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

• -unsaturated carbonyl compounds catalyzed by bifunctional squaramide catalysts has been developed. This methodology offers both enantiomers of β-silyl nitroalkanes in good to excellent yields (up to 92%) and enantioselectivities (up to 97.5% ee) under solvent-free conditions at room temperature. Control

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• tetrazoles from bile acid precursors was developed. Mild reaction conditions using TMSN3 instead of hydrazoic acid as an azide source produced good yields of the desired tetrazoles. These conditions could be applied to other steroidal precursors. Additionally, an improved methodology for the synthesis of

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• the asymmetric aza-Michael addition reactions. Mahe et al. reported an effective, eco-friendly and cost-effective enantioselective synthesis of 3,5-diarylpyrazolines 49 by using phase-transfer methodology. They carried out a set of reactions between chalcones 46 and N-tert-butoxycarbonylhydrazine (47

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• ]. Recently, a methodology for the synthesis of dihydromethanodibenzoazocines based on a combination of Friedel–Crafts and Pictet–Spengler reactions was proposed by Moshkin et al. [18]. We have developed a convenient method for the preparation of C-1-substituted tetrahydroisoquinoline derivatives by using the

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• , we present a novel synthetic methodology for the photoinduced CuAAC reaction utilizing exfoliated two-dimensional (2D) few-layer black phosphorus nanosheets (BPNs) as photocatalysts under white LED and near-IR (NIR) light irradiation. Upon irradiation, BPNs generated excited electrons and holes on

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• organocatalytic synthesis of molecules with this moiety uses the reaction between aldehydes and anthranilamide building blocks. The advantage of this methodology lies in the fact that both starting materials are readily available, and the enantioselectivity of such cyclization reactions can be controlled by

• -workers, using an (S)-TRIP derivative as the chiral catalyst (Figure 1) [14]. Soon after, Rueping et al. developed a similar methodology catalyzed by other chiral BINOL-phosphoric acids [15]. However, the reaction suffered from limited scope to aromatic aldehydes without an ortho-substitution; the

• enantiocontrol of the process, and highly enantiomerically enriched dihydroquinazolinones can be achieved by crystallization (up to 97% ee). The developed methodology can also be used to form tetrahydrobenzodiazepinones; however, a significant drop in the yield and enantioselectivity was observed. Synthetic

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

• methodology utilized in Scheme 5 had been successfully employed for the preparation of C-glycopyranosyl derivatives of common and uncommon sugars like α-gluco, α-manno, β-altro, β-ido, α- and β-gulo, β-talo, α-galacto, and α-allo C-glycopyranosides [42]. Vinylated derivatives of aldopentoses 11 were treated

• with Hg(OAc)2 affording the corresponding cyclized pyanosylmethylmercuric chloride derivatives 12 (Scheme 5). This methodology can be used to synthesize rare C-glycosyl carbohydrates from easily available sugars. In a similar manner, stereoselective cyclization of C-glycosyl amino acid derivative 13

• [46]. A similar type of reaction methodology was employed for the formation of a bicyclic nucleoside analog. 4'-C-vinylribofuranoside derivative 21 on treatment with Hg(TFA)2 followed by reduction with NaBH4 leads to the formation of bicyclic nucleoside derivative 22 (Scheme 10) [49]. Pyrrolidine and

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

• exposed to UV radiation affording phenanthridines. The scope and limitations of this novel reaction were explored. For example, exposure of 2',3'-dimethoxy-[1,1'-biphenyl]-2-carbaldehyde O-acetyl oxime to UV radiation afforded 4-methoxyphenanthridine in 54% yield. This methodology was applied to the

• group is a leaving group resulting in the formation of phenanthridines is unprecedented. As is outlined in this paper we set out to investigate the scope and limitations of this reaction resulting in the formation of the phenanthridine skeleton. We also report on the application of this methodology to

• with O-phenylhydroxylamine as reagent were not successful and only resulted in the formation of the benzonitriles 16a, 16c and 16e. Presumably, the oximes were formed but were unstable and the facile elimination of phenol took place to liberate the benzonitriles. Finally, the use of this methodology

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• summary, a new method for the synthesis of 3-monohalooxindoles via acidolysis of isatin-derived 3-phosphate-substituted oxindoles with haloid acids was developed. The present methodology involves the formation of an oxindole having a phosphate moiety at the C-3 position via the [1,2]-phospha-Brook

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

• of HBr in these processes. The influence of steric and electronic factors from both the perspective of the nucleophile and electrophile were investigated and levels of enantiocontrol up to 90% ee obtained. The synthetic utility of the methodology was demonstrated via the concise enantioselective

• charged intermediates, could be an excellent methodology for the enantioselective SN2 alkylation of enolates derived from the 2-oxindole core [13][14][15][16][17][18][19][20][21][22][23]. In recent years, several examples regarding the alkylation of 3-subsituted-2-oxindoles, via asymmetric phase-transfer

• ), presenting instead a fixed – not easily modifiable – group which is not ideal for a modular approach to the construction of more complex molecules such as those shown in Figure 1A. Recently, we partially overcame this challenge by developing a highly enantioselective phase-transfer-catalysed methodology for

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• xanthone as the photocatalyst and NiCl2·6H2O as the nickel catalyst can efficiently catalyze the transformation of methylarenes 25 into arylacetic acids 91 under UV light irradiation (Scheme 47). Furthermore, the authors also applied this methodology to functionalize unactivated alkanes such as cyclohexane

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

• Reactions associated with carbon–carbon bond formations are explored for their synthetic utility in extending the carbon framework in organic molecules [1][2][3]. Among the known C–C bond forming methodologies the Friedel–Crafts reaction is the most utilized methodology. As a result of its broad scope of

• efficient, novel and efficient Friedel–Crafts reaction methodology in presence of novel catalysts will widely serve its purpose in synthesising molecules of biological interest. Thereby with the goal of operating FC reactions in terminal allylic units of Morita–Baylis–Hillman adducts we sought to screen the

• Friedel–Crafts cyclization in electron-deficient Morita–Baylis–Hillman adducts. The present methodology is attractive because it directly utilizes MBH adducts over the possible reports on utilizing allylic-OH protected MBH adducts [12][13] to access indenes. The chiral Cr(III)(salen)/BF3·OEt2-catalyzed

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• methodology, as illustrated by the preparation of the cyano- (4bn), boron- (4ao), or silicon- (4ap) substituted SMAHOs. The efficiency of the saponification step was also illustrated by the case of α-halomalonates 3aq and 3br. Upon application of the above-mentioned conditions, the useful reagents 4aq and 4br

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

• ]. Although the scope of the reaction was broader for 1,2,3,4-substituted naphthalenes, the authors developed a potentially applicable methodology to synthesize substituted anthracenes and other polysubstituted fused aromatic compounds. A few years later, Bao et al. employed a similar approach to synthesize

• methodology was notable for being an alternative method to synthesize 2,3,6,7-halogenated anthracene derivatives, which are difficult to obtain. In 2010, Okamoto et al. published a three-step procedure to synthesize substituted anthracenes, pentaphenes, and trinaphthylenes via a [2 + 2 + 2] alkyne

• anthracene derivatives 33. The strategy involved a palladium(II)-catalyzed tandem transformation with diphenyl carboxylic acids 31 and acrylates 32 (Scheme 7) [41]. This new methodology involved a carboxyl-directed C–H alkenylation, a carboxyl-directed secondary C–H activation, an intramolecular C–C-bond

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

• yields (2–5%). This approach circumvented the precipitation of the water-insoluble oligomers and allowed for chain elongation [72][73]. This methodology was improved employing a protic co-catalyst system to yield DP > 120 in a 26% conversion [74]. Generally, an acid catalyst would promote the hydrolysis

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• hydroquinolinone, chromene, piperidine, peptide, lipid, and glycoside moieties (Scheme 2). Bojanowski and co-workers developed a methodology to synthetize 3,4-dihydrocoumarins 10 through a decarboxylative and dearomatizative cascade reaction [33]. This reaction was carried out using coumarin-3-carboxylic acids 8

• obtained with good to excellent yields and enantiomeric excesses. Besides, the one-pot synthesis of coumarins followed by the Michael addition step was proven to be a good alternative, affording the desired product with excellent yield and ee. The applicability of the methodology was also demonstrated by a

• oxidative [4 + 2] cycloaddition with unsaturated aldehydes 57 [51]. The methodology draws attention for the wide variety of products 58 obtained with moderate to excellent yields and enantiomeric excesses (Scheme 18). Activation via noncovalent bonding Besides the activation mode via a covalent bond, as

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

• to be, there is still a demand for applying this relevant methodology to obtain new compounds with known pharmacological properties. However, several molecules based on structural scaffolds related to important biological activities have been successfully achieved via scandium-catalyzed C–H

• -containing substrates, and its high efficiency makes it an excellent methodology for late-stage modifications (Scheme 20D). Biaryl structures are present in several important drugs currently commercially available (57, 58, and 59, Scheme 21A) [141] and synthetic methods to achieve the aryl–aryl connection

• in the azidation of inert C(sp3)–H bonds using organic electrosynthesis in a straightforward procedure, enabling the azidation of a series of primary, secondary and tertiary alkyl moieties (Scheme 22B and C) [144]. In general, the new methodology proved to be resource-economic and straightforward

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

• showcase his methodology, they first synthesized acyclic optically active N-fluoro sulfonamides 27-7–9 (Scheme 62) and attempted the enantioselective fluorination of some enolates in 1997 [92]. However, the best result was an enantiomeric excess of 48% with a chemical yield of 53% after the enolate anion

Cerium-photocatalyzed aerobic oxidation of benzylic alcohols to aldehydes and ketones

• Girish Suresh Yedase,
• Sumit Kumar,
• Jessica Stahl,
• Burkhard König and
• Veera Reddy Yatham

Beilstein J. Org. Chem. 2021, 17, 1727–1732, doi:10.3762/bjoc.17.121

• benzaldehydes 2f–h. Our methodology tolerates a variety of functional groups containing benzylic alcohols such as -OH (1h), -CN (1i), -NO2 (1j), methyl ester (1k), and benzyloxy (1v) to produce the corresponding aldehydes (2h–k and 2v) in moderate yields. Next, electronically different ortho-substituted

2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli,
• Noureddine Chaaben,
• Kamel Alimi,
• Stefan Jopp and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 1629–1640, doi:10.3762/bjoc.17.115

• . In order to elucidate these experimental observations, quantum chemical calculations based on density functional theory (DFT) methodology were performed. The estimated visualization of highest occupied and lowest unoccupied molecular orbitals, as well as the molecular electrostatic potential (MEP) of

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

• EDAMs (R1 ≠ R2) were also applied to check the regioselectiveness of this addition and cyclization reaction. The methodology provides a simple, straightforward, and facile path to access fully decorated 1,2,3-triazoles 25 in moderate to good yield. Noticeably, this uncatalyzed addition and cyclization

• derivatives from azidophilic substrates and different azide derivatives. A short reaction time, good to high yield of products, high diversity, high selectivity, and ease of operation were some benefits of this methodology. The enolate reactivity with azides was compared to enamines. The best conditions were

• methodology for aerobic C–H activation; ii) PEG as green and recyclable reaction medium; and iii) a reusable palladium catalyst complex [65]. Fully functionalized 1,2,3-triazolo-fused chromenes 162, 164, and 166 were regioselectively prepared in moderate yield. The isoindoline-fused triazoles 164 were

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

• reported the use of active methylene compounds as suitable nucleophiles in intramolecular hydroalkylation reactions (Scheme 2) [25]. In the presence of PdCl2(CH3CN)2, the hydroalkylation of β-diketones 1 gave only 6-endo-trig cyclization products 2 in moderate to good yields (Scheme 2). The methodology

• -cyclization products was attributed to the better overlap between the π-orbital of the enolic carbon atom and the π*-orbital of the complexed olefin terminal carbon. This suggests that, in these cases, the 6-endo-trig cyclizations are under kinetic control. The substrate generality in the methodology

• substrates (Scheme 2 and Scheme 4), and an external proton source (acetic acid) was required to furnish the hydroalkylated products 7 (Scheme 5A). The quaternary carbon centers were synthetized in moderate to excellent yields by this methodology, and its potential use in late-stage functionalization was

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• (2) (31 kcal mol−1 and 13 kcal mol−1, respectively) [33][34]. [2.2]Metaparacyclophane (3) was first isolated by Cram et al., the pioneer of [2.2]cyclophane chemistry, by the acid-catalyzed rearrangement of [2.2]paracyclophane (1) [35][36]. This methodology furnished the non-substituted cyclophane. A

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• methodology for the preparation of pyrido[2,1-a]pyrrolo[3,2-c]isoquinoline derivatives A (Scheme 1). The previously developed Pd-catalyzed protocol for the preparation of these compounds could be used only for arylation of pyrrole N-benzyl protected starting materials C [17]. The deprotection of the product

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• 1,2,4-trisubsitituted tetralin 14ga was isolated as a 17:83 mixture of cis/trans isomers, but with 20% yield. The poor yield may be attributed to the enhanced steric hindrance. This cyclization methodology was also applicable to 2-(1-vinylnaphthalen-2-yl)acetaldehyde (13h), for which the reaction with

• veratrole or furan led to the formation of the respective tricyclic 4-aryl-1,2,3,4-tetrahydrophenanthren-2-ols 14ha and 14hb in 73% and 43% yields, respectively. In order to further explore the generality of this cascade Prins/Friedel–Crafts cyclization, the established methodology was also applied to the