Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• ). Access to allylic alcohol 8 was also achievable (55%, E/Z = 56:44) in a tin-free process using a sulfonyl leaving group, via α-lithiation of sulfone 15 [18] and in the presence of LTMP (Scheme 7). γ-Hydroxysulfone 16 was formed competitively (44%, dr = 50:50), by direct addition of the lithiated sulfone

• epoxide 5. Synthesis of vinylsilane 14. Allylic alcohol 8 from epoxide 5 and sulfone 15. Allylic amines from aziridine 17. Cyclopropylidene synthesis from aziridine 20. Cinnamylamine 23 synthesis from aziridine 17. Cinnamylamine 23 synthesis from isopropyl or neopentyl benzylic ethers 26 and 27

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• triarylphosphines TPP, MMTPP and TMTPP as catalysts for the oxa-Michael reaction three varyingly strong Michael acceptors, namely acrylonitrile (1), acrylamide (2) and divinyl sulfone (3) were reacted with four different alcohols of similar molecular mass but different acidity (Figure 1). The stoichiometry of

• , the difunctional divinyl sulfone was tested as the strongest Michael acceptor (E = −18.36, for phenyl vinyl sulfone [19]) under investigation. In distinction from the experiments described above, three equivalents of the alcohol were used. In general, the different catalysts perform very similar in

• this reaction giving high double-bond conversions of about 80% after already 1 h [26]. A mixture of mono- (3monoa–d) and di-adducts (3dia–d) are observed and only in case of 2-propanol also divinyl sulfone is still present. With 2-propanol a slight but significant influence of the catalyst choice on

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

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

• trifluoromethyl alkynylation product 84 with alkynyl sulfone 83, alkene 81, and Togni reagent 82 as substrates catalyzed by 2,4,6-trimethylpyridine (TMP). The EDA complex formed by electron donor TMP and electron acceptor Togni reagent 82 facilitated electron transfer, yielding trifluoromethyl radical to initiate

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

• , which have potent activity against breast cancer. The easy access to the corresponding sulfones presents a versatile route for the implementation of a new biologically active moiety, the sulfone, to the β-naphthyl-β-sulfanyl ketones. The enantioenriched products of both classes can be evaluated as

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

Isolation and structure determination of a tetrameric sulfonyl dilithio methandiide in solution based on crystal structure analysis and ⁶Li/¹³C NMR spectroscopic data

• Jürgen Vollhardt,
• Hans Jörg Lindner and
• Hans-Joachim Gais

Beilstein J. Org. Chem. 2020, 16, 2057–2063, doi:10.3762/bjoc.16.172

• substructure of which could be disclosed [15]. We describe in this paper the isolation of a tetramer of 2a and the determination of its structure in solution based on crystal structure analysis and previously described NMR spectroscopic data. Results and Discussion Crystal structure Treatment of sulfone 4 in a

• (2a)4·(THF)6 are in the range of those found in the hexamer (2a)6·Li2O·(THF)6 and functionalized dilithio sulfonyl methandiides [40][43]. Solution structure The synthesis of 2a from sulfone 6Li and 13C-labelled 4 with Li2O-free n-BuLi had yielded the methandiide, being readily soluble in THF. 13C and

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• oxidation stereoselectively generated the spirocyclic epoxide 76. A second-protecting group shuffle afforded the primary alcohol 77. A Mitsunobu substitution of 77 with 2-mercaptobenzothiazole, followed by an oxidation with a large excess of mCPBA afforded the sulfone 78. While not producing the identical

• afforded the fragment 125. The cross-metathesis of 125 with an excess of methacrolein in the presence of the Ru catalyst 122 gave the aldehyde 126. This coupling is analogous to Koide’s cross-metathesis of 121 (cf. Scheme 20). A modified Julia olefination of 126 with the anion generated from the sulfone 78

• , followed by the cleavage of the 4’-TBS protecting group gave 127 in an acceptable yield (52%). A protecting-group adjustment finalized the synthesis of 124. Notably, these authors found that switching the sulfone and aldehyde functionalities, i.e., an olefination of the aldehyde generated by the oxidation

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

• investigations on their more stable analogs resulted in the synthesis of stable 1-O-phoshono-β-ᴅ-psicofuranosyl sulfone, which was prepared by a simultaneous phosphorylation and oxidation of ethyl 2-thio-β-ᴅ-psicofuranoside with dibenzyl N,N-dimethylphosphoramidite catalyzed by 1H-tetrazole and followed by

• thiol from exo-face of the bicyclic skeleton. Subsequent simultaneous phosphorylation and oxidation of ethyl 2-thio-ᴅ-tagatofuranoside 13 under identical conditions as used for the fructofuranose pathway provided 1-O-dibenzyloxyphosphoryl-ᴅ-tagatofuranosyl sulfone 14 (Scheme 3). Removal of the pivaloyl

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• testing a variety of reaction conditions. More complex biorelevant examples such as isatin derivatives were also suitable substrates, affording the corresponding spirocyclic derivatives, albeit in low yields (Scheme 21) [59]. Unfortunately, thioether and sulfone-based linkers were unsuitable in this

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• (Figure 11) [129]. Four conjugated polymers containing dibenzothiophene sulfone (FSO) monomers, linked by either biphenyl (FSO-BP), fluorene (FSO-F), 2,8-dibenzothiophene (FSO-FSz), or 3,7-dibenzothiophene (FSO-FS) monomers were synthesised and applied in the photocatalytic hydrogen evolution reaction

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

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• Tianjin University, Fuzhou 350207, China 10.3762/bjoc.16.60 Abstract A diastereo- and enantioselective approach to access chiral CF2-functionalized aziridines from difluorodiazoethyl phenyl sulfone (PhSO2CF2CHN2) and in situ-formed aldimines is described. This multicomponent reaction is enabled by a

• phosphoric acid (Scheme 1a) [26]. In comparison, there is a significant dearth of available synthetic approaches to CF2-functionalized aziridines, particularly in a stereocontrolled manner. Indeed, a handful of reported methods document the employment of difluoromethylimines, difluoromethyl phenyl sulfone

• phenyl sulfone under mild conditions by a combined strong Brønsted acid system consisting of chiral disulfonimide and 2-carboxyphenylboronic acid. The optical purity of the obtained CF2-substituted aziridines could be further improved by a practical dissolution–filtration procedure. Substrate expansion

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

• isolated in moderate to good yields. Using the more reactive allyl sulfone, a panel of symmetrical diaryliodonium salts was reacted, giving the products in good yields. The authors conducted some mechanistic studies and suggested a plausible catalytic cycle involving [Cu(I)]/[Cu(I)]*/[Cu(II)] species. The

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• arylcopper(I) species was the key intermediate. Terminal alkynes were also investigated under similar reaction conditions (Scheme 13) [37]. Aromatic and π-activated aliphatic substrates led to the desired products in moderate to very good yields. Moreover, vinyl sulfone derivatives were formed when the

Iodine-mediated hydration of alkynes on keto-functionalized scaffolds: mechanistic insight and the regiospecific hydration of internal alkynes

• Zachary Lee,
• Brandon R. Jones,
• Nyochembeng Nkengbeza,
• Michael Phillips,
• Kayla Valentine,
• Alexis Stewart,
• Brandon Sellers,
• Nicholas Shuber and
• Karelle S. Aiken

Beilstein J. Org. Chem. 2019, 15, 2747–2752, doi:10.3762/bjoc.15.265

• were used to probe the existence of an α-iodo intermediate 9, and methodology work was used to investigate the outcome of the reaction using alkyl-capped, asymmetric, internal alkynes 11. The NMR investigations utilized different electrophilic iodine sources and the β-keto sulfone 8, which allowed for

• intermediate 9, we turned our attention to investigating the reaction of internal alkynes 11 to examine the regioselectivity of the hydration process. Ester, sulfone, and phosphonate substrates were employed and, in all cases, the internal alkyne unit was capped by an ethyl group (Scheme 2). In general

• recovered. In contrast, the phosphonate 11d and the sulfone 11e smoothly converted to 15d and 15e in yields of 68% and 71%, respectively. The hydration of the phosphonate required 22 h, while the reaction of the sulfone was complete in 3.5 h. Overall, successful outcomes were obtained for the phosphonate

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

• significantly more slowly to the sulfone. When the substrate was (p-OMe)PhSCF2CH3, then the resultant (demethylated) phenol sulfoxide had an enantiomeric excess of 60%, and when the substrate was the β-substituted-SCF2CH3 naphthalene, then the enantiomeric excess of the resultant sulfoxide was 54%. There was no

• 19F NMR spectrum consistent with non-equivalence of the fluorines, immediately indicative of sulfoxide formation. Isolation and subsequent 1H and 19F NMR analyses as well as high-resolution mass spectrometry secured the identity of these metabolites as sulfoxides 6 and 7 and sulfone 8. The structure

• . Sulfone 8 was a relatively minor metabolite, at only 10% of sulfoxide 6. A chiral HPLC (IC column, solvent: 5% isopropanol in hexane; 1 mL/min) enantiomeric assay was conducted for sulfoxide 6 and the outcome compared with a racemic sample of 6, prepared by chemical oxidation of thioether 4 [22]. Although

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

• 5-HT1 receptor agonist for the treatment of migraine) [7], and apremilast (3, Otezla®, inhibitor of the PDE4 for the treatment of certain types of psoriasis and psoriatic arthritis) [8] (Figure 1). Recently we have shown that racemic sulfone 4 exhibits high antiviral activity against BVDV with low

• 8a or 9a. Оne of the stereoisomers can be formed directly during the reaction. To test this hypothesis, we decided to study the evolution of dr on the course of reaction by 1H NMR spectroscopy (Figure 3). The reaction of sulfone 5a with ω-nitrostyrene (6a) was chosen as the model reaction. Conversion

• was determined by decrease of the integral intensity of the sulfone 5a methylene group signal at 4.75 ppm. The diastereomers 8a:9a ratio was determined by the ratio of the integral intensities of signals of the methine groups of 8a and 9a at 4.62–4.57 and 4.53–4.47 ppm, respectively. As the studies

An anomalous addition of chlorosulfonyl isocyanate to a carbonyl group: the synthesis of ((3aS,7aR,E)-2-ethyl-3-oxo-2,3,3a,4,7,7a-hexahydro-1H-isoindol-1-ylidene)sulfamoyl chloride

• Aytekin Köse,
• Aslı Ünal,
• Ertan Şahin,
• Uğur Bozkaya and
• Yunus Kara

Beilstein J. Org. Chem. 2019, 15, 931–936, doi:10.3762/bjoc.15.89

• material was 2-ethyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione (9), which we have synthesized in previous studies [16][17]. Imide 9 was synthesized via the cycloaddition of 3-sulfone to maleic anhydride. The reaction of ethylamine with anhydride 8 in the presence of a toluene/triethylamine mixture (3

An efficient and concise access to 2-amino-4H-benzothiopyran-4-one derivatives

• Peng Li,
• Yongqi Wu,
• Tingting Zhang,
• Chen Ma,
• Ziyun Lin,
• Gang Li and
• Haihong Huang

Beilstein J. Org. Chem. 2019, 15, 703–709, doi:10.3762/bjoc.15.65

• and ethyl sulfone 3, respectively (Scheme 2). With the substrates including sulfide, sulfoxide and sulfone in hand, we screened various solvents with compounds 1a, 2a, 3a and 1-benzylpiperazine as the model substrates and the results are summarized in Table 1. No target compound 4a was obtained at

• , thereby providing opportunities for discovering more active compounds for medicinal chemistry research. Representative strategies for the synthesis of N-substituted 2-aminobenzothiopyranones. The synthesis of sulfide 1, sulfoxide 2, and sulfone 3. Scope of the synthesis of versatile 2

Thiol-free chemoenzymatic synthesis of β-ketosulfides

• Adrián A. Heredia,
• Martín G. López-Vidal,
• Marcela Kurina-Sanz,
• Fabricio R. Bisogno and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2019, 15, 378–387, doi:10.3762/bjoc.15.34

• generate the corresponding chiral sulfoxides or sulfone derivatives [32]. Multicomponent reactions (MCRs), in which three or more reagents react giving rise to generally complex molecules in one-pot, have arisen as a powerful tool to connect fragments in a simple manner, avoiding cost and time-consuming

• chromatography (petroleum ether/EtOAc 9:1) a 68% isolated yield was obtained for the S-allyl-β-ketosulfide 2h. The obtained β-ketosulfides can be chemoselectively converted into the corresponding sulfoxide/sulfone derivative [47][48]. It is well known that β-ketosulfoxides and β-ketosulfones are valuable

Synthesis of mono-functionalized S-diazocines via intramolecular Baeyer–Mills reactions

• Miriam Schehr,
• Daniel Hugenbusch,
• Tobias Moje,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2018, 14, 2799–2804, doi:10.3762/bjoc.14.257

• sulfur bridge is oxidized to the sulfoxide or sulfone. Hence, neither reductive nor oxidative conditions are compatible with the –CH2-S– bridge. An alternative strategy, that applies weakly acidic conditions is the condensation of aryl nitroso compounds with anilines. This Baeyer–Mills reaction was

Unprecedented nucleophile-promoted 1,7-S or Se shift reactions under Pummerer reaction conditions of 4-alkenyl-3-sulfinylmethylpyrroles

• Takashi Go,
• Akane Morimatsu,
• Hiroaki Wasada,
• Genzoh Tanabe,
• Osamu Muraoka,
• Yoshiharu Sawada and
• Mitsuhiro Yoshimatsu

Beilstein J. Org. Chem. 2018, 14, 2722–2729, doi:10.3762/bjoc.14.250

• determined by analysing the single-crystal X-ray diffraction spectrum of the corresponding sulfone of 4a; the structure was a pyrrole bearing both 3-sulfanylmethyl and 4-allylaminomethyl groups (see Supporting Information File 1). To develop a useful Pummerer reaction procedure, we selected allylamine

• Information For crystallographic data see also CCDC 1824587 and 1824588. Supporting Information File 226: Schemes S1 and S2 on the syntheses of compounds 1, 2, and 3a–g; the NMR study for the structure determinations, further DFT calculations, the ORTEP drawing of both sulfone of 5a, 11d and the 1H and 13C

• NMR charts. Supporting Information File 227: Crystallographic information of compound 11d. Supporting Information File 228: Crystallographic information of the sulfone of compound 5a.

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• (III) form of 1 has recently been found to catalyze atom transfer radical addition of alkyl halides to olefins (phenyl vinyl sulfone and acrylates) in the presence of NaBH4 [115]. In addition, a new light-driven method for generating acyl radicals from 2-S-pyridyl thioesters was developed through the

Visible light-mediated difluoroalkylation of electron-deficient alkenes

• Vyacheslav I. Supranovich,
• Vitalij V. Levin,
• Marina I. Struchkova,
• Jinbo Hu and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2018, 14, 1637–1641, doi:10.3762/bjoc.14.139

• were coupled with alkenes 2 (Figure 1). Esters and amides of acrylic acid, acrylonitrile, and vinyl phosphonate used in a small excess (1.2 equiv) were successfully fluoroalkylated. For vinyl(phenyl)sulfone, significant amounts of hydrodeiodination product RfH was formed, likely because of the

• decreased reactivity of the sulfone double bond toward fluorinated radicals. In this case, two equivalents of the alkene have to be used to achieve good yields of products 3t,u. It should also be pointed out that the reaction tolerates aromatic bromide substituents (products 3b,c,n,o), a boryl fragment