Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• and Molecules, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001 Leuven, Belgium 10.3762/bjoc.20.3 Abstract A novel and efficient base-catalyzed, transition-metal-free method for the synthesis of diheterocyclic compounds connected by an amidine linker, including apart from the common

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides

• Kan Tang,
• Megan R. Brown,
• Chad Risko,
• Melissa K. Gish,
• Garry Rumbles,
• Phuc H. Pham,
• Oana R. Luca,
• Stephen Barlow and
• Seth R. Marder

Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142

• bibenzyls being the dominant products. These reaction conditions represent an alternative metal-free approach to the conventional synthesis of bibenzyls through the reaction of Grignard or organolithium reagents with benzyl halides, or to the use of highly active metal reagents [33][34][35][36] or metal

Aromatic systems with two and three pyridine-2,6-dicarbazolyl-3,5-dicarbonitrile fragments as electron-transporting organic semiconductors exhibiting long-lived emissions

• Karolis Leitonas,
• Brigita Vigante,
• Dmytro Volyniuk,
• Audrius Bucinskas,
• Pavels Dimitrijevs,
• Sindija Lapcinska,
• Pavel Arsenyan and
• Juozas Vidas Grazulevicius

Beilstein J. Org. Chem. 2023, 19, 1867–1880, doi:10.3762/bjoc.19.139

• Organic Synthesis, Aizkraukles 21, LV-1006, Riga, Latvia 10.3762/bjoc.19.139 Abstract The pyridine-3,5-dicarbonitrile moiety has gained significant attention in the field of materials chemistry, particularly in the development of heavy-metal-free pure organic light-emitting diodes (OLEDs). Extensive

• pyridine-3,5-dicarbonitrile moiety attracted a great deal of attention in the last decade in the field of materials chemistry, precisely in the development of novel heavy-metal-free pure organic light-emitting diodes (OLEDs). Inexpensive and environmentally friendly emitters are vital for organic

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

• mechanistic aspects of the reaction and highlighted the potential of the NaI/PPh3 catalytic system for achieving efficient and transition-metal-free photocatalytic transformations. Following that, Li and his research group documented similar results (Scheme 4) [10]. They extensively investigated the

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• down to 10 ppm [56], which to some extent, solves the problem of metal impurities. Meanwhile, the presence of external stimuli in eATRP, photoATRP, and ultrasonic ATRP, allows spatial and temporal control over the polymerization [57]. Hawker et al. proposed a metal-free ATRP in 2014 using an organic

• mechanism (cf. section 3.2) [86]. 2.3 Metal-free ring opening metathesis polymerization (MF-ROMP) ROMP is a powerful and broadly applicable technique for synthesizing polymers. Traditional ROMP systems are initiated by transition-metal complexes and Ru-based alkylidene complexes, which are also known as

• propagation. However, removing this residue from the product by traditional chromatographic methods can be a challenging task and limits the application of ROMP-produced polymers in biomedical and microelectronic fields [88]. To avoid such drawbacks, the development of a metal-free (MF) procedures is

C–H bond functionalization: recent discoveries and future directions

• Indranil Chatterjee

Beilstein J. Org. Chem. 2023, 19, 1568–1569, doi:10.3762/bjoc.19.114

• its combination with organometallic chemistry for site-selective C−H bond functionalization [3][4]. Recent years have witnessed many viable strategies for the synthesis of complex targets utilizing photoredox catalysis, electroorganic catalysis, Lewis acid catalysis, and transition-metal-free

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

• Tzu-Yu Huang Mario Djugovski Sweta Adhikari Destinee L. Manning Sudeshna Roy Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA 10.3762/bjoc.19.111 Abstract Here, we report the first transition-metal-free defluorinative cycloaddition of

• are typically accessed in two ways: (1) direct synthesis using metal or metal-free catalysis and (2) post-functionalization of disubstituted-1,2,3-triazoles [17][18]. The direct synthesis of fully substituted triazoles entails either metal-free carbonyl-based [19][20][21] or metal-mediated and strain

• organic azides in morpholine as a solvent forming C-4-morpholine functionalized fully decorated 1,2,3-triazoles with potential applications in pharmaceutical, biomedical, agrichemical, and materials sciences. This study fills a critical gap in the literature as it is a transition-metal-free and

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

• functional materials and indispensable synthetic intermediates in drug discovery [31][32][33]. Because of their value, constructing C–S bonds has attracted significant attention via metal-catalyzed cross-coupling reactions and metal-free C–S bond formation [34][35][36][37]. Direct sulfenylation of the C–H

• 102 were obtained in moderate to excellent yields with good to excellent enantioselectivities (Scheme 42) [76]. It should be noted that the authors did not define the exact role of the organocatalyst in the reaction mechanism. Transition-metal-free C–H sulfenylation of electron-rich arenes 103 by N

• . developed a metal-free procedure for the synthesis of functionalized alkynyl disulfides 149 and acyl disulfides 151 under acid catalysis (Scheme 64) [94]. In this regard, they used N-alkynylthiophthalimides in the reaction with thiols to make a series of bioactive disulfides. Various simple thiols, cystines

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• attractive features of this approach. Li et al. reported a new strategy for a metal-free CDC alkylation under mild conditions using 2,3-butanedione (diacetyl) as the hydrogen atom abstractor to extrude a hydrogen from the ether substrate to generate the radical intermediate which affords the products (Scheme

Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors

• Grace A. Lowe

Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88

• various acids [49]. This system is completely metal-free and uses one photocatalyst rather than separate sensitizer and catalyst species. However, the electron source for the reductions was a thiolate sacrificial donor and not water. Thiolates are used as redox mediators in other systems such as dye

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• elimination) more commonly associated with transition metal-mediated chemistry; however, halogen- or σ-hole bonding has recently emerged as a credible explanation for the diverse reactivity that iodonium ylides undergo. σ-Hole bonding theory offers a means to explain the occurrence of transition metal-free

• ]. However, numerous inconsistencies have been observed when comparing the outcomes of diazo- and iodonium ylide-based metallocarbene reactions, especially during metal-free control experiments, which led researchers to propose alternative, carbene-free reaction pathways for iodonium ylides. This was first

• reported by Hadjiarapoglou, Varvoglis and co-workers [107][108][109][110][111][112] and Moriarty et al. [113][114][115], who observed metal-free cycloadditions between iodonium ylides and olefins in the absence of a transition metal catalyst. These reactions proceeded under mild conditions without catalyst

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• , catalyzed by a copper catalyst [39]. Murphy and co-workers reported blue LED-mediated metal-free cyclopropanation of alkenes with iodonium ylides through a diradical intermediate [40]. However, iodonium ylides are relatively unexplored for the arylation of amines. So far only Spyroudis’s group reported N

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• process has many advantages because it is a metal-free, easy to use, and environmentally friendly method that also gives good product yields with a wide range of substrates. The deep eutectic solvent used in this protocol is cheap, reusable, non-toxic, and biodegradable. In this study, it was found that

• of N-arylpyrroles from various amines 78 via the reaction with 2,5-dimethoxytetrahydrofuran (2). Oxone is a mild, inexpensive, nontoxic, stable, and transition-metal-free catalyst that is very easy to handle during this transformation and provided high yields of the product. The authors also proposed

• (2). Further, a nucleophilic attack of amines 40 with intermediate A, MeOH removal, dehydration, and aromatization steps produce N-substituted pyrroles 41 in good to excellent yields. In 2019, Wani et al. [73] used the alkaline-earth metal-based catalyst Ca(NO3)2∙4H2O for a mild, transition metal

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• , diversely functionalized pyridines have been synthesized via C–H activation under transition-metal and rare earth metal catalysis, including C–H alkylation, alkenylation, arylation, heteroarylation, borylation, etc. Recently, metal-free approaches have also been developed for the C–H functionalization of N

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• acetylating agent. The developed method is heavy-metal free, as shown by the use of inexpensive PTH, as well as a base-free approach, and involves aerial oxygen to generate exciting derivatives, which may prove to be valuable in the field of radical chemistry research in future. Strategies of C-3

Direct C2–H alkylation of indoles driven by the photochemical activity of halogen-bonded complexes

• Martina Mamone,
• Giuseppe Gentile,
• Jacopo Dosso,
• Maurizio Prato and
• Giacomo Filippini

Beilstein J. Org. Chem. 2023, 19, 575–581, doi:10.3762/bjoc.19.42

• and Technology Alliance (BRTA), Paseo de Miramón 194, 20014, Donostia San Sebastián, Spain Basque Fdn Sci, Ikerbasque, 48013 Bilbao, Spain 10.3762/bjoc.19.42 Abstract A light-driven metal-free protocol for the synthesis of sulfone-containing indoles under mild conditions is reported. Specifically

• to photochemically generate electrophilic radicals that can drive the functionalization of suitable electron-rich substrates [23]. Exploiting this strategy, here we report a novel metal-free methodology for the direct homolytic aromatic substitution (HAS) reaction of indoles 1 with α-iodosulfones 2

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• to domino reactions which include at least two distinct reactions. The review is divided on the basis of the transition-metal catalyst used in the reaction and will not cover metal-free methods. The literature is covered up to and including January 2023. For reasons of clarity, newly formed bonds are

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• 85 and porphyrin-psoralen conjugate 87 could be potential candidates for PDT applications. Recently, Charisiadis et al. [45] explored this modular click chemistry protocol for the synthesis of a noble metal-free meso-triazole cobalt porphyrin diimine-dioxime conjugate 91 by covalently connecting a

• Cheng [63] designed a click inspired synthesis of novel discotic mesogen bearing a porphyrin unit, a triazole linkage, and a peripheral 3,4,5-trialkoxybenzyl unit (Scheme 32). Firstly, free-base porphyrin conjugates 151a–c were obtained by the CuAAC reaction between metal free tetraalkynylporphyrin 149

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

• Department of Chemistry, Central University of Punjab, Bathinda, 151401, Punjab, India, Department of Chemistry, National Institute of Technology (NIT) Manipur, Imphal, 795004, India 10.3762/bjoc.19.22 Abstract An operationally simple and metal-free approach is described for the synthesis of pyrazole

• , metal-free and easy to perform reaction conditions. Moreover, the pyrazole C-3/5-linked amide conjugates were also synthesized via an oxidative amination of pyrazole carbaldehydes and 2-aminopyridines using hydrogen peroxide as an oxidant. Keywords: C–S/O bond formation; metal-free; oxidative amidation

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• is mediated by visible light irradiation. A wide range of substrates bearing different substituents and derived from ubiquitous carboxylic acids, including α-amino acids, were synthesized and examined under this very mild, efficient, and cost effective transition-metal-free synthetic method. These

• afforded various functionalized oxindoles featuring a C3 quaternary stereogenic center. Mechanistic experiments suggest a radical mechanism. Keywords: decarboxylative cascade cyclization; iodide catalysis; metal-free photocatalysis; oxindole; phosphine catalysis; Introduction Radical-initiated cascade

• limited substrate scopes (Scheme 1a). With the rapid development of sustainable chemistry, developing low-cost and transition-metal-free photocatalytic methods has become a strategic priority. In 2019 [54], the groups of Fu and Shang pioneered the photocatalytic decarboxylative alkylation of silyl enol

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• blocks for the synthesis of natural products [16][17][18][19][20][21]. One subclass of HVIs is diaryliodonium salts (DIS), which have been used as versatile electrophilic arylation reagents in metal-catalyzed and metal-free reactions [22][23]. The corresponding cyclic diaryliodonium salts (CDIS) have

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• include their synthetic availability, wide opportunities for rational structure design, generally lower toxicity, air and water stability, metal-free nature, and the scalability of their production and use. These features have made organocatalysis a prospering area and an even more promising methodology

• in the case of chelating substrates [80]. In order to avoid the usage of transition metal salts, metal-free oxidative systems for the generation of imide-N-oxyl radicals were proposed. In the majority of such systems, an N-hydroxyimide undergoes single-electron oxidation photochemically by a

• were used as redox-active organocatalysts for the oxidative coupling of aryl- and alkenylmagnesium compounds employing molecular oxygen as the terminal oxidant [154] (Scheme 38). Frustrated Lewis pairs (FLP) have gained much attention in the last decade due to unique reactivity, such as metal-free H2

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• scaffolds. Recently, we reported a novel, metal-free synthesis of 1,5-disubstituted 1,2,3-triazoles via a three-component reaction of α-acetyl-α-diazomethanesulfonamide (1) with aldehydes and amines [4]. The reaction proceeded, presumably, through the formation of the initial 1,2,3-triazoline adduct 2 [5

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• , like cycloaddition, metal-free coupling reactions, three-component or multicomponent reactions etc., which use N-oxide chemistry. In 2021 Timofey D. Moseev and co-workers unfolded an attractive procedure of the coupling reaction between 2H-imidazole 1-oxides and polyphenols under metal-free conditions

• the past years are discussed. This review contains cycloaddition reactions, nucleophilic halogenation reactions, metal-free coupling reactions, formation of N-heterocyclic carbenes, and multicomponent reactions, mainly three-component reactions. The mentioned methodologies have been performed by

• substitution reactions Metal-free coupling reaction through nucleophilic substitution of H-atom (SNH) In 2020, a C–H/C–Li coupling reaction between 2H-imidazole 1-oxides and pentafluorophenyllithium under transition metal-free conditions was reported by Timofey D. Moseev and co-workers [17]. The reaction