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

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• Kohn–Sham orbitals produced from DFT are localized to describe the system as one dominant resonance structure. As the Fock matrix is not diagonal in terms of the NBOs, coupling between orbitals can be quantified with second order perturbation theory. These couplings represent donation from an occupied

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

• catalysts’. While the concept of generality was recently explored in a closed-loop fashion for Suzuki–Miyaura cross couplings to find the most general catalyst and reaction conditions [131], the application of this concept in the context of ML has found comparatively less attention in organocatalysis

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• predicted protein interfaces into the docking process through ambiguous interaction restraints and allows the specification of precise distance restraints (e.g., based on MS cross-links). It also supports a range of experimental data, including NMR residual dipolar couplings, pseudo contact shifts, and cryo

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

• = Cl, Br). The resulting 4-halopyrazoles 111 can either be isolated or undergo further Suzuki coupling with arylboronic acids. Both couplings use the Pd catalyst in a sequential fashion. To increase the yields, both cyclization and Suzuki coupling are carried out with microwave support. Some of the

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• the blue region. This complex then accelerates the oxidative addition of the aryl halide to the metal, which is usually the rate-limiting step for palladium-catalyzed cross-couplings. Based on these results we decided to perform all Negishi reactions under blue light irradiation. With the optimized

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• previous mechanistic study [20][21] which revealed that the intermolecular C–N and C–C couplings are disfavored in case of the diarylamines with two electron-deficient phenyl rings. To our surprise, the procedure did not work in the case of amine A3: only traces of pyridoindazolium salt S3 were detected in

Phenotellurazine redox catalysts: elements of design for radical cross-dehydrogenative coupling reactions

• Alina Paffen,
• Christopher Cremer and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2024, 20, 1292–1297, doi:10.3762/bjoc.20.112

• -substrate interaction. Phenotellurazine-catalyzed cross-dehydrogenative couplings. Screening of new Te(II)-catalyst candidates. ODCB: ortho-dichlorobenzene. Phenotellurazine-catalyzed cross-dehydrogenative indole dimerization. Supporting Information Supporting Information File 84: Experimental section and

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• performed in 68% and 74% yields, respectively (Scheme 4a). Furthermore, the iodanyl group on these products serves as a versatile handle for downstream transformations, thus allowing for the stereoselective preparation of various trisubstituted N-vinylazoles (Scheme 4b). Pd-catalyzed C–C couplings such as

• Suzuki–Miyaura and Sonogashira couplings on 4aa or 4ba afforded the desired products 5 and 6 in 47% and 74% yields, respectively. In the former case, the C–Br bond on the pyrazole moiety remained intact, highlighting the superior leaving group ability of the BX group. Cu-catalyzed Ullmann coupling

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

• reaction classes, we discuss the utility of the NHPI esters, with an eye towards their continued development in complexity-generating transformations. Keywords: decarboxylative couplings; mechanisms; NHPI-esters; radical reactions; Introduction The historical challenges of using radicals in synthetic

• phthalimidyl anion would generate the aminoalkylation product 119, completing the catalytic cycle. In addition to this aminoalkylation method, the synthetic utility of radical intermediates derived from NHPI esters under photoinduced Pd-catalysis has been demonstrated in Heck-type couplings [81][82] and in the

• decarboxylative cross-coupling (DCC) of NHPI esters with organometallic reagents, resembling classic Kumada, Negishi, and Suzuki couplings, has been enabled by nickel (Ni), cobalt (Co), iron (Fe), and copper (Cu) catalysts [84][85][86][87][88][89][90][91] (Scheme 23A). The typical mechanism begins by

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• structure, 3H-phenoxazin-3-ones can easily be accessed through oxidative couplings of o-aminophenols [3][4] or N-aryl-o-benzoquinone imines [5][6]. Further, they can serve as efficient precursors of pentacyclic N,O-heterocyclic compounds that possess promising properties for application in fluorescent

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• performing the reaction of o-phenylenediamine (1a) with 2-bromophenylboronic acid (7) in the presence of Cu(OAc)2, Et3N as base in DCM at 50 °C (entry 1, Table 4), and gratifingly under these conditions, the reaction afforded compound 3a in 48% yield. The Chan–Lam couplings were undertaken under an aerobic

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• variety of reactions; that are, phosphite- or Lawesson’s reagent-mediated olefination reactions (to introduce DTF motifs), Ramirez/Corey–Fuchs dibromo-olefinations followed by Sonogashira couplings (to introduce enediynes motifs), and Knoevenagel condensations (to introduce the vinylic diester motif). By

• various elaborate systems [24][25][26][27]. Next, we wanted to explore IF-DTFs as motifs for acetylenic scaffolding (Scheme 4). Starting from IF-DTF building block 6, dibromo-olefinated compound 18 was obtained by a Ramirez/Corey–Fuchs reaction. Two-fold Sonogashira couplings with trimethylsilylacetylene

• Sonogashira couplings of compound 25 with triisopropylsilylacetylene and ((2-ethynylphenyl)ethynyl)triisopropylsilane yielded compounds 26 and 27, respectively. A two-fold, intramolecular Glaser–Hay coupling of compound 27 (after desilylation) was attempted under the conditions that were successful in the

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

• novel metallaphotoredox catalysis by combining the NaI/PPh3 photoredox catalyst with a Cu(I) catalyst to accomplish diverse C–O/N cross-couplings of alkyl N-hydroxyphthalimide esters 3 with various phenols/secondary amines 30 (Scheme 13) [24]. It was anticipated the utilization of computational methods

• bioisostere for a range of functional groups (such as CH2OH, CH2OCH3, CH2NH2, and CH2SH). Among the various methods available, radical-involving cross-couplings have proven to be the most effective [48][49]. However, the generation of the CH2F radical remains to be a challenging task. Therefore, there is an

• alkylation employing ammonium iodide. NaI/PPh3/CuBr cooperative catalysis for photocatalytic C(sp3)–O/N cross-coupling reactions. Proposed mechanism of NaI/PPh3/CuBr cooperative catalysis for photocatalytic C(sp3)–O/N cross-couplings. Photocatalytic decarboxylative [3 + 2]/[4 + 2] annulation between enynals

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

• couplings in PATs. Scheme 10 redrawn from [79]. General thiol-ene photopolymerization process. Scheme 11 redrawn from [81]. (a) Three generations of Grubbs catalysts. (b) Proposed mechanism for photo-ROMP via a reductive quenching pathway and (c, d) chemical structures of the (c) initiators and (d) monomers

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

• well as famous Noble-prize-winning cross-couplings, therefore approaching another step up towards sustainability. Likewise, a free-radical process is also a classical way to functionalize nonactivated C−H bonds in which site selectivity arises either from the relative strength of the C−H bonds or from

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

• metal-like, orchestrating ligand couplings within its ligand sphere. Iodonium ylides were recently confirmed to possess two σ-holes of differing strengths, and theories about these ylides react now explicitly invoke halogen bonding and EDA complexes between iodine and Lewis basic reactants. Many of

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

• 2.1.1 C(sp2)–X activation: In the rise of visible light-mediated PRC, the generation of aryl radicals for C(sp2)–C(sp2/3) couplings under mild conditions (room temperature, visible light activation of a catalyst) was heavily investigated [34][35][36]. However, initially the procedures were generally

• (pinacolato)diboron (B2pin2) as trapping agents for C(sp2)–Het(Arene) couplings (Figure 9B). The successful activation of electron-neutral and electron-rich aryl halides via conPET mostly remained an unsolved challenge until the Nicewicz group in 2020 disclosed a modified acridinium (Fukuzumi) salt Mes-Acr

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• virtually opposite to the order of ECR reactivity. Thus, the substrates with the lowest barriers for ECR couplings have the highest energies for the Hantzsch reaction and vice versa. The calculated reaction profiles show that there are two factors that influence whether the reaction gives ECR or Hantzsch

Bromination of endo-7-norbornene derivatives revisited: failure of a computational NMR method in elucidating the configuration of an organic structure

• Demet Demirci Gültekin,
• Arif Daştan,
• Yavuz Taşkesenligil,
• Cavit Kazaz,
• Yunus Zorlu and
• Metin Balci

Beilstein J. Org. Chem. 2023, 19, 764–770, doi:10.3762/bjoc.19.56

• temperatures yielding mixtures of addition products. The structural elucidations of the formed compounds were achieved by NMR spectroscopy. Particularly, the γ-gauche effect and long-range couplings were instrumental in assigning the stereochemistry of the adducts. However, in a recent paper, Novitskiy and

• atoms were determined by measuring the couplings between the relevant protons. Proton–proton couplings beyond the three bonds are observed frequently in some strained bicyclic compounds. The long-range coupling exists in a zigzag arrangement (Figure 2). In the case of norbornane if the bonding

• arrangement of the protons meets the W or M criterion as shown below, long-range couplings between the protons Ha and Hb as well as between the protons Ha and Hc are observed [5][6]. However, no coupling is observed between the protons Ha and Hd. These values are extremely important for determining the

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• synthesis has increased dramatically and has rapidly become a routine tool for classical synthesis [26][27][28][29]. In particular, many efforts have been devoted to the development of flow alternatives for transition-metal-catalyzed cross-couplings [30] and for some C–H functionalizations [31

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• conformation was determined by calculation using force field methods (MMFF94 [16]) and is shown in Figure S2 of Supporting Information File 1. Key NOE couplings were observed between bridgehead H-8a, H-4a and H-4. The latter also couples with the methyl group at C-1, indicating a cis-decalin configuration with

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• insect sex pheromones as an alternative to conventional pesticides is in constant growth. In this report, we discuss the recent contributions brought by our groups in the field of iron-catalyzed cross-couplings applied to the synthesis of insect pheromones. The pivotal question of the development of

• cross coupling reaction developed by Kochi, leading to better yields, with no need to use an excess of one of the coupling partners (Scheme 2b) [12]. The yields obtained using this ligand-free method are comparable to those obtained in recent palladium-mediated alkyl–vinyl cross-couplings using

• reactions, which witnessed considerable development in the last two decades [14], several cross-coupling methodologies involving soft nucleophiles, such as iron-mediated Suzuki–Miyaura cross-couplings, being reported [15]. The introduction of alkyl–alkenyl linkage by means of iron-catalyzed cross-coupling

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• -formation processes (Scheme 12) [82][83]. These recently obtained results indicate that a sulfur-stabilized carbon radical derived from 1,4-dithiane (1) is a viable reaction intermediate, opening up the use of 1,4-dithianes in various free radical-type cross-couplings. 5 Synthetic equivalents of the allyl

• untapped potential in this area of research, and expect the utility of these building blocks to grow in the coming years. In particular, the recently established options to elaborate and functionalize 1,4-dithianes using mild transition-metal-catalyzed couplings, and their use in cycloaddition reactions