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

• (Scheme 3 and Scheme 9) [41][60]. In stoichiometric amounts, they generally add efficiently to π-systems and can be applied in thiol-ene reactions. Recently, Dilman and co-workers published a hydrosulfenylation of the β-difluorostyrenes 41.2 for the synthesis of the thioethers 41.3 using 9-PhAcr (OD1) as

• a photocatalyst (Scheme 41) [168]. The formed thioethers 41.3 could then be used as a gem-difluoroalkyl radical source for further transformations. Interestingly, 9-PhAcr (OD1) can only act as a photocatalyst in its protonated form. The thiol 41.1 acts as a proton source for OD1, allowing it to

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

• desired products 140n–t in moderate to good yields (Scheme 30). A few months later, the same research group extended this methodology to an α-C(sp3)–H bond functionalization of nitrogen-containing molecules and thioethers [58]. In order to achieve the highest yield, an optimum concentration of acetone (4

• of the 2-position, yielding 149a, rather than for the N-methyl group, which would yield 149b (Scheme 33). In the same manner, thioethers were also susceptible to α-arylations or alkylations, using bromides containing a variety of functional groups, giving moderate to good yields (Scheme 34). The

• proposed mechanism for the C(sp3)–H functionalization of N-containing molecules and thioethers is in accordance with the one described previously for ether functionalizations and is presented in Scheme 35. In 2019, Kokotos and co-workers employed 4-cyanobenzaldehyde (53) as the photoinitiator for the

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

• reaction was excellent as bromides, phenols, thioethers, esters, boronic esters, and heterocycles, including pyridine and quinolines, were well tolerated. The authors carried out mechanistic studies and demonstrated the H-bonding ability of their catalyst by NMR studies. The following mechanism was

Synthesis of six-membered silacycles by borane-catalyzed double sila-Friedel–Crafts reaction

• Yafang Dong,
• Masahiko Sakai,
• Kazuto Fuji,
• Kohei Sekine and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2020, 16, 409–414, doi:10.3762/bjoc.16.39

• in good to excellent yields. The optimized reaction conditions were also applicable for diaryl thioethers to afford their corresponding six-membered silacyclic products. The gram-scale synthesis of a representative bis(dimethylamino)phenoxasilin and the transformation of its amino groups have also

• dilithiated diaryl thioethers with a range of dichlorosilane derivatives (Scheme 1a) [15][16][17][18][19][20][21][22][23][24]. An intramolecular silylation via Si–C bond cleavage can also be used to prepare a variety of six-membered silacyclic derivatives (Scheme 1b) [25]. However, some problems still remain

Self-assembled coordination thioether silver(I) macrocyclic complexes for homogeneous catalysis

• Zhen Cao,
• Aline Lacoudre,
• Cybille Rossy and
• Brigitte Bibal

Beilstein J. Org. Chem. 2019, 15, 2465–2472, doi:10.3762/bjoc.15.239

• silver(I) catalysts based on sulfur ligands were reported so far, although alkyl thioethers are soft σ-donor ligands such as crown thioethers that were largely developed as macrocyclic ligands for silver(I) [35][36][37][38][39][40][41][42][43]. Interestingly, depending on their design, these known silver

• candidates for directional metal coordination. Herein, a new syn-atropisomer of 9,10-DPA ortho-substituted by two thioethers is exploited as a ligand for silver(I) salts. The impact of this bis-thioether ligand on silver(I) homogeneous catalysis is evaluated in two tandem addition/cycloisomerization

Synthesis and properties of sulfur-functionalized triarylmethylium, acridinium and triangulenium dyes

• Marco Santella,
• Eduardo Della Pia,
• Jakob Kryger Sørensen and
• Bo W. Laursen

Beilstein J. Org. Chem. 2019, 15, 2133–2141, doi:10.3762/bjoc.15.210

• occurred with ethanethiol, a high selectivity was observed for para-substitutions, giving Sx-(DMP)3C+ 1, 2, and 3 in reasonable yields of 20–50% after column chromatography purification. It is important to note that the gradual introduction of thioethers into the carbenium systems did not significantly

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

• reduces relative to the perfluoro substituents [13][14][15]. In this context we recently introduced aryl α,α-difluoroethyl thioethers such as 1 as a motif of this class [16][17][18]. Log P assessments of PhSCF2CH3 (1) indicate that it is more polar than the PhSCF3 (2) and also the aliphatic PhSCH2CH3

• context, the potential for P450 oxidation at sulphur is the most obvious metabolic vulnerability, and also hydrolytic susceptibility to release fluoride. We chose to explore the metabolism of aryl α,α-difluoroethyl thioethers 4 and 5 by Cunninghamella elegans as representative compounds of this class

• . This fungus is rich in cytochrome P450 activity and has been used as a model organism in which to mimic phase one mammalian metabolism of xenobiotics [19][20][21]. Results and Discussion The two aryl α,α-difluoroethyl thioethers 4 and 5 in Figure 3 were selected for C. elegans incubations rather than 1

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

• the formation of aromatic thioethers by functionalising C–H bonds of imidazo[1,2-α]pyridines and benzo[d]imidazo[1,2-b]thiophenes using Eosin B and sulfinic acids (Scheme 8) [51]. The manipulated heterocycles, particularly the imidazopyridines, are motifs which are commonly encountered in medicinal

Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

• Alphonse Fiebor,
• Richard Tia,
• Banothile C. E. Makhubela and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1859–1870, doi:10.3762/bjoc.14.160

• reactions [32][33]. As it was elegantly reviewed by Singh and co-workers [33], these organosulfur ligands can be classified into pincer type (symmetrical and unsymmetrical), thioethers, thiourea-based ligands, sulfur-substituted NHCs, thiosemicarbazones and sulfated Schiff bases. Of the pincer ligands

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

• group from succinimide 103 to the chiral pre-catalyst 104 to generate the active species 110 (Scheme 40). Reaction of the alkene with the active species 110 results to the formation of the thiiranium intermediate 111, which then undergoes a stereoselective nucleophilic addition to provide the thioethers

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

• economy for this transformation is rather low (26% for Ar = Ph). However, 45% of the molecular weight of the starting iodonium salt 1 is present in the product 3’. Diaryl thioethers 5 can be synthesized using either cyclic iodonium salts (will be discussed briefly in section 1.2) or their acyclic

• counterparts 1 (Scheme 4) [26][27]. Jiang and co-workers developed a Cu(II)-catalysed methodology for the conversion of acyclic diaryliodonium salts 1 and potassium thioacetate to the corresponding thioethers 5 (pathway (a)) and later applied the optimized reaction conditions towards cyclic iodonium salts. In

• of the corresponding λ3-iodane. (a) Structure of diaryliodonium salts 1. (b) Diarylation of a suitable substrate A with one equivalent of diaryliodonium salt 1. Synthesis of biphenyls 3 and 3’ with symmetrical diaryliodonium salts 1. Synthesis of diaryl thioethers 5. Synthesis of two distinct S-aryl

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• chalogenate nucleophiles in a mixer ball mill using zirconia components [22]. Highly efficient transformations to the corresponding 4-methoxybenzyl thioethers were achieved in 15–60 minutes such that pure products could be isolated without the need for chromatography (Scheme 7). Of particular note was the

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

Selective synthesis of thioethers in the presence of a transition-metal-free solid Lewis acid

• Federica Santoro,
• Matteo Mariani,
• Federica Zaccheria,
• Rinaldo Psaro and
• Nicoletta Ravasio

Beilstein J. Org. Chem. 2016, 12, 2627–2635, doi:10.3762/bjoc.12.259

• Federica Santoro Matteo Mariani Federica Zaccheria Rinaldo Psaro Nicoletta Ravasio CNR ISTM, via C. Golgi 19, 20133 Milano, Italy 10.3762/bjoc.12.259 Abstract The synthesis of thioethers starting from alcohols and thiols in the presence of amorphous solid acid catalysts is reported. A silica

• substrates under mild reaction conditions. Keywords: no solvent; S-alkylation; solid acids; thioethers; transition-metal-free; Introduction The need for more sustainable processes in the fine chemical industry is growing continuously. An optimal use of resources, both energy and starting materials, and a

• are a very important field of research as traditional coupling methods, although they proved effective in industrial applications, generate harmful metal waste and many byproducts [3]. Thioethers are important building blocks for the synthesis of antibacterial and antifungal agents [4][5] and as

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• only been described bioinformatically [123]. Subtilosin is a Bacillus RiPP antibiotic that belongs to the sactipeptide family of natural products that are defined by the presence of one or more sulphur to α-carbon bonds [125]. Three thioethers in subtilosin are formed by a single SPASM protein, AlbA

• -catalysed formation of thioethers in the biosynthesis of subtilosin. The mechanism for deoxyadenosine radical formation is consistent throughout most radical SAM enzymes. B) Mechanism of carbon–carbon cross-linking in streptide biosynthesis. C) Proposed carbon–carbon bond formation by SPASM protein PqqE in

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• , including alkyl, phenethyl, pendant esters and thioethers, and an α-acetyloxy group (81–98% yield, 95.5:4.5 to 97:3 er). Slightly lower enantioselectivity was observed only when R1 was benzyl (93.5:6.5 er). Methyl, ethyl, n-butyl, and isopentyl R2 substituted nitroalkenes were efficient substrates (84–98

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• -addition to allenoates, which after elaboration of the resulting adducts, affords tertiary thioethers and alcohols [36] (Scheme 15). Starting from readily available L-valine and L-threonine the authors first synthesized different phosphine catalysts and then screened in the γ-addition reaction of both

• -catalyzed allylation substitution reaction of oxazol-4(5H)-ones and thiazol-4(5H)-ones to afford enantioenriched tertiary alcohols and thioethers (Scheme 19) [42]. In this case the diastereoselectivity is controlled by cations, in contrast to most of the described protocols wherein it is modulated by anions

• and to tertiary thiols and thioethers in the case of thiazolones. In the future, other Brønsted base or bifunctional catalyst promoted reactions with these compounds can be envisaged. Some α-substituted heterocycles for asymmetric catalysis, their reactivity patterns against enolization, and resulting

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• preparation of CD thiols and thioethers is an emerging challenge because of the importance of intermediary azido derivatives [96] and favorable aggregation properties in nanomedicines and particularly the antidote Sugammadex [97]. The reaction between 6I-O-monotosyl-β-CD and various nucleophiles opens a new

Lewis acid-promoted hydrofluorination of alkynyl sulfides to generate α-fluorovinyl thioethers

• Davide Bello and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 1902–1909, doi:10.3762/bjoc.11.205

• Davide Bello David O'Hagan University of St Andrews, School of Chemistry, North Haugh, St Andrews, Fife, KY16 9ST, UK 10.3762/bjoc.11.205 Abstract A new method for the preparation of α-fluorovinyl thioethers is reported which involves the hydrofluorination of alkynyl sulfides with 3HF·Et3N, a

• process that requires Lewis acid activation using BF3·Et2O and TiF4. The method gives access to a range of α-fluorovinyl thioethers, some in high stereoselectivity with the Z-isomer predominating over the E-isomer. The α-fluorovinyl thioether motif has prospects as a steric and electronic mimetic of

• thioester enols and enolates, important intermediates in enzymatic C–C bond forming reactions. The method opens access to appropriate analogues for investigations in this direction. Keywords: alkynyl sulfides; α-fluorovinyl thioethers; hydrofluorination; Lewis acids; organofluorine; Introduction

Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

• Luke J. O’Driscoll,
• Sissel S. Andersen,
• Marta V. Solano,
• Dan Bendixen,
• Morten Jensen,
• Troels Duedal,
• Jess Lycoops,
• Cornelia van der Pol,
• Rebecca E. Sørensen,
• Karina R. Larsen,
• Kenneth Myntman,
• Christian Henriksen,
• Stinne W. Hansen and
• Jan O. Jeppesen

Beilstein J. Org. Chem. 2015, 11, 1112–1122, doi:10.3762/bjoc.11.125

• functionalised with thioethers, exemplified by a series of ethylene glycol derivatives. Additionally, the merits of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as an alternative to the most common deprotecting agent, CsOH·H2O are discussed. Finally, we show how a copper-mediated Ullman-type reaction can be applied

• -cyanoethyl-protected thiols as a means to further functionalise MPTTFs with thioethers and (ii) copper-mediated N-arylation of both MPTTFs and BPTTFs. Results and Discussion An improved large-scale synthesis of N-tosyl-(1,3)-dithiolo[4,5-c]pyrrole-2-one (6) The known compound 6 [4][25] is an important

• bearing a 2-cyanoethyl-protected thiol The 2-cyanoethyl protecting group offers a convenient means of synthesising MPTTFs where one or both of R1 and R2 are thioethers. When only simple alkyl thioethers are targeted, it is often more effective to incorporate these moieties prior to the cross-coupling step

Electrochemical oxidation of cholesterol

• Jacek W. Morzycki and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2015, 11, 392–402, doi:10.3762/bjoc.11.45

• reaction carried out with 1,2:3,4-di-O-diisopropylidene-α-D-galactopyranose yielded glycoconjugate 23 with an ether bond between the sugar and steroid molecules. In further studies on the preparation of glycoconjugates from 3β-hydroxy-Δ5-steroids, various derivatives were applied, such as thioethers [44

3α,5α-Cyclocholestan-6β-yl ethers as donors of the cholesterol moiety for the electrochemical synthesis of cholesterol glycoconjugates

• Aneta M. Tomkiel,
• Adam Biedrzycki,
• Jolanta Płoszyńska,
• Dorota Naróg,
• Andrzej Sobkowiak and
• Jacek W. Morzycki

Beilstein J. Org. Chem. 2015, 11, 162–168, doi:10.3762/bjoc.11.16

• derivatives show similar reactivities to those of previously studied 3α,5α-cyclocholestan-6β-thioethers. Keywords: cholesterol; electrochemical oxidation; glycosylation; i-cholesteryl ethers; i-steroids; Introduction We have recently elaborated an electrochemical method for the preparation of glycosides and

• cholesterol wins the competition, the dimer 2 (dicholesteryl ether) is formed. A large excess of sugar was used to avoid this undesired side reaction. In our further study, instead of cholesterol, cholest-5-en-3β-yl and 3α,5α-cyclocholestan-6β-yl thioethers (3 and 4) were applied as cholesteryl donors [4]. Of

• the two, the latter appeared to be much more efficient in cholesteryl transfer to the sugar moiety. The problem, however, with 6β-steroidal thioethers is that they are not easily accessible. Therefore, we searched for the best leaving group at C-3. A series of cholesterol derivatives was tested and

Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs

• Lisa F. Becker,
• Dennis H. Schwarz and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 2920–2927, doi:10.3762/bjoc.10.310

• affinity towards rocuronium [24][25]. Furthermore, hydrophilic γ-CD thioethers show high affinities to other guests such as polycyclic aromatic hydrocarbons [26], botulin [27][28], and fullerene C60 [29]. Hydrophilic β-CD thioethers also tightly complex volatile benzene derivatives leading to a significant

• decrease of their vapour pressure [30]. Therefore we were encouraged to investigate the inclusion of volatile hydrophobic APIs, e.g., sevoflurane, in CD thioethers. Sevoflurane, a versatile inhalational anaesthetic [31], was already included in native CDs and hydroxypropyl-β-CD, but these complexes are

• either nearly insoluble in water or the binding constants are rather low [32][33][34]. We focussed our effort on the design of hydrophilic and/or amphiphilic CD thioethers, because only amphiphilic molecules can form [35][36] or incorporate into bilayer membranes [37][38]. Amphiphilic CD carriers can

Synthesis of nanodiamond derivatives carrying amino functions and quantification by a modified Kaiser test

• Gerald Jarre,
• Steffen Heyer,
• Elisabeth Memmel,
• Thomas Meinhardt and
• Anke Krueger

Beilstein J. Org. Chem. 2014, 10, 2729–2737, doi:10.3762/bjoc.10.288

• nitrogen and sulfur content. All analytical methods yield comparable results around 0.2 mmol g−1. The further reaction depicted in Scheme 1 enables the formation of an aromatic amine at the 2-position of the ring by the oxidation of the thioethers and subsequent substitution of the sulfone by an amino

• function. Throughout the transformation the surface loading (see TGA data and elemental analysis in the experimental part) with the organic moieties remains the same showing the high stability of the double grafting by covalent C–C bonds. However, during the oxidation of the thioethers to the sulfones a

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218