Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• reaction mechanisms: free radical autoxidation, cation radical autoxidation, and thermal intersystem crossing (ISC), using 18O2 labeling, spin-trapping, spectroscopic, mass spectrometric, kinetic, and computational techniques. After several experiments, the obtained results have demonstrated that the 2

• 24–75% yields (Scheme 28). Alkylation and acylation by free radicals One of the largest groups of reactions that use menadione (10) as substrate comprises free radical alkylation and acylation reactions. The most useful alkylation approach is the Kochi–Anderson method [76] or (Jacobsen–Torssell

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

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• . Both TBS and SEM protecting groups were tolerated, as demonstrated by the syntheses of the fluorenones 10u and 10v (52 and 46% yields). As expected, the O-benzyl group was not tolerated, giving only trace amounts of product 10w, as benzyl ethers are well known to undergo side reactions with free

• -radical reagents [62]. An extremely poor yield was further obtained with methylenedioxy substrate 15p. Our application of this new protocol to the first total synthesis of the natural product nobilone (1d) is depicted in Scheme 7. The commercially available phenol 16 was TBS-protected to give compound 17

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• -polymerised precursors can cause free radical damage or react with proteins in the human body containing thiols and amino groups [84]. Further toxicity research would be required for all of these cryogels to fully understand how they react in the human body as opposed to animal substitutes. However, the use

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• photocatalysts have been successfully applied in both small- and large-scale synthesis such as organic reactions [16][17], free radical polymerization (FRP) [18][19][20], controlled radical polymerization (CRP) [21][22], CuAAC chemistry [23][24][25], and thiol–ene chemistry [26][27]. However, most of the

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• -annulation reaction may undergo a free-radical addition pathway. Firstly, NFSI oxidizes Cu(I) to form bissulfonylamidyl radical 10. Secondly, intermolecular nitrogen free-radical addition to the alkyne provides the vinyl radical 11. Then, there may be two possible pathways. Path a: vinyl radical 11 is

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• brevipes Poit., furthermore, exhibited free radical scavenging and potential antitumor activities [2]. The ethnomedicinal background and preliminary biological studies triggered researchers to further examine the chemical constituents of the plant. In 2009, Kinghorn and co-workers reported the first study

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• contrast. Azulene-methacrylate copolymers Emrick and co-workers [45] reported the synthesis of azulene-substituted methacrylate polymers derived from a free radical polymerization strategy, where azulenes were used as pendants. The key starting points to make these polymers were azulene-2-yl methacrylate

• free radical polymerization by using azobis(isobutyronitrile) (AIBN) to obtain the polymers 151 and 152 in 73 and 82% yields, respectively (Scheme 26A and B). The Mn and PDI for these polymers 151 and 152 were 13500 Da, 2.5 and 13600 Da, 2.2, respectively, and their solubility was good in organic

• solvents. In order to obtain polymers containing a varying degree of pendant azulene units, such as 154, 155, 157, and 158, the authors performed the free radical copolymerization of the monomers 146 and 150 with methyl methacrylate (153) (Scheme 27A and B) and sulfobetaine methacrylate (156) (Scheme 27C

An initiator- and catalyst-free hydrogel coating process for 3D printed medical-grade poly(ε-caprolactone)

• Jochen Löblein,
• Thomas Lorson,
• Miriam Komma,
• Tobias Kielholz,
• Maike Windbergs,
• Paul D. Dalton and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2021, 17, 2095–2101, doi:10.3762/bjoc.17.136

• scaffolds, which may be required for suitable interaction with cells or other materials. SIPGP does not require special equipment other than a UV lamp or special reagents. As a proof-of-concept, we demonstrated the feasibility using HEMA as monomer, but essentially any monomer polymerizable by free radical

Towards new NIR dyes for free radical photopolymerization processes

• Haifaa Mokbel,
• Guillaume Noirbent,
• Didier Gigmes,
• Frédéric Dumur and
• Jacques Lalevée

Beilstein J. Org. Chem. 2021, 17, 2067–2076, doi:10.3762/bjoc.17.133

• filled samples can be potentially used for composite materials and/or adhesives. Both photochemical and photothermal NIR approaches were proposed to initiate polymerization, e.g., for free-radical processes, interpenetrating polymer network (IPN) synthesis, or photopolyaddition reactions [3][4][6][7][8

• combination with an amine and an iodonium salt, iod, for the free radical polymerization of a benchmark acrylate monomer and compared to a reference initiating system based on IR 813 (Scheme 2) [7]. As the different dyes presented above exhibit good absorption properties at 785 nm, the photoinitiating

• depicted in Figure 2 and Figure 3. The NIR dyes proposed have strong abilities to initiate the free radical polymerization. Indeed, the polymers obtained are tack-free after only a few seconds of irradiation (Scheme 6). Without NIR dyes, no polymerization occurs. At 785 nm, in most cases, the final

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• formation of C–C bonds involving free radical species means that the new bond is formed at a reasonable distance from the carbon radical acceptor, thereby reducing the expected steric hindrance [74][75]. As mentioned above, a useful strategy for generating the desired tertiary carbon radicals is the use of

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• new pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline skeleton was synthesized by free-radical intramolecular cyclization of o-bromophenyl-substituted pyrrolylpyridinium salts using the (TMS)3SiH/AIBN system. The cyclization provides generally good yields of pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline hydrobromides

• , attempts to assemble this framework using Pd-catalyzed intramolecular arylation of compounds C' (X = Br, I) failed [17]. In this work, we report an effective method for the assembly of pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline and related frameworks via a free radical cyclization of pyrrolylpyridinium salts

• . Results and Discussion Although the intramolecular free-radical cyclization is widely used for the synthesis of heteroaromatic compounds [23][24][25][26], only a few examples of the successful use of radical cyclization for the synthesis of pyrrole-containing fused heteroaromatics are known in the

Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• , ascorbic acid/hydrogen peroxide, respectively. The mixture was immediately placed in a Petri dish to complete the gelation via free radical polymerization under dark conditions. After 3 hours, the resulting hydrogel was purified with water to remove the unreacted species (monomers and redox mediators

• modification platform [49]. The as-prepared hydrogel network (HGCM) was immersed in various acrylic monomers. Following that, photoinduced free radical polymerization of employed monomers performed under visible light irradiation by taking advantage of embedded g-CN nanosheets in HGCM. According to literature

• capped and left for 3 hours to obtain a gelation via redox-induced free radical polymerization. Afterwards, it was washed with distilled water to remove the unreacted species and freeze dried for 24 hours. The resulting light and brittle g-CN nanosheets embedded hydrogel was ready for further usage. In

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• polycyclic derivatives was designed. The procedures towards such polycyclic building blocks include C–H-arylation strategies. In the classical Meerwein reaction, aryldiazonium salts are used as the reagents to couple aryl groups to electron-poor alkenes, and this process is assumed to proceed via a free

• -radical mechanism [29]. Similar reaction intermediates can be prepared using precursors such as organoboron reagents [30]. However, due to the accessibility, aryldiazonium salts are the reagents of choice. They can be prepared starting from the commercially available corresponding anilines. The present

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• -metal catalysts, such as in the Suzuki–Miyaura and Heck coupling reactions. Methodologies for forming different C–C bonds have recently been developed in the field of single-electron chemistry [63][64][65]. Considering that EDA-complex-initiated free-radical reactions are carried out under mild

• over the last five years. Cyclization reactions In the pharmaceutical industry, retail drugs with a heterocyclic composition have exceeded 60% of the market volume. Hence, cyclization reaction innovation seems to be a requisite for pharmaceutical industry and human health. As an outstanding way, free

• -radical cascade reactions could efficiently construct various carbocycles and heterocycles with multifarious structures and complexity [59][60][61]. Centered on this context, we give a clear overview on a variety of novel cyclization reactions initiated by EDA complexes from the recent years. In 2016

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• coordination ability towards metal ions. The versatile chemistry of precursors used for annulation of the 1,3-dithiole moiety to an o-quinone ring allows a wide variety of substituents at the 2-position of the 1,3-dithiole cycle, including additional redox-active, coordination-capable or free-radical functions

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• . Further applications of free radical chemistry have developed through the use of radical initiators under comparatively mild conditions to form cyclopropylmethyl radicals, which can readily release their strain by opening to give homoallyl radicals. gem-Difluorocyclopropanes, because of their

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• ,E,E)-triene (rac)-11 in 50% yield [59]. Since triene (rac)-11 has been previously transformed into inthomycin C, this study demonstrated the formal synthesis of racemic inthomycin C ((rac)-3) [21][22][43][50]. An interesting application of the O-directed free radical hydrostannation reaction was

• 82% yield (83% ee). Subsequent free radical hydrostannation on (−)-98 produced (+)-99 as the major product of a 46:1 mixture of (Z/E)-α-stannylated geometric isomers. The purified vinylstannane (+)-99 underwent iodination stereoselectively with excess N-iodosuccinimide to give (−)-100, which was then

Silver-catalyzed synthesis of β-fluorovinylphosphonates by phosphonofluorination of aromatic alkynes

• Yajing Zhang,
• Qingshan Tian,
• Guozhu Zhang and
• Dayong Zhang

Beilstein J. Org. Chem. 2020, 16, 3086–3092, doi:10.3762/bjoc.16.258

• selectflour to generate Ag(III)F. Subsequently, ethyl phosphite is oxidized by Ag(III)F to generate a P-centered radical (INT-I) and Ag(II)F. The electrophilic phosphonyl radical addition to the triple bond of 1a generates the vinyl-free radical INT-II, which is subsequently trapped by AgF(II) to afford the

Amine–borane complex-initiated SF₅Cl radical addition on alkenes and alkynes

• Audrey Gilbert,
• Pauline Langowski,
• Marine Delgado,
• Laurent Chabaud,
• Mathieu Pucheault and
• Jean-François Paquin

Beilstein J. Org. Chem. 2020, 16, 3069–3077, doi:10.3762/bjoc.16.256

• SF5Cl addition on unsaturated compounds goes through a free-radical mechanism, and is promoted by the radical activation of SF5Cl by Et3B, which leads to the formation of the propagating species SF5• [32][33]. Trialkylboranes are common low-temperature radical initiators, and Et3B is one of the most

• recently, it has been shown that some of these common amine–borane complexes can also be used as radical initiators for atom transfer radical addition of alkyl halides to alkenes [48]. They were also used in the free-radical polymerization of alkene-containing monomers such as methyl methacrylate or

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• –20-fold amount. Furthermore, the aryl radical/cation addition onto the aromatic reactant may lead to a mixture of regioisomers when using non-symmetrical Ar–H. A possible solution is having recourse to an intramolecular free radical ipso substitution reaction where an XSO2 tether is placed between

• the presence of increasing amounts of TFE (up to 20% v/v, continuous line). Synthesis of biarenes via a) photogenerated triplet aryl cations and aryl radicals (PC = photocatalyst), b) intramolecular free radical ipso substitution, c) thermally catalyzed extrusion of CO and SO2, d) photoinduced

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• (DPPO) was not suitable for the transformation (Scheme 1b). So the development of metal-free and greener methods to approach chroman-4-ones bearing a phosphine oxide moiety is still highly desirable. Herein, we present a transition-metal-free radical cascade cyclization to access the desired chroman-4

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• of a [3 + 2] cycloaddition reactions under UV irradiation with azobis(isobutyronitrile) (AIBN) as the free radical initiator and phenyl disulfide as the catalyst, in which the three-membered rings containing double bonds and substituted olefins were transformed into five-membered-ring structures with

• by the excitation with visible light, the homolytic cleavage of disulfide generates an arylthiyl radical (ArS•), which adds to diphenylacetylene to form a free-radical intermediate 28. Subsequently, this intermediate traps a molecule of singlet oxygen (1O2), and the thiyl radical is regenerated to

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• and the difficulties associated with the interpretation of the obtained data [53]. During EPR monitoring of the generation and decomposition of iminoxyl radicals, the formation of several free-radical products of a non-iminoxyl type, probably of the general formula R1R2NO•, was observed. It was

• hindered tert-butylmethyliminoxyl and diisopropyliminoxyl radicals, as well as for diaryl and alkylaryliminoxyl radicals, the radical–dimer equilibrium was reached slowly, it was shifted toward the free radical, and a second-order decay kinetics was observed. The first synthesized long-lived iminoxyl

• radical 20 and complex 49 results in the coupling product 48 (Scheme 18). The formation of radical 20 from the oxime 19 under the action of Cu(ClO4)2 in acetonitrile was proved by EPR spectroscopy [46]. Free-radical oxidative C–O coupling of pyrazolones 50 with different classes of N-hydroxy compounds