Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• in natural products, drug molecules, biologically active molecules, and functional materials. However, the highly selective incorporation of two different sulfur-bearing moieties across double bonds remains challenging [42]. Herein, we describe a visible-light-enabled cascade radical

• -induced cascade radical difunctionalization of unactivated alkenes to provide partially trifluoromethylated dithioethers. The approach features practical conditions, good functional group tolerance, and a broad substrate scope allowing the incorporation of two distinctive sulfur-containing motifs into

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• from Aspergillus niger (AnFaeA, Figure 1C). Coloration is the result of successive reactions: (i) release of the free 5-bromo-4-chloro-indoxyl-3-ol by an enzyme cascade, wherein TxAbf-catalyzed cleavage of the glycosidic bond was made possible by the prior release by AnFaeA of the ferulate moiety [21

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• prepared the (−)-adaline (1) and the non-natural isomer (−)-euphococcinine (2) through a four-step intramolecular Mannich cyclization cascade reaction [57]. In this methodology, the alkaloids were prepared by treating the convenient N-sulfinylamino ketone ketal precursor on heating with NH4OAc:HOAc. Oxo

• %, respectively. The conversion of precursors N-sulfinylamino ketone ketals directly to the desired homotropanes represents a four-step intramolecular Mannich cyclization cascade reaction, being the most efficient method to date for the (−)-adaline (1) and (−)-euphococcinine (2) syntheses. Specific rotation was

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• substrates. Keywords: DFT calculations; gold catalysis; Nazarov reaction; N-heterocycles; Introduction In the development of new and effective catalysts, step economy is surely one of the major goals. A reduction of the number of steps in the synthesis of complex compounds can be attained by cascade

• reactions, which allow for structural modifications on the organic compounds by forming several chemical bonds in one pot. To this end, gold catalysis [1][2][3][4][5][6][7] has been widely exploited to construct various cyclic and heterocyclic frameworks through cascade reactions triggered by the activation

• of a triple bond, which has ultimately led to the total synthesis of several natural compounds [2][8]. The gold-catalyzed rearrangement of suitably substituted propargylic esters in particular provides a platform for cascade processes that involve a cationic or an allene intermediate generated in the

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

• % yield (Scheme 6B). This adduct 92a underwent decarboxylation to afford 92b in 72% yield [42]. Exposure of freshly prepared 92b to triazabicyclodecene [45] led to a ring-expansion/aromatization/aldol cascade producing 93, which was reduced with Et3SiH/TFA smoothly to give indane 94 in 68% yield over two

• -cation equivalent in [3 + 2] cycloaddition in the synthesis of (±)-cuparene (13) [69]. The recent advances of [3 + 2] annulation in natural product synthesis. (A) The preparation of meloscine (158) features a cascade radical annulation of divinylcyclopropane [70]. (B) Thiyl-radical-mediated [3 + 2

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

• Within the last few years, we have developed and implemented a number of novel synthetic methodologies in our laboratories, involving acid-mediated cascade transformations of nitroalkenes and nitroalkanes, which target materials science and medicinal chemistry applications. It was demonstrated that upon

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• triggered the back cascade translocation. Excitingly, when the self-sorted system in SelfSORT-I was treated with 2-cyano-2-phenylpropanoic acid (50) [62][63] as a chemical fuel, the protonation of 49 entailed the same cascade translocation resulting in SelfSORT-II but now with the effect that it slowly

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• initiate a cationic cyclisation cascade, leading to structurally highly complex and usually polycyclic terpenes in just one enzymatic transformation. The initially formed products are non-functionalised terpene hydrocarbons or, if the terminal cationic intermediate of the cyclisation cascade is trapped by

• rearrangement to a2•+ and a hydride shift to b2•+ (Scheme 3A). This hydride migration is in reverse order compared to a similar step along the cationic cyclisation cascade during the biosynthesis of 2 (Scheme S1 in Supporting Information File 1). The subsequent inductive ring opening to c2•+ and α-cleavage of

Anion exchange resins in phosphate form as versatile carriers for the reactions catalyzed by nucleoside phosphorylases

• Julia N. Artsemyeva,
• Ekaterina A. Remeeva,
• Tatiana N. Buravskaya,
• Irina D. Konstantinova,
• Roman S. Esipov,
• Anatoly I. Miroshnikov,
• Natalia M. Litvinko and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2020, 16, 2607–2622, doi:10.3762/bjoc.16.212

• of magnesium ions on metabolic transformations of nucleosides [45], in particular on the phosphorylation of the primary hydroxy group of pentoses, catalyzed by ribokinases [46], as well as on the cascade synthesis of nucleosides starting from pentoses [47][48][49][50] has been described. Based on the

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• radical precursors in this system, allowing for both alkyl [44] and acyl [45] RCA reactions. In the case of acyl DHPs, they propose that direct excitation of the DHP leads to radical generation rather than the iminium intermediate (Scheme 9c). The same system was used for the radical cascade reaction

• separately developed a Minisci-type reaction using phthalimide esters 123; however, their system did not extend past isoquinoline substrates 124 (Scheme 17b) [62]. Zheng and Studer expanded the scope of this type of reactivity to a three-component cascade reaction with alkyl bromides 125 and enamides 126

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• to the possibility of creating enantiomerically pure compounds with several stereocenters through the directed regulation of diastereoselectivity in subsequent transformations, which can be realized as stepwise or cascade processes. Due to this reason, the Michael reaction was successfully used over

• addition of β-keto phosphonates to nitroolefins and subsequent reductive cyclization of enantioenriched, diastereomerically pure Michael adducts was developed. The present study also demonstrates that the diastereoselective cascade Henry/acetalyzation reaction with keto nitro phosphonates and aldehydes

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• even anthracene. At higher temperature, the cycloadducts undergo an intramolecular SE(Ar) reaction leading to condensed carbocycles incorporating a 1-(trifluoromethyl)-1-(dimethylamine)indene ring system. With styrenes and some substituted styrenes, cascade reactions take place, which likely include

• cyclobutene and several cationic intermediates and mainly yield 2-(1-phenylvinyl)indenes. In a similar reaction cascade, a fulvene derivative was obtained with 1,4-diphenylbutadiene as the substrate. Keywords: alkynes; aromatic substitution; cyclization; cycloaddition; iminium salts; Introduction In recent

• consider the reactivity of the electrophilic (“electron-poor”) acetylenic bond toward 1,3-dienes, and show how the expected [4 + 2] or [2 + 2] cycloaddition products can enter subsequent cascade reactions toward carbocycles which incorporate a C(CF3)NMe2 structural unit. Results and Discussion The Diels

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

•  1a). Besides, in 2016 Li’s group [28] reported a silver-catalyzed straightforward approach for the synthesis of phosphonate-functionalized chroman-4-ones via a phosphoryl radical-initiated cascade cyclization of 2-(allyloxy)arylaldehydes using K2S2O8 as an oxidant, however, diphenylphosphine oxide

• (DPPO) was not suitable for the transformation (Scheme 1b). So the development of metal-free and greener methods to approach chroman-4-ones bearing a phosphine oxide moiety is still highly desirable. Herein, we present a transition-metal-free radical cascade cyclization to access the desired chroman-4

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

• double activation catalysis (Figure 2, (2)) [49][50]. Similarly, if both catalysts activate the same coupling partner but in a sequential fashion (the activated substrate leads to an intermediate further activated by the second catalyst), this falls in the category of cascade catalysis (Figure 2, (3

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• : phosphonium salt-catalysed triazolation of MBH adducts. Scope of the one-pot cascade reaction of the unprotected Morita–Baylis–Hillman adducts 3a–q. Comparative analysis of the sequential one-pot reaction. Optimization of the triazolation of the MBH adduct 1a. Optimization of the reaction conditions for 3

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

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

• sulfonyl radical, prone to start a tandem sulfonylation/annulation of vinyl azides [84]. Recently, the phenanthridine core was assembled through a radical cascade triggered by the trifluoromethylthiolation of N-(o-cyanobiaryl)acrylamides. The process occurred under visible-light irradiation (6 W blue LED

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

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

• of vinylcyclopropanes with olefins [8]. The reaction mechanism of this cycloaddition process was similar to other thiyl radical-catalyzed cycloaddition cascade reactions. The alkylthiyl radical generated by the homolysis of a disulfide-bridged peptide precatalyst under UV-light irradiation triggers

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

• (Scheme 38) [128]. Both aliphatic (example 118c) and aromatic (examples 118a,b,d–h) β,γ-unsaturated oximes enter this cascade cyclization. Relatively low yields were obtained with electron-withdrawing substituents in isonitrile 117 (examples 118g,h). Another example of a cascade oxidative cyclization

• (products 135a,d–h) and alkyl substituents (products 135b,c) at the oxime fragment (R1). An oxime with a disubstituted double bond (R2 = Me) also reacts with the formation of isoxazoline 135g having a quaternary carbon atom. Under the action of t-BuOOH (TBHP), β,γ-unsaturated oximes 136 undergo a cascade

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

• possible, such as halogenations, azidations, olefinations, or alkynylations. This activation mode was employed by the same group in a cascade strategy, which allowed a remote functionalization [143]. To extend the scope of such transformations, our group reported novel organic dyes in 2018, such as

• oxidation of 29.1 was achieved using Mes-Acr-Me+ (OD2) and a cobalt cocatalyst, ensuring an efficient dehydrogenation. Various N-heterocycles 29.3 were accessed via a radical cyclization cascade with the alkyne derivatives 29.2. Amidyl radical generation The oxidation of amides is more difficult compared to

• previously described approach for iminyl radical formations was employed [140]. The same tunable aryloximes 31.1 were used as electrophores to generate the desired amidyl radicals. This methodology allowed the development of a hydroamination/cyclization cascade to give the heterocycles 31.2 and

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• (Te), Italy 10.3762/bjoc.16.95 Abstract Cascade cyclocarbopalladation of the readily available aryl/alkyl-substituted propargylic amides containing an aryl iodide moiety, followed by Suzuki–Miyaura coupling with arylboronic acids, allowed an efficient regio- and stereoselective synthesis of

• tetrasubstituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones. Moreover, cascade cyclocarbopalladation, followed by the reaction with 2-alkynyltrifluoroacetanilides, accomplished a double cyclization to afford challenging 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones bearing a 3-indolyl substituent through

• stereoselective Pd-catalyzed cascade reactions, consisting of the addition of in situ-generated arylpalladium complexes over a proximate carbon–carbon triple bond, followed by cross-coupling reactions, have been reported [26][27][28][29][30][31]. Our continuing interest in the palladium-catalyzed reactions of

Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates

• Phil M. Pithan,
• Sören Steup and
• Heiko Ihmels

Beilstein J. Org. Chem. 2020, 16, 904–916, doi:10.3762/bjoc.16.82

• + and Fe3+ ions most likely induced a ring opening/ring closing cascade of the spirooxazine unit in 3a and 3b including an electron transfer to the respective metal cations. These reaction steps seemed to have different rates in the presence of Cu2+ or Fe3+, which may even allow the differentiation

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• that a specific geometry of the tethered alkene is required, as no 6-membered ring formation was observed. Interestingly, Cárdenas’ precursor 35 [30] led, after a cascade of reactions, to the formation of compound 36. Computational as well as experimental studies suggested that the ligand and

• -derived benzylic copper species with an electrophilic source of a cyano residue, Yang and co-workers reported on the Cu-catalyzed borylation of styrenes bearing an allylic group at the 1-position. After the initial addition, a cascade of reactions occurred, including cyanation generating a dearomatized

• electrophiles, such as N-cyanosulfonamides, leading to 1,2 or 4,3-borocyanation in a regiospecific fashion from borocuprative intermediates, respectively [111]. Extending earlier efforts from the Montgomery group for Cu-catalyzed cascade diborylation/ortho-cyanations of terminal allenes [112] and styrene

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• ][28][29] of complex heterocyclic compounds. Recent advance has been focused in the area toward the development of one-pot [30][31][32] Ugi cascade protocol [33][34] as the powerful synthetic strategy for the construction of increasingly complex heterocyclic compounds in the absence of metal catalysts

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Science, Chinese Academy of Science, 345 Lingling Lu, Shanghai 200032, China 10.3762/bjoc.16.62 Abstract A cascade oxidative trifluoromethylthiolation and cyclization

• )propioloyl]indole and N-propargylindoles, respectively. Inspired by these elegant results, we became interested in the preparation of SCF3-substituted pyrrolo[1,2-a]indol-3-ones, which might be potentially useful in medicinal chemistry. Radical cascade reactions constitute highly efficient strategies for the

• construction of compounds with structural diversity and complexity. In 2014, Wang reported the first radical cascade trifluoromethylthiolation and cyclization of activated alkenes (Scheme 1a) [23]. Afterward, Nevado [24], Hopkinson and Glorius [25], Dagousset and Magnier [26], as well as Fu [27] applied this