Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• isoquinolones is very wide and may be extended to the preparation of complex compounds having heterocyclic moieties such as pyridone, furan, thiophene and pyrrole, as well as the corresponding benzo-fused derivatives. The developed procedure is simple, reproducible and does not require inert conditions

• rings, such as furan, benzofuran, pyrrole, benzopyrrole, thiophene, benzothiophene and naphthalene were also successfully synthesized (5d–l) in moderate to very good yields. The exceptions were the cases of indolopyridone 5i and thiazolopyridone 5k, the latter one could not be obtained even after many

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

• 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

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Enantioselective PCCP Brønsted acid-catalyzed aza-Piancatelli rearrangement

• Gabrielle R. Hammersley,
• Meghan F. Nichol,
• Helena C. Steffens,
• Jose M. Delgado,
• Gesine K. Veits and
• Javier Read de Alaniz

Beilstein J. Org. Chem. 2019, 15, 1569–1574, doi:10.3762/bjoc.15.160

• furan ring required to initiate the cascade sequence. This highlights that a balance between nucleophilicity and hydrogen bond capabilities are required to obtain an efficient and selective reaction. Compared to the rearrangement of furylcarbinol 1a, sterically bulky aryl groups attached to the

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• Abstract The multicomponent synthesis of prolyl pseudo-peptide catalysts using the Ugi reaction with furfurylamines or isocyanides is described. The incorporation of such a polymerizable furan handle enabled the subsequent polymerization of the peptide catalyst with furfuryl alcohol, thus rendering

• synthesis of prolyl pseudo-peptides having a furan ring handle, which could be subsequently incorporated into PFA during the polymerization process. Results and Discussion To this end, a solution-phase multicomponent procedure based on the Ugi four-component reaction (Ugi-4CR) [14], was employed to

• incorporate proline [15] and the furan functionality into pseudo-peptide catalysts. As shown in Scheme 2, Boc-L-proline and acetone were employed as acid and oxo components, respectively, in combination either with furfurylamine and cyclohexyl isocyanide or with (S)-α-methylbenzylamine and furfuryl isocyanide

Switchable selectivity in Pd-catalyzed [3 + 2] annulations of γ-oxy-2-cycloalkenones with 3-oxoglutarates: C–C/C–C vs C–C/O–C bond formation

• Yang Liu,
• Julie Oble and
• Giovanni Poli

Beilstein J. Org. Chem. 2019, 15, 1107–1115, doi:10.3762/bjoc.15.107

• combination may allow direct access to either fused bicyclic cyclopentanic (pentalene-, indene-, or azulene-type) structures via a γ-C-allylation/β-C-1,4 addition process, or annulated furan-based motifs through a γ-C-allylation/β-O-1,4 addition process, both motifs being incorporated into biologically

• or C–C/O–C annulation at will, thus providing an easy access to annulated cyclopentanic structures III or annulated furan-based motifs IV, respectively. Additionally, in the case of C–C/C–C bond forming annulations, the products III can undergo two decarboxylation steps leading to bis-cycloalkanone

• annulated cylopentanic (top) and furan-based (bottom) substructures in natural products. Previously developed bis-nucleophile/bis-electrophile [3 + 2] annulations. Concept: [3 + 2] C–C/C–C vs C–C/O–C bond-forming annulations. C–C/O–C bond forming annulations with dimethyl 3-oxoglutarate (1a). C–C/C–C bond

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• -dihydroisobenzofuran-5-ol intermediate has been tested and oxidation parameters of the dedicated structures were optimized. Finally, a rapid deprotection step was initiated to afford 4-MeO-OPA and 4-HO-OPA with 51% overall yield. Results and Discussion Firstly, 2-((prop-2-ynyloxy)methyl)furan (2) was synthesized

• . Synthetic procedures 2-((Prop-2-ynyloxy)methyl)furan (2). Adapted from reference [17]: Furfuryl alcohol (9.0 mL, 103.8 mmol) was added dropwise to a solution of NaH (5.0 g, 207.5 mmol) in DMF (100 mL) at 0 °C. After 90 minutes, propargyl bromide (12.7 mL, 114.2 mmol) was added dropwise and the resulting

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

• -c]pyrazoles, where both the fused pyrazole and furan moieties are aromatic, are still quite limited, and their chemistry and functional properties remain largely underexplored. Huang et al. have reported the synthesis and the evaluation of antiplatelet and anti-allergic activities of 2,3,4

• alkoxide [11]. Notably, the 2H-furo[2,3-c]pyrazole ring system is structurally similar to the benzo[b]furan system, which is a privileged motif in natural products and biologically active compounds [13][14]. As a result, numerous strategies have been developed for the construction of benzo[b]furan and its

• alkynylation/cyclization reaction between 2-iodophenol and (triethoxysilyl)alkynes [20]. In recent years silver and gold salts have found application as versatile and mild catalysts to access the benzo[b]furan ring system through intramolecular cyclization of 2-alkynylphenol substrates [21], including

Synthesis of 1,2-divinylcyclopropanes by metal-catalyzed cyclopropanation of 1,3-dienes with cyclopropenes as vinyl carbene precursors

• Jesús González,
• Alba de la Fuente,
• María J. González,
• Laura Díez de Tejada,
• Luis A. López and
• Rubén Vicente

Beilstein J. Org. Chem. 2019, 15, 285–290, doi:10.3762/bjoc.15.25

• proceeded in reasonable yields while the diastereoselectivity strongly depends on the structure of the diene. An example of an intramolecular process as well as the use of furan and 1,4-cyclohexadiene as dienes are also reported. Keywords: cyclopropanation; cyclopropenes; dienes; divinylcyclopropanes

• good yield (77%) in a stereoctive manner (Scheme 4). Finally, we were curious to study the reactivity of metal–vinyl carbenes generated from 3,3-disubstituted cyclopropenes with some particular dienes (Scheme 5). Interestingly, we found that the reaction of cyclopropenes 1a,b with furan (6) using ZnCl2

• compounds, which led again to oxy-Cope rearranged or [4 + 3]-cycloaddition products using rhodium catalysts [14][28][29][30], or to a C2-allylation of furan with gold catalysts [31]. Finally, to compare the reactivity of cyclopropenes and vinyldiazo compounds, we probed the reaction of 1a with 1,4

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• L-malic acid [62], was carefully reduced and immediately acetylated to (S)-52 which was reacted with furan to produce a 67:33 mixture of readily separable (2S,3S)-53 and (2R,3S)-53, respectively. Steric hindrance of the acetoxy substituent controls the formation of higher amounts of the trans-isomer

• . Ozone efficiently completed the degradation of the furan ring to the carboxyl group which was esterified with diazomethane to give methyl (2S,3S)-3-acetoxypyroglutamate (2S,3S)-54, a cyclized variant of 3-hydroxyglutamic acid. Treatment with a concentrated acid afforded (2S,3S)-2 as the hydrochloride

• (2S,3R)-2 via Sharpless epoxidation. Reagents and conditions: a) TBHP, D-(−)-DIPT, Ti(OiPr)4, MS, CH2Cl2; b) t-BuMe2SiCl, imidazole, DMAP, DMF; c) NaIO4, RuO2, AcOEt/H2O. Synthesis of (2S,3S)-2 from the imide 51. Reagents and conditions: a) NaBH4, MeOH/CH2Cl2; b) Ac2O, pyridinium perchlorate; c) furan

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• yields of α-hydroxyimino esters 2t–v reached 49, 59 and 62% from aldehydes 5t–v, respectively. Of note is that we also tried this reducing agent to improve the overall yield of the benzyloxy-bearing oxime 2ab, but to no avail. We next focused on the furan-bearing α-hydroxyimino esters such as compound

• 2ae. First of all, reduction of the alkylidenemalonate 6ae using a palladium-based catalytic hydrogenation also led to the concomitant hydrogenation of the furan ring to give compound 8. As depicted, this actually allowed us to prepare to the 2-tetrahydrofuranyl-bearing α-aminoester 10 in a 35

• % overall yield via α-hydroxyimino ester 9, but it also forced us to use borohydrides to avoid the furan ring hydrogenation. Accordingly, an extensive study of the reduction of compound 6ae with borohydrides was made. Trials included reactions run at 0 °C overnight, the use of wet ethanol or dry THF, the

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• improvements were observed with these conditions. Other series of trials were made to improve the overall yields of the furan-bearing α-nitro esters 6n–r. We first tried to avoid the preparation of the acetals 5n or 5o and used the previously reported direct condensation between furfural (3n) and ethyl

• acid in ethanol overnight gave a sufficient amount of the (pure) target phenyl-bearing α-amino ester 10 which had been previously obtained by catalytic hydrogenation using palladium [20]. The same transformation sequences were used starting with compound 6n and provided the furan-bearing α-amino ester

Novel photochemical reactions of carbocyclic diazodiketones without elimination of nitrogen – a suitable way to N-hydrazonation of C–H-bonds

• Liudmila L. Rodina,
• Xenia V. Azarova,
• Jury J. Medvedev,
• Dmitrij V. Semenok and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2018, 14, 2250–2258, doi:10.3762/bjoc.14.200

• %. Further irradiation of hydrazones derived from furan-fused tricyclic diazocyclopentanediones culminates in the cycloelimination of furans to yield 2-N-(alkyl)hydrazone of cyclopentene-1,2,3-trione. By contrast, the direct photolysis of carbocyclic diazodiketones gives only Wolff rearrangement products

• unexpected side reaction was observed during irradiation of furan-fused tricyclic diazodiketones 1d,e (Scheme 1). In the case of diazodiketone 1d, hydrazone 3 (47%) was isolated from reaction mixture in addition to the expected hydrazone 2d (35%; total yield 82%, Table 1, entry 11), whereas the same reaction

• light-induced cycloelimination of furan from the initially generated tricyclic hydrazones 2d,e. Hence it was established that the sensitized photoexcitation of diazodiketones 1a–d,f in THF solution proceeds through the insertion of the terminal N-atom of the diazo group in the α-С–Н-bond of THF with the

Studies towards the synthesis of hyperireflexolide A

• G. Hari Mangeswara Rao

Beilstein J. Org. Chem. 2018, 14, 2106–2111, doi:10.3762/bjoc.14.185

• . Experimental procedures and analytical data Methyl 1,1,5-trimethyl-3,4-dioxohexahydro-1H-cyclopenta[c]furan-5-carboxylate (8): To a solution of the γ-lactone-fused cyclopentanone 6 (16 mg, 0.07 mmol) in dry acetone (0.4 mL) under argon was added anhydrous K2CO3 (9.7 mg, 0.07 mmol) and methyl iodide (12 mg

• . Methyl 1,1,3a,5-tetramethyl-3,4-dioxohexahydro-1H-cyclopenta[c]furan-5-carboxylate (9): To a solution of the γ-lactone-fused cyclopentanone 8 (15 mg, 0.07 mmol) in dry acetone (0.4 mL) under argon was added anhydrous K2CO3 (9.7 mg, 0.07 mmol) and methyl iodide (12 mg, 0.08 mmol) at 0 °C. The reaction was

• -dioxohexahydro-1H-cyclopenta[c]furan-5-carboxylate (4): To a solution of the γ-lactone-fused cyclopentanone 6 (75 mg, 0.331 mmol) in dry acetone (1 mL) under argon was added anhydrous K2CO3 (55 mg, 0.3972 mmol) and allyl bromide (48 mg, 0.3972 mmol) at 0 °C. The reaction was stirred at 0 °C for 21 h. Completion

Synthesis of pyrazolopyrimidinones using a “one-pot” approach under microwave irradiation

• Mark Kelada,
• John M. D. Walsh,
• Robert W. Devine,
• Patrick McArdle and
• John C. Stephens

Beilstein J. Org. Chem. 2018, 14, 1222–1228, doi:10.3762/bjoc.14.104

•  1). The heterocyclic furan and thiophene substituents allowed generation of the desired 5-aminopyrazoles in 75% and 81% yields, respectively (Scheme 1). Alkyl groups appeared to be less well tolerated, where the corresponding alkyl-substituted 5-aminopyrazoles were isolated in lower yields. With a

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• heterocyclic rings such as furan 62 and 63 [126], thiophene 64 [127] and pyridine 65 (Figure 11) [128]. These conjugates exhibit potent antibacterial and antiprotozoal activity with much reduced toxicity. It was further concluded that π-stacking, H-bonding with the floor of the minor groove along with

Hypervalent iodine-mediated Ritter-type amidation of terminal alkenes: The synthesis of isoxazoline and pyrazoline cores

• Sang Won Park,
• Soong-Hyun Kim,
• Jaeyoung Song,
• Ga Young Park,
• Darong Kim,
• Tae-Gyu Nam and
• Ki Bum Hong

Beilstein J. Org. Chem. 2018, 14, 1028–1033, doi:10.3762/bjoc.14.89

• (3a–c, 3f) [31]. However, electron-rich aryl allyl ketone oximes such as 1d, 1e and 1g proved inferior. Also the furan-substituted allyl ketone oxime delivered the desired product 3h albeit in a moderate yield. In addition, various alkyl allyl ketone oximes were investigated. While cyclopropyl allyl

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• explored (to generate 2k and 2l, respectively). Unsurprisingly, whilst the 6-membered ring formed in 42% yield, cyclisation to form the analogous 7-membered ring failed. It was, however, possible to generate heterocyclic species such as the 9-fluorenonyl-substituted oxazoline 2m (48%) and the furan 2n (59

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

• phenolic Mannich bases, leading to the disappearance of the only aromatic ring. In a recent publication by same research group [72], they elaborated a simple route to 1,2-dihydronaphtho[2,1-b]furan and 2,3-dihydrobenzofurans via base-induced desamination. They also reported the development of a simple

Diels–Alder cycloadditions of N-arylpyrroles via aryne intermediates using diaryliodonium salts

• Huangguan Chen,
• Jianwei Han and
• Limin Wang

Beilstein J. Org. Chem. 2018, 14, 354–363, doi:10.3762/bjoc.14.23

• diaryliodonium salts can generate benzynes under severe basic conditions, the resulted benzynes were allowed to undergo cycloaddition reaction with furan or N-arylation of secondary amides and amines. Due to the easy accessibility of the diaryliodonium salts, this kind of benzyne precursor is attracting

• extensive attention [14][15][16]. Also as a five-membered heterocyclic ring, the cycloaddition reaction of N-substituted pyrroles is much less than that of furan [17][18][19][20][21]. As a matter of fact, the Diels–Alder adduct formation of pyrroles with benzyne has been postulated in 1965 as transient

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

• 5 hours for T13-based OLEDs. A comparison established with an iridium complex, i.e., tris[1-(2,4-diisopropyldibenzo[b,d]furan-3-yl)-2-phenyl-1H-imidazole]iridium(III) (Ir(dbi)3) evidenced the relevance of the TADF approach, as a device lifetime of only 18 hours was found while operating OLEDs in the

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• -alkylation compound 7e was obtained instead of the desired furan (Table 1, entry 5). It is possible to consider that the d orbitals of the sulfur atom in a sulfide group could possibly stabilize the adjacent carbanion [73][74]. To expand the scope of substituted N,S-acetals that could provide the desired

• compounds 7f and 7g, the low reactivity resulted from the decreased mesomeric effect of the furan structure: the higher electronegativity of oxygen facilitated the polarized form [71]. Among various arenes, the 4-nitrophenyl substituent 7p only afforded the desired thiophene 8p in a moderated yield (42

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -(furan-2-yl)-2-phenylpyrazolo[1,5-a]pyrimidine (168) using a similar synthetic strategy from the reaction of 5-aminopyrazole 16/126 with sodium 3-(furan-2-yl)-3-oxoprop-1-en-1-olate (167, Scheme 47). Ren et al. [108] described the synthesis of 6-aminopyrazolo[1,5-a]pyrimidine derivatives 172 involving

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• obtained by flash vacuum pyrolysis of furan-2,3-dione 6 and dimerizes to 1,3-dioxin-4-one 3, which is a stable but reactive ketene. The transannular addition and rearrangement of enols formed by the addition of nucleophiles to the ketene function in 3 generates axially chiral 2,6,9-trioxabicyclo[3.3.1

• dimerization of dipivaloylketene (2), itself obtained in high yield by FVP of furan-2,3-dione 6 (Scheme 3). Ketene 3 reacts with a variety of nucleophiles in an addition reaction to the ketene function, thereby transforming the ketene to enol derivatives 14 or 9 of 1,3-dioxin-4-ones. Subsequently, these enols