Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• discovered the synergistic combination of nickel catalysis and benzaldehyde for the arylation of C(sp3)–H bonds adjacent to nitrogen or sulfur in amides 6 and thioethers 28, respectively, under UVA light irradiation [68]. As shown in Scheme 16, both primary and secondary C(sp3)–H bonds of amides were

• irradiation with UVA light enabled the cross-coupling of α-oxy C–H bonds of acyclic/cyclic ethers 9 with alkyl bromides 40 (Scheme 24) [86]. The catalytic system was not limited to α-oxy C–H bonds of cyclic ethers, substrates having other heteroatoms such as nitrogen and sulfur that can imbue a hydridic

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• , nitrogen, oxygen, silicon, phosphorus, sulfur, selenium, and tellurium. This review will skip the reports on the corresponding carbon-centered analogs. Boranes First discovered in 1894 [34], 2,2’-bisarylborinates are used for treating prostate cancers utilizing their property of inhibiting the transient

• -atom (80, Scheme 9b) [66]. A similar protocol was adopted by van de Watering in their recent syntheses [67][68]. Sulfides The C2 tethering of indoles with sulfur can be achieved in neutral medium by treatment with various SL2 (L is a leaving group) moieties [69][70]. This is a common method for the

• synthesis of bis(indol-2-yl)sulfides which are the precursors of potent bioactive molecules [71][72][73]. The simple synthetic strategies for the molecular units 82 were first reported by Barbier in 1989. The condensation of tryptamine monoacetate (81a) or indole oxime (81b) with sulfur dichloride in a

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• direct access to several sulfur-containing pharmacological compounds that present valuable biological activities, such as anti-HIV (9) [51], inhibition of snake venom enzymes (10) [52], or even anti-estrogenic effects (11) [53] (Scheme 4A). Recently, Hou and co-workers also explored the utility of a

Cerium-photocatalyzed aerobic oxidation of benzylic alcohols to aldehydes and ketones

• Girish Suresh Yedase,
• Sumit Kumar,
• Jessica Stahl,
• Burkhard König and
• Veera Reddy Yatham

Beilstein J. Org. Chem. 2021, 17, 1727–1732, doi:10.3762/bjoc.17.121

• -dichlorobenzaldehyde (2w) in 70% yield. The sulfur-containing compounds 4-(phenylthio)benzyl alcohol (1r) and the heterocyclic compound thiophene-2-ylmethanol (1x) gave the corresponding aldehydes 2r and 2x in 61 and 80% yield, respectively. Finally, 2-naphthylmethanol (1y) was subjected to the reaction conditions and

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• recent studies show that J can be further optimized. Chen and co-workers reported that substitution of oxygen-4 of J with sulfur improved the Hoogsteen binding properties of 4-thiopseudoisocytosine (L, Figure 6) [98]. UV thermal melting and gel electrophoresis studies showed that L formed more stable L•G

• sulfur modification removed the undesired ability of J to form a Watson–Crick base pair with G in single-stranded nucleic acids. This is important for avoiding off-target binding to single-stranded RNA and DNA in biological systems. L appears to be a promising improvement of J as a neutral analogue of

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• achieved by a tautomerization process. A highly decorated 1,2,3-triazole 11 was formed via cyclization of the intermediate 17 along with the loss of one molecule of TsNH2 [41]. Fully decorated 1,2,3-triazoles 19 containing a sulfur-based side chain have been synthesized via a cyclization of β-thiolated

• . Finally, a reductive elimination takes place to give the corresponding final product and the catalyst for the next run [51]. A tandem Click/intramolecular sulfenylation procedure for the synthesis of sulfur-cycle-fused 1,2,3-triazoles 75 and 77 was described by Xu et al. The reaction was performed through

• -membered sulfur-containing cycle (Scheme 23) [52]. Some reactions were performed to screen the reaction mechanism in detail. To find out if the reaction proceeds through a radical pathway, tetramethylpiperidine-1-oxyl (TEMPO) was added to the reaction. The corresponding product was obtained in high yield

Recent advances in the application of isoindigo derivatives in materials chemistry

• Andrei V. Bogdanov and
• Vladimir F. Mironov

Beilstein J. Org. Chem. 2021, 17, 1533–1564, doi:10.3762/bjoc.17.111

• possibility of varying optoelectronic properties, and good solubility in a wide range of solvents [59][60][61]. In this regard, the most studied and promising are π-conjugated polymer structures based on sulfur, oxygen, nitrogen, and selenium heterocyclic compounds [62][63]. One of the systems for creating

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• more general route to [2.2]metaparacyclophane (3) derivatives involves synthesis of 2,11-dithia[3.3]metaparacyclophane followed by the extrusion of sulfur, or more commonly sulfur dioxide, and this has become the de facto route to these molecules [25][37][38][39][40][41][42][43]. Even though this

• but these are substrate specific [71][72]. Conclusion Currently, substituted [2.2]metaparacyclophanes are synthesized through a long sequence involving either high temperature extrusion of sulfur dioxide or photoextrusion of sulfur. We have found a serendipitous route to a disubstituted [2.2

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

• results of HGCM-vTA are exhibiting a sulfur content allocation in accordance with the nitrogen atom distribution in a fair amount of abundance (Figure 2b). Determination of the sulfur content is a facile approval for the surface modification as neither monomers nor g-CN from HGCM are possessing a sulfur

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• dienolate reacted at α-position with the chiral imine 14. The addition was highly diastereoselective, being the configuration of the newly created stereogenic center dependent on the configuration of the sulfur atom of the starting imine 14. After nucleophilic addition, and subsequent elimination, 3

• the Re face of the imine with S configuration at the sulfur atom, through a chelated transition state. The reaction of chiral aldimine (SS)-104b with pentylmagnesium bromide gave compound 106 in 75% yield. Further successive N-desulfinylation, intramolecular palladium-catalyzed N-arylation, and final

• influence on it the configuration of the sulfur atom of the sulfinyl unit. This methodology was applied to the asymmetric synthesis of (−)-CP-99,994 (128), the enantiomer of a promising clinical agent which displays a variety of biological activities, including neurogenic inflammation, pain transmission

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• , Riga, LV-1006, Latvia Department of Chemistry, University of Latvia, Jelgavas str. 1, Riga, LV-1004, Latvia 10.3762/bjoc.17.78 Abstract Liquid SO2 is a polar solvent that dissolves both covalent and ionic compounds. Sulfur dioxide possesses also Lewis acid properties, including the ability to

• during the glycosylation with glycosyl fluorides in liquid SO2 is proved by 19F NMR spectroscopy. A sulfur dioxide-assisted glycosylation mechanism that proceeds via solvent separated ion pairs is proposed, whereas the observed α,β-selectivity is substrate-controlled and depends on the thermodynamic

• equilibrium. Keywords: fluorosulfite; glycosyl fluoride; Lewis acid; liquid sulfur dioxide; metal-free glycosylation; Introduction The glycosylation reaction is still one of the most important and basic synthetic strategies in carbohydrate chemistry that provides access to the various types of

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• phosphorothioate Rp-stereoisomer (Rp-PS, i.e., phosphate with one of the non-bridging oxygens replaced by sulfur) in bacterial genomes, where it may serve a protective role against nucleases [4] and its loss results in genomic instability [5]. There are over a hundred known base modifications in RNA and the Rp-PS

• monobenzoylethanedithiol. The 3'-phosphorothioamidites are incorporated into an oligonucleotide by standard solid-phase synthesis conditions, however, the oxidation step is replaced with sulfurization by elemental sulfur (Scheme 2) [85]. It should be noted that more efficient sulfurization agents exist with faster

• in the vicinity of a hydrophobic patch that is surrounded by lysine and arginine residues [15]. The latter generate an electric field that could polarize sulfur atoms (the PS2 group still carries a negative charge), thereby enhancing the interaction of the PS2 moiety with the edge of phenylalanine as

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• was complete, sulfur (3 equiv) was added under inert atmosphere and then the mixture was stirred at 60 °C for 6 h to provide the stable adduct 3. The purification of the products was performed by silica gel column chromatography using isohexane/MeOAc as an eluent. Radical addition of Ph2PPPh2 and Ph2P

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• ; thioamide; thionation; Introduction The transformation of a carbonyl into a thiocarbonyl group is one of the most important reactions in organic synthetic chemistry [1]. Lawesson’s reagent (LR) is widely applied in this transformation, as well as for the syntheses of various sulfur-containing heterocyclic

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

• of N-heterocyclic compounds. In 2017, Wu and colleagues [58] uncovered the use of the bis(sulfur dioxide) adduct of DABCO, 1,4-diazabicyclo[2.2.2]octane·(SO2)2, as sulfone source in the EDA complex formation by 4-methyl-1-(p-tolyl)pentan-1-one O-(2,4-dinitrophenyl)oxime (11) towards the

• atom transfer) occurs in nitrogen radical 14 to give radical 16, which further transforms to radical 17 after the addition of sulfur dioxide. Finally, HAT happens between 15 and 17, yielding quaternary ammonium salt 18 and product 12, respectively. In 2017, Chen and colleagues [47] accomplished the

Synthesis, structural characterization, and optical properties of benzo[f]naphtho[2,3-b]phosphoindoles

• Mio Matsumura,
• Takahiro Teramoto,
• Masato Kawakubo,
• Masatoshi Kawahata,
• Yuki Murata,
• Kentaro Yamaguchi,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2021, 17, 671–677, doi:10.3762/bjoc.17.56

• phosphorus atom of 2 was carried out; the results are shown in Scheme 1. The reaction of 2 with hydrogen peroxide or elemental sulfur afforded the corresponding phosphine oxide 3 and sulfide 4 in 92% and 88% yield, respectively. Treatment of 2 with methyl triflate afforded phospholium triflate 5 in 81% yield

• (Figure 4). The HOMO and HOMO−1 levels of oxide 3 are delocalized in the π orbitals of the benzonaphthophosphoindole skeleton, while HOMO−2 and HOMO−3 have a large contribution from the lone-pair and π orbitals. In sulfide 4, the sulfur analog of the oxide 3, the HOMO and HOMO−1 energy levels are

• delocalized in the lone-pair orbitals on the sulfur atom, resulting in considerable destabilization and significantly small HOMO–LUMO gap compared to those of other phospholes 2, 3, 5, and 6. This result is similar to the reduction potentials of compounds 2 and 6. According to time-dependent DFT calculations

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• -(allylmethylsulfonio)propanoate (AllMSP), were synthesized and fed to marine bacteria from the Roseobacter clade. These bacteria are able to degrade DMSP into dimethyl sulfide and methanethiol. The DMSP analogues were also degraded, resulting in the release of allylated sulfur volatiles known from garlic. For unknown

• (Scheme 1A) [2]. The antibacterial principle in garlic was identified in 1944 by Cavallito et al. as allicin (5) [3], a formal oxidation product of disulfide 2. Not only 5, but also several other sulfur compounds from garlic are today known to exhibit diverse biological activities, including inter alia

• antibacterial, antifungal, antioxidant, anti-inflammatory, and anticancer effects [4]. Later on, also heterocyclic compounds including 2-vinyl-4H-1,3-dithiine (6) and 3-vinyl-3,4-dihydro-1,2-dithiine (7) were discovered [5]. The formation of these volatile sulfur compounds starts from alliin (9) [6], a non

Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• in natural products, drug molecules, biologically active molecules, and functional materials. However, the highly selective incorporation of two different sulfur-bearing moieties across double bonds remains challenging [42]. Herein, we describe a visible-light-enabled cascade radical

• -induced cascade radical difunctionalization of unactivated alkenes to provide partially trifluoromethylated dithioethers. The approach features practical conditions, good functional group tolerance, and a broad substrate scope allowing the incorporation of two distinctive sulfur-containing motifs into

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• high amounts of the undesirable isoindigo 9a [32] (route c). In order to accelerate the Eschenmoser coupling reaction and to enhance the reaction yield (route b) an addition of a suitable thiophile assisting the sulfur extrusion should be beneficial [36]. Therefore, we tested two P(III) compounds as

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• phosphonodepsithioxopeptides 198 via the reaction of N-protected aminoalkylphosphonochloridites 196 with the hydroxy ester (S)-106b followed by sulfur oxidation. They first transformed the N-Boc-protected 1-aminoalkylphosphinate 195 to the corresponding phosphonochloridite 196 with dichlorotriphenylphosphorane. The

• phosphonochloridite 196 was then further reacted with methyl (S)-lactate ((S)-106b) followed by sulfurization with sulfur, affording the phosphonodepsithioxopeptide 198 in a one-pot activation–coupling–oxidation procedure (Scheme 36) [55]. Although it was mentioned that the phosphonochloridites were a more active

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• effect on the yield of the reaction of 1g (Table 2, entries 3–6, 58–72%). Next, a range of common oxygen and sulfur-containing compounds such as furan, tetrahydrofuran, 1,4-dioxane, thiophene, benzo[b]thiophene, dibenzo[b,d]thiophene, and diphenylsulfane were also screened. These substances also have

Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• , Inhoffenstraße 7b, 38124 Braunschweig, Germany 10.3762/bjoc.17.38 Abstract The volatiles emitted from six marine Rhodobacteraceae species of the genus Celeribacter were investigated by GC–MS. Besides several known compounds including dimethyl trisulfide and S-methyl methanethiosulfonate, the sulfur-containing

• compound is likely of anthropogenic origin, because 2-mercaptobenzothiazole is used in the sulfur vulcanization of rubber. Also in none of the feeding experiments incorporation into ethyl (E)-3-(methylsulfanyl)acrylate could be observed, questioning its bacterial origin. Our results demonstrate that the

• Celeribacter strains are capable of methionine and DMSP degradation to widespread sulfur volatiles, but the analysis of trace compounds in natural samples must be taken with care. Keywords: GC–MS; isotopes; Roseobacter; sulfur metabolism; volatiles; Introduction Bacteria from the roseobacter group belong to

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• /cycloaromatization sequence (Scheme 3a, route a). Thus, hetero[4]-, [5]-, and [6]helicenes involving an oxygen, sulfur, or nitrogen atom were efficiently synthesized (Scheme 6). Hetero[4]helicenes 9 were synthesized via coupling of 3-bromobenzoheteroles 10, prepared from commercially available benzoheteroles, and

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• . This observation suggests that lutidine allows the isomerization of 90 into 93, followed by a nucleophilic attack of the solvent at the sulfur atom (Scheme 25). The reactivity of analogous monotrifluoromethyl-substituted allyl derivatives 94, bearing an aryl group in the vinylic position was also

• treatment with strong Lewis acids (best with AlCl3) [139]. In this case, the only product formed in the course of the reaction was 205, isolated in 83% yield (Scheme 50). The proposed cationic intermediate in this reaction is a sulfur-stabilized α-(trifluoromethyl)carbenium ion 206 (an α-(trifluoromethyl

• )-substituted sulfonium cation). Analogous to thioacetals 204a, chloroalkylthio derivatives 207a–c, bearing an adjacent CF3 group, were also investigated [140]. It appeared that a sulfur-stabilized α-(trifluoromethyl)carbenium ion 208 can be generated from 207a by chloride abstraction following Lewis acid