α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• step [55]. Radical 5-exo or 5-endo cyclizations of substituted N-allyl or N-vinyl α-halo amides VIII [56][57][58][59][60][61] or X [62][63][64][65][66] using atom transfer and other chain reactions, as well as non-chain methods [67][68][69][70][71][72][73] have been used to approach diverse γ-lactam

• cyclizations to lactams of type 10 based on the persistent radical effect (PRE) are unknown and may provide a simple access to 3,4-disubstituted γ-lactams. We report here that tandem nucleophilic epoxide ring-opening/Brook rearrangement/radical oxygenation reactions are indeed very effective for the synthesis

• (2R*,4S*)-9l as the major product (Scheme 8). The outcome of the thermal radical cyclizations of the dioxygenated amides 9 is dependent on the structure of the alkene unit, but the general trend is similar (Scheme 9). Amides with a terminal alkene unit furnished dioxygenated pyrrolidones 12a–f,h–j as

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

• ) were successful. Therefore, alternative methods such as intramolecular cyclizations, exchange fluorination, and transformation of functional groups in fluorinated rings have been developed in order to provide access to fluorinated cyclopropanes with electron-withdrawing substituents. 1.1

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

• starting materials, rather expensive catalysts, harsh reaction conditions or low product yields. Transition-metal-catalyzed, electrophile-induced and oxidative radical cyclizations of ortho-alkynylated biaryls are widely used for the synthesis of polynuclear aromatics [57][58][59][60][61][62][63][64][65

• -2-carbazolylpyridine 6 in 74% yield (Scheme 3). Electrophilic cyclizations of 3-alkynyl-2-carbazolylazines 2a,b and 6 into azine-fused carbazoles 7a–c were carried out with ICl in dry acetonitrile at room temperature in the dark (Table 3). In the cases of compounds 2a,b, the reaction was found to be

• steps of the method are electrophile-induced 6-endo-dig cyclizations of ortho-alkynylated biaryls. The overall yields of helicenes in five stages of the synthesis exceed 30%. The single-crystal X-ray diffraction analysis revealed the non-planar crystal structures of the synthesized helicenes responsible

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

• discovered that the nucleophilic amines 3 can be successfully employed in this type of transformations as well, providing the amidinium intermediates 4, which are susceptible to a variety of subsequent cyclizations. This approach opens up a novel avenue by which to access the benzoxazoles 5 [40

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• interactions are marked with two-headed arrows. Mechanism of the halofluorination reactions of the substrate 19. X = Br (compounds a), I (compounds b), Cl (compounds c). Synthesis and halofluorination of the imide 24. Cyclizations of halofluorinated diesters with potassium tert-butoxide. Relevant NOESY

• interactions are marked with blue two-headed arrows. Mechanism of the reaction of the cyclopropanation of the compounds (rac)-2a,b and (rac)-5a with t-BuOK. Presumed mechanism of the reaction of the compound (rac)-6b with t-BuOK. Cyclizations of halofluorinated tetrahydrophthalimides with DBU. Relevant NOESY

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• innovative transformations, including cycloadditions [5][6][7][8][9], intramolecular cyclizations and intermolecular addition reactions [10][11][12][13][14][15][16][17][18], as well as the use of the allenamide building block in natural product synthesis [1]. Addition reactions of allenamides, which can also

• encompass intramolecular cyclizations, are typically promoted by the electrophilic activation of the β-carbon of the allenamide. This can be achieved using various electrophilic methods, including the use of Brönsted acids [15][19][20][21][22], halogenation sources [16][18][23][24][25][26][27][28], by means

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• oxa-Michael additions of 2’-hydroxychalcones [9][10], or through condensation cyclization reactions of o-hydroxyacetophenones with ketones/aldehydes [11][12], in addition to other alternative transformations [13][14]. Moreover, radical cascade cyclizations of o-allyloxybenzaldehydes by employing

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• -aldehyde 7. For example, we have explored the potential of the peptidyl reactive site in a number of enolization-driven post-Ugi cyclizations leading to the assembly of pyrrol-2-ones 9 and 10 [59][60]. We have also taken advantage of a 1,3-dicarbonyl moiety present in 8 by engaging them in an enolization

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• intermediate α-imino ketone undergoes when a solution in ChCl/urea is stirred at rt for 4 h in the presence of Et3N (3 equiv) as a base. These cyclizations proved to be relatively sensitive to the electronic properties of the starting phenacyl azides as they did not take place in the presence of strong

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• [15][16][17][18], nucleophilic and electrophilic cyclizations [19][20][21][22][23][24][25], reductive and oxidative cyclizations [26][27], and transition-metal catalysis [28][29][30][31][32][33][34][35][36][37]. There are fewer ways to access indolone derivatives, mainly based on the use of di- [12

• ][38][39] or triketones [10][13] and enaminones [40][41][42][43] as starting materials. For the synthesis of cinnoline derivatives, aryldiazenes and aryltriazenes are substrates of choice for transition-metal-catalyzed (Rh, Pd, Cu) cross-coupling reactions, followed by intramolecular cyclizations [44

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• Phenanthrenes and their aza-analogues have important applications in materials science and in medicine. Aim of this review is to collect recent reports describing their synthesis, which make use of radical cyclizations promoted by a visible light-triggered photocatalytic process. Keywords: phenanthrenes

• cyclizations for the synthesis of polycondensed aromatics, with a focus on those containing heteroatoms [36][37][38][39]. The aim of the present review is to summarize the recent efforts in the design and optimization of photocatalyzed procedures for the synthesis of phenanthrenes and their nitrogen-containing

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• excellent radical properties also made these thiyl radicals powerful HAT catalysts. They have increasingly been proven useful in various types of organic photoreactions, such as cyclizations, anti-Markovnikov additions, aromatic olefin carbonylations, isomerizations, etc. They are a class of green, economic

• variety of reactions, renders them a class of green, economic, mild, and chemoselective radical catalyst. Apart from this, they are also excellent HAT catalysts in photoredox catalysis systems [2][3]. In various types of organic photochemistry reactions, such as cyclizations, anti-Markovnikov additions

• nonpolar solvent, PhSSPh accelerates the [4 + 2] cycloaddition of the radical cation 19, but the electron-relay catalyst promotes the [2 + 2] cycloaddition. The radical cation 19 can undergo two different types of cyclizations, subject to the relative reactivity of its radical and cation center. The α

Recent synthesis of thietanes

• Jiaxi Xu

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

• + 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

[3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin

• Margareta Sohora,
• Leo Mandić and
• Nikola Basarić

Beilstein J. Org. Chem. 2020, 16, 1296–1304, doi:10.3762/bjoc.16.110

• the macrocyclic host affected the stereochemistry of the reaction. Moreover, we studied photodecarboxylation reactions initiated by the phthalimide chromophore [17][18][19] and applied them in cyclizations with memory of chirality [20] and diastereoselective peptide cyclizations [21

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

• reactions of oxime radicals. These reactions are classified into cyclizations involving C–H bond cleavage and cyclizations involving a double C=C bond cleavage. Keywords: iminoxyl radicals; isoxazolines; oxidative cyclization; oxime radicals; oximes; Introduction Free radicals in which an unpaired

• under the action of photocatalysts [109][110], cyclization of nitroso intermediate [111], etc. [112][113]. At least some of these reactions do not involve oxime radicals as intermediates. It should be noted that free-radical cyclizations mediated by iminoxyl radicals frequently afford products that are

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• metathesis (RCM) [67][68]. Starting from 3-cyanocyclohex-2-enone, the authors obtained a versatile intermediate able to provide the appropriate dienyne precursors (A–C, Scheme 4) by multicomponent Grignard addition-alkylations. Through divergent cyclizations involving a chemoselective enyne metathesis

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• electrophilic cyclizations to generate intermediate A. Intermediate A undergoes a 1,5-hydride shift, forming intermediate B. A subsequent cyclization forms intermediate C. Intermediate C generates intermediate E via one of two possible pathways: either a direct 1,3-hydride shift or an indirect pathway involving

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• a linear polyene with branching methyl groups that form the core hydrocarbon structure in a single enzyme-catalyzed step [9]. The enzyme, which is called terpene cyclase, holds the linear methyl-branched polyene in a defined conformation that initiates a series of carbocation-driven cyclizations and

• oxidative [66] and reductive cyclizations [67] have been described. The reductive cyclization reaction is particularly noteworthy, as the reduction and cyclization step are catalyzed by two distinct enzymes [67]. These examples show that the classical division of terpene biosynthesis into a cyclization and

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• could form isoquinolones and pyridones linked to a tetrazole ring, since such class of hybrid compounds is not described in the literature. Several protocols based on C–H activation or metal-catalyzed cyclizations are known to generate the isoquinolone and pyridone moieties and further assist their post

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• -bromobenzo[c][2,7]naphthyridines 12a–d in hand we aimed at the synthesis of the respective pyrido[2,3,4-kl]acridines by intramolecular ring-closing steps. Similar C–C couplings were performed previously by application of palladium-catalysed cross-coupling reactions, photochemical cyclizations or even in

Click chemistry towards thermally reversible photochromic 4,5-bisthiazolyl-1,2,3-triazoles

• Chenxia Zhang,
• Kaori Morinaka,
• Mahmut Kose,
• Takashi Ubukata and
• Yasushi Yokoyama

Beilstein J. Org. Chem. 2019, 15, 2161–2169, doi:10.3762/bjoc.15.213

• could be considered reasonable that the reactions of the sterically more congested ethynes and benzyl azide gave triazoles with less chemical yields. Details of the synthesis are described in Supporting Information File 1. Photochromic reactions Photochemical cyclizations Triazoles were dissolved in

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• highly functionalized 1,2,3-triazolium macrocycles under optimized reaction conditions, although cyclizations also have been carried out starting from triazolium building blocks (Figure 2). Using a small variation in the reaction protocols of the click reaction, iodine atoms can be introduced at the 5

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• widely described in the literature encompassing a number of reactions like oxidative cyclizations [11], oxidative coupling reactions [12], Vilsmeier type cyclizations [13], intramolecular aminooxygenation/C–H amination reactions [14][15], Groebke–Blackburn–Bienayme (GBB) reactions [16][17][18] and many

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• the 1,4-dihydropyridine scaffold. As depicted in Scheme 14, compound 46 was later subjected to a variety of post-MCR cyclizations, including the reaction with carboxylic acids to form the fused steroidal pyridopyrimidinones 47 and with carbon disulfide to form pyridopyrimidinedithione 48 in very good

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• alkynylpalladium complex 25 in the proposed pathway. Other benzoic acid derivatives such as those bearing a formyl substituent at the ortho position also take part in several multicomponent cyclizations leading to isoindolinones. Thus, 2-formylbenzoate 29, primary amines 2 and terminal alkynes 18 react under