Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• saturated NaHCO3 solution (10 mL) and brine (10 mL). The solution was dried over MgSO4 and the solvent was evaporated under reduced pressure. The resulting crude oxime esters were purified by silica gel column chromatography (using EtOAc/hexane mixtures as eluent). Experimental details for the preparation

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• this plant have been used as a Korean traditional medicine for treating sore throat, respiratory illness, constipation, and dieresis [2][3]. Phytochemical investigations of A. fordii reported coumarins, diterpenoid esters, triterpenoids, and tannins [4][5][6][7]. Some phorbol diterpenoids isolated from

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• % ee (Table 2, entry 10). Consistent with the goal of developing a protocol of the best possible synthetic utility; alkylating agents which would be easily modified after installation on the oxindole core – such as α-iodoesters – were also evaluated (Table 2, entries 10–12). Although, alkyl esters

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• heterolytic cleavage of HCl as displayed in Scheme 7 [55]. Moreover, other catalysts with amine functional groups were found more efficient in the enantioselective α-alkylation of aldehydes (Scheme 10b) [48] or in the asymmetric Mannich synthesis of α-amino esters using Takemoto’s bifunctional catalyst 44 [67

• have been provided by the group of Jacobsen in the nucleophilic addition of indoles 17 to pyranones 62 (Scheme 14a) [71], as well as in the enantioselective synthesis of α-allyl amino esters 67 by the reaction of α-chloro amino acid derivatives 65 with allyltin and allylsilane 66 nucleophiles [72

• , and c) asymmetric Mannich synthesis of α-amino esters. Thiourea-catalyzed enantioselective polycyclization reaction of hydroxylactams 51 through cation–π interaction. Enantioselective aza-Sakurai cyclization of hydroxylactams 56 implicating additional cation–π and Lewis base activation

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• of their important biological and fluorescent uses. To summarize the main syntheses of these studies: in particular, transition metal-catalyzed cascade benzylation–cyclization [17], cyclization of polycyclic aryl triflate esters [18], reaction of β-naphthol and aldehydes [19][20] or inter- or

Facile and innovative catalytic protocol for intramolecular Friedel–Crafts cyclization of Morita–Baylis–Hillman adducts: Synergistic combination of chiral (salen)chromium(III)/BF₃·OEt₂ catalysis

• Karthikeyan Soundararajan,
• Helen Ratna Monica Jeyarajan,
• Raju Subimol Kamarajapurathu and
• Karthik Krishna Kumar Ayyanoth

Beilstein J. Org. Chem. 2021, 17, 2186–2193, doi:10.3762/bjoc.17.140

• (15 mol %)/BF3·OEt2 (2.5 mol %) in 10 mL dichloromethane (Table 2). A series of indene derivatives were obtained from moderate to excellent yield (58–85%). The steric hindrance and electronic effect of electron-withdrawing substituents such as nitriles and methyl/ethyl esters did not significantly

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• , which possess AhR affinity [93]. Janosik presented a synthesis of such selenopyrans 132 via the bis(indol-2-yl)selanes 131 [73]. Treating these compounds with orthoformate esters in the presence of the Brønsted acid MeSO3H led to the target selenopyrans (Scheme 17b). The methylated analogs of 132

• -mediated coupling of N-silylated 6-hydroxyindole 174 with the corresponding boronic acid 173 (Scheme 24) [114]. For further synthetic transformations of 175, N-protection with bromo esters 176 followed by hydrolysis towards acids 177a and 177b were performed. The products 177a and 177b are potent anti-HIV

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• reactivity might be sufficient to overcome the reactivity limitations of pronucleophiles derived from other α-amino esters [42]. In this paper, we describe the use of cyclopropenimine catalysis for the enantioselective catalytic Michael reaction of α-substituted amino ester imines. Results and Discussion To

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• number of fluorine-containing alkenes (Figure 3). Compounds 7a and 7b as well as 7f–h were type I olefins, while acrylate esters 7c–e were type II olefins. Because 1st generation metathesis catalysts usually perform poorly in CM reactions with acrylates [31][32][36][39][41], only G-2, HG-2 and G-3 were

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• -bifunctional organomagnesium alkoxide reagent 107, which converted esters into di- and monofunctionalized anthracenes (Scheme 25) [59]. They prepared this reagent by deprotonation–magnesiation of compound 106. Then, the treatment of aromatic esters with 107 produced dialkoxide 108, which could be easily

• substituents on the benzaldeydes 169 [72]. Cycloaddition reactions In 2014, Gao, Li, and their co-workers published a facile strategy to synthesize polysubstituted aromatic compounds from the reaction of quinones or maleimides with β-enamino esters (Scheme 39) [73]. They synthesized anthraquinone derivatives

• 173 in good yield (62–94%) via a cycloaddition/oxidative aromatization sequence involving quinone 171 and substituted β-enamino esters 172 as precursors. They prepared anthraquinone 173a starting from three different β-enamino esters; a less bulky β-enamino ester favored the reaction. The scope of the

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• (Table 4, entries 5–7). While C-4 and C-5 substituted indazole methyl esters showed no apparent N-1 or N-2 regioselectivity under conditions A (ratio N-1:N-2 of both 61:62 and 63:64 = 1:1.3) (Table 4, entries 6 and 7), the corresponding C-6 substituted indazole methyl ester demonstrated a notable

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• benzylic, allylic, 3°, 2°, and 1° aliphatic, using unsubstituted linear sulfamate esters (Scheme 17A and B) [130]. This method is also compatible with substrates containing adjacent substituents like protected amines and tolerates the presence of electron-withdrawing groups as well as α-substituted alkynes

• full agonists (54 and 55, Scheme 20A) [139]. Ackermann and co-workers presented a manganese(I)-catalyzed C–H allylation, installing α,β-unsaturated esters in peptide analogues bearing indole motifs (Scheme 22B) [140]. Starting with tryptophan, the enantioselective allylation reaction afforded the

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• -fluoropiperidine (1-1) [21] and then in 1991, Banks et al. reported the improved yields of the reactions of 1-1 with sodium salts of 2-nitropropane, malonate esters, and a keto ester, and phenylmagnesium bromide [22]. However, the fluorinated products were still accompanied by considerable amounts of byproducts

•  30). NFSI is a stable and non-hygroscopic crystalline solid with a mp of 114–116 °C. NFSI was shown to fluorinate a variety of nucleophiles. As seen in Scheme 31, trimethylsilyl enol ethers, enolate anions of ketones and esters, and aryl- and vinyllithiums were fluorinated with NFSI in moderate to

• ], electron-rich alkenes (entry 3) [65][66], alkyl sulfides (entry 4) [65][67], 1,3-dicarbonyl compounds [65][68], phosphonate esters (entry 5) [65], steroidal silyl enol ethers and enol acetates (entry 6) [65], pyrimidine bases and nucleosides (entry 7) [67][69], phenylalkynes (entry 8) [70], anthraquinones

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• , azidated N-protected memantine 13a was successfully generated by employing electricity and visible-light irradiation in the presence of a Mn catalyst. High regioselectivity was observed at tertiary or benzylic positions (see 13a–c). For commercially available drug derivatives, methyl esters of ibuprofen

Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

• Christin Walther,
• Pamela Baumann,
• Katrin Luck,
• Beate Rothe,
• Peter H. W. Biedermann,
• Jonathan Gershenzon,
• Tobias G. Köllner and
• Sybille B. Unsicker

Beilstein J. Org. Chem. 2021, 17, 1698–1711, doi:10.3762/bjoc.17.118

• blends of these endophytes grown on agar medium consist of typical fungal compounds, including aliphatic alcohols, ketones and esters, the aromatic alcohol 2-phenylethanol and various sesquiterpenes. Some of the compounds were previously reported as constituents of the poplar volatile blend. For one

• ]. Endophytic fungi themselves can produce VOCs. Currently, around 300 fungal VOCs have been characterized, including aliphatic alcohols, ketones, aldehydes, acids and esters, terpenoids, benzenoids, naphthalene derivatives, and cycloalkanes [25][26][27]. Endophytic fungal VOCs are frequently described to

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• -containing 1,2,3-triazole derivatives 30 from the reaction of glycosyl azides 28 with enolates of active ketones and esters 29 in the presence of DBU in DMF at 70 °C (Scheme 12) [43]. Diverse monosaccharide and disaccharide azides were successfully reacted with a variety of enolates of active ketones and

• esters 29, such as 1,3-diketones, β-ketoesters, cyclic 1,3-diketone (dimedone), and β-ketoamide, respectively, to afford desired 1,4,5-trisubstituted 1,2,3-triazoles containing glycosyl with high yield. It should be pointed out that no byproducts were recognized under optimized reaction conditions. In

• via intramolecular cyclization reaction of ketones 31, p-nitrophenyl azide (PNA, 32) and amino esters 33 has been described by Dehaen et al. The products were often obtained in good yield and in all cases with the retention of the configuration of the stereocenter. The reaction was carried out by

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• as Mn(0) and MnO2, that had been employed in the previous work by the same authors to ensure catalytic turnover [110]. Substrates containing functional groups, like esters, phthalimides, silyl enol ethers, boronates, ketones, tertiary alcohols, epoxides, and cyclobutanes, were compatible with the

• of a Lewis acid (LA) to activate 1,3-dicarbonyls through the formation of metallic enolates was recently explored by Schindler’s group for the intramolecular tert-alkylation of prenylated β-keto esters 103 (Scheme 39A

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• of Technology Indore, Khandwa Road, Simrol, Indore-453 552, India, School of Chemical Sciences, National Institute of Science Education and Research, Bhubaneswar-752 050, Odisha, India 10.3762/bjoc.17.101 Abstract 1,5-Disubstituted indole-2-carboxaldehyde derivatives 1a–h and glycine alkyl esters 2a

• formation of γ-carboline derivatives 3aa–ac and 3ba–ea involves the initial formation of trans-iminoester 4 from the N-protected indole-2-carboxaldehydes 1a–e and 1g, and glycine alkyl esters 2a–c. The Hünig’s base, DIPEA, helps abstract the active methylene proton from iminoester 4 to generate enolate ion

Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones

• Chandrakanta Parida and
• Subhas Chandra Pan

Beilstein J. Org. Chem. 2021, 17, 1447–1452, doi:10.3762/bjoc.17.100

• -nitroketones have been found to be a popular nucleophilic acyl transfer reagent. In 2011, three research groups namely Wang, Yan and Kwong independently revealed the organocatalytic asymmetric conjugate addition of α-nitroketones to β,γ-unsaturated α-keto esters with the concomitant acyl transfer reaction to

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• ) from 5′-O-DMTr-2′-deoxy-5-iodouridine (135). Boronic esters N1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl) and N1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-substituted N3-benzoylthymine (136a,b) were synthesized by N3-benzoylthymine from the procedure given by Gothelf and co

• -workers [74][75]. The boronic esters (136a,b) were coupled with 5′-O-DMTr-2′-deoxy-5-iodouridine (135) via Suzuki coupling to give double-headed nucleosides 137 and 138 (Scheme 34) [73]. The double-headed nucleosides 5′-O-dimethoxytrityl-5-(3-(thymin-1-yl)phenyl)ethynyl-2′-deoxyuridine (140) and 5′-O

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• work used preformed β-aminocarbonyl compounds. The classification we propose is based on the molecularity of the reaction (two, three, or four components), calculated based on preformed β-aminocarbonyl species and the use of cyanoacetic esters or cyanoacetamide as the cyanocarbonyl reagent. We suggest

• literature. To avoid the formation of two isomers, the reaction is generally carried out with β-ketoesters, α,γ-dicarbonyl esters, β-ketoaldehydes, or in later modifications acetylenic ketones [47][48]. The reaction was used for the 1939 commercial synthesis of pyridoxine (vitamin B6) [2], the first

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• the generation of cyanomethyl radicals from readily available acetonitrile has not been reported yet. Herein, we disclose a CN-K-catalyzed cyanomethylarylation of both unactivated and activated alkenes with acetonitrile utilizing readily available alkyl N-hydroxyphthalimide (NHPI) esters as the

• CN-K-based heterogeneous protocol for the cyanomethylarylation of N-arylallylamines with acetonitrile. Pleasingly, after the systematic evaluation of various NHPI esters, which are easily prepared from readily available carboxylic acids, the yield of the product 3a could be increased to 75% when

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• -triazine-3-thiones with acetylenedicarboxylic acid dimethyl and diethyl esters (DMAD and DEAD) and subsequent base-catalyzed rearrangement of the obtained imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazines into regioisomeric imidazo[4,5-e]thiazolo[2,3-c]-1,2,4-triazine derivatives. Keywords: amidine

• derivatives consists in the condensation of acetylenedicarboxylic acid esters with heterocyclic compounds containing a thiourea fragment, e.g., pyrimidinethiones [18][19], 1,2,4-triazolethiols [20], and 1,2,4-triazinethiones [21][22]. An important feature of the reactions of dialkyl acetylenedicarboxylates

• selectivity. However, the total yields of the corresponding methyl esters were often higher. The optimized conditions found for each group of starting substrates 3a–g were applied to prepare a series of imidazo[4,5-e]thiazolo[3,2-b]triazines 4a–n with a linear structure (Scheme 2). Precipitates of compounds