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

• irradiation (Scheme 61). It was worth mentioning that longer reaction times and increased DIPEA loading were required owing to the inactivity of α-bromoketones, esters, and nonactivated sulfones; however, corresponding products could be given in high yield. When the DIPEA molarity was double that of

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• %) catalyst loading. Selected enantiomerically enriched sulfa-Michael addition products were subjected to oxidation to obtain the corresponding sulfones. Keywords: asymmetric synthesis; bifunctional catalysis; cinchona alkaloids; organocatalysis; sulfa-Michael reaction; Introduction Derivatives of the

• inhibitor activity [33]. Due to the shown biological attractiveness of those 1,3-biarylsulfanyl derivatives, the enantioenriched products can serve as important building blocks for new drugs. The sulfide moiety of β-naphthyl-β-sulfanyl ketones can be oxidized to form sulfones. Despite that sulfones were

• -Michael reaction. The low yields of the oxidation and the fluctuations in enantioselectivity compared to the starting sulfa-Michael adducts can be attributed to this unpreventable retro-reaction. Despite this setback, the target sulfones were obtained with moderate to good ee values. Conclusion In

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• alkynylation of cyclopropanes 161 with terminal alkynes that led to the formation of the isomeric fluorinated enynes 164 and 165. Shortly before, a Pd-catalyzed ring-opening sulfonylation of gem-difluorocyclopropanes with the formation of 2-fluoroallylic sulfones 166 has been reported (Scheme 71) [122]. The

• reaction of 2-(2,2-difluorocyclopropyl)naphthalene (167) with sodium arylsulfinates 168 under palladium catalysis afforded the 2-fluoroallylic sulfones 166 in moderate to good yields with (Z)-selectivity. This method showed a good compatibility with a broad range of substrates and substituents. As

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• iodides) [30][31] or by the direct photolysis of arylazo sulfones [38][39][40] and employed for the desired arylations. These reactions have the advantage of being applied to non-functionalized arenes but have the drawback to require a large excess of the nucleophilic reagent (the arene Ar–H) in up to 10

• the real extrusion of CO in diaryl ketones [48][49] or of SO2 in diaryl sulfones (Scheme 1c) [50]. Nevertheless, a recent publication demonstrated that a metal-free photoextrusion was feasible when starting from benzene sulfonamides I (Scheme 1d, path a) [51]. Following the same approach, sparse

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• initiate the chain reaction that produces the desired products 43 and 44 in excellent yields and enantioselectivities (15 examples, up to 97:3 er and 12 examples, up to 97:3 er, respectively). Subsequent progress using this methodology expanded the scope to the use of α-iodo sulfones 45, which is proposed

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• through an olefination reaction with benzothiazoyl sulfones (Scheme 1) [22]. With these fluoroalkylidene-oxetanes in hands, we studied the selectivity of ring-opening reactions with heteroatom nucleophiles in order to access tetrasubstituted fluoroalkenes. A control of the geometry of these reactions

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• , Ilkovičova 6, SK-842 15 Bratislava, Slovakia 10.3762/bjoc.16.152 Abstract A series of ten novel ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones bearing a 1-O-phosphono moiety and three different substituents at C-2 has been prepared. Due to the structural similarities of these scaffolds to the native

• originally suggested by molecular modeling having the 1-O-phosphate group stabilized by anomeric sulfones on the ᴅ-fructofuranose and ᴅ-tagatofuranose skeleton (1–3, Figure 1). Similarities in the TS structures of GnT-I and GlfT2 prompted us to examine these molecules against GlfT2, a possible target for the

• complex structure and also mimic its partial charges and charge distribution. Herein, the molecular docking, synthesis and inhibitory activity of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones 1–3 against GlfT2 are discussed. Moreover, we extended the scope of the simultaneous phosphorylation and

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• aromatic coupling partner, including frequently used Weinreb amides or functionalized secondary and primary amides. Regarding the scope of olefin substrates, the reaction tolerated numerous functional groups including acrylates, vinyl silanes or sulfones which was interesting from the post

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• desired trifluoromethylated products 7.3a–d in satisfactory yields (Scheme 7, path a) [57]. Tri-, di-, and monofluoroalkylated derivatives were also obtained by using fluoroalkyl heteroaryl sulfones [58] or sodium sulfinates (in the presence of persulfate) [59] as the alkylating agents. In an alternative

• lamp (280–780 nm), in a photocatalyst-free fashion [61]. Easily scalable and thermally stable arylthiodifluoromethyl 2-pyridyl sulfones were likewise exploited in the visible-light photocatalyzed arylthiodifluoromethylation of differently substituted isocyanides [62]. 6-Arylphenanthridines were

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• example, based on N-containing heterocycles (isoxazolones, pyrazolones, pyrazolidin-3,5-diones, and 1,2,3-triazolones [52]), sulfones [65], and phosphonates [54] (Scheme 8). Based on the data of EPR spectroscopy [35][38][49][50][66] and quantum chemical calculations [67], the maximum spin density in

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• reaction (Scheme 23) [100]. The alkynes 23.1 could be successfully converted to the vinyl sulfones 23.3 in the presence of the aryl sulfones 23.2 using eosin Y (OD13) as a photocatalyst. A tentative mechanism was proposed by the authors: under visible-light irradiation, the arylsulfinic acid could be

• desired vinyl sulfones. C–X radical anions and derived neutral radicals Amidst charged radical species, ketyl radicals play a central role in organic synthesis (Figure 3). As intermediates, they are more stable because the charge is mainly localized on the oxygen atom. They are postulated to be the

Accelerating fragment-based library generation by coupling high-performance photoreactors with benchtop analysis

• Quentin Lefebvre,
• Christophe Salomé and
• Thomas C. Fessard

Beilstein J. Org. Chem. 2020, 16, 982–988, doi:10.3762/bjoc.16.87

• of complex amines: bicyclopentanamines, azetidines, spiroazetidines, spiropyrrolidines and spiropiperidines. Functional group tolerance was probed by using functionalized building blocks bearing esters, carbamates, alcohols, tertiary amines, ethers, sulfones and fluorine atoms (Scheme 2 and Scheme 3

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• radical reenters the catalytic cycle. Various alkyl substituents on the cyclobutene ring, such as substituents bearing a chlorine atom, or silyl ethers were well-tolerated. However, bulky groups (e.g., TBDMS) led to lower yields. Methyl, ethyl, or aryl sulfones were all compatible with this methodology

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• decade later, Molander et al. made use of the same disilane as a source of the nucleophile for additions to α,β-unsaturated alkenes and alkynes as Michael acceptors bearing sulfones, nitriles, cyano, amido, and carboxyl ester groups to form β-silylated alkanes and alkenes in good to moderate yields [55

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• chlorides [20]. This ATRA reaction was carried out with various fluoroalkylsulfonyl chlorides, such as CFH2SO2Cl, CF2HSO2Cl, CF3SO2Cl, CF3CH2SO2Cl, and C4F9SO2Cl, electron-deficient alkenes, including α,β-unsaturated ketones, amides, esters, carboxylic acids, sulfones, and phosphonates (Scheme 4). In

• ) [25]. This copper-catalyzed photocatalytic reduction generated an aryl radical that was trapped with various allylating reagents. First, the phenyl radical generated from the corresponding diphenyliodonium salt was added to various allyl sulfones substituted in the 2-position. The products were

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• , and Grignard reagents to Michael acceptors. In that respect, since the pioneering example reported by Alexakis and co-workers in 1993 [5], a wide range of cyclic and acyclic electron-deficient alkenes, such as α,β-unsaturated ketones, esters, nitriles, sulfones, or nitroolefines, was intensively

• vinyl sulfones as electrophiles (Scheme 3). Of note, both the anti- and the syn-product could be predominantly formed (with a anti:syn ratio from 83:17 to 15:85), and no diastereocontrol occurred in the absence of the organocatalyst. Interestingly, this simple protocol was successfully applied to the

Fluorine-containing substituents: metabolism of the α,α-difluoroethyl thioether motif

• Andrea Rodil,
• Alexandra M. Z. Slawin,
• Nawaf Al-Maharik,
• Ren Tomita and
• David O’Hagan

Beilstein J. Org. Chem. 2019, 15, 1441–1447, doi:10.3762/bjoc.15.144

• compounds that are of commercial significance [8][9][10]. Metabolism studies in both of these cases show that the major metabolites are their corresponding sulfoxides (Ar–S(O)CF3) and sulfones (Ar–S(O)2CF3) [8][9]. Indeed, in the case of the insecticide fipronil it is actually the sulfoxide (Ar–S(O)CF3

• very active and outcompetes demethylation, however, that demethylation is significantly more active that the second oxidation of sulfoxides to sulfones. Incubation of naphthalene 5 with C. elegans, generated three new metabolites 11–13 which arose by oxidations at sulphur and hydroxylations of the

• analysed by 1H and 19F NMR before further purification by HPLC. Purification of the fluorometabolites The fluorometabolites (sulfoxides and sulfones) were isolated by reversed-phase HPLC using a Shimadzu Prominence (SIL-20A HT autosampler, CL-20AT ternary pump, DGU-20A3R solvent degasser, SPD 20A UV

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• University, Leninskie Gory, 1, 119991, Mosсow, Russian Federation 10.3762/bjoc.15.127 Abstract Functionally substituted sulfones with stereogenic centers are valuable reagents in organic synthesis and key motifs in some bioactive compounds. The asymmetric Michael addition of β-ketosulfones to conjugated

• ; Michael addition; nickel complexes; nitroalkenes; Introduction Sulfones are widely used in organic synthesis, particularly, in various reactions of C–C and C=C-bond formation [1][2][3][4]. The use of sulfones in Julia–Kocienski [1] and Ramberg–Bäcklund reactions [2] made this class of compounds

• cytotoxicity [9]. However, it is of great importance to obtain all stereoisomers for the study of biological activity. Therefore, the development of methods for the asymmetric synthesis of polyfunctional sulfones is valuable. The most notable of them are Ag- and Cu-catalyzed 1,3-dipolar cycloaddition reactions

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• forms. For example, aryl cyclopropyl sulfones have been used in the preparation of glucokinase (GK) activators for the treatment of type 2 diabetes [1][2][3][4][5] while aryl cyclopropyl sulfoximines have been utilized for the synthesis of modulators of glucokinase regulatory protein (GKRP) [6][7][8

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• ]. The dithioketal groups in the dM-Dmoc and Dmoc functions of 32 were then oxidized with a solution of sodium periodate at room temperature to give 33. The 5'-trityl tag survived the conditions. It should be pointed out that some sulfoxides might be further oxidized to sulfones, which should not affect

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• sulfonylation of teriary cyclopropanols 91 with sodium sulfinates 129 for the synthesis of γ-keto sulfones 130 in excellent yields (Scheme 34) [114]. The reaction was compatible with a series of fluoroalkyl, aryl and alkyl sulfinate salts. Notably, oxygen instead of THBP as oxidation was viable in this

Cross metathesis-mediated synthesis of hydroxamic acid derivatives

• Shital Kumar Chattopadhyay,
• Subhankar Ghosh and
• Suman Sil

Beilstein J. Org. Chem. 2018, 14, 3070–3075, doi:10.3762/bjoc.14.285

• CM-mediated synthesis of functionalized alkenes of various kinds continue to appear. For example, cross metathesis with acrylates [8][9][10], α,ß-unsaturated acid chlorides [11], acrylamides [12][13][14], vinyl sulfones [15], vinylphosphine oxides [16], vinyl phosphonates [17], enones [18], and

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• chemistry. The formation of the thioether is also quite interesting, due to the possibility of accessing sulfones, which are abundant in drugs and drug-like molecules. The scope of the reaction covers the basics in terms of substituents on both reactants and investigates various substitution patterns. Most

• the modified substituted imidazo[1,2-a]pyridines contains scaffolds commonly found in pharmaceuticals, such as sulfones 9a and trifluoromethyl groups 9b. Hence, this publication provides an easy route to access scaffolds with diverse aromatic systems, allowing for the construction of interesting

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• . The same group has then developed a radical method to access the corresponding sulfones from cyclic diaryl-λ3-iodanes (Scheme 33) [73]. The reaction is catalyzed by a 1,10-phenanthroline-copper complex and affords the dibenzothiophene-5,5-dioxides 76 in moderate to high yields. The transformation has

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• . General concepts, synthetic strategies and the substrate scope of reactions yielding thiols, disulfides, sulfoxides, sulfones and other organosulfur compounds are discussed together with the proposed mechanistic pathways. Keywords: disulfides; photocatalysis; sulfones; sulfoxides; thiols; visible light

• of allyl and vinyl sulfones In 2015, our laboratory reported the first metal-free visible-light photoredox-catalyzed method for the preparation of vinyl sulfones from the respective aryl sulfinate salts (Scheme 42a) [77]. Eosin Y was applied as photocatalyst to produce a diverse scope of vinyl

• sulfones. For styrene derivatives, the solvent had to be changed from ethanol to a mixture of DMF/H2O as the nucleophile ethanol leads to a byproduct formation. The reaction proceeds via oxidative quenching of the photoexcited state of Eosin Y by nitrobenzene to generate the Eosin Y radical cation. In