On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• , parallel/combinatorial synthesis, multicomponent chemistry, metal-catalyzed coupling reactions as well as NMR, preparative/analytical liquid chromatography and mass spectrometry). – An improved understanding of molecular pharmacology along with in vitro or in vivo assays to detect various aspects of drug

Synthesis and electrochemical properties of 3,4,5-tris(chlorophenyl)-1,2-diphosphaferrocenes

• Almaz A. Zagidullin,
• Farida F. Akhmatkhanova,
• Mikhail N. Khrizanforov,
• Robert R. Fayzullin,
• Tatiana P. Gerasimova,
• Ilya A. Bezkishko and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1338–1345, doi:10.3762/bjoc.18.139

• transition metal-catalyzed cross-coupling reactions broadly used for the preparation of different diarylacetylenes and, rarely, bis(chlorophenyl)acetylenes. Next, starting substituted benzaldehydes were treated with an excess of SOCl2 for 24 h at 25 °C. Corresponding substituted benzal chlorides 4 were

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• reaction of hydrazones and p-benzoquinones [16], and Co3+/Cu2+-catalyzed C−N/N−N coupling of imidates with anthranils as both aminating reagents and organic oxidants [17]. Additional established routes to 1H-indazoles comprise transition metal‐catalyzed [18][19][20] and metal-free [21][22] intramolecular

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• halides are valuable compounds with potent bioactivities [1][2][3][4][5] (Figure 1) and are utilized as crucial precursors for various metal-catalyzed cross-coupling reactions [6][7][8][9]. They are frequently used as synthetic intermediates in several value-added syntheses of natural products

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• attention [15][19][20][21][22][23][24][25][26]. This method involves a transition-metal-catalyzed one-pot, three-component reaction in which two functional groups are simultaneously introduced on the Se atom via double selenation. As examples, the following Cu-catalyzed one-pot reactions have been reported

Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

• Shao-Cong Zhan,
• Ren-Jie Fang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80

• underwent a [4 + 2] cycloaddition reaction (reaction 1 in Scheme 1) [69][70][71][72][73][74]. This metal-catalyzed one-pot reaction not only combined the advantages of a traditional Diels–Alder reaction and the recently developed multicomponent reactions, but also meets the goal of green and sustainable

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• ; N-halosuccinimide; palladium(II); Introduction Electrophilic aromatic substitution [1][2][3] and ligand-directed transition-metal-catalyzed reactions [4][5][6][7][8] are among the most widely used synthetic approaches for the preparation of halogenated arenes. They are important precursors in cross

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• , 3o, 3q, 3s, 3t and 3x) gave a good yield of the corresponding product, respectively. Here also, the halo-substituted aryl ring on 1 can be further used for transition-metal-catalyzed cross coupling reactions, thus providing a very good application. Then the effect of N-protecting groups on the

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• the art and science of selective molecular engineering [1]. To date, organic synthesis has largely been governed by the interconversion of pre-existing functional groups through the use of more traditional transition-metal-catalyzed cross-coupling reactions [2][3][4][5]. Although these reactions have

• attractive. Transition-metal-catalyzed reactions of strained bicyclic derivatives have been an intense area of research in the last 20 years (Scheme 1) [14][15][16][17]. Of particular interest is oxabenzonorbornadiene (OBD, 1), as it bears multiple points of reactivity that allow for diverse

• reported metal-catalyzed reactions of heterobicyclic alkenes and applications towards the synthesis of biologically active compounds (top). Representative examples of regioselectivity in different metal-catalyzed ring-opening reactions of C1-substituted oxabenzonorbornadiene derivatives (bottom left

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

• using a silver-BINAP catalyst combination [25]. Later, the same group could successfully tune the catalytic system to control the regioselectivity in the addition of metal enolate to nitrosoarenes to achieve an α-hydroxyamination [26]. Since then, several groups have shown the use of metal-catalyzed

• metal-catalyzed reactions [31][32][33][34][35][36]. The most successful among them are the ʟ-proline-catalyzed reactions of enolizable aldehydes with nitrosoarenes [37][38][39][40][41][42][43]. Besides ʟ-proline and its derivatives, various secondary amines derived from BINOL and cinchona alkaloids were

Earth-abundant 3d transition metals on the rise in catalysis

• Nikolaos Kaplaneris and
• Lutz Ackermann

Beilstein J. Org. Chem. 2022, 18, 86–88, doi:10.3762/bjoc.18.8

• alternatives. Furthermore, metal-catalyzed cross-couplings do require prefunctionalizations on both substrates and generate stoichiometric quantities of undesired chemical waste, thus reducing the sustainability of these catalytic transformations. To address these major limitations, the past decades have

• witnessed major momentum in metal-catalyzed C–H activation [4][5] as a more resource-economical strategy. This approach involves the efficient and selective cleavage of otherwise inert, yet omnipresent C–H bonds. This strategy avoids a variety of steps and reduces the amount of chemical waste. Very recently

• laboratories calls for a critical analysis of these methods to enable an efficient transition of these methods. Hence, manganese-catalyzed C–H functionalization for late-stage functionalizations of biomolecules and drug-like scaffolds are summarized [8]. Likewise, 3d transition metal-catalyzed C–H

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• demanded the need of an alternative method for the synthesis of nitriles. Nowadays transition-metal-catalyzed reactions have received tremendous interest. Various transition metals such as Fe [15], Co [16], Ni [17], Pd [18], Cu [19], Rh [20] etc. were well explored in cyanation owing to its cost-effective

• achieved significant progress in recent times. Transition-metal-catalyzed cyanation reactions have emerged as an alternative approach to conventional cyanation strategies. Nowadays ruthenium has gained much acceptance owing to its wide range of oxidation states and ability to form a large number of

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• conveniently and comprehensively. However, as we know, the construction of these compounds is mostly carried out through transition-metal-catalyzed cyclization reactions [11][12][13][14], whereas strategies using bifunctional chiral thiourea catalysts are rarely reported. In 2018, Du's group reported a novel

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• the design of novel domino reactions. Keywords: cascade; catalysis; coupling; earth-abundant; iron; Introduction Over the past couple decades, the use of transition-metal-catalyzed cross-coupling reactions have become a staple within the organic chemist’s arsenal of carbon–carbon and carbon

• reasons of clarity, newly formed bonds are sketched in red, with newly formed cyclic structures being highlighted. Review Iron-catalyzed cross-coupling Metal-catalyzed cross-coupling reactions have become a staple for carbon–carbon bond formation. The late TMs that have dominated the field of cross

• . Iron-catalyzed cross dehydrogenative coupling Transition-metal-catalyzed carbon–carbon (C–C) or carbon–heteroatom (C–X) bond formation involving two different C–H bonds or one C–H and one X–H bond is formally known as cross dehydrogenative coupling (CDC) and is quite attractive to synthetic organic

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• sulfones is a valuable and appealing task in synthetic chemistry. Traditionally, diarylmethyl sulfones are synthesized by transition-metal-catalyzed deoxy C–S bond-coupling reaction of sodium arylsulfinates with diarylmethanols [11], C–H functionalization of alkyl sulfones with aryl halides [12], and via a

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• amidines with alkynes catalyzed by either rhodium or ruthenium [55][56][57], or a metal-catalyzed aminative cyclization of 2-alkynylbenzonitriles with secondary amines [58]. Despite the advantages associated with the aforementioned protocols such as the functional group tolerance and huge substrate scope

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• be prepared by asymmetric C–H activation. The C–H activation or functionalization can be achieved by a metal-catalyzed chiral phosphoric acid ligand-assisted method, which offers distinct possibilities to provide various chiral biaryl compounds by changing different directing groups (DGs) [46]. Since

• ]. Organocatalytic aryl C–H activation via a nonradical process represents an enormous challenge in organic synthesis, although the nucleophilic aromatic substitution with cleavage of the electrophilic aryl C–H bond has only recently been developed by transition-metal-catalyzed aryl C–H activation [57]. In the

• ][21] (Figure 2), and chiral building blocks in modern organic synthesis [5]. During the past decades, both C2 and non-C2 symmetric axially chiral biaryl compounds such as BINAP, BINAM, NOBIN and their derivatives BINOL have played a crucial role as ligands in the development of transition-metal

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• introduction on important classical approaches and older yet creative methods to provide the reader with a historical context. For comparison, this will be followed by a discussion of more modern techniques, including chiral auxiliaries for neighboring group participation and transition metal-catalyzed

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• radical cyclizations [22], Pschorr reactions [23], and diverse cycloaddition protocols [24][25]. Especially transition-metal-catalyzed cross-coupling reactions starting from benzophenones, benzoic acids, dihalogenated benzene building blocks and others have emerged as new approaches in recent years [26

• ][27][28]. Various approaches starting from functionalized biaryls have hereby attracted considerable interest, since the precursors are readily available by established cross-coupling reactions. Beyond transition-metal-catalyzed reactions, acid-mediated cyclizations of biphenylcarboxylic acids and

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• -silylmethylene malonates (Scheme 1b) [29]. As the catalytic enantioselective route is limited to accessible β-nitrosilanes, there is an urgent need to develop efficient catalytic protocols to deliver enantioenriched β-nitrosilanes from easily available starting materials. Metal-catalyzed reaction of various

• the best of our knowledge, organocatalyzed or metal-catalyzed enantioselective conjugate additions of nitroalkanes to β-silyl enones are not yet known. Results and Discussion The optimization study began with the conjugate addition reaction between β-TMS enone 1a and nitromethane (2) as the model

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• study [41][42] in 2017. This metal-catalyzed, photoinduced, and asymmetric radical transformation requires two catalysts, namely, (i) a metal catalyst that promotes electron transfer and (ii) a separate chiral catalyst that facilitates the highly stereoselective bond formation. In 2016, Fu [82

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• acetamides and acetates catalyzed synergistically by a metal acyclic iridium complex and a chiral Cu(I) complex [19]. Besides transition-metal-catalyzed allylic substitution reactions, Lewis-base-catalyzed allylic functionalizations using Morita−Baylis−Hillman (MBH) adducts as electrophilic allylic

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• ][10][11][12]. However, the above protocols generally proceeded under harsh conditions that led to poor functional group tolerance and generated stoichiometric amounts of waste. Thus far, the transition-metal-catalyzed C–H functionalization strategy has innovated the way to producing ferrocene

• preparation of ferrocene–drug conjugates effectively. Mechanistic studies indicated that the C–H activation step was the rate-determining step. 3d-Transition-metal-catalyzed C–H functionalization to access functionalized ferrocenes. Scope of ferrocenes with morpholine. Scope of various amines with 1a

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• condensation of α-halogenated carbonyl compounds, β-dicarbonyl compounds and amines; and iv) the latest developed multicomponent tandem reactions and transition metal-catalyzed coupling reactions [30][31][32][33][34][35][36][37][38][39]. Recently, substantial achievements have been made using azides as a

• synthesis [47]. Further, the Liu group reviewed the synthesis of allenes via transition metal-catalyzed 1,4-functionalizations of unactivated 1,3-enynes [48]. In this review, we will highlight the recent advances in the tandem annulation reactions of 1,3-enyne structural motifs for the construction of

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• , such as ionic liquid- and transition metal-catalyzed and other metal-free transformations [1]. A strategically diverse route to phenanthridines involves intramolecular cyclization of biaryl oximes, allowing for the formation of a new C–N bond. Such a strategy was explored by Deb and Yoshikai in the Fe