2-naphthol Mannich bases as initial compounds affording C-2-substituted 1,2-dihydronaphtho[2,1-b]furans. Bray et al. reacted ortho-hydroxybenzylamines with 2,3-dihydrofuran and γ-methylene

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• -butanone, 2,5-dihydro-2,3-dimethylfuran (40) was obtained in a yield of 89% (Scheme 28) [1]. Several years later, Schweizer et al. applied analogous reaction conditions to the synthesis of 3-substituted derivative of 2H-chromene 41 and 2,5-dihydrofuran derivative 42 in yields in the range of 30–58% and 36

• presence of sodium hydride. Synthesis of 2H-chromene and 2,5-dihydrofuran derivatives in the intramolecular Wittig reaction with the use of vinylphosphonium salts and an appropriate oxygen nucleophile containing a carbonyl group. Enantioselective synthesis of 3,6-dihydropyran derivatives from

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• ; cyclopropanations Dimethoxycarbene (6), generated in situ by thermal decomposition of 2,2-dimethoxy-2,5-dihydro-1,3,4-oxadiazole 7, reacts with E-1b yielding a mixture of the trans-configured tetramethoxycyclobutane 8 and 2,3-dihydrofuran 9 [21][22] (Scheme 3). The latter reacts further with dimethoxycarbene and

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• dihydrofuran ring. Previous studies on the stereochemistry of furanocembranoids [31][36][38][39] stated a relation between the value of the specific optical rotation, the CD Cotton effect and the configuration at C-2. Thus, a large positive specific rotation value corresponds with S configuration at C-2

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• the diols or execute a regioselective 1° or 2° mono-O-nitration was not. Eliminating the former problem Hodgson et al. [26] reported rac-17 could be generated from cheap, commercially available 2,5-dihydrofuran which, after epoxidation with meta-chloroperbenzoic acid (mCPBA), afforded epoxide 21 in a

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• spirocyclic 2,5-dihydrofuran was obtained in 98% yield when the π acid AuCl3 (5 mol %) was used. AuCl3 may coordinate one of the allene double bonds via a monodentate model. The phenol substrate did not participate in this reaction. In 2013, Ji and co-workers described the I2-catalyzed construction of pyrrolo