Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• -arylations utilizing diaryliodonium salts, marked by significant contributions, notably from research teams led by Sanford [53] and Gaunt [54]. The synthesis of carbon–carbon bonds through metal-free approaches serves as a valuable complement to transition-metal-catalyzed couplings. This is particularly

• salt, subsequently leading to decarboxylative C–C coupling. Notably, this method achieves the incorporation of two fluorine atoms in the benzyl position without resorting to hazardous fluorination reagents, transition-metal catalysts, or organometallic compounds. The utility of this reaction is

• efficiency and effectiveness as a synthetic approach. Furthermore, a transition-metal-free arylation of quinoxalines 17 and quinoxalinones 19 via aryl radicals was discussed by Li and co-workers in 2022. In this report the aryl radicals were generated by planetary ball milling of diaryliodonium salts 16 at a

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• various transformations [54][55][56][57][58][59][60][61][62][63][64]. In consequence, a large number of transition-metal-catalyzed or radical-mediated processes for C–H functionalization of aldehyde hydrazones has flourished over the years. An ideal scenario for a direct and sustainable synthetic route

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• further substitution directly on the meso- or a meso-phenyl ortho/meta/para positions of a porphyrin, is the introduction of C–C bond forming chemistry. This is typically achieved using palladium and/or another transition-metal catalyst [20]. Sonagashira [21], Suzuki–Miyaura [22], Heck [23], Stille [24

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• expand the scope of transition metal-catalyzed substitution reactions. Since its discovery in 2022, copper-catalyzed yne-allylic substitution has undergone rapid development and significant progress has been made using the key copper vinyl allenylidene intermediates. This review summarizes the

• rearomatization In 2023, Lin and He et al. [72] achieved the challenging dearomatization of heteroarenes through d-orbital electron of the transition-metal center and thus completed the asymmetric substitutions with remote stereoselective control induced by alkynylcopper. A newly electron-rich ligand was

• propargylic substitution and allylic substitution, but represents a new type of reaction mode, and greatly expands the scope of transition metal-catalyzed substitution reactions. Currently, yne-allylic substitutions affording 1,3- or 1,4-enynes, remote substitutions through dearomatization-rearomatization

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• studies, but the stereochemical aspects of this reaction, particularly through the use of FLP catalysts, have been largely overlooked, despite the prevalence of racemic epoxide solutions. Only one study has addressed the asymmetric insertion of CO2 into propylene oxide (PO) using a transition-metal

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• , Trombay, Mumbai-400085, India Homi Bhabha National Institute, Anushaktinagar, Mumbai, PIN-400094, India 10.3762/bjoc.20.223 Abstract A transition-metal-free decarbonylation–oxidation protocol for the conversion of 3-arylbenzofuran-2(3H)-ones to 2-hydroxybenzophenones under mild conditions has been

• abilities has been verified by mathematical calculations. Keywords: decarbonylation–oxidation; hydroperoxide; 2-hydroxybenzophenone; transition-metal-free; UV-protection; Introduction Benzophenone compounds are ubiquitous in nature, and show biological activities such as anti-inflammatory, antiviral, and

• environmental hazards, and this can only be circumvented using a transition-metal-free synthesis protocol. Although eco-friendly methods for the synthesis of 2-hydroxybenzophenones have been reported via a cycloaromatization of α-alkenoyl ketene dithioacetals and nitroethane in water [15], an alternate and more

Transition-metal-free synthesis of arylboronates via thermal generation of aryl radicals from triarylbismuthines in air

• Yuki Yamamoto,
• Yuki Konakazawa,
• Kohsuke Fujiwara and
• Akiya Ogawa

Beilstein J. Org. Chem. 2024, 20, 2577–2584, doi:10.3762/bjoc.20.216

• under transition-metal-free and open-air conditions. Conventional methods required photoirradiation or electrolysis to generate aryl radicals from triarylbismuthines. In this study, it was found that simply heating the solution of triarylbismuthines in benzotrifluoride (BTF) in air successfully led to

• the generation of aryl radicals, and the subsequent reaction with bis(pinacolato)diboron afforded a variety of arylboronates in moderate to good yields. Keywords: arylboronates; bis(pinacolato)diboron; radical reactions; transition-metal-free synthesis; triarylbismuthines; Introduction Arylboronates

• variety of transition-metal-catalyzed reactions and photoredox reactions using arylboronates as aryl sources have been energetically investigated for the construction of carbon–carbon or carbon–heteroatom bonds [12][13][14][15]. The preparation of arylboronates often requires pre-functionalized substrates

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• [3]. Transition-metal-catalyzed LSF strategies have been well-established over the past decades. More recently, with the vigorous development of photochemistry and electrochemistry, numerous innovative reports on LSF using photo-, electro-, and photoelectrochemistry have emerged. These areas have

• was demonstrated by the LSF of primary natural and pharmaceutical amines carrying potential competing nucleophiles, such as tryptamine and primaquine (Scheme 16). In the context of electrochemical difunctionalizations the Lei group published a transition-metal-free electrochemical difunctionalization

• group. Based on extensive mechanistic studies, they proposed the formation of a formal Ni(IV) complex during the process. Remarkably, nickel proved to be uniquely effective for this protocol, as other transition-metal catalysts based on Cu, Co, Pd, Ir, Ru, and Rh did not catalyze the reaction (Scheme 36

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• equimolar chiral controller. However, recent years have witnessed the rise of asymmetric transition-metal catalysts and, importantly, organocatalytic allylation, reshaping the landscape of modern synthetic chemistry. This review explores the latest developments in the asymmetric allylation of imines

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• general, transition metal catalysts are required to effect efficient NGT to unactivated olefins because iminoiodinanes are insufficiently electrophilic to engage in direct aziridination chemistry. Here, we demonstrate that 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) activates N-arylsulfonamide-derived

• ]. Iminoiodinanes (ArI=NR) are a subclass of hypervalent iodine reagents that function as nitrene equivalents in synthesis [5][6]. The direct reaction of iminoiodinanes with olefins, which could be envisioned to give rise to aziridines directly, is typically not observed and thus families of transition metal

• Discussion Treatment of cyclohexene (1a) with a stoichiometric amount of simple iminoiodinane such as PhINTs (2a) in CH2Cl2 resulted in <10% conversion to the corresponding N-sulfonylaziridine 3a, which is consistent with the previously reported need for transition metal catalysts to promote nitrene transfer

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• Research (NCCR) Catalysis, ETH Zurich, Zurich CH-8093, Switzerland 10.3762/bjoc.20.196 Abstract Organocatalysis has established itself as a third pillar of homogeneous catalysis, besides transition metal catalysis and biocatalysis, as its use for enantioselective reactions has gathered significant

• . Keywords: catalyst design; machine learning; modelling; organocatalysis; selectivity prediction; Introduction Since the beginning of the 21st century, organocatalysts [1] have established themselves as a third group of homogeneous catalysts, next to biocatalysts [2] (enzymes) and transition metal-based

• pitfall regarding computational data is its accuracy with respect to the ground truth, in particular for multiple factors relevant throughout catalysis, such as non-covalent interactions (NCIs) for organocatalysis or spin properties for transition metal catalysis [35][36]. While most quantities can in

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• fluorobenziodoxole, are also utilized as F+ equivalents to introduce fluorine atoms into organic molecules. In addition, various trifluoromethylation reagents have been developed so far [5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Transition-metal-catalyzed fluorination and trifluoromethylation methods have

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• is a promising synthetic reagent not only as a one-carbon homologation reagent but also as a nitrogen source for nitrogen-containing molecules. Because of their isoelectronic structure with carbon monoxide, isocyanides also react with nucleophiles, electrophiles, carbon radicals, and transition metal

• ), but is also widely used in transition-metal-catalyzed carbonylation reactions [1][2]. However, carbon monoxide is a flammable gas with a wide explosive range, although colorless and odorless, and requires special care in handling due to its high toxicity. In addition, when carbon monoxide is used in a

• conditions (as mentiond above), they worked well for the photoinduced radical cyclization of o-diisocyanoarenes (Scheme 18d) [39]. The obtained quinoxaline-2,3-diphosphines 28 are promising ligands for transition metal catalysts such as palladium catalysts. Aza-Bergman cyclization of o-alkynylaryl

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• (Scheme 26) [76]. Electrochemical access to diazo compounds Diazo compounds are highly useful synthetic reagents in organic chemistry. For instance, they are regularly utilized as 1,3-dipoles in cycloaddition reactions or as precursor of carbenes under thermal, photochemical, and catalytic transition

• -metal-based transformations. However, their use is significantly hampered by their inherent instability and hazardous nature. Therefore, it is endlessly highly demanding to find a new mode of generation of diazo compounds from stable and safe precursors. The third part of this review is dedicated to

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• Medicus (Figure 1) [9]. Therefore, in recent years, isoquinolinone derivatives have attracted considerable attention, and successful synthetic methods involving the isoquinolinone framework have been reported. A number of appealing methods for the synthesis of isoquinolinone scaffolds using transition

• metal reagents, including cobalt [10], copper [11], rhodium [12][13][14], palladium [15][16][17], silver [18], and gold [19] catalysts, have been reported. However, compared to the widespread use of metal catalysts, the synthesis of isoquinolinone scaffolds mediated by environmentally friendly

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• (41–67%). Multicomponent polymerizations are simple and efficient methods to construct a library of polymers with great structural complexity and diversity, including fused-heterocyclic polymers[64]. Tang et al. [65] reported the transition-metal-free multicomponent polymerization of dialdehydes 96a–c

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• oxidants in combination with transition-metal catalysts. Metal-free methods employ chlorodimethylsulfonium compounds as the reactive species and have gained great popularity under the name Swern oxidation or the Corey–Kim oxidation [11]. Hypervalent iodine compounds have also been studied and are well

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• transition-metal complexes to generate metal–fluorine bonds capable of FAT to benzylic substrates. In a follow-up to their work using electrophilic fluorine sources for palladium-catalysed benzylic C–H fluorination (Figure 5), the Sanford group demonstrated in 2012 the same transformation could be achieved

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• electrophotochemical transition metal catalysis [26][27][28][29][30][31] as a unique and powerful synthetic platform for radical decarboxylative functionalization of aliphatic carboxylic acids [32][33][34][35][36][37]. In particular, the commonly required high activation energy for radical decarboxylation was provided

• invention of cooperative catalysis with electrochemical transition metal catalysis, which generally has mild oxidation potential for the generation of persistent radicals in the form of nucleophile-bound metal complexes. We and other groups have successfully applied this reaction design to enantioselective

• functional group compatibility and is applicable to alkyl acids with all substitution pattern. Due to the wide utility of alkylnitriles, we expect this method to be widely adopted within the synthetic and medicinal chemistry communities. The present work also demonstrated electrophotochemical transition

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• are not always readily accessible. Typically, the preparation methods involve SNAr reactions with N-centered nucleophiles [5], nitroarene reduction [6] and transition metal (e.g., Pd, Cu)-catalyzed C–N cross coupling of aryl halides, aryl sulfonates or arylboronic acid reagents with ammonia or NH

• of anilines through Brønsted acid or transition-metal-promoted conversion of 2-cyclohexanone oximes [15][16][17][18] (Scheme 1, (2)). Moreover, Strauss and co-workers described a green, multicomponent reaction of aromatic aldehydes, 2-cyclohexenone and amines to afford 2-arylmethyl N-substituted

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• remarkable advantages such as an environmentally benign alternative to traditional transition-metal catalysis, a low cost, nontoxicity, good stability, and easy handling [30][31]. Upon increasing the amount of FeCl3 to 20 mol %, the time of the reaction was reduced from 86 to 38 hours, and the yield of 5a

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• photocatalysts, transition-metal photoredox catalysts, and metallaphotocatalysts to produce acyl and alkyl radicals driven by visible light. Keywords: acyl radical; alkyl radical; sustainable catalysis; visible light; Introduction The growing awareness of the necessity for sustainable developments has been

• . Different photocatalysts, such as transition metal complexes [23][24], organic dyes [25], and semiconductors [26], can be employed for visible-light-induced chemical processes. The choice of photocatalyst depends on the specific requirements of the catalytic process, including the type of reaction, the

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• . Therefore, alternative procedures for homo-coupling reactions using other transition-metal catalysts such as palladium, nickel, manganese, and iron have been developed [5][6][7][8][9][10][11][12][13]. In recent years, transition-metal-free coupling reactions have also been developed for environmentally

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

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

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• high regioselectivity. Herein, we report the electroreductive hydroarylation of electron-deficient alkenes and styrene derivatives using (hetero)aryl halides under mild reaction conditions. Notably, the present hydroarylation proceeded with high efficiency under transition-metal-catalyst-free

• versatile building blocks in organic syntheses. To achieve this transformation with high efficiency and predictable regioselectivity, numerous efforts have been made to develop transition-metal-catalyzed reactions based on a C–H activation strategy [1][2][3][4] or the reductive coupling of aryl halides with

• by preventing overreduction [39]. While the metal-catalyst-free radical cyclization of alkene-tethered aryl halides has been well documented in the literature [40][41][42][43], the efficient intermolecular hydroarylation of alkenes still relies on the use of transition-metal catalysts, including Pd