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

• the solvent for toluene, dichloromethane, dimethylformamide or DMF/H2O (4:1) led to lower yields of the desired aryl cyclopropyl sulfide 1a (Table 1, entry 5) while decreasing the temperature to 50 °C almost completely shut down the reaction (Table 1, entry 6). 1,10-Phenanthroline was found to be the

• , respectively, with no obsevable traces of the desired S-cyclopropylated product 1a (Table 1, entries 11 and 12). Interestingly, however, potassium cyclopropyl trifluoroborate (29) provided the desired aryl cyclopropyl sulfide 1a in 23% yield, albeit with 30% of the diaryl disulfide side-product 26a (Table 1

• (II) acetate, 0.1 equivalents of 1,10-phenanthroline, 2.0 equivalents of potassium carbonate under oxygen atmosphere at 70 °C for 20 hours in a 3:1 mixture of toluene and water afforded the aryl cyclopropyl sulfide 1a in 38% along with 8% of the corresponding side-product 26a and 24% of recovered

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• with the nucleophilic aromatic ring in a Friedel–Crafts alkylation process, thus incorporating the carbon atom in a formal C(sp2)–H/C(sp3)–H cross-dehydrogenative coupling. Finally, an oxidation of sulfide 7 to sulfoxide 8 and the subsequent attack of amide 2 with cleavage of the C–S bond and formation

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• route to 2-deoxyhepuloses 3, 5 and 7 [27][28][29][30]. The hydroboration of enol ethers 2, 4, and 6 with borane dimethyl sulfide in THF, followed by oxidation using hydrogen peroxide and sodium hydroxide gave 2-deoxygalactoheptulose 3 and 2-deoxymannoheptulose 5 in good yields (89% and 78%) and with

• -galactoheptulose (3): Compound 2 (3.66 g, 6.82 mmol) was dissolved in dry tetrahydrofuran (130 mL) under nitrogen and cooled to 0 °C. Borane dimethyl sulfide complex in dry tetrahydrofuran (4.78 mL, 9.55 mmol, 2 M) was added slowly, and the reaction was kept at 0 °C for 2 h. The reaction mixture went from light

• yellow to colorless during the addition of the borane dimethyl sulfide complex. Upon complete consumption of 2, distilled water (15 mL) was added to the reaction mixture slowly (dropwise at first) while vigorous gas evolution was observed. After completion of the gas evolution, sodium hydroxide (14 mL

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• to that for 1 and 2 [37]. Asymmetric reduction of the carbonyl group of 2’-bromobenzophenone (a) with borane dimethyl sulfide in the presence of (S)-(−)-2-methyl-CBS-oxazaborolidine catalyst gave (S)-(2-bromophenyl)(phenyl)methanol (S)-b in 93% yield and 94% ee (Scheme 2 and Figure S1 in Supporting

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

• be the optimum leaving group by thorough investigations on the elimination of sulfide, sulfinyl, and sulfonyl groups at the 2-position of benzothiopyranone. Most 2-aminobenzothiopyranones were obtained in good to excellent yields under refluxing in isopropanol within 36 h. This method is base-free

• substituent leading to 2-methylamino-3-cyanobenzothiopyranones was disclosed by Rudorf and co-workers (method C, Scheme 1) [9]. Recently, a similar strategy was successfully utilized to afford N-substituted 2-aminobenzothiopyranones through the replacement of sulfide, sulfinyl or sulfonyl groups with amines

• -imidazolylbenzothiopyranones [10]. It is well known that the sulfide, sulfinyl and sulfonyl groups are generally used as the leaving group for the synthesis of 2-substituted 4H-chromen-4-ones [11][12][13][14][15][16][17][18][19][20][21][22]. Due to the higher electronegativity of the oxygen atom compared to the sulfur atom

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• allyl-sulfide on the surface of the protein. Cross metathesis of the modified protein 82 with allyl alcohol gave the CM product with over 90% conversion (Scheme 18). To achieve this challenging reaction, 200 equivalents (equiv) of HG-II catalyst were employed in a reaction mixture containing 0.01 mM 82

• for the cross metathesis of the allyl-sulfide 99 with allyl alcohol, yielding 50% of product 100 in aqueous mixture (40% t-BuOH) in the presence of 4000 equiv of Mg2+ (Scheme 20). In another recent study, Touissant et al. described the synthesis of two metathesis-based fluorescent probes suitable for

• -metathesis reaction of allyl sulfide 99. Preparation of BODIPY-containing profluorescent probes 102 and 104. Metathesis-based ethylene detection in live cells. First example of stapled peptides via olefin metathesis. RCM of challenging substrate 17 in air and in the presence of water. RCM of N,N

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

• ; sulfoxide; thiol-free; Introduction Throughout the years, several strategies have been developed to build up organic compounds bearing a sulfide moiety [1][2]. Often, thiols (or the corresponding thiolate anions) are employed as nucleophilic sulfur reagents in order to react with a suitable electrophile [3

• temperature one-pot two-step preparation of the phenacyl allyl sulfide 2h. cIsolated yield. Selective oxidation of the β-ketosulfide 2a. Screening of hydrolases and conditions towards a model substrate.a Lipase-catalysed hydrolysis–protonation sequence over a series of β-thioalkyl enol esters.a Supporting

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• (0.5 mol % relative to the vinylsilyl group, Scheme 3) [9]. Effective cross metathesis was observed when OVS was treated with vinyl sulfide in the presence of second generation Grubbs’ catalyst (Ru-2). The product was obtained in 91% isolated yield, however, the process required a temperature elevation

A tutorial review of stereoretentive olefin metathesis based on ruthenium dithiolate catalysts

• Daniel S. Müller,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2018, 14, 2999–3010, doi:10.3762/bjoc.14.279

• which leads to the formation of methylidene-ruthenium species Ru-A (Scheme 4). Once complex Ru-A is formed, it is prone to be attacked by the electron-rich sulfide ligand positioned opposite to the NHC ligand (trans-influence). This 1,2-sulfide shift generates a new ruthenium complex Ru-B which is

• probably catalytically inactive. This assumption is supported by the isolation of ruthenium complex Ru-13 which was formed by nucleophilic attack of a sulfide ligand onto the electron-poor benzylidene ligand [4]. Hoveyda reasoned that replacing the thiocatecholate ligand (Ru-2) by an electron-deficient

• dichloro catecholthiolate (Ru-3) should render the sulfide ligand less nucleophilic and therefore less prone for nucleophilic attack. This hypothesis gained credence by increased isolated yield for the cross metathesis of allylbenzene with cis-butenediol: Ru-2 (42% yield) versus Ru-3 (61%) yield (Scheme 2c

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• post-expressional protein modifications [10][11][12]. For example, a single cysteine mutant of subtilisin from Bacilus lentus (SBL-S156C) was modified via sulfide bond formation with allyl cysteine displaying an allyl function on the protein surface. This allyl group was modified with a GH-type

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

• ). First, we examined the Pummerer reactions in the presence of p-methoxybenzenethiol or p-chlorobenzenethiol; however, the reactions yielded the reductive sulfide 4a. We next examined the stepwise process: i) the Pummerer reaction of 5a with TFAA, followed by ii) the usual work-up and successive treatment

Synthesis of aryl sulfides via radical–radical cross coupling of electron-rich arenes using visible light photoredox catalysis

• Amrita Das,
• Mitasree Maity,
• Simon Malcherek,
• Burkhard König and
• Julia Rehbein

Beilstein J. Org. Chem. 2018, 14, 2520–2528, doi:10.3762/bjoc.14.228

• photocatalyst and complete the catalytic cycle forming the sulfate dianion 5 and sulfate radical anion 6. The phenyl sulfide radical 2 formed upon homolytic cleavage of diphenyl disulfide adds to the radical cation of the arene to form the unstable cationic intermediate 3. Aromatization by deprotonation leads

• obtained from the difference spectrum [Ir] and [Ir] + TMB and represents the transient absorption spectrum of 1,3,5-TMB•+ with λmax of 473 nm (solution A). Synthetic routes to organosulfur compounds. Aryl sulfide synthesis. Substrate scope for arylthiol syntheses. The reaction was performed with 1a–g (0.1

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• since sulfur, in the form of the sulfate ion, is the second most abundant anion in sea water after chloride. As part of natural products, sulfur can appear in a multitude of combinations and oxidation states: thiol, sulfide (acyclic or heterocyclic), disulfide, sulfoxide, sulfonate, thioaminal

• , sulfide (acyclic or heterocyclic), disulfide, sulfoxide, sulfonate, thioaminal, hemithioacetal, various thioesters, thiocarbamate and isothiocyanate [3]. The three simplest sulfur-containing natural products are perhaps, (E)-2-butene-1-thiol (1), the principal ingredient of the repulsively malodorous

• . The pteriatoxins such as pteriatoxin A (7), were isolated from a Japanese shellfish by Uemura and co-workers in 2001 and proved to be extremely potent neurotoxins in mice [10]. Leukotrienes, which are a family of eicosanoids that are produced in leukocytes, also contain β-hydroxy sulfide moieties, as

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• in the case of 2’-deoxy-4’-thionucleosides [25][26]. When synthesizing 4’-thionucleosides by the way of a sulfide derivative 31, the known chemistry should lead us to use a classical Pummerer reaction to produce 1-acetoxy derivative 33 after converting 31 to the corresponding sulfoxide 32. Even

• ’-thionucleoside derivatives by other groups and became a standard approach for the glycosylation [33][34][35][36][37]. On the other hand, the conversion from the sulfide to 4’-thionucleoside using the Pummerer-type glycosylation included an oxidation step. If the oxidation of sulfide 31 and the Pummerer-type

• thietane nucleosides [47]. The substrate of the coupling reaction was prepared as shown in Scheme 6 starting from benzyloxyacetaldehyde (50). When a hypervalent iodine reagent was used for glycosylation with a diastereomeric mixture of sulfide 53, the reaction stereoselectively gave the ring-expanded

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• reaction mechanism starts with the oxidative addition of the diaryliodonium salt 1 to copper(I) iodide affording the Cu(III) species A, releasing aryl iodide 2. Coordination of the disulfide 6 to the metal centre leads to complex B, followed by the base-induced formation of arylcopper sulfide complex C and

• substituted acrylamidines 35 (Scheme 19). The proposed reaction mechanism starts with the activation of DMSO (A) via the iodine(III) species 20b. Iodosoarene C is released under basic conditions, forming the sulfonium intermediate D. This intermediate reacts with the amidine 34 to give the sulfide E, which is

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• ) triethyl phosphonoacetate, NaH, DCM; b) TMSN3, Pd(PPh3)4, EtOH; c) i) DOWEX H+, MeOH; ii) O3, dimethyl sulfide, DCM/MeOH; iii) Ac2O, DMAP, pyridine; d) H2, Pd/C, Ac2O; e) MeOH/H2O/Et3N (10:10:1). Proposed mechanism of the Pd-catalyzed azide substitution of 6a in protic solvent. Approach towards

• peracetylated D-IdoNAc 2c, reactions and conditions: a) Ti(OiPr)4, t-BuOOH, D-DET, DCM; b) i) (COCl)2, DMSO, Et3N, DCM, ii) triethyl phosphonoacetate, NaH, DCM; c) TMSN3, Pd(PPh3)4, EtOH; d) i) DOWEX H+, MeOH; ii) O3, dimethyl sulfide, DCM/MeOH; iii) Ac2O, DMAP, pyridine; e) H2, Pd/C, Ac2O. Supporting

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• underlying idea behind the latter application is that protonation of the leaving group by a general acid is not needed with 5´-thiosubstituted analogs, since the sulfide ion is a much better leaving group than the alkoxide ion. Most extensively used thiosubstitution, however, is replacement of either one of

• state resembles the transition of ribonucleoside 3´-aryl phosphates rather than 3´-alkyl phosphates, which is expected on the basis of 105-fold lower basicity of sulfide ions compared to alkoxide ions. The effect of non-bridging thiosubstitution on the cleavage rate is modest compared to the bridging

• conditions. The hydrogen sulfide ion is 105 times less basic than the hydroxide ion and, hence, able to compete with the sugar oxyanions as a leaving group upon breakdown of the thiophosphorane intermediate (the bond energies of P–O and P–S bonds are 86 kcal mol−1 and 55 kcal mol−1, respectively [103

The selective electrochemical fluorination of S-alkyl benzothioate and its derivatives

• Shunsuke Kuribayashi,
• Tomoyuki Kurioka,
• Shinsuke Inagi,
• Ho-Jung Lu,
• Biing-Jiun Uang and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2018, 14, 389–396, doi:10.3762/bjoc.14.27

• well as 2-(tert-butoxycarbonyl)oxy-3,3,3-trifluoropropyl phenyl sulfide [29]. Conclusion In summary, we have achieved the regioselective anodic fluorination of various S-alkyl and S-substituted alkyl benzothioate derivatives in Et4NF·4HF/CH2Cl2 and a fluorine atom was selectively introduced in the α

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• -alkylation compound 7e was obtained instead of the desired furan (Table 1, entry 5). It is possible to consider that the d orbitals of the sulfur atom in a sulfide group could possibly stabilize the adjacent carbanion [73][74]. To expand the scope of substituted N,S-acetals that could provide the desired

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

• apply cysteine-containing glutathione for the reaction with a series of highly functionalized alkenes to form the respective sulfide adducts with yields up to 99%. This concept attracted attention from different fields of chemistry. Boyer and co-workers for example applied the redox mediator accelerated

• β-ketosulfoxide. No additional sacrificial substrates are needed in order to regenerate the photocatalyst or for the oxidation of the sulfenyl intermediate to the respective sulfoxide moiety. Hydrogen peroxide, which is generated as a byproduct, directly is consumed by oxidizing the sulfide to the

• and were able to couple a series of electron-rich and electron-poor styrene derivatives with aromatic and also long-chain aliphatic thiols to the respective sulfoxides, after aerobic oxidation (Scheme 15a). They describe a photocatalyzed thiol–ene reaction mechanism, where the sulfide-adduct is

Synthesis and photophysical properties of novel benzophospholo[3,2-b]indole derivatives

• Mio Matsumura,
• Mizuki Yamada,
• Atsuya Muranaka,
• Misae Kanai,
• Naoki Kakusawa,
• Daisuke Hashizume,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2017, 13, 2304–2309, doi:10.3762/bjoc.13.226

• ]indole 3 in 66% yield. Then, the chemical modification of the phosphorus atom of 3 was carried out and the results are shown in Scheme 2. The treatment of 3 with hydrogen peroxide, elemental sulfur, and elemental selenium afforded the corresponding phosphine oxide 4, sulfide 5, and selenide 6

• , respectively. The reaction of 3 with methyl triflate afforded phospholium triflate 7. Phosphole 3 was treated with chloro(dimethyl sulfide)gold in CH2Cl2, resulting in P-complexation and thus affording the gold complex 8. The borane complex 9 was readily prepared from 3 by treating with borane in THF. The

• = 75%) was high, comparable to that of phosphole and indole-fused pentacyclic heteroacene (Ф = 70%) [35]. On the other hand, a low fluorescence intensity was observed for phosphine sulfide 5 and selenide 6 (Ф = 1% and 0.3%, respectively). Quenching of fluorescence emission due to a soft sulfur

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• product [30] (Scheme 6). The analogous reaction with phenyl vinyl sulfide (22) gave the expected cyclobutane 23 exclusively. However, in the absence of ZnCl2, a mixture of 23 and 3,4-dihydro-2H-pyran 24 was obtained, with the latter compound formed through a competitive hetero-Diels–Alder reaction [30

• aromatic systems. Miscellaneous reactions The oxidation of E-1a with H2O2 in acetonitrile gave oxirane 101, which subsequently was used for reactions with diverse nucleophiles [80] (Scheme 32). Upon treatment with diheptyl sulfide, 101 was transformed into ethoxalyl cyanide (102) [81]. The aziridination of

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• oximes 95, if the elimination of dimethyl sulfide from 94 proceeds faster than the cyclization. The cyclization/elimination selectivity was found be highly dependent on the nature of substituents in ylide 92. Only when R3 was an acyl or phenacyl group, exclusive formation of isoxazoline products 93 was

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• to afford the corresponding glycosyl amide 26. Two possible reaction pathways have been proposed for this dehydrative glycosylation (Scheme 7) [37]. Upon mixing diphenyl sulfoxide and triflic anhydride, diphenyl sulfide bis(triflate) (27) is formed in situ (Scheme 7a). In pathway 1, hemiacetal 28

• could attack the sulfonium center of diphenyl sulfide bis(triflate) (27) to give the glycosyl oxosulfonium intermediate 29, which subsequently glycosylated the acceptor to yield the product 30 (Scheme 7b). Alternatively, in pathway 2, hemiacetal 28 could attack the sulfonyl center of diphenyl sulfide

• [19] found that with BSP/Tf2O promoter, the glycosylation of donor 72 and acceptor 74 gave a moderate yield of 44% (α:β = 2:1) of the desired product 75 (Scheme 14). This was attributed to the formation of (N-piperidino)phenyl(S-thioethyl)sulfide triflate (73) from the reaction of BSP/Tf2O with the