Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• an alkene to generate a radical intermediate, followed by oxidation, which enables radical-polar crossover (RPC) and the subsequent nucleophilic attack of the cationic intermediate [67]. Alternatively, the initial radical intermediate can be trapped by a transition-metal catalyst, followed by a cross

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

• publications by the Doyle and Musacchio groups in 2021 and 2022 demonstrated the effective use of photochemical oxidative radical-polar crossover mechanisms to achieve this. The Doyle group reported the use of an iridium-catalysed system in this context with Et3N·3HF as the fluoride source (Figure 32) [83

• under these conditions, but required first generating the monobenzyl fluoride in situ from the corresponding benzyl chloride before undergoing the photochemical transformation to give the difluorination product. The authors showed that this HAT-radical-polar crossover approach could be applied to other

• , non-photochemical, silver-catalysed HAT radical-polar crossover mechanism for nucleophilic benzylic fluorination (Figure 34) [85]. The authors proposed a similar mechanistic pathway to the photochemical methods, citing the use of amide ligands as important for modulating the silver catalyst stability

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

• that a reductive radical-polar crossover pathway is likely to be involved in this transformation. Keywords: aryl halides; C–C bond formation; electroreduction; radicals; visible light; Introduction Alkene hydroarylation is an attractive method for the construction of alkylarenes, which serve as

• electroreductive reaction would proceed through a reductive radical-polar crossover pathway [57]. On the basis of mechanistic investigations and a literature report [47], a plausible mechanism for this electroreductive hydroarylation is depicted in Scheme 4. 1,3-DCB (Ep/2 = −1.9 V vs SCE in MeCN) [58] undergoes

• to high yields. A large-scale reaction was successfully carried out, highlighting the potential synthetic utility of the present transformation. The mechanistic study proposed that a reductive radical-polar crossover pathway would be involved in the present transformation. Electrochemical

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• discovery and development of the synthesis of homopropargylic azides by the azido-alkynylation of alkenes. Initially, a strategy involving SOMOphilic alkynes was adopted, but only resulted in a 29% yield of the desired product. By switching to a radical-polar crossover approach and after optimization, a

• alkyne substituent. Arylalkynes are expected to perform well but in multiple cases alkyl substituents were reported to afford low yields or no reaction [35][36][37][38]. Finally, a radical-polar crossover (RPC) approach could be envisaged [39][40]. Instead of attempting to trap the C-centered radical

• reaction. Radical-polar crossover Due to the disappointing results obtained with EBX reagents as SOMOphilic alkynes, we turned our attention to the development of a radical-polar crossover approach using photoredox catalysis. The final results obtained were described in our previous publication [45], but

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• -light-mediated palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines, affording unsaturated γ- and ε-amino acid derivatives with diverse structures. In this methodology, the diazo compound readily transforms into a hybrid α-ester

• alkylpalladium radical with the release of dinitrogen. The radical intermediate selectively adds to the double bond of a 1,3-diene or allene, followed by the allylpalladium radical-polar crossover path and selective allylic substitution with the amine substrate, thereby leading to a single unsaturated γ- or ε

• multicomponent reaction protocol. Keywords: carboamination; diazo chemistry; palladium catalysis; radical-polar crossover; three-component reaction; Introduction Since the discovery of the existence of non-canonical amino acids (AAs) in organisms, such structural motifs have attracted considerable attention

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

• , leading to their strategic incorporation as "synthons" in modern organic chemistry, with complementary reactivity to more common polar reaction manifolds [12][13][14][15]. The utility of radicals has also been expanded through the recent development of transformations involving radical-polar crossover

• . Radical intermediate 9 formed upon fragmentation of 25, adds to the styrene acceptor forming radical 26. Finally, a radical-polar crossover event between 26 and the IrIV complex regenerates the IrIII ground state while delivering cation 27 that is then trapped by the oxygen-nucleophile to form the

• radical-polar crossover affords cation 27 that delivers functionalized product 31 upon nucleophilic addition. The Doyle and Knowles groups reported the use of NHPI esters as radical precursors in the context of a radical redox annulation method [48] (Scheme 8A). This transformation occurs through an

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• that α-(aminomethyl)acrylates are suitable acceptors for 1,4-additions of dialkylzincs in aerobic conditions. The air-promoted radical–polar crossover process involves the 1,4-addition of an alkyl radical followed by homolytic substitution at the zinc atom of dialkylzinc. Coordination of the nitrogen

• levels of chiral induction, paving the way to enantioenriched β2-amino acids and β2,2-amino acids. Keywords: β-amino acids; tandem reactions; radical–polar crossover; tert-butanesulfinamide; zinc radical transfer; Introduction Dialkylzinc reagents react in aerobic medium with a range of α,β-unsaturated

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

• , such as hydrogen atom transfer (HAT), alkene addition, and decarboxylation. At least as important has been innovation in radical functionalization methods, including radical–polar crossover (RPC), enabling these intermediates to be engaged in productive and efficient bond-forming steps. However, direct

• ], and decarboxylation [7], enabling these intermediates to be easily accessed from diverse starting materials. Functionalization methods have also seen significant development, with elementary steps such as radical–polar crossover (RPC) finding significant purchase [8]; however, these steps are not

• (XAT) from the alkyl halide reagent and further oxidation of the transient radical to a carbocation by radical polar crossover (RPC), providing two mechanistic pathways to form the ATRA products [32]. While powerful, this approach is inherently incompatible with introducing alternative functionality

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

• applications, the most marked difference between the two types of processes, however, is that conPET is more appropriate for redox-neutral reactions, whereas PEC is more appropriate for net oxidations or reductions due to the radical polar crossover nature of its reactivity [30][31]. In the former, the neutral

• indoline scaffolds (22a,b) via a radical-polar crossover mechanism (Figure 12C) [65], showcasing the power of conPET in dearomatization reactions. Finally, the synthesis of tetraphenylphosphonium chloride (20a) could be scaled up efficiently in an operationally very simple continuous-flow setup with only

Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor

• Yuki Naito,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 350–359, doi:10.3762/bjoc.18.39

• (route (5)). However, these methods involve the use of toxic acids, bases, or transition metal catalysts, and typically require elevated temperatures [14][15][16][17][18][19][20]. In addition, very recently, Molander and co-workers have developed a photoredox-mediated radical/polar crossover process

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

• theory (DFT) mechanistic study. The authors proposed a radical-polar crossover mechanism. First, a SET from Fe(II) to the alkyl diacyl peroxide generates the alkyl acyloxy radical which decarboxylates to afford the alkyl radical 165. Addition of the radical across the alkene affords the benzylic radical

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

Reduction of arenediazonium salts by tetrakis(dimethylamino)ethylene (TDAE): Efficient formation of products derived from aryl radicals

• Mohan Mahesh,
• John A. Murphy,
• Franck LeStrat and
• Hans Peter Wessel

Beilstein J. Org. Chem. 2009, 5, No. 1, doi:10.3762/bjoc.5.1

• . The radical-polar crossover reaction [5][6][7][8][9][10][11][12][13][14][15] of arenediazonium salts, developed in our group since 1993, also features aryl radical intermediates and is a more recent addition to these reactions. It involves a novel splicing of radical and polar reactions in one pot

• formation of aryl radicals had never been reported using TDAE meant that we were keen to compare its reactions with those of the structurally related TTF (4a). Thus, as shown in Scheme 2, the radical-cation of TTF intercepts intermediates with the formation of C-S bonds in the radical-polar crossover

• convenient. Further extensions of this methodology in the construction of several heterocyclic ring systems and complex synthetic targets for natural product synthesis are currently in progress in our laboratory. Aza- and thia-substituted electron donors. Radical-polar crossover reaction of arenediazonium