Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• leading to an electron transfer to the iodine atom, thereby liberating iodide, an alkyl radical, and a radical cation of the Cu complex. Recombination of the latter radicals leads to the formation of the desired silane along with the regeneration of the active Cu species (Scheme 8). This strategy was also

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

• Goki Hirata,
• Yu Yamane,
• Naoya Tsubaki,
• Reina Hara and
• Takashi Nishikata

Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45

• alkyl radicals generated from the reaction of a copper catalyst and an α-bromocarbonyl compound can undergo i) Sonogashira type couplings via an alkynyl-Cu intermediate [20], ii) cis-hydro tertiary alkylations via 1-alkenyl-Cu [21], and iii) trans-hydro tertiary alkylations via atom-transfer radical

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• coordination chemistry, and also valuable protecting or directing groups in catalysis [1][2][3]. 2-Oxazolines are a readily stable class of heterocycles resistant to a range of nucleophiles, bases, or radicals [4][5], which can be easily generated from amino alcohols and carboxylic acids, and from alkenes or

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• development. Furthermore, photocatalysis allowed to realize elusive transformations as this approach provided better control over the formation of radicals or the reduction or oxidation of reagents, for instance. For all these reasons, photocatalysis is nowadays at the forefront of cutting-edge research in

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• their use in applications based on sensitized photoinduced electron transfer. This can be NIR-sensitized photopolymerization resulting in formation of initiating radicals and conjugate acid [5][6][13][14][15][63][64]. Recently, the use of NIR-LEDs exhibiting high excitation intensity brought more light

• where the absorber uptakes the function of a sensitizer to generate initiating radicals and conjugate acid [13][14][15][16][17][58][65]. The fact that these systems work upon turning ON/OFF cycles facilitates their use in Industry 4.0 related applications where printing represents one feasible

• excited state possesses several competitive reaction pathways for deactivation. This is a photochemical reaction such as photoinduced electron transfer serving as source to generate reactive intermediates such as initiating radicals or conjugate acid [5]. Photophysical events of S1 occurring after one

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• . Single-electron oxidation can produce carbon-centered radicals from substrates such as amines [17], alkenes [18], and carboxylates [19], or by hydrogen-atom transfer to an oxidatively formed thiolate radical [20]. Single-electron reduction produces carbon-centered radicals from, for example, aryl

• nitriles [21], carbonyl or imine species [22], iodonium or diazonium salts [23], or halide species [24]. The formation of radicals from halide species by photoredox catalysis has been widely studied. It has been applied as a mild method for the dehalogenation of several compounds [25][26][27]. In the light

• decarboxylative activation we anticipated its possibilities in cyclopropanation. The chloromethyl radical generation by photoredox catalysis is a useful strategy for cyclopropanation [58]. Most photoredox catalyzed, decarboxylative generations of carbon-centered radicals are based on the formation of “stabilized

Room-temperature Pd/Ag direct arylation enabled by a radical pathway

• Amy L. Mayhugh and
• Christine K. Luscombe

Beilstein J. Org. Chem. 2020, 16, 384–390, doi:10.3762/bjoc.16.36

• reported for decarboxylative coupling between indole and 2-nitrobenzoic acids at 110 °C [18]. Under such conditions, silver carboxylates decompose to produce carbonyl and phenyl radicals, which could explain the origin of nitrobenzene incorporation [19][20]. When the radical trapping agent BHT was added to

• that proceed under mild conditions, improving energy requirements and scalability. Work is ongoing to leverage this insight into new direct arylation methods utilizing palladium-involved radicals. 1H NMR (500 MHz, CDCl3) of (a) 5-iodo-1-octylindole monomer (b) PIn prepared according to conditions in

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• addition of P–H to unsaturated organic compounds (hydrophosphination) presents an atom economical, efficient and green strategy for the preparation of phosphines. The process can be initiated thermally, chemically or by UV irradiation. Radicals can also be used in hydrophosphination reactions. For example

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• studies seem to allow the prediction of the activity of derivatives able to pass intersystem crossing to their triplet energy state and thus create radicals able to damage DNA. With this study, it is shown that oxime carbamate derivatives have the potential to act as novel effective photobase generating

• , Figure 1) are also recognized as DNA “photocleavage” agents owing their action to the homolysis of their vulnerable N–O bond, at 312 nm [9][39][40][41][42][43] or 365 nm [44][45] yielding photogenerated carbonyloxyl radicals (CRs), which are able to cause oxidative DNA damage. We have recently reported

• the DNA photocleavage from sulfonylamidoximes and ethanone oximes (IV and V, Figure 1), which were found to attack DNA via sulfonyloxyl radicals (SRs) [10][11]. All the above radical species exhibit photoreactivity towards DNA. Those oxime derivatives are considered photoacid generators (PAGs) since

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• still in its infancy. Nowadays, photoredox catalysis is on the forefront as a potent strategy for bond modifications through multicatalytic strategies and the invention of nontraditional methodologies. It is enormously effective in the generation of radicals by manipulating the transition metal

• ]. From mechanistic studies it can be inferred that the photoredox catalysis process is independent from the C–H activation process. They also successfully demonstrated the importance of a photoredox catalysts in the generation of superoxide radicals. On the other hand, recently, Xiong and co-workers

The interaction between cucurbit[8]uril and baicalein and the effect on baicalein properties

• Xiaodong Zhang,
• Jun Xie,
• Zhiling Xu,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2020, 16, 71–77, doi:10.3762/bjoc.16.9

• has a strong activity to eliminate superoxide radicals in cell-free systems [25]. It is also considered as an anti-inflammatory agent [26][27] that generally protects against oxidative stress [28], more specifically in cardiac cells [29], and in cisplatin-induced acute kidney injury [30]. However

• activity of BALE–Q[8] was investigated using the ABTS+· method. The BALE–Q[8] inclusion complex had no significant influence on the scavenging effect toward ABTS+· radicals when compared to BALE; the IC50 vales were 1.87 × 10−6 mol·L−1 and 2.14 × 10−6 mol·L−1, respectively. In vitro release studies have

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• catalytic amount of 61 (Scheme 24) [59]. A similar strategy using N-oxalyl radicals as chiral mediators has also been explored for the enantioselective electrocatalytic oxidation of secondary alcohols [60]. Tanaka and co-workers subsequently published another article on the kinetic resolution of sec

• oxidation. The radical–radical coupling reaction between 101 and 95 is proposed to afford the corresponding intermediate 102. Then release of the Lewis acid catalyst gives the final product 97. The stereocontrol step is related to the in situ generation of radicals with π-systems of chiral enamines and

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• the phase relaxation of nitroxides with two spirocyclohexane moieties adjacent to the N-O• group [8][9][10] or for nitroxide 6. The temperature dependence of 1/Tm is similar for both radicals in Figure 5 with some divergence above 180 K. Conclusion An unexpected formation of a highly strained

Thermal stability of N-heterocycle-stabilized iodanes – a systematic investigation

• Andreas Boelke,
• Yulia A. Vlasenko,
• Mekhman S. Yusubov,
• Boris J. Nachtsheim and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2019, 15, 2311–2318, doi:10.3762/bjoc.15.223

• alkyl and aryl radicals through thermogravimetry [16][17]. In 2013 Kumar and co-workers compared the thermal properties of open-chained aryl-λ3-iodanes with their polymer bound derivatives and found an endothermic decomposition behavior [18]. In the same year Haller and co-workers investigated the

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• [12]. Our group demonstrated that nucleophilic radicals (1,3,5-trioxanyl, ethoxycarbonyl, methyl [14], but not benzoyl [15]) generated with peroxide under Minisci conditions, readily add to C-5 of 4-bromo- (9d) and 4-acetylbenzo[c][2,7]naphthyridine (9e) to give 5-substituted-5,6-dihydro derivatives

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

• by chemists. In the radical fluorination, C–F bonds are produced by carbon-based radicals (generated in situ by various methods) with "atomic fluorine" sources, such as XeF2, hypofluorite, or molecular fluorine (Scheme 1c). Notably, transition metals are not biased to one reaction class, and the same

• (Scheme 60). Also, mechanistic studies, a radical clock experiment, revealed the intermediacy of −Cu(CF3)3Me, which undergoes reductive elimination and subsequent oxidation to give the active species Cu(CF3)2. Meanwhile, aliphatic carboxylic acids give the corresponding alkyl radicals via Ag(II)-mediated

• oxidative decarboxylation. Then, Cu(CF3)2 provides a CF3 group to alkyl radicals to obtain the final product. Very recently, MacMillan et al. [120] discovered an efficient approach to the decarboxylative trifluoromethylation of aliphatic carboxylic acids via the combination of photoredox and copper

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• [TCNQ]−· radical anion, dragging the second [TCNQ]− near to the cavity by the help of the electrostatic stabilization supplied by the 1,2,3-triazolium cations, coupling of the two [TCNQ]−· anion radicals in the cavity and rapid formation of the sigma-connected dimer, reduction of the photogenerated

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• radicals [1]. Introduction of spirocyclic moieties has a smaller effect on the reduction rates of nitroxides than the introduction of linear alkyl substituents does; however, spirocyclic nitroxides may have much longer spin relaxation times at 70–125 K [3] and even at room temperature [4]. The latter

• group of the cyclopentane ring (Scheme 7). The ester groups in 11a–c were easily cleaved in an aqueous–methanol solution of ammonia. Nitroxides 12a–c were isolated as orange compounds moderately soluble in water. Overall yields of these radicals via the acylation–oxidation–deprotection pathway were in

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• for the generation of carbon radicals via single-electron transfer (SET). In 2016, Barriault and co-workers reported a methodology that features the utilization of dimeric gold complex [Au2(dppm)2]Cl2 and ultraviolet A (UV, 365 nm) light to direct arylation of bromide-substituted butenolides or cyclic

Vicinal difunctionalization of alkenes by four-component radical cascade reaction of xanthogenates, alkenes, CO, and sulfonyl oxime ethers

• Shuhei Sumino,
• Takahide Fukuyama,
• Mika Sasano,
• Ilhyong Ryu,
• Antoine Jacquet,
• Frédéric Robert and
• Yannick Landais

Beilstein J. Org. Chem. 2019, 15, 1822–1828, doi:10.3762/bjoc.15.176

• functionalities, have the potential for further elaboration. Keywords: CO; multicomponent reaction; radicals; sulfonyl oxime ethers; xanthogenates; Introduction Multicomponent reactions constitute a powerful and highly efficient tool in organic synthesis to build up intricate compounds from simple molecules in

• /acceptor type C1 synthons [6][7][8][9][10][11][12][13][14][15]. In this context, sulfonyl oxime ethers are powerful acceptors of type C1 synthon [8][16][17], which terminates the multicomponent reaction by a β-scission of RSO2 radicals [18][19][20]. Recently, one of us reported on a three-component radical

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Insertion of [1.1.1]propellane into aromatic disulfides

• Robin M. Bär,
• Gregor Heinrich,
• Martin Nieger,
• Olaf Fuhr and
• Stefan Bräse

Beilstein J. Org. Chem. 2019, 15, 1172–1180, doi:10.3762/bjoc.15.114

• , which was opened with free radicals in most cases. The reaction with diacetyl and subsequent oxidation leads to the important intermediate bicyclo[1.1.1]pentane-1,3-dicarboxylic acid which provides access to unsymmetrically substituted BCPs (not shown) [13]. It is assumed that the reaction of 1 with

• thiyl radicals is critical to the reaction and most aliphatic disulfides do not absorb UV light at the used wavelength, radical initiators should be taken into account for other disulfides. However, for 12 the reaction was successful without radical initiator and the BCP 13 was obtained as the main

• ]. Presumably, there are two factors contributing to the lowered yield. The bond dissociation energy (BDE) of dialkyldisulfides is higher than the BDE of diaryl disulfides [30]. Therefore lower concentrations of thiyl radicals are present to initiate the reaction. The second reason could be the absorption of

Photochemical generation of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical from caged nitroxides by near-infrared two-photon irradiation and its cytocidal effect on lung cancer cells

• Ayato Yamada,
• Manabu Abe,
• Yoshinobu Nishimura,
• Shoji Ishizaka,
• Masashi Namba,
• Taku Nakashima,
• Kiyofumi Shimoji and
• Noboru Hattori

Beilstein J. Org. Chem. 2019, 15, 863–873, doi:10.3762/bjoc.15.84

• counterparts (65.8% vs 85.5%). Keywords: caged compound; nitroxide; photolysis; radical; theranostics; two-photon; Introduction Nitroxides (aminoxyl radicals) possess a delocalized unpaired electron and exhibit negligible dimerization reactivity, making them persistent open-shell species [1][2][3][4]. In

• new caged nitroxides (nitroxide donors) 2a and 2b having the TP-responsive NPBF chromophore and the NIR TP-triggered generation of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical under atmospheric conditions using these species (Scheme 1). Because free radicals are cytotoxic due to their

• strong DNA-damaging activity [65], they play important roles as anticancer therapeutic agents [66]. Among the free radicals, nitroxides including the TEMPO radical have unique properties, where they can act not only as radical scavengers, but also as anticancer agents [67]. Due to the unique properties

A diastereoselective approach to axially chiral biaryls via electrochemically enabled cyclization cascade

• Hong Yan,
• Zhong-Yi Mao,
• Zhong-Wei Hou,
• Jinshuai Song and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2019, 15, 795–800, doi:10.3762/bjoc.15.76

• -centered radicals (NCRs) are attractive reactive intermediates for organic synthesis as they provide opportunities for the efficient construction of C–N bonds [15][16][17][18][19]. Recently, the generation of NCRs through electron transfer-based methods has been attracting attention. Organic

Synthesis of polydicyclopentadiene using the Cp₂TiCl₂/Et₂AlCl catalytic system and thin-layer oxidation of the polymer in air

• Zhargolma B. Bazarova,
• Ludmila S. Soroka,
• Alex A. Lyapkov,
• Мekhman S. Yusubov and
• Francis Verpoort

Beilstein J. Org. Chem. 2019, 15, 733–745, doi:10.3762/bjoc.15.69

• gradually happen during the exposure time of polydicyclopentadiene thin layers in the air as a result of the oxidation of double bonds. A new vibrational band at 1410 cm−1 in the IR spectrum appears which is originating from the primary radicals which are formed alongside the chain initiation. The kinetics

• deformation vibrations and the layer exposure time in air at ambient temperature. The correlation presented in Figure 10 demonstrates that the kinetics of double bond consumption during oxidation occurs in two stages. During the first stage, the chain (formation of primary radicals) initiates, and then the

• chain process of PDCPD oxidation follows. Various mechanisms of chain initiation are possible, e.g., the formation of primary free radicals initiating the chain reaction of polymer oxidation (Equation 1). More often, the chain initiation step is described as a bimolecular interaction between oxygen and