Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• also important substructures in a variety of non-natural compounds and their pharmacological effects against bacteria [13][14][15][16], inflammation [17][18], viruses [19], radical [20], and cancer [21][22][23][24][25][26] have been proven. It is undoubtedly true that heterocyclic compounds containing

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• , Supporting Information File 1). Other plant polyketides, such as anthraquinones 19 and 20 and phenylpropanoids 21–24, failed to be dimerized. The reaction mechanism of P450-mediated phenol dimerization is believed to involve oxidative radical–radical coupling, though other mechanisms, such as radical

• addition, radical cation addition, and electrophilic aromatic addition, have also been proposed [1][10][29]. A proposed mechanism is depicted in Scheme 2: First, the hydroxy group on the A- or B-ring is converted into a radical by a P450-induced single-electron transformation. The resulting radical then

• migrates to the π-system and is stabilized in the ortho- and para-positions, generating diverse carbon radical intermediates. As a result, various dimers are formed via promiscuous coupling of these radical intermediates. Although we cannot exclude the possibility that other P450 enzymes in S. cattleya may

Radical cation Diels–Alder reactions of arylidene cycloalkanes

• Kaii Nakayama,
• Hidehiro Kamiya and
• Yohei Okada

Beilstein J. Org. Chem. 2022, 18, 1100–1106, doi:10.3762/bjoc.18.112

• 183-8509, Japan 10.3762/bjoc.18.112 Abstract TiO2 photoelectrochemical and electrochemical radical cation Diels–Alder reactions of arylidene cycloalkanes are described, leading to the construction of spiro ring systems. Although the mechanism remains an open question, arylidene cyclobutanes are found

• to be much more effective in the reaction than other cycloalkanes. Since the reaction is completed with a substoichiometric amount of electricity, a radical cation chain pathway is likely to be involved. Keywords: arylidene cycloalkane; Diels–Alder reaction; radical cation; single-electron transfer

• ; spiro ring system; Introduction Single-electron transfer is one of the simplest modes for small molecule activation, employing a polarity inversion to generate radical ions which have proven to be unique reactive intermediates in the field of synthetic organic chemistry. A radical cation Diels–Alder

Electrochemical formal homocoupling of sec-alcohols

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

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• from the corresponding vic-1,2-diol. Water may play a role as a proton source to facilitate the formation of the protonated ketyl radical through a concerted proton-electron transfer toward the ketone or smooth protonation of the radical anion species, which readily dimerize to vic-1,2-diol 2a [46][49

Electrochemical vicinal oxyazidation of α-arylvinyl acetates

• Yi-Lun Li,
• Zhaojiang Shi,
• Tao Shen and
• Ke-Yin Ye

Beilstein J. Org. Chem. 2022, 18, 1026–1031, doi:10.3762/bjoc.18.103

• diverse α-azidoketones in good yields without the use of a stoichiometric amount of chemical oxidant. A range of functionality is shown to be compatible with this transformation, and further applications are demonstrated. Keywords: azide; azidoketone; electrosynthesis; enol acetate; radical

• have reported a manganese dioxide-catalyzed radical azidation of enol acetates to afford the corresponding azidoketones using dioxygen as the oxidant (Scheme 1A) [14]. The adoption of electrosynthesis in green and sustainable redox transformations has been experiencing a dynamic renaissance [15][16][17

• ). The enol acetate A first undergoes anodic oxidation to form a radical cation intermediate B, which is then intercepted by azidotrimethylsilane to afford the benzyl radical C. Subsequently, this radical is further anodically oxidized to its oxocarbenium ion intermediate D, which finally reacts with

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• nitrogen radical coupling mechanism in the biosynthesis of azoxymycins [12][13], which are aromatic azoxy natural products. A similar mechanism has been envisioned for the autoxidation and spontaneous dimerization of aliphatic hydroxylamines via the azoxy linkage in malleobactin D biosynthesis [14]. A

Electrochemical and spectroscopic properties of twisted dibenzo[g,p]chrysene derivatives

• Tomoya Imai,
• Ryuhei Akasaka,
• Naruhiro Yoshida,
• Toru Amaya and
• Tetsuo Iwasawa

Beilstein J. Org. Chem. 2022, 18, 963–971, doi:10.3762/bjoc.18.96

• , dyes, liquid crystals, and light-emitting materials. A number of substituted DBCs have been reported in this context [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46]. To develop charge-transport materials, Rathore et al. reported on the stability of radical cations of

• groups are introduced in place of the isopropyl groups, which has a 0.06 V higher oxidation potential than that of MeO-DBC-1. This indicates that alkyl substituents in the X position are effective in stabilizing the radical cation, thus making it more susceptible to oxidation. Unlike DBC-H, an

Electroreductive coupling of 2-acylbenzoates with α,β-unsaturated carbonyl compounds: density functional theory study on product selectivity

• Naoki Kise and
• Toshihiko Sakurai

Beilstein J. Org. Chem. 2022, 18, 956–962, doi:10.3762/bjoc.18.95

• Scheme 5. The first one is a radical addition of O-trimethylsilyl radical A, which is formed by a one-electron reduction of 1 and subsequent O-trimethylsilylation, to 2a and a following one-electron reduction of the resultant radical B to give enolate anion D (path a). The second one is an anionic

• acrylate (2c) is much less reactive as an acceptor in this reaction as shown in Scheme 6. The main product in this case was the same dimeric phthalide 9 as the product without the acceptor. These results suggest that this reaction proceeds with the radical addition of A to form anion D (path a). Next, the

• Shimadzu IRAffinity-1 infrared spectrometer. HRMS were measured on a Thermo Scientic Exactive FTMS spectrometer. Melting points were uncorrected. Column chromatography was performed on silica gel 60. THF was distilled from sodium benzophenone ketyl radical. TMSCl, TEA, and DMF were distilled from CaH2

Introducing a new 7-ring fused diindenone-dithieno[3,2-b:2',3'-d]thiophene unit as a promising component for organic semiconductor materials

• Valentin H. K. Fell,
• Joseph Cameron,
• Alexander L. Kanibolotsky,
• Eman J. Hussien and
• Peter J. Skabara

Beilstein J. Org. Chem. 2022, 18, 944–955, doi:10.3762/bjoc.18.94

• Figure 9, for the generation of a radical cation and dication at half-wave potential values of +0.65 V (ΔEp = 0.05 V) and +0.87 V (ΔEp = 0.06 V), respectively. Two reduction waves, corresponding to the radical anion and dianion, can be seen at the half-wave potentials of −1.51 V (ΔEp = 0.06 V) and −1.64

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• with excess PCl5. However, the radical chlorination of 2-methylphenyl(methyl)phosphinic chloride (9) gave the desired 2-chloromethylphenyl(methyl)phosphinic chloride (10) in 65% yield with unreacted starting 9 in 25–30%, and the dichlorinated product 11 in 5–10%. The reaction of 2-chloromethylphenyl

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• bromodifluoromethyl phenyl sulfide (1) using o-phthalonitrile as a mediator generated the (phenylthio)difluoromethyl radical, which reacted with α-methylstyrene and 1,1-diphenylethylene to provide the corresponding adducts in moderate and high yields, respectively. In contrast, chemical reduction of 1 with SmI2

• ; (phenylthio)difluoromethyl radical; Introduction Organofluorine compounds containing a difluoromethylene group have been of much interest from biological aspects since the difluoromethylene group is isopolar and isosteric with an ether oxygen [1][2]. Particularly, organic molecules bearing a (arylthio

• olefins in moderate yields [5]. Prakash et al. also achieved fluoride-induced nucleophilic (phenylthio)difluoromethylation of carbonyl compounds using PhSCF2SiMe3 [6]. Quite recently, Shen et al., developed various nucleophilic, electrophilic, and radical difluoromethylthiolating reagents [1]. However

Thiophene/selenophene-based S-shaped double helicenes: regioselective synthesis and structures

• Mengjie Wang,
• Lanping Dang,
• Wan Xu,
• Zhiying Ma,
• Liuliu Shao,
• Guangxia Wang,
• Chunli Li and
• Hua Wang

Beilstein J. Org. Chem. 2022, 18, 809–817, doi:10.3762/bjoc.18.81

• (radical)–C(radical) bond and randomly directed annelated products [30]. Moreover, compounds 5a–c bear two C=C bonds, which may lead to more complex photocyclization products. 5-(Trimethylsilyl)dithieno[2,3-b:3′,2′-d]thiophene-2-carbaldehyde (4a) [19], 5-(trimethylsilyl)diseleno[2,3-b:3′,2′-d]thiophene-2

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• perfluorinated chains into aromatic rings have been developed since the first reports of such transformation by George Tiers in 1960, and McLoughlin and Thrower in 1969 [2][3]. Most approaches have made extensive use of organometallic chemistry, radical initiators, photocatalysis, electrochemistry, and more

• -sulfonylpropiophenone moiety readily undergoes homolysis into three parts upon irradiation of light: a propiophenone radical – forming a stabilized and bulky “dummy group” –, a molecule of SO2, and our radical of interest. Once this radical is formed in solution, radical addition to the aromatic substrate undergoes

• readily, and is subsequently followed by a hydrogen atom transfer (HAT) process aided by the “dummy group” radical. These reagents thus fit the paradigm of a green methodology as their implicit design and photoactivity allows them to react without the use of external metal catalysts. The intrinsic

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• chilled tube containing PRP (1), appeared to undergo free-radical polymerization when increasing the temperature to 25 °C. Despite this failed experiment, in general, PRP (1) has established itself as a highly reactive 1,3-dipole towards cyclopropene dipolarophiles 2. In this study, we did not confine

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• state of the decatungstate anion generates carbon-centered radical 48 which is trapped in a segmented flow with molecular oxygen provided by a mass flow controller. Peroxide 49 is formed as intermediate which further reacts to phthalide (50) in 71% yield. This method efficiently utilizes the advantages

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• ] could be simplified by in situ generation of the catalyst. Moreover, in the debromination of norbornene imide 11, the expected Diels−Alder adduct with furan was not obtained, but compound 12 incorporating a tetrahydrofuran ring at position 2, presumably by radical reaction (Figure 2) [19][20]. We

• also found in the reaction of bicyclo[2.2.2] dibromide 42 (Scheme 3), which suggests that the mechanism may involve radical anion intermediates. This result further supports a single electron transfer (SET) and radical anion mechanism which was postulated earlier for the Zn/Ag debromination reaction

• and was supported by a CH3OD trapping experiment [13]. Thus, DPIBF in this reaction acts both as Diels−Alder trap reagent for reactive alkene [28] as well as radical anion quencher [29][30]. The N,N-Boc-protected N-amidinylpyrrole 28 [31] and 1-guanidinoanthracene (29) [10][32] have functional groups

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• . Catalytic residue in the cyclooxygenase reaction The formation of a tyrosyl radical during the catalytic cycle was proved by EPR and kinetic analyses [59][60][61]. Moreover, chemical and molecular biology analyses and a mutagenesis experiment identified the position of the tyrosyl radical. Treatment of the

• in the crystal structure, indicating that a tyrosyl radical abstracts the pro-S hydrogen atom from C13 of AA (Figure 2B and 2C) [48][52][53]. Mechanism of the cyclooxygenase reaction The enzyme reaction is initiated upon Tyr385 activation by the oxyferryl heme cation radical, which is generated

• through the two-electron reduction of PGG2, to form a tyrosyl radical in the active site of the cyclooxygenase-site (Scheme 2) [24][34][63]. The tyrosyl radical then abstracts a C13-pro-S hydrogen atom from AA to produce the arachidonoyl radical, which is delocalized over C11 to C15. An oxygen molecule

Rapid gas–liquid reaction in flow. Continuous synthesis and production of cyclohexene oxide

• Kyoko Mandai,
• Tetsuya Yamamoto,
• Hiroki Mandai and
• Aiichiro Nagaki

Beilstein J. Org. Chem. 2022, 18, 660–668, doi:10.3762/bjoc.18.67

• residence time was elongated, leading to a significant decrease in the yield of cyclohexene oxide (Supporting Information File 1, Figure S2) [32]. Overall, we assume that, in our flow system, the highly efficient contact of acyl radical 5 with oxygen during the autoxidation of aldehyde could produce the

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• the amidyl radical precursor under air is reported. A possible mechanism is proposed that proceeds via a radical reaction in the presence of CuBr and triethyl phosphite. Keywords: amination; copper; N-hydroxyphthalimides; radical reactions; triethyl phosphite; Introduction Practical methods for

• (reaction 3) [27]. Herein, we report a method for the construction of aromatic amines via the copper-catalyzed intermolecular radical amination of arenes with N-hydroxyphthalimide (NHPI) under air. Results and Discussion Initially, N-hydroxyphthalimide (NHPI, 2a) was reacted with benzene, catalyzed by CuBr

• -electron transfer (SET) between CuBr and intermediate 5 forms intermediate 6, which initiates the N–O bond homolytic cleavage resulting in forming an N-centred phthalimidyl radical 7 (PhthN•) and anion 8. Meanwhile, Cu(I) is oxidized to Cu(II) in this step. Next, radical 7 attacks the benzene via radical

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• performed radical trapping experiments using TEMPO and BHT in the reaction of substrate 1c (Figure 5a). Under the standard reaction conditions in the presence of TEMPO or BHT, the expected product 2c was formed in 66 and 72% yields. These results indicate that a radical pathway may not be involved in the

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• radical addition of a thiol-based stopper to the α,β-unsaturated carbonyl unit in 12% yield. In this reaction, addition of the thiyl radical to the β-position first gives rise to the corresponding rotaxane radical with the unpaired electron in the α-position, followed by hydrogen abstraction from the next

Tetraphenylethylene-embedded pillar[5]arene-based orthogonal self-assembly for efficient photocatalysis in water

• Zhihang Bai,
• Krishnasamy Velmurugan,
• Xueqi Tian,
• Minzan Zuo,
• Kaiya Wang and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2022, 18, 429–437, doi:10.3762/bjoc.18.45

• donor absorbs light energy and changes to the excited state (TPEWP5G*) energy level. Through energy transfer from TPEWP5G* to ground state EsY the latter undergoes excitation to the excited state EsY* and is reduced by the Hantzsch ester to generate the radical anion EsY•−. Subsequently, electron

• transfer from EsY•− to the substrate α-bromoacetophenone (1a) gives the corresponding acetophenone radical, whilst EsY•− is oxidized to EsY. The acetophenone radical combines with a H-atom abstracted from the radical cation of the Hantzsch ester to form acetophenone (2a) as the final product and diethyl

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

• •−), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and hydroperoxyl radical (•OOH) (Figure 3) [35]. Additionally, the menadione semiquinone radical can participate in another redox cycle, such as, the Fenton reaction, also resulting in the production of hydroxyl and hydroperoxyl radicals (Figure 3) [39][40

• 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

• an interesting artifice to track the dimerization reaction path: they synthesized 2-(methyl-13C)-1,4-naphthoquinone (10) (Scheme 1) [81]. For that, sodium acetate-2-13C was used as the source of the methyl radical, generated by its treatment with K2S2O8 and AgNO3. After 3 hours at 60 °C, the 13C

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

• ]. Conventional synthetic methods for piperidine derivatives include nucleophilic substitution (route (1) in Scheme 1), reductive amination (route (2)), intramolecular cyclization of amines and alkenes (route (3)), the Diels–Alder reaction and subsequent reduction (route (4)), and the radical cyclization reaction

• (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

• only one report on the electroreductive synthesis of piperidine derivatives: namely Degrand and co-workers demonstrated electroreductive cyclization using imines and terminal dihaloalkanes to provide piperidine derivatives (Scheme 2) [27]. In this reaction, a stable radical anion is produced from the

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• authors reported similar site-selective Diels–Alder reactions between 2 and inert aromatics including aceanthrylene and 1H-cyclopenta[l]phenanthrene [49]. Generally, it is difficult to achieve site- and stereoselective control over radical reactions. The radical species are very reactive and a complex

• mixture of different products will form through various pathways [50][51][52][53]. By applying the cage host A, the authors realized a highly site-selective radical addition reaction of o-quinone 10 and substituted toluene 11, giving rise to the unusual 1,4-adduct 15 (Figure 3) [54]. Specifically, upon

• irradiation, biradical species 12 was generated and immediately abstracted a hydrogen atom from the methyl group of 11. Site-selective radical coupling at the oxygen atom between 13 and 14 produced the 1,4-adduct 15. The unusual site-selectivity of this reaction was also traced from the restricted geometry