Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• synthetic utility of this tetrazole scaffold continues, particularly in other MCRs and post-modification processes, we anticipate more applications in the near future. Investigation of these drug-like molecules for the targets PD-1/PDL-1, caspase-1, and IL-17A are currently in progress in our laboratory

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• motif in bioactive compounds and the synthetic utility of its olefinic C=C bond. The most extensively explored approach to this transformation is the transition metal-catalyzed C–N coupling between azoles and vinylating agents, including vinyl halides [4], boronates [5], sulfonium salts [6][7][8], and

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• of reaction of more general synthetic utility”. Two distinct approaches, denoted as method A and B, were delineated in the study, yielding a relatively restricted scope of products derived from various styrenes bearing few functional groups. The decision to present only the conditions for method B is

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• phthalimidyl anion would generate the aminoalkylation product 119, completing the catalytic cycle. In addition to this aminoalkylation method, the synthetic utility of radical intermediates derived from NHPI esters under photoinduced Pd-catalysis has been demonstrated in Heck-type couplings [81][82] and in the

• cathode surface restores the Ni0 species 175 giving rise to a new catalytic cycle. Reductive cross-electrophile couplings that incorporate redox-active esters and aryl halides have the potential to simplify the syntheses of drug-like compounds through C(sp3)–C(sp2) bond formation. However, their synthetic

• utility is frequently restricted due to various challenges, such as RAE decomposition and a limited aryl halide scope. In recent years, the Baran lab has made progress in enhancing the practicality and applicability of electrochemically driven decarboxylative couplings involving NHPI esters and aryl

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• milder conditions in 55% yield. For increased synthetic utility, the latter could be converted in a straightforward manner into the corresponding thiophene under Pummerer conditions. A 6-membered ring contraction through SO-extrusion was also introduced as key step in a molecular “surgical” method

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• dibenzodiazepinones in good yields (up to 45%; 2 steps) and much milder conditions using copper as the catalyst. The synthetic utility of this novel strategy was showcased by demonstrating a formal synthesis for the antipsychotic drug clozapine and to an anticancer triazole–DBDAP hybrid. Keywords: Buchwald–Hartwig

• occurs first at the amide position. This approach enabled the successful synthesis of a broad spectrum of dibenzodiazepinone units in a one-pot fashion. The synthetic utility of Laha’s approach was highlighted by preparing the corresponding dibenzodiazepinone which was further reacted with N

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• readily accessible redox-active esters 3 and cost-effective NaI/PPh3 photoactivators under mild reaction conditions (Scheme 8) [14]. The methodology exhibited remarkable efficacy when applied to a wide range of natural products and pharmaceuticals, significantly expanding the synthetic utility of this

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• stereoselectivity which limits the synthetic utility of non-stabilized AMYs of type C. There are over 300 papers on the amino acid-based decarboxylative [3 + 2] cycloadditions of N–R-type AMYs B1 (such as that derived from proline) and B2 [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• product 3a was obtained. This shows the synthetic utility of this method; however, additional investigations into process chemistry may be necessary to accommodate a larger reaction scale. Conclusion In conclusion, we have shown for the first time a [3 + 2] cycloaddition of gem-difluoroalkenes with

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• ‑mediated electrophilic cyclization of aryl alkynoates. Construction of 6-substituted benzo[b]thiophenes. Plausible mechanism for construction of 6-substituted benzo[b]thiophenes. AlCl3‑catalyzed cyclization of N‑arylpropynamides with N‑sulfanylsuccinimides. Synthetic utility of AlCl3‑catalyzed cyclization

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• decarboxylative functionalization Aside from its strategic application in alkene difunctionalization methods, RLT has also found synthetic utility in radical decarboxylative reactions. Radical decarboxylative functionalization reactions to form C–X bonds have been demonstrated, with bond construction being

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• synthetic utility of the developed protocol, a tandem “one-pot” synthesis of N-heterocycles was successfully executed (Scheme 3). Thus, exposition of substrates 1 under the optimized reaction conditions followed by the addition of ortho-substituted anilines 3 and K2S2O8 (1 equiv) and heating the reaction

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• thoroughly examined using DFT calculations. Other than the broad substrate scope, the synthetic utility of this method was demonstrated by a scale-up reaction (3.73 mmol scale, 87% yield, 88% ee), and by several different transformations of the tandem products. Similarly, Ghorai et al. studied a Cu-catalyzed

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• good to very good yields. Keywords: alkenes; cyclopropanation; diazo compounds; difluoromethylphosphonate; DFT calculations; Introduction Cyclopropanes constitute a fascinating class of organic compounds due to their unique structure and bond properties [1]. However, their synthetic utility is

• target diazo reagent 5, which contains both a trifluoromethyl and a difluoromethylphosphonate moiety, was isolated as a stable, non-volatile liquid (Scheme 2). To highlight the synthetic utility of the novel carbene precursor 5, subsequent [2 + 1] cycloaddition reactions with selected terminal aromatic

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• ]. Substituted pyrazoles are also of considerable interest because of their synthetic utility as chiral auxiliaries [32], synthetic reagents in multicomponent reactions [33][34], and guanylating agents [35]. The installation of a thioamide functionality has attracted an immense attention in medicinal chemistry

• , and good to excellent yields of the desired molecules. Moreover, a practical synthetic utility of pyrazole-3/5-carbaldehydes has been explored through the formation of amide bond-tethered pyrazole-pyridine conjugates. This developed methodology was successfully carried out by employing commercially

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• the alkyne terminus significantly decreased the yield. Finally, non-natural and natural dienone-containing terpenes were synthesized such as β-ionone (3), which was available in 4 steps (6% overall yield). Thereby, the synthetic utility was demonstrated by a late-stage introduction of the dienone unit

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• synthesis of complex target products with original attachment place of 1,4-dithiane ‘scaffolding’ groups shown with dashed purple lines, references indicated with structures. 1,3-Dithianes as useful synthetic building blocks: a) general synthetic utility (in Corey–Seebach-type reactions) [1][2][3][4][5][6

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• . The success of gram-scale reaction and diverse functionalization of isocoumarins demonstrated the synthetic utility of this protocol. Keywords: C–H activation; enaminone; iodonium ylide; isocoumarin; rhodium catalysis; Introduction Isocoumarins are an important structural motif in many naturally

• , methyl, and phenyl groups underwent the current reaction efficiently, delivering the desired products 3ab–ae in moderate to good yields (43–93%). To demonstrate the synthetic utility of this methodology, a gram-scale synthesis of isocoumarin 3ia was firstly performed. Under the optimal conditions, the

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• . The present reaction smoothly proceeded in a simple undivided cell with platinum electrodes under constant current conditions, affording pinacol-type products in moderate to good yields with good to high diastereoselectivities. The successful large-scale experiment showed the potential synthetic

• utility of this transformation. Further investigations of the reaction mechanism are currently underway in our laboratory. Strategies for the synthesis of vic-1,2-diols. Substrate scope. Reaction conditions: 1 (1.0 mmol), Et4NBr (0.1 equiv), imidazole (0.05 equiv), MeCN (5 mL), H2O (125 μL), 50 mA cc, 4 F

Electrochemical vicinal oxyazidation of α-arylvinyl acetates

• Yi-Lun Li,
• Zhaojiang Shi,
• Tao Shen and
• Ke-Yin Ye

Beilstein J. Org. Chem. 2022, 18, 1026–1031, doi:10.3762/bjoc.18.103

• ketones, such as cyclohexanone (see Supporting Information File 1 for details). As illustrated in Scheme 3, the synthetic utility of α-azidoketone was further evaluated [37][38]. Click reaction between 2-azido-1-phenylethan-1-one (2) and ethisterone (28) [39][40][41] readily afforded the target triazole

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• its synthetic utility were investigated employing various dienes such as furan (18), 1,3-diphenylisobenzofuran (24) (DPIBF) and substituted anthracenes 31, 36 and 39 (Figure 3). Exclusive norbornene exo-π selectivity [24] was observed in all cycloadddition reactions. Selected five-membered dienes were

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• , followed by hydride abstraction to generate the desired product 2a. On the other hand, the formation of quinazolin-4(3H)-ones starts with the formation of an imine intermediate and then it will follow the similar mechanistic pathway. To explore the synthetic utility of the oxidative C–N cross-coupling

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• ). Disappointingly, the reactions carried out by varying the α-substitution did not afford the desired product. In order to demonstrate the synthetic utility of the oxyaminated compounds, the reductive cleavage of the N–O bond was attempted under Zn/AcOH conditions. Pleasingly, the reaction afforded the aniline

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• scope of alkylidene oxindoles is reasonably wide including aromatic and aliphatic substituents at the double bond and also substituents in the oxindole core. The work widens the synthetic utility of cyclopentane-1,2-diones. Model of the catalyst action. Catalysts screened. Screening of different N

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• ). Conclusion In summary, a concise, simple, clean and efficient synthesis of paullone isomer C was achieved in 4 steps with a crucial transformation, the Fischer indole ring-closure reaction, at the early stage of the synthesis (Scheme 6). The synthetic utility of the elaborated route was validated by gram