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

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• powerful strategy in organic synthesis due to the improved atom-, step- and resource economy in comparison with cross-coupling or classical organic functional group transformations. Despite the significant advances in the metal-catalyzed C‒H activations, recent developments in the field of

• developments in the field of photoredox nickel-catalyzed C‒H functionalization reactions with a range of applications until summer 2021. Keywords: C–H activation; functionalization; nickel; photocatalysts; photoredox; visible light; Introduction During the last decades, transition-metal-catalyzed

• transition-metal-catalyzed direct allylation of unactivated C–H bonds is considered as the prevalent strategy in organic synthesis. Despite significant advances were accomplished in the allylation of (hetero)aromatic and alkenyl C(sp2)‒H bonds [109], related reactions of C(sp3)–H are less explored [110][111

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• of their important biological and fluorescent uses. To summarize the main syntheses of these studies: in particular, transition metal-catalyzed cascade benzylation–cyclization [17], cyclization of polycyclic aryl triflate esters [18], reaction of β-naphthol and aldehydes [19][20] or inter- or

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• years (2008–2020) and focuses on direct and indirect methods to construct anthracene and anthraquinone frameworks. Keywords: anthracenes; anthraquinones; Friedel–Crafts cyclization; intramolecular cyclization; metal-catalyzed; Introduction Anthracene is an important aromatic hydrocarbon consisting of

• has been reported over the years. The most familiar methods to obtain substituted anthracenes include Friedel–Crafts reactions [17], Elbs reaction [18], aromatic cyclodehydration [19][20], Bradsher-type reactions from diarylmethanes [21][22][23], and, more recently, metal-catalyzed reactions with

• -catalyzed reactions with alkynes Metal-catalyzed reactions with alkynes have gained attention in the last years and have provided new methodologies to prepare anthracene derivatives. In 2009, Miura and co-workers were the first to obtain substituted anthracenes selectively by homologations with

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• synthesis of biologically relevant coumarins in aqueous medium [21]. Catalysis is one of the fundamental pillars of green chemistry [22], and the transition-metal-catalyzed synthesis of coumarins has been reviewed by Sharma et al. [23]. More recently, Kanchana et al. published an account on the palladium

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• , antipsychotic (12) [54], anticonvulsant (13) [55], and antiparkinsonian activities (14) [56][57] (Scheme 5A). A few years earlier, Hou and co-workers reported the very first metal-catalyzed C–H hydroaminoalkylation of tertiary amines using norbornene as the coupling partner [41]. For this method, the scandium

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• constitute an important structural modality in small-molecule drugs, such as levonorgestrel (birth control drug), efavirenz (HIV/AIDS treatment), and erlotinib (anticancer). Although step-economical C–H alkynylations have been investigated with 4d and 5d transition metals, 3d metal-catalyzed late-stage C–H

• -containing peptide 37g. Conclusion Metal-catalyzed late-stage functionalization has shown significant potential in the fields of medicinal chemistry, agrochemistry, and chemical biology. While transition metal catalysis has been a reliable and efficient strategy for late-stage functionalization, it suffers

• several disadvantages, such as the need for additional prefunctionalization and the use of expensive and toxic precious metals. To avoid these issues, 3d-metal-catalyzed C–H functionalization has recently been realized as a sustainable catalytic system and is actively being investigated for various late

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• applications of these five-membered N-heterocycles are the result of both their easy synthetic procedures and ring functionalization [9][31][32]. Typically, 1,2,3-triazole derivatives are prepared via a 1,3-dipolar cycloaddition reaction between azides and alkynes [33]. It is worth noting that the metal

• -catalyzed Huisgen cycloaddition reaction could provide disubstituted 1,2,3-triazoles. The selective introduction of substituents to three different positions on the 1,2,3-triazole frame can notably improve the features of the molecule. Therefore, practical and cost-effective strategies for the selective

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• -catalyzed C−H activations with the MHP auxiliary [41][42][43][44]. In continuation of studies on sustainable 3d transition metal-catalyzed C−H activation [41][42][43][44][45][46][47][48][49], we have now discovered a robust copper-promoted oxidative C−H/N−H functionalization with terminal alkynes (Figure 1d

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• C, which undergoes an oxidation process to generate carbocation D. A proton abstraction from D then affords the observed product. Cross-coupling reaction between unactivated olefins and alkyl halides under nickel catalysis The use of alkyl halides in transition-metal-catalyzed cross-couplings to

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• metal-catalyzed arylation [17][18][19]. We have recently successfully applied this approach to synthesize the new luminescent heterocyclic system pyrido[2,1-a]pyrrolo[3,2-c]isoquinoline A [17], which turned out to be useful for bioimaging [13] and as a ligand for the preparation of luminescent metal

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• extreme thermal conditions with the use of corrosive reagents. Much later, Larock and co-workers developed a Pd/Cu-catalyzed imino-annulation of internal alkynes [15], which paved the way for transition-metal-catalyzed cyclizations as easy access to these scaffolds. Notably, the gold-catalyzed tandem

• , alkyl N-arylideneglycinates have attracted much attention in recent years. For instance, the metal-catalyzed asymmetric [3 + 2] cycloaddition of ethyl N-benzylideneglycinates with electron-deficient alkenes has been reported to yield substituted pyrrolidines [30]. Recently, we reported the synthesis of

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• ][19][20]. There are several types of transition-metal-catalyzed C(sp3)−H halogenation reactions reported in the literature (Scheme 1b–d). Transition-metal-catalyzed 1,5-hydrogen atom transfer (1,5-HAT) is effective for promoting regioselective C(sp3)−H halogenation reactions (Scheme 1b) [21][22][23