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

• . Noteworthy, this methodology demonstrated a wide substrate scope, namely reacting smoothly with all-carbon backboned substrates 36c, as well as being applicable to esters and tosylamides, proving it to be a powerful protocol for the synthesis of stereocontrolled tetrasubstituted alkenes. In 2017, Sweeney and

• classically sensitive functionalities like esters and aryl chlorides. Exposure of the iron catalyst to one equivalent of aryl Grignard reagent 2b in the absence of the halide substrate afforded the bimetallic Fe(II) complex FeBr2[Mg(acac)2](THF)2. Using FeBr2[Mg(acac)2](THF)2 in place of Fe(acac)3 in the

• . Notably, the reaction did not proceed in the dark or in the absence of the photosensitizer at 30 °C; further, the reaction generated the desired product in lower yield at 120 °C. The scope was broad and tolerated a wide array of 1,3-keto esters and 1,3-diketones, as well as both benzylic and aliphatic C

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• elimination as opposed to styrenyl selectivity. In addition, the methacrylates were used as allyl surrogates to overcome the reactivity problem caused by steric hindrance of 1,1,-disubstituted alkenes, and the electron-withdrawing esters enhance the migratory insertion to form palladacycle I-2. The CPA

• the yields, whereas the electronic properties of the substituents on the indole ring did. In 2019, Lin and co-workers reported the asymmetric three-component cascade reaction of 2,3-diketo esters 28, aromatic amines 29, and 1,3-cyclohexanediones 30 to prepare axially chiral arylindoles 31 in a highly

• , Wang and co-workers reported the organocatalytic asymmetric synthesis of tetrasubstituted α-amino allenoates by a dearomative γ-addition reaction of 2,3-disubstituted indoles 99 to β,γ-alkynyl-α-imino esters 100 [103]. In the presence of chiral phosphoric acid CPA 13, a series of tetrasubstituted α

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• reaction with ʟ-menthol, afforded the relevant thiol-substituted esters 54, which further reacted with sulfuryl chloride to give compound 55. The reaction of compound 55 with vinyl acetate constructed a sulfur–carbon bond and produced 3k. The sulfuryl chloride reagent simultaneously allowed for

• -(−)-2',3'-dideoxy-5-fluoro-3'-thiacytidine (2). However, hydrolysis was observed to occur with a comparable rate to that of the 5'-O-valerate and 5'-O-propionate esters. Additionally, the rate of hydrolysis for the ester derivatives of FTC (2) was significantly higher than for the corresponding 3

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• ][35][36]. In this context, Huang, Fu and co-workers reported carbene-catalyzed enantioselective formal [4 + 2] annulation reactions of β-silyl enones with enals and with active acetic esters (Scheme 1g) for the preparation of chiral organosilanes [34][35][36]. Very recently, during the final stage of

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• found with Pd(OAc)2/bpy as the catalyst, N-methylacetamide as the solvent, and a temperature of 80 °C. Variously substituted indoles as well as esters of 118 (R = aryl, alkyl, vinyl) were generally well tolerated, but oxa- (X = O) and azo- (X = NR) cyclobutanes met with limited success. Alternative

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• synthetic utility, we surmised that replacing the aroyl component of the N-phenacyl substituent by electrophilic groups such as esters, amides or nitriles might yield 2,3-dihydro-1H-pyrrolizin-6-ones 13 or their hydroxypyrrole tautomers 13’. Our findings with N-(ethoxycarbonylmethyl)enaminones 14 are

• conditions yielded pyrrolo[2,1-a]isoquinoline products. A somewhat comparable cyclization of N-benzylenaminones has been reported under superbasic conditions [52], while base-induced pyrrole formation from N-(ethoxycarbonylmethyl)enamino esters (vinylogous urethanes) and the corresponding nitriles

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

•  9). In addition to perfluoroalkyl iodides, this protocol was further extended to alkyl halides, trifluoromethylthiolate, amines, cycloketone oxime esters, and carboxylic acid N-hydroxyphthalimide esters (NHPI). In 2018, Peters and Fu [57] explored the copper-catalyzed three-component coupling of

• , Xiao and Yu et al. [61][62] disclosed a series of copper-catalyzed cyanoalkylation reactions among alkenes, oxime esters, and boronic acids or alkynes. Mechanistic studies implied that the CuI complex gets photoexcited via a SET process to generate a cyanoalkyl radical from the oxime esters. The

• ). In 2020, Zhang’s group [77] described the photoinduced copper-catalyzed decarboxylative alkynylation of redox-active esters with terminal alkynes. N-Hydroxy-tetrachlorophthalimide (TCNHPI, 36) derived from carboxylic acids was identified as the ideal radical precursor. Under irradiation, the CuI

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• pyridylic C(sp3)–H bond (Scheme 1b). For examples, Tunge et al. developed a Pd-catalyzed intramolecular decarboxylative coupling of heterocyclic ally esters via a tandem allylation/Cope rearrangement strategy [18]; Hartwig and co-workers reported a stereo-divergent allylic substitution with azaarene

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• pyrrole derivatives: i) Knorr reaction: the condensation of α-aminoketones or α-amino esters in the presence of zinc powder and sodium acetate; ii) Paal–Knorr reaction: the condensation of 1,4-dicarbonyl compounds and amines, catalyzed by formic acid in anhydrous alcohol; iii) Hantzsch reaction: the

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• develop new synthetic methodologies toward the 1H-1,2,3-triazole group containing organic entities. However, earlier methods of the synthesis of aliphatic and aromatic esters of metronidazole are associated with different drawbacks such as long conversion times, low yields and preparation of their

• respective acid chlorides by using thionyl chlorides and these acid chlorides were then made to react with the -OH functionality of metronidazole to get different esters [7]. Here we report a convenient method for the synthesis of aliphatic and aromatic esters of metronidazole. Furthermore, derivatives of

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• had also performed experiments with different isoprenoid derivatives (carboxylic acid, ketones alcohols, and keto esters) to form different bicyclic products (Scheme 19). A Hg(II)-salt-promoted cyclization of amidal 56 was performed to synthesize optically active cyclic alanine derivatives 57 as 1:1

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