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

• photocatalysis has emerged as an alternative to the classical conventional synthetic methods to construct carbon–carbon and carbon–heteroatom bonds [34][35][36][37]. As a mild, efficient, and environmentally friendly approach it has the potential to unlock unique reactions that are previously inaccessible under

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

• therapeutic for psychoses, addiction, and other neuropsychiatric disorders. Although 4-substitituted tetralin-2-ols and derivatives with significant pharmaceutical activities have been identified, only a limited number of synthetic methods is documented in the literature (Scheme 1) [7][8][9]. Moreover, these

• methods generally require multiple steps, proceed in low overall yields, and have a limited ability for structural modifications to prepare analogues with new substitution patterns for enhancing activities. Consequently, it is highly desirable to develop new synthetic methods that provide efficient access

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• ]. However, synthetic methods for efficient synthesis of unsymmetrical 3,3'-DIMs with a quaternary carbon center, including trifluoromethyl-substituted 3,3'-DIMs, are still rare. Sasaki et al. reported the reaction of trifluoromethyl(indolyl)phenylmethanols with indoles in the presence of trifluoroacetic

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

• activity within the field today (Figure 2). Flow chemistry Batch-based synthetic methods have enabled a wide variety of transformations to be performed at industrial scales, however, the implementation of flow-based protocols often lends itself to the creation of superior synthetic systems. Improved

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• ligands [52][53][54][55] and as chiral auxiliaries [56]. The most widely used synthetic methods to form the aziridine ring [57][58][59][60][61] include intramolecular cyclizations in amines bearing potential leaving groups. Stereoselective syntheses of aziridines have been successfully carried out by

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• for their synthesis, work-up, and purification. In this context, the aim of the next part of this review is to propose a generalized and comparative overview of the synthetic methods to access this particular scaffold. We chose to sort the synthetic routes by reaction types, from the most general and

• examples have also been reported for the addition of amines to arylcyanoguanidines (vide infra). Fusion of cyanoguanidine and amine hydrochlorides: The direct fusion of a mixture of cyanoguanidine and amine salts was one of the earliest synthetic methods of biguanides, described for the first time in 1892

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• , and pharmaceutical agents. These structural motifs are frequently used as synthons and as key intermediates for natural product synthesis. Therefore, the development of stereoselective synthetic methods for the substituted THP subunit has long been the area of fundamental research in organic chemistry

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• derivatives having various substituents on the ethylene moiety. In particular, synthetic methods that do not use metal catalysts and reagents are expected to be very effective in manufacturing precision materials and pharmaceuticals [32][33][34][35][36][37]. To develop metal-free methods for the synthesis of

Stereoselective syntheses of 3-aminocyclooctanetriols and halocyclooctanetriols

• Emine Salamci and
• Yunus Zozik

Beilstein J. Org. Chem. 2021, 17, 705–710, doi:10.3762/bjoc.17.59

• biological activities [1][2][3][16][17][18][19][20][21][22][23][24][25][26]. However, only a limited number of synthetic methods are available for the synthesis of seven- [27][28], eight- [29][30][31][32][33][34][35][36][37][38], and nine- [35] membered aminocyclitols. Therefore, we were inspired to work on

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• processes, among which reactions leading to methanofullerenes are widely used. Two main synthetic methods for the production of methanofullerenes can be distinguished (Scheme 1): nucleophilic cyclopropanation with stabilized carbanions that occurs by the addition–cleavage mechanism – the Bingel reaction (I

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• toxic oxidants. Keywords: chemoenzymatic synthesis; cortisol; hydroxylation; secosterol; whole-cell catalysis; Introduction Developments in the chemistry of steroids have stimulated extensive research interest in the exploration of new synthetic methods since the 1960s. Advances in synthetic biology

• synthetic methods for secosteroids is wide. However, usually these are multistep sequences exploiting toxic oxidants. Marine invertebrates are a rich source of oxidated and highly functionalized steroidal metabolites, including secosteroids. Since the first isolation of 9,11-secosterol from

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• °C min−1 to 320 °C and operated in the splitless mode (60 s valve time); carrier gas (He): 1.2 mL min−1. The retention indices were determined from n-alkane standards (C8–C32) [42]. General synthetic methods All chemicals were purchased from TCI (Deutschland) or Sigma-Aldrich Chemie (Germany), and

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• phthalazinone derivatives 5 and 6 (Scheme 1, route B). In the literature, the number of reported synthetic methods for 4-aminophthalazin-1(2H)-ones is limited to a few examples and they usually involve two main approaches: 1) the application of multicomponent reactions starting from, e.g., the available o

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• the phosphinylation of hydroxy esters 2 with N-protected aminoalkylphosphonochloridites 9 followed by oxidation (method V) (Figure 2). This review focuses on the synthetic methods of phosphonodepsipeptides and phosphonodepsipeptides with C-1-hydroxyalkylphosphonic acids, excluding peptides with side

• , haptens for the production of antibodies, biological agents, and prodrugs. Various synthetic methods of phosphonodepsipeptides have been developed, including the phosphonylation of hydroxy esters with phosphonochloridates or with phosphonic monoesters in the presence of coupling reagents, the alkylation

• synthetic methods, the multicomponent Mannich-type condensation strategy shows a high efficiency, convergent feature, and product diversity. It can be expected that the convergent multicomponent condensation synthetic strategy will show wide applications in the preparation of biologically active

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