CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• material sciences [14][15][16][17]. In this context, deciphering the impact that can be exerted by the trifluoromethyl group on a cation and the associated consequences when facing the challenge of developing innovative synthetic methods are the subjects of this review. Review Quantitative parameters

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• : DMSO-d6, 90 °C. Single-crystal X-ray analysis of diethyl (9-heptyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-9H-purin-6-yl)phosphonate (4d). CCDC-2044976. Structural diversity and synthetic methods of purinylphosphonates. MWI = microwave irradiation; LG = leaving group. Synthetic routes for the formation of

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• [6]helicenes 10a (a), 10b (b) and 10c (c) (X-ray data). Crystal packing of carbazole-based [6]helicenes 10a (a, b), 10b (c,d) and 10c (e). Hydrogen atoms are hidden. Overview of the synthetic methods for the carbazole-based heterohelicenes. i) Pd2dba3, xantphos, K3PO4, xylene, 100 °C, 123 h, 64–88

Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD^®/Olah’s reagent under solvent-free conditions

• Yumeng Liang,
• Akihito Taya,
• Zhengyu Zhao,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2020, 16, 3052–3058, doi:10.3762/bjoc.16.254

• fluorides. Acyl fluorides, which are one type of acyl halides, show distinct stability in the presence of moisture, indicating their suitable reactivity only in selected conditions [19]. In addition to our direct cross-coupling reaction method, several useful synthetic methods for the formation of acyl

• fluorides have become available in recent years [19][20][21][22][23]. In this context, we were interested in the functional transformation of an acyl fluoride unit into a CF3 motif. Despite the current rich availability of acyl fluorides and a strong market demand for trifluoromethyl compounds, synthetic

• methods for the direct transformation of acyl fluorides to trifluoromethyl compounds are rare [24][25][26]. A seminal example is the work by Lal and co-workers reported in 1999 (Scheme 1a) [24][25]. The acyl fluorides were converted into the trifluoromethyl compounds in good yields using Deoxo-Fluor®, but

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• the all-carbon [3 + 2] cycloaddition with selected natural product syntheses reported before 2011 [22][23][24][25][26]. Next, we discuss the synthetic methods including the proposed mechanism and/or catalytic cycle and focus on illustrative examples of natural product syntheses. Moreover, several

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• garnered significant attention in the literature because of their presence in various natural products [1][2][3][4] and pharmaceutically relevant drugs [5][6]. Accordingly, numerous synthetic methods to construct pyrrole skeletons were reported, including the classical Hantzsch [7][8] and the Paal–Knorr

• ][18] are some of the commonly used approaches for the construction of pyrrole scaffolds. Additionally, the biocatalytic synthesis of substituted pyrroles was also developed [19]. Though sustained efforts have been achieved to develop efficient synthetic methods for the preparation of this structural

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• development of efficient synthetic methods to access imidazo[1,5-a]pyridines, with more than 120,000 individual compounds prepared to date. Most synthetic approaches rely on various cyclocondensations of nucleophilic (2-aminomethyl)pyridine precursors, introducing a new five-membered ring. Typically

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• were involved, among other things [5], in binding with UDP-Gal mutase [14], immunoglobulin [15][16], and glycogen phosphorylase [17]. The synthesis of complex polyfluorinated carbohydrates is challenging and new synthetic methods must be developed. Pioneering work by many groups brought significant

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• 501-1193, Japan 10.3762/bjoc.16.227 Abstract New synthetic methods for spirolactams bearing an α-methylene-γ-butyrolactone or its analogous methylene-lactam have been developed. The allylation of γ-phenylthio-functionalized γ-lactams with 2-(acetoxy)methyl acrylamides was accomplished by using 2.5

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• contains the trifluoromethylpropargylamine moiety and has been developed as the inhibitor against non-nucleoside reverse transcriptase for the treatment of human immunodeficiency virus [27] (Figure 1). Thus, the development of synthetic methods for the preparation of these compounds, featuring

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• fused thiophene unit by a pyrrole ring. For TTA various synthetic methods have been developed and it has been broadly implemented as building block into materials for organic electronic devices [32][33]. We have disclosed the first SN4 derivative with the heteroatom sequence ‘SSNS’ in the context of

Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193

• , we report a comprehensive research on synthetic approaches to BTAs III. Results and Discussion To develop an approach to target the BTAs III, we analyzed the general synthetic methods to enaminones I and II, which involve the reaction of the acylpyruvic acids or their esters IV, 5-arylfuran-2,3

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• of C–H bond functionalization reactions encompasses also direct diversification of heteroaromatic compounds. Aromatic heterocycles are key molecular motifs in natural products and biologically active compounds and thus, the development of synthetic methods allowing their site-selective C–H

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• anticancer [10][11], antimicrobial [12], antiviral agents [13][14], and eosinophilia inhibitors [15]. Therefore, it is highly desirable to develop efficient and practical synthetic methods for triazinethione architectures and to expand the structure diversity of this class of compounds for medicinal

Recent synthesis of thietanes

• Jiaxi Xu

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

• thiaheterocycles that are found in the pharmaceutical core and structural motifs of some biological compounds. They are also useful intermediates in organic synthesis. Various synthetic methods of thietanes have been developed, including inter- and intramolecular nucleophilic thioetherifications, photochemical [2

• + 2] cycloadditions, ring expansions and contractions, nucleophilic cyclizations, and some miscellaneous methods. The recently developed methods provide some new strategies for the efficient preparation of thietanes and their derivatives. This review focuses on the synthetic methods to construct

• of sulfur-containing acyclic and heterocyclic compounds [10][11]. Several synthetic methods for thietanes have been developed and reviewed [12][13][14]. One traditional route is the intermolecular double substitution (cyclic thioetherification) of 1,3-dihaloalkanes, sulfonates of 3-haloalkan-1-ols

Distinctive reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines under photoredox conditions

• Shrikant D. Tambe,
• Kwan Hong Min,
• Naeem Iqbal and
• Eun Jin Cho

Beilstein J. Org. Chem. 2020, 16, 1335–1342, doi:10.3762/bjoc.16.114

• applications as core structures in a variety of natural products, pharmaceuticals, and agrochemicals [34][35][36][37][38] and are valuable ligands [39][40] in stereoselective organic synthesis. Despite the availability of a plethora of synthetic methods for 1,2-diamines [41][42][43][44][45], the reported

• photocatalytic synthetic methods are mainly limited to aniline-based substrates and do not encompass aliphatic amines. We planned the synthesis of 1,2-diamine compounds having an aliphatic amine moiety by the intermolecular coupling of N-benzylidines with aliphatic amines that not only act as coupling partner

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• the last decade, when numerous selective reactions of oxidative cyclization, functionalization, and coupling mediated by iminoxyl radicals were discovered. This review is focused on the synthetic methods based on iminoxyl radicals developed in the last ten years and also contains some selected data on

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• important intermediates to develop new synthetic methods [62]. Their reactivity was first explored in the Meerwein arylation as well as the Gomberg–Bachman and the Sandmeyer reaction [63][64][65]. Similar to C(sp3) radicals, aryl radicals add to unsaturated systems, such as (hetero)arenes, alkenes, or

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• pharmaceutical applications with a focus on published synthetic methods that introduce fluorine into the phenyl, the β-carbon or the α-carbon of ᴅ-or ʟ-phenylalanines. Keywords: α-fluorophenylalanine; β- and β,β-difluorophenylalanine; fluorinated phenylalanines; PET; pharmaceuticals application; Introduction

• 114 with >99% ee. A following alkaline hydrolysis of the ester 114 gave N-Boc-(R)-2,5-difluorophenylalanine 115 (Scheme 26) [50]. After compiling the above synthetic methods, a number of conclusions can be drawn regarding the synthesis of FPhe analogues of type I and II. The most convenient method

Accelerating fragment-based library generation by coupling high-performance photoreactors with benchtop analysis

• Quentin Lefebvre,
• Christophe Salomé and
• Thomas C. Fessard

Beilstein J. Org. Chem. 2020, 16, 982–988, doi:10.3762/bjoc.16.87

• collections. These are of high value to medicinal chemists to provide defined exit vectors and facilitate rational lead evolution [2][3][4][5][6][7]. Thus, we were interested in developing reliable synthetic methods and technologies to apply metal-catalyzed cross-coupling reactions to such scaffolds, which

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• shown that the corresponding 2-phospholene oxides are the thermodynamically more stable isomers. This paper seeks simple synthetic methods for the preparation of 2-phospholene oxides via the isomerization of the corresponding 3-phospholene derivatives. The isomerization reactions were carried out under

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• -type pentacyclic triterpenoids, and the synthetic methods studied here can also apply to the modification of structurally similar other triterpenoic acids, but further experimental verification is needed. Results and Discussion The synthetic route to 18β-glycyrrhetinic acid piperazinyl amide 4 was

One-pot synthesis of dicyclopenta-fused peropyrene via a fourfold alkyne annulation

• Ji Ma,
• Yubin Fu,
• Junzhi Liu and
• Xinliang Feng

Beilstein J. Org. Chem. 2020, 16, 791–797, doi:10.3762/bjoc.16.72

• pentagons could be realized [11][12][13][14][15][16][17]. Among them, the cyclopenta-fused pyrenes are an important class of CP-PAHs owing to their unique physical and photophysical properties, such as high electron affinities and anomalous fluorescence [17][18][19][20]. However, the reported synthetic

• methods towards the (di-)cyclopenta-fused pyrene congeners (i–iii, Scheme 1) have mainly been reliant on the flash vacuum pyrolysis of suitable precursors under harsh conditions (T ≥ 900 °C), which resulted in relatively low yields [21][22][23][24]. Palladium-catalyzed annulation has been recently proven