Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• refluxing acetonitrile for 6 h. It underwent a radical cyclization in refluxing benzene for 20 h to give rise to a nine-membered phostone thieno[2,3-d]pyrimidine-fused 2-hydroxy-1,2-oxaphosphonane 2-oxide 46 as a potential inhibitor after the deprotection of the benzyl group in the presence of DABCO in

• -bromohex-5-en-1-yl methylphosphinate (63), 2-methyl-3-methylene-1,2-oxaphosphepane 2-oxide (64) was obtained in low 17% yield at 110 °C (Scheme 13) [34]. The Mn-catalyzed intramolecular radical arylation of 2-(naphthalen-1-yl)ethyl phenylphosphinate (65) gave a mixture of 4-phenyl-1,2-dihydronaphtho[2,1-c

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• reaction conditions, generating the corresponding acetoxymalonylated products 4u–w in good to excellent yields. Several control experiments were performed to gain insights into the mechanistic pathway of this reaction. Firstly, a radical scavenging experiment using the radical scavenger TEMPO was performed

• the involvement of a malonyl radical and an acetyl radical in the course of the reaction (see Supporting Information File 1 for details). Additionally, when an aliphatic alkene, 5-hexen-1-ol was introduced into the reaction mixture under standard conditions without Zn(OAc)2, an ATRA product 9 was

• isolated, further confirming the involvement of a malonyl radical generated by the cleavage of the C–Br bond of 2a [28]. Next, an attempt was made to identify the key intermediate of the reaction (Scheme 3B). When compound 5 was subjected to the acetylation reaction individually with Zn(OAc)2 and AcOH

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• ) [32]. The third group of approaches to the PBTA scaffold includes only one example, the intramolecular radical substitution reaction in 1-(2-bromophenyl)-5-(butylsulfanyl)pyrrolidin-2-one (Scheme 3, entry 13) [8]. The fourth group of approaches to the PBTA scaffold is the intramolecular cyclization of

• proceeds through a different pathway from the one to pyrrolobenzothiazoles 3, 7, and 12. Biologically active PBTAs. Electrophilic centers in FPDs. Approaches to PBTAs via annulation of benzothiazoles. Approaches to PBTAs via annulation of o-aminothiophenols. Approach to PBTAs via radical substitution

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• , transformation to potassium trifluoroborate salt, hydrolysis, C–C cross-coupling, base-mediated elimination, radical C–B cleavage) [72]. Therefore, enantioenriched boronates are commonly applied intermediates in organometallic, medicinal, and other fields of chemistry. At the same time, some organoboronic acid

Direct C2–H alkylation of indoles driven by the photochemical activity of halogen-bonded complexes

• Martina Mamone,
• Giuseppe Gentile,
• Jacopo Dosso,
• Maurizio Prato and
• Giacomo Filippini

Beilstein J. Org. Chem. 2023, 19, 575–581, doi:10.3762/bjoc.19.42

• charge transfer state which results in a bathochromic shift of the absorption towards the visible range [19][20]. Upon light irradiation, the EDA complex may undergo an intramolecular single-electron-transfer (SET) process to produce a radical ion pair (D•+, A•−). To avoid the occurrence of a back

• -electron-transfer (BET), a suitable leaving group (LG) needs to be included in one of the precursors. In this manner, reactive intermediates (e.g., radical species) may be generated in solution through the irreversible fragmentation of the substrates [15][21][22]. These intermediates eventually react to

• yield the final products "A–D". This approach is not limited to reagents with appropriate donor–acceptor characteristics [13][19]. Indeed, sacrificial electron donors and electron-deficient radical precursors can be used to form photoactive EDA complexes. Specifically, these aggregates can be employed

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

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

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• dimerization of the Schiff base complex and the radical cation formed under one-electron electrochemical oxidation will be sufficiently stable, opening a route to further oxidative modification of the amino acid side chain under appropriate conditions. Additionally, this bulky group may significantly alter the

• fragment in the oxidized (GlyNi)L7 and (ΔAlaNi)L7 complexes bears a certain spin density (as it has been previously shown for the t-Bu-free analogs [31]), the bulky t-Bu substituent does prevent dimerization of the radical cations formed in the electron-transfer step increasing their kinetic stability

• the C=N bond), diffusion controlled (the slope of the ln ipc vs ln v dependence is 0.48), and reversible; the direct and reverse peak separation value was 57 mV at 100 mV/s, and Ia/Ic peak current ratio was close to unity. This means that the radical anion of (GlyNi)L7 is stable, at least in the

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• photoexcitation of the photosensitizer 43 to form 44 which can oxidize aniline 36a to give radical cation 46 (Scheme 7). Deprotonation by DBU produces the radical 40. The radical anion photosensitizer 45 can reduce Ni(I) to Ni(0), closing the first catalytic cycle. The Ni(0) complex can undergo oxidative addition

• into the C–O bond of the oxabicyclic alkene 30a to afford the σ-allyl intermediate 38 which can isomerize to the more stable π-allyl intermediate 39. Addition of the α-amino radical to the Ni(II) center generates the Ni(III) complex 41. Reductive elimination, followed by protodemetalation, leads to the

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• pathway was proposed by Ponnapalli and co-workers [14] and was initially based on the conversion of phenylalanine into tyrosine by phenylalanine hydroxylase and m-tyrosine via radical hydroxylation (Scheme 2). Subsequent deamination of tyrosine, with concomitant hydroxylation/deamination of m-tyrosine

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• domestica Borkh.) on the basis of antioxidant properties and radical scavenging kinetics [27][60][61]. However, only few studies have been published on the discrimination of CD-based complexes using multivariate statistical analysis. They are especially related to the retention behavior of various

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• construction of the 8-membered ring from an appropriate cyclopentane precursor. The proposed strategies include metathesis, Nozaki–Hiyama–Kishi (NHK) cyclization, Pd-mediated cyclization, radical cyclization, Pauson–Khand reaction, Lewis acid-promoted cyclization, rearrangement, cycloaddition and biocatalysis

• precursor. The proposed strategies include metathesis, Nozaki–Hiyama–Kishi (NHK) cyclization, Pd-mediated cyclization, radical cyclization (including SmI2), Pauson–Khand reaction, Lewis acid-promoted cyclization, rearrangement, cycloaddition, and biocatalysis. In particular, the purpose will focus on the

• by a vinyl ketone (compound 135) or a butenolide (compound 137) moiety dramatically influenced the outcome of the reaction and no cycloadduct was observed in both cases (Scheme 27). 4 Radical cyclization (including SmI2) Introduced by Kagan more than four decades ago, samarium diiodide (SmI2) has

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• ) in 86% yield. To find out more information about the mechanistic route of the reaction, we performed a control experiment in the presence of TEMPO as a radical scavenger as depicted in Scheme 6. The reaction of pyrazole-3-carbaldehyde 1, pyrrolidine (A) and elemental sulfur in the presence of 1.1

• equiv of TEMPO delivered the targeted product in 76% yield. On the basis of this experiment, it was concluded that TEMPO did not affect the progress of the reaction and the formation of product 1A. Hence, a radical mechanism of the reaction may be ruled out. The successful synthesis of pyrazole C-3/4/5

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus

• Naoya Oku,
• Saki Hayashi,
• Yuji Yamaguchi,
• Hiroyuki Takenaka and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2023, 19, 133–138, doi:10.3762/bjoc.19.13

• ear, and decrease writhing response induced by intraperitoneal injection of acetic acid in rodent models [11], thus supporting the ethnophamacological testimonies. Moreover, radical scavenging activity [11][12], hyaluronidase inhibitory activity [13], and tyrosinase inhibitory activity [14] were

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

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• lead compounds without the need for de novo synthesis [5]. Baran et al. has developed an operationally simple, radical-based functionalisation strategy that allows direct transformation of C–H bonds to C–C bonds in a practical manner [11]. This strategy involves the utilisation of sodium and zinc

• [14], we had undertaken some preliminary investigations into the use of commercially available Diversinate™ reagents and showed the bicyclic nitrogen-rich core of Series 4 was amenable to this chemistry, with radical sulfinate substitution occurring with high-selectivity at C-8 and in respectable

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• reactions and radical transformations [36][37][38]. Based on the literature precedents [27] and our previous work [33][34][35], a mechanism for this Rh-catalyzed C–H activation/annulation reaction was proposed and depicted in Scheme 5. In the presence of AgSbF6, dimeric [Cp*RhCl2]2 transforms into the

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• Dan Liu Yue Zhao Frederic W. Patureau Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany 10.3762/bjoc.19.5 Abstract A practical NaI/PPh3-catalyzed decarboxylative radical cascade cyclization of N-arylacrylamides with redox-active esters is described, which

• afforded various functionalized oxindoles featuring a C3 quaternary stereogenic center. Mechanistic experiments suggest a radical mechanism. Keywords: decarboxylative cascade cyclization; iodide catalysis; metal-free photocatalysis; oxindole; phosphine catalysis; Introduction Radical-initiated cascade

• reactions constitute a powerful synthetic approach to construct multiple C–C or C–X bonds in one pot. As such, these tend to allow facile access to many complex natural molecules and drugs [1][2][3][4][5][6]. Recently, radical-initiated cascade cyclizations involving acrylamides have attracted considerable

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• of atom economy and protecting-group-free synthesis dominating the field of total synthesis. In this new era, total synthesis is moving towards natural efficacy by utilizing both the biosynthetic knowledge of divergent synthesis and the latest developments in radical chemistry. This contemporary

• for biological screening. The era of scalability [2] in total synthesis prompts researchers in this field to make use of more direct retrosynthetic disconnections with the aid of “radical” retrosynthetic analysis, as the advancement in the area now allows to harness one-electron power in a highly

• disconnections. As radical disconnections are gaining ground, more sophisticated retrosyntheses of natural products are unlocked, enriching thus their synthetic scalability [6][7]. A direct comparison of a classic vs a radical approach highlights the complementarity and, more often than not, the superiority of

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• , obtaining excellent selectivity in all cases. Alternatively, the same year, the authors published a vinyl radical cyclization occurring in presence of n-Bu3SnH, providing a stereoselective access to the bicyclo[3.2.1]octane unit corresponding to the CD rings [25]. Newhouse’s synthesis of principinol D In

• [3.2.1]octane 67 was achieved by a radical cyclization using n-Bu3SnH in refluxing toluene. A sequence involving an ester reduction, Ley–Griffith oxidation and Seyferth–Gilbert homologation with Bestmann–Ohira reagent allowed to obtain the alkynyl bicylo[3.2.1]octane 69. On the other hand, the five

• radical cyclization of an alkynyl ketone as the key step. The synthesis started by a Cu-catalyzed conjugate addition of the vinyl Grignard reagent, followed by TMS α-propargylation under basic conditions, affording the TMS-alkynyl ketone 76 as the major diastereomer (Scheme 11). Originally a Au-catalyzed

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• are a number of reviews on specific groups of redox-organocatalyzed oxidative transformations [43][44][45][46][47][48][49][50][51][52][53][54][55][56] and organocatalyzed enantioselective radical reactions were recently discussed [57]. However, the field remains not overviewed in general and it is not

• (Scheme 2). In the enamine type of catalysis (Scheme 2A) the key enamine intermediate can undergo one-electron oxidation (route 1), electrophilic radical attack (route 2), or electrophile attack (route 3). The one-electron oxidation leads to the electrophilic cation radical which can further undergo

• a nucleophilic reacting center. In addition to umpolung reactions with electrophiles, Breslow intermediates can undergo oxidation with the formation of radical cations or electrophilic acylazolium cations. The acylazolium cation in turn can undergo nucleophilic attack resulting in C–O and C–N

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• spectroelectrochemistry of the compounds was studied (Figure 7). For NI-PTZ, when a positive potential of +0.53 V (vs Ag/AgNO3) was applied, the hallmark absorption bands of the PTZ•+ radical cation centered at 516, 794, and 891 nm are observed [20]. These bands are similar to the ones observed for the previously

• reported NI-N-PTZ dyad. Upon a negative potential at −1.83 V (vs Ag/AgNO3) applied, the absorption bands of the NI•− radical anion at 424, 492, 720, and 801 nm are observed, which are also similar to the ones of the analogous dyad [20]. For NI-PTZ-O, similar NI•− absorption bands were observed. However

• the impact of the conformational restriction on the photophysical properties of NI-PhMe2-PTZ. We underline that the absorption of the CT states of the dyads may not be the “simple sum” of the absorption of the radical cation and the radical anion of the dyads, obtained by the spectroelectrochemistry

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• compound I (intermediate G), it is now generally accepted as a ferryl (Fe(IV)) oxo species with a radical cation in the porphyrin system [18][23]. In the case of hydroxylations, the oxygen from compound I (intermediate G) can then be transferred by an oxygen rebound mechanism (steps 7 and 8) via the ferryl

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• ketones and thiourea via an oxidative cyclization initiated by a radical process and a following condensation reaction (Scheme 1c) [29]. Although these methods are practical, most of these strategies require stoichiometric or excess amounts of halogenating reagents or oxidants, which are toxic, hazardous

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• in the formation of H2 and O2 from the water splitting reaction by donating strain-induced electrons and holes [53]. The piezoelectricity obtained upon ultrasonication of BaTiO3 has also been used to trigger and sustain atom transfer radical polymerization (ATRP) reactions of acrylate monomers by

• -known mechanophore that generates diarylacetonitrile radicals under force. Hence, when TASN derivative 8, bearing diarylurea moieties, was ball milled, the corresponding radical 9 was detected by electron paramagnetic resonance (EPR) spectroscopy. Similar treatment proved that 6 was 28 times less prone

• a collision between the ball and a particle of a chitin sample and (b) mechanical treatment of a particle of a lignin sample in a ring-and-puck mill. (a) Ultrasound-induced ATRP using piezoelectric BaTiO3 and (b) mechanochemical atom transfer radical cyclization (ATRC) using BaTiO3 by ball milling

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

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

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• radical anions influenced by substituents in the cyclopropane ring are discussed. Optimization of the reaction conditions opens a route to the non-proteinogenic amino acid derivatives containing an α–β or β–γ double C=C bond in the side chain; the regioselectivity can be tuned by the addition of Lewis

• donor–acceptor substituents contribute to the rich chemistry of these compounds. However, strict requirements for the nature of substituents somewhat narrow the applicability of the method. The electrochemical one-electron opening of a cyclopropane ring results in the formation of an ion-radical species

• stereoselective functionalization has not been probed as yet. Herein, reductive three-membered ring opening in the chiral α,α-cyclopropanated amino acids involved in the Ni(II)–Schiff base coordination environment is reported. Follow-up transformations of thus formed radical anions will be discussed, including

Electro-conversion of cumene into acetophenone using boron-doped diamond electrodes

• Mana Kitano,
• Tsuyoshi Saitoh,
• Shigeru Nishiyama,
• Yasuaki Einaga and
• Takashi Yamamoto

Beilstein J. Org. Chem. 2022, 18, 1154–1158, doi:10.3762/bjoc.18.119

• propose a reaction mechanism (Table 2). First, we carried out the electrolysis of 1 in MeCN–MeOH to confirm whether the reaction intermediate is a radical or cationic species (Table 2, entry 1). As a result, methyl cumyl ether, a methoxy adduct to the benzyl position of 1, was obtained as the main product