Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• sulfur-containing fluorinated groups. Although the transition-metal-catalyzed direct C–H bond functionalization appeared to be a powerful tool for the installation of C–C, C–N, or C–O bonds, the direct formation of a C(sp2)–SRF or a C(sp3)–SRF bond remains a challenging task. In this context, key players

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

• synthesis of combretastatin D-1 (1) using the flash vacuum pyrolysis (FVP) technique, which consisted on the contraction of 16-membered sulfone derivatives, by extrusion of sulfur dioxide [58]. The synthesis of the required sulfone was initiated by a Horner–Wadsworth–Emmons reaction between the aldehyde 52

Synthesis and reactivity of azole-based iodazinium salts

• Thomas J. Kuczmera,
• Annalena Dietz,
• Andreas Boelke and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 317–324, doi:10.3762/bjoc.19.27

• both C–I bonds giving the iodinated N-arylbenzimidazoles 6a and 6b as a mixture with 54% and 25% yield [37]. A ring opening/closing cascade reaction with elemental sulfur resulted in the formation of the imidazo[4,5,1-kl]phenothiazine (7a) in 47% yield. The corresponding phenoselenazine 7b and the

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

• -tethered thioamide and amide conjugates. The thioamides were generated by employing a three-component reaction of diverse pyrazole C-3/4/5 carbaldehydes, secondary amines, and elemental sulfur in a single synthetic operation. The advantages of this developed protocol refer to the broad substrate scope

• ; pyrazole carbaldehydes; sulfur insertion; thioamides; Introduction During the past years, the significance of pyrazole chemistry has been notably escalated which is attributed to the discovery of their amazing biological properties. Among the heterocyclic molecules, pyrazoles are considered as privileged

• product isolation procedures [58][59][60][61][62]. In the recent past, our group also reported two methods towards the exploration of elemental sulfur for the formation of a sulfur-containing framework; however, these methods suffer from some drawbacks such as lack of diversity in starting substrate, need

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

• and carbohydrates to various carbocyclic scaffolds. This versatility arises from the possibility to chemoselectively cleave or reduce the sulfur-heterocycle to reveal a versatile C2-synthon. Keywords: 1,4-dithianes; 1,4-dithiins; 2,3-dihydro-1,4-dithiins; heterocycles; target synthesis; Introduction

• rapid build-up of target molecules (see Scheme 1a) [7]. Once the important skeletal carbon–carbon bonds have been formed around the thioketal carbon, the sulfur-heterocycle can perform its primary function as a temporary protecting group and be chemoselectively hydrolyzed to afford a carbonyl functional

• group. Alternatively, the carbon–sulfur bonds can be chemoselectively hydrogenolyzed to reveal a methylene moiety. Since their introduction into synthesis by the work of Corey and Seebach [1], the use of 1,3-dithianes as powerful C1-synthons has significantly expanded from this original strategic scheme

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

• , protection of the secondary alcohol as a benzyl ether, oxidation of the sulfur and Pummerer rearrangement (Scheme 3). A Wittig reaction gave compounds 8, as a 10:1 separable diastereomeric mixture. A diastereoselective Diels–Alder cycloaddition followed by oxidation of the resulting epimeric mixture gave

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• ] which underwent aromatization with the loss of sulfur dioxide and N-Boc-aniline. The multicomponent character and the fairly large scope of this reaction allows to place pairwise reactive groups in the aldehyde and the amine components, which would set a scene for further elaboration of the product’s

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• reactions with elemental sulfur [23][24][25], resulting in the generation of non-enolizable imidazole-2-thiones. At first, the alkylation of 2-unsubstituted imidazole N-oxides 40 took place in the presence of an equimolar quantity of benzyl bromide in CH2Cl2 at rt providing the (N-benzyloxy)imidazolium

• salts 41. The latter underwent deprotonation in the presence of triethylamine in pyridine to generate the carbene intermediates 42 (Scheme 9). After that, the optically active imidazole-2-thiones 43 were obtained through the reaction with elemental sulfur. In CHCl3 solutions, the study of the optical

• followed by the treatment of elemental sulfur, through the formation of the optically active intermediate N-butoxyimidazol-2-ylidenes 46 (Scheme 10). Conclusion Although there is a limited number of reports for synthetic approaches using imidazole N-oxides as substrates, the procedures are highly diverse

Comparison of crystal structure and DFT calculations of triferrocenyl trithiophosphite’s conformance

• Ruslan P. Shekurov,
• Mikhail N. Khrizanforov,
• Ilya A. Bezkishko,
• Tatiana P. Gerasimova,
• Almaz A. Zagidullin,
• Daut R. Islamov and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1499–1504, doi:10.3762/bjoc.18.157

• phosphines, a relatively small number of trivalent phosphorus derivatives has been used to construct multiferrocene compounds. The use of ferrocene derivatives containing a phosphorus–sulfur bond is a promising direction, since coordination with a metal atom can occur both at the phosphorus and sulfur atoms

• [7]. It is important to know the conformational capabilities of such ligands for construction of such complexes [8][9][10][11]. However, to date, XRD data on phosphorus derivatives containing a ferrocenyl substituent at the sulfur atom are presented only in oxidized and sulfurized forms

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• isomerization with the elimination of the sulfur-and-bismuth moiety. Aminophenol then reacts with D to generate intermediate F via E, which is converted to the benzoxazole 8, accompanied by the elimination of 19 by aromatization. The generation of hydrochloric acid was important in this reaction, and the

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• ]. Based on the fact that the cis-configuration between the sulfur and the pivalate was absolutely required for enantioselectivity, an interaction between both the sulfur and pivalate carbonyl oxygen with the hydrogen of Hantzsch ester's NH was proposed (Scheme 5). Thus, rather weak interactions might

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

• produce α-iodo ketone with the molecular I2 produced by anodic oxidation. Subsequently, the nucleophilic substitution between intermediate 4 and thiourea tautomer gives α-sulfur substituted ketone 5. Intermediate 5 undergoes intramolecular nucleophilic addition to the carbonyl group and followed by

Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• -phosphaindolizines having an EWG at the 3-position only, namely 3-ethoxycarbonyl-1-methyl-2-phosphaindolizine (1: R1 = Me, R2 = COOEt) did not undergo the DA reaction with DMB alone or in the presence of sulfur even when refluxing in toluene [12]. The reaction could be accomplished only in the presence of a Lewis

• of 1-aza-2-phosphaindolizines 3 with DMB and isoprene occurred at rt, although slowly and were speeded up by the use of sulfur or selenium which oxidized the phosphorus atom of the initially formed product thereby pushing the reaction in the forward direction [14]. The difference in the reactivities

Mechanochemical bottom-up synthesis of phosphorus-linked, heptazine-based carbon nitrides using sodium phosphide

• Blaine G. Fiss,
• Georgia Douglas,
• Michael Ferguson,
• Jorge Becerra,
• Jesus Valdez,
• Trong-On Do,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2022, 18, 1203–1209, doi:10.3762/bjoc.18.125

• ; Introduction The development of heteroatom-doped graphitic carbon nitrides (g-CN) has been a rapidly growing area of research since their first report towards water splitting in 2009 [1]. Since that time, the addition of elements such as boron [2], phosphorus [3][4][5], sulfur and oxygen [6] have shown to help

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

• nucleophilic functionalization of the double bond of the dehydroalanine derivatives formed after the reductive ring opening and subsequent protonation. Such an approach opens a route to double functionalization of the amino acids side chain. Insertion of the sulfur-containing fragments is of special interest

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• colleagues reported in 2000 that the reaction between a Michael acceptor such as diethyl fumarate and a sulfur-ylide, prepared from ethyl 2-diazoacetate and tetrahydro-2H-thiopyran in the presence of Cu(acac)2, yielded triethyl cyclopropane-1,2,3-tricarboxylate in 68% yield (Scheme 1, reaction 1) [10]. The

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• from the anodic electroactivity of the electrogenerated carbene. In order to have NHC accumulation in the catholyte, the Nafion membrane (cell separator) was pretreated with an alkaline solution. The formation of NHC was quantified as its reaction product with elemental sulfur. The NHC was successfully

• NHCs are generated in situ, where they may be used as basic or nucleophilic species. Due to the difficulty isolating highly reactive NHCs, the concentration of the obtained NHC solution can be determined indirectly by addition of elemental sulfur after the electrolysis, which realizes quantitative

• . Firstly, the conditions for electrogeneration of the carbene in flow were optimized, quantifying the amount of NHC by means of its reaction with elemental sulfur. All the experiments were carried out using a 0.1 M solution of BMImBF4 in acetonitrile as catholyte in a divided cell using Nafion® 438

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

• pairs of sulfur atoms. In the CV of DBC-Br, a one-electron redox was observed as a reversible process, but a second redox process was not observed (Figure 2d). On the other hand, both the first and second oxidation processes were observed in the SWV of DBC-Br (Eox1 and Eox2 are 0.79 V and 1.15 V

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

• , we published a series of ‘bent’ diindenodithienothiophene derivatives (2–4, Figure 2) [16]. It was observed that oxidising the central sulfur atom significantly increased the solution photoluminescence quantum yield (PLQY) from 0.004 (3) to 0.72 (4). The diketo derivative 5 of compound 2 has been

• all the sulfur atoms of the DTT core and the electron-withdrawing [20] keto groups. The LUMO is presented strongly in the seven fused rings, but is poorly represented in the outer ethylhexylthiophenes, which are electron-rich and twisted out of plane. The LUMO is strongly localised at the electron

• -deficient keto groups. Interestingly, neither the HOMO, nor the LUMO, is present at the central sulfur atom of the DTT motif. Organic field-effect transistors To estimate the charge carrier mobility from the saturation regime of the current–voltage plot, bottom gate/bottom contact (BG/BC) OFETs [76][77

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

• )(phenyl)phosphinate (53) was reduced with lithium aluminum hydride to 2-aminobenzyl(phenyl)phosphine (57). It was oxidized with sulfur to give zwitterionic 2-aminobenzyl(phenyl)dithiophosphinic acid (58), which underwent thermal elimination of hydrogen sulfide to yield 2-phenyl-1,3-dihydrobenzo[d][1,2

• )phosphine (57) with two atom-equivalents of sulfur in refluxing benzene, affording the zwitterionic 2-aminobenzyl(phenyl)dithiophosphinic acid 58 in 80% yield. It was converted to 2-phenyl-1,3-dihydrobenzo[d][1,2]azaphosphole 2-sulfide (59) in 91% yield by heating at 100–120 °C under vacuum (Scheme 10) [30

• peroxide and sulfurization with sulfur, respectively (Scheme 16) [37][38]. Synthesis via formation of the C–C bond neighboring at the ring phosphorus atom In 1984, Collins and co-workers attempted the synthesis of benzo-γ-phosphonolactams 56a and 93 from (chloromethyl)(phenyl)-N-methyl-N

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

• , regioselective double oxidative photocyclization was observed during the construction of three S-shaped double helicenes DH-1–3 based on thiophene/selenophene. From DH-1 to DH-3, sulfur atoms in the molecular framework were gradually replaced by selenium atoms. The crystal structures of DH-1 and DH-2 and

• )2-bb-DSS, the notation bb means that the positions of the heteroatoms of the outer two heterocycles are on the same side as those of the middle heterocycle. Taking dithienothiophene as example, according to the positions of sulfur atoms, there are six isomers of dithienothiophene, in which the

• sulfur atoms on the same side is defined as bb by us. The double Wittig reaction of 4a and 4b with 1,3-phenyldimethyltriphenylphosphonium bromide afforded compounds 5a and 5b with yields of 46% and 64%, respectively. After the double Wittig reaction of 4c we obtained a mixture of cis and trans isomers of

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

• , while other synthetic approaches were explored to obtain these reagents, the SN2 strategy described in this work was the most efficient. Such synthetic alternatives included: first, a sulfur(VI) fluoride exchange (SuFEx) between perfluoroalkylsulfonyl fluorides and the corresponding silyl enol ether

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• Martin Posta Vaclav Zima Lenka Postova Slavetinska Marika Matousova Petr Beier Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Flemingovo nám. 2, 16610 Prague 6, Czech Republic 10.3762/bjoc.18.57 Abstract The only known sulfur-containing karrikin, 3-methyl-2H-thiopyrano[3,4

• oxygen with sulfur. In particular, we present synthetic procedures toward bioisosteres of karrikins with one or two sulfur heteroatoms incorporated into the core backbone together with evaluation of their biological activity in inhibition of acetylcholinesterase. Keywords: acetylcholinesterase

• ; butenolides; karrikin; sulfur; Introduction Neurological disorders, especially the Alzheimer’s and the Parkinson’s diseases represent a serious problem for elderly populations worldwide. Studies of these neurodegenerative diseases led to the discovery of a deficit of acetylcholine and dopamine levels in the

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• . Interestingly, the oxidation of the sulfur atom in pyrazole 9d (EC50 = 1.1 ± 0.04 µM) improved the antimalarial activity by a factor of more than three (sulfoxide 10d, EC50 = 0.3 ± 0.01 µM). In our experiments we used the established antimalarial drug amodiaquine as control. As shown in Table 1, the EC50 of

Substituent effect on TADF properties of 2-modified 4,6-bis(3,6-di-tert-butyl-9-carbazolyl)-5-methylpyrimidines

• Irina Fiodorova,
• Tomas Serevičius,
• Rokas Skaisgiris,
• Saulius Juršėnas and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 497–507, doi:10.3762/bjoc.18.52

• -bonded phenyl substituents (compounds 2a–d) are almost coplanar with the pyrimidine core (dihedral angle 0.5–1.5°), while a phenyl group connected with the pyrimidine ring via a sulfur atom (compounds 5 and 6) is twisted out of the pyrimidine plane and is not conjugated with the pyrimidine ring. Despite