Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• space group P212121. The presence of sulfur anomalous scatters allowed to unequivocally establish the absolute configurations, which reads S at the chiral center C2 and R at the C10 (C numbering as in Figure 1). The absolute configuration of the two sulfur stereogenic centers is confirmed to be R

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• spectroscopy (Scheme 3h). Formation of 4a could have occurred from the direct reaction of the N–H nitrogen of 3a with NFSI, which would agree with the propensity for NFSI to react with some hard oxygen and nitrogen nucleophiles at the sulfur atom instead of at the fluorine atom [39][40]. Similarly, NFSI has

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• naturally occurring HDAC inhibitors contain sulfur moieties like, e.g., disulfides or thioesters. They seem to lack a zinc-chelating group at first sight, but the disulfide or thioester acts as a prodrug and are reduced/cleaved in vivo to liberate the free thiol, a strong Zn-binding group [24][25]. Results

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• . The solvolyses of these additional types of sulfur(VI) substrates will be the topics of a future review. Keywords: correlation; Grunwald–Winstein equation; Hammett equation; mechanism; solvolysis; sulfonyl halides; Review 1. Introduction to solvolyses of sulfonyl halides In medicinal chemistry

• to synchronous bond-making and bond-breaking, with a small negative charge development on the sulfur at the transition state, for the solvolytic process. Subsequent to this 1927 study, Hammett reported [5][6] in 1937, the development of the Hammett equation, involving the consideration of a scale

• changes observed as the water content increased were consistent with an SN2 reaction becoming a mixed SN2–SN1 situation and then, eventually, an essentially SN1 pathway was followed. It was concluded that nucleophilic attack at sulfur has many of the characteristics of attack at carbon, including the

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• methyl ethyl ketone (MEK) was as effective. In addition, in situ-generated α-bromo-δ-valerolactone was directly converted into a sulfur-substituted functional lactone without difficulty by reacting it with a sulfur nucleophile in one pot without isolation. This new bromination system is expected to

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• ligands that could coordinate several metal centers with the aid of sulfur, nitrogen or oxygen donor atoms that allow multiple bindings [13]. Moreover, compounds bearing a –C(O)NHC(S)– moiety and their metal complexes have assorted biological and pharmacological properties such as anti(myco)bacterial

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• sulfur atom at the 3’-position, these compounds have proved to be structurally potent nucleoside analogues, and the best example is BCH-189. The majority of methods traditionally involves the chemical modification of nucleoside structures. It requires the creation of artificial sugars, which is

• sulfur atom instead of C-3', and an unnatural ʟ-configured sugar [20]. The presence of oxygen as a second heteroatom in the sugar ring was also found to result in anti-HIV activity in 1,3-dioxolane nucleosides [21]. A good example for the preparation of 2’,3’-dideoxy-3’-oxacytidine in a stereospecific

• reverse transcriptase [25]. Nucleosides with sulfur atom-containing heterocyclic sugar rings at the 3’-position are important pharmaceutical substances. Two well-known important molecules in this category are lamivudine (1) and emtricitabine (2), as shown in Figure 1. It was found that there is a

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• Michael additions of aldehydes to nitroalkenes both under solvent-free conditions and in solution. The N-sulfinylurea catalyst was more efficient than the corresponding thiourea. For some substrates, enantioselectivities reached 98% ee. The stereogenic center on the sulfur did not have a considerable

• acidity of the hydrogen-bond donating unit. This notion has often been realized with substituted aryls such as 3,5-bis(trifluoromethyl)phenyl. Ellman introduced a different approach and developed N-sulfinylureas. An additional potentially useful feature is the stereogenic center on sulfur. tert

• unit, which should engage in enamine activation of enolizable carbonyl compounds. The urea or thiourea moiety shall provide hydrogen-bond donating ability. Furthermore, these compounds possess a sulfinyl group with an additional stereogenic center on the sulfur. To verify the influence of a matched

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• [57][58][59][60][61][62][63][64][65]. Results are summarized in Table 2. Triphenylphosphine and triethyl phosphite could be used interchangeably in the sulfur extrusion step. However, in most cases the co-elution of enaminones 15 with phosphorus-derived byproducts during chromatographic purification

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• nucleophile and the alkyl or aryl radicals. From 2013 to 2019, the authors disclosed a series of nitrogen, sulfur, oxygen, and carbon nucleophiles for photoinduced, copper-catalyzed cross-couplings with organic halides. The copper–nucleophile complexes that were generated in situ as photoredox catalysts

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

• -promoted double bond migration. The cyclopropyl functionality in 46 can be assembled from the reaction of sulfur ylide and the α,β-unsaturated ketone 47, which in turn can be realized from the cross metathesis between commercially available ethyl vinyl ketone (48) and the C2-symmetrical diene-diol 49. The

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• frameworks 57 were accessed in excellent yields up to 93% and enantioselectivities up to 94% ee. Increased aromaticity proved again to be essential for achieving high enantioselectivities. Additionally, Lewis base activation of the allylsilane substrates through the thiourea sulfur atom is proposed to be

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