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

• respect, a bifunctional quinine-derived sulfonamide organocatalyst was developed to catalyze the asymmetric sulfa-Michael reaction of naphthalene-1-thiol with trans-chalcone derivatives. The target sulfa-Michael adducts were obtained with up to 96% ee under mild conditions and with a low (1 mol

• %) 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

• building blocks for the construction of more elaborate structures [7][8][9][10][11]. An outstanding class of quinine derived organocatalysts exhibits a bifunctional mode of activation by the incorporation of an acidic unit, such as urea, thiourea, squaramide or sulfonamide moieties, giving rise to the

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• , such as pipecolic acid [66]. In E. coli, the catabolism of proline occurs via the action of the bifunctional enzyme putA (Figure 9B) [67]. It sequentially degrades proline to glutamate, which can be later deaminated to an essential metabolite, α-ketoglutarate, with many metabolic options, such as an

• some therapeutic dehydrogenase inhibition schemes [71]. Conversely, there is strong evidence that other proline analogues, dehydroproline and thiaproline, are oxidatively degraded in E. coli by the action of the bifunctional enzyme putA and the reductase proC [72]. Future research should examine

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• ring seems promising since β-diketones as well as o-quinones are known as chelating ligands. The combination of two different chelating sites in the same molecule should give a bifunctional bridging ligand. Such species are interesting from the viewpoint of assembling of ordered structures in a crystal

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• isoindigo 100 was used as substrate, enantioselective [3 + 2] annulation with allene 101 in the presence of amino acid-derived bifunctional phosphine 102 produced adduct 103 in 90% yield with 92% ee and 4:1 regioisomeric ratio (rr). The authors suggested that the observed regioselectivity could be

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• . If a signal broadens beyond detection and thus disappears from the spectrum, be it due to aggregation or intermediate exchange kinetics, it is also impossible to trace its trajectory and determine the chemical shift perturbation. In the case of a bifunctional GCP ligand binding to survivin [46], the

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

• different approaches have been developed that use a single catalyst. Alemán et al.’s approach combines the two catalytic motifs into a single bifunctional catalyst 38, using thioxanthone as the chromophore (Scheme 5) [31]. The catalyst 38 was then applied to known reactions such as the α-functionalization

• that is trapped intermolecularly by N-hydroxycarbamates 152 (Scheme 21b) [71]. Bach et al. has recently reported a bifunctional catalyst 154, which contains both a photoactive thioxanthone unit and a CPA (Scheme 22) [72]. They have applied this photocatalyst to the [2 + 2] photocycloaddition of

• :33 rr) but this example does demonstrate an interesting proof of concept with potential for the development of processes using alternative bifunctional catalysts. Phase-transfer catalysis Phase-transfer catalysis (PTC) is another non-covalent mode of catalysis that has been combined with

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

• targets for new antitubercular drug developments [6]. Mycobacterial galactan is synthesized by two bifunctional galactofuranosyltransferases, GlfT1 and GlfT2 (Supporting Information File 1, Figure S1). The former one initiates the galactan biosynthesis by addition of the first two Galf residues to

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

• , if both the nucleophile and the electrophile are activated independently by distinct functional groups on the same catalyst, this is referred to as bifunctional catalysis (Figure 2, (1)) [48]. When the two catalysts work in a cooperative way to activate only one substrate, this is classified as

One-pot synthesis of isosorbide from cellulose or lignocellulosic biomass: a challenge?

• Isaline Bonnin,
• Raphaël Mereau,
• Thierry Tassaing and
• Karine De Oliveira Vigier

Beilstein J. Org. Chem. 2020, 16, 1713–1721, doi:10.3762/bjoc.16.143

• first run was observed. A sustainable method for the isosorbide production from cellulose is the use of a bifunctional catalyst (Scheme 7). A series of Ru catalysts on acid support were prepared by the adsorption of colloidal Ru nanoparticles on mesoporous and bulk niobium phosphate, mesoporous and bulk

• (5.0 wt % Ru, Ru nanoparticles (NPs): 0.9 nm) in 30 mL H2O after 1 h of reaction at 220 °C under 60 bar of H2. Trace amounts or even no isosorbide was obtained over microporous HZSM-5, NaY, and γ-Al2O3-supported Ru catalysts. A bifunctional Ru catalyst supported on mesoporous niobium phosphate with a

• . This study shows that a bifunctional catalyst can be a more sustainable solution to produce isosorbide from (ligno)cellulose. Conclusion The isosorbide synthesis from cellulose is performed via acid-catalyzed hydrolysis of cellulose, followed by hydrogenation of glucose to sorbitol and further

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• proceed via enamine intermediates (Figure 1B) [14][15][16][17][18][19]. The state of the art within this area has been recently demonstrated by Dixon and co-workers, who showed that bifunctional BIMP catalysts could promote the enantioselective addition of typically recalcitrant aryl ketones to

Mechanochemical green synthesis of hyper-crosslinked cyclodextrin polymers

• Alberto Rubin Pedrazzo,
• Fabrizio Caldera,
• Marco Zanetti,
• Silvia Lucia Appleton,
• Nilesh Kumar Dhakar and
• Francesco Trotta

Beilstein J. Org. Chem. 2020, 16, 1554–1563, doi:10.3762/bjoc.16.127

• degree of crosslinking, thus influencing the final properties [1][2]. Among the various bifunctional compounds that could be used as crosslinking agents, active carbonyl compounds, such as carbonyldiimidazole (CDI) and diphenyl carbonate have given interesting results in the last 20 years. The produced

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

• postsynthetic modifications in flow [63]. Poliakoff, George, and co-workers reported a porphyrin photosensitiser ionically immobilised to sulphonate-cross-linked ion exchange polystyrene resins (amberlyst-15) for the synthesis of artemisinin (49). This resulted in a bifunctional material, which acts as a HPCat

• to fuse samarium oxide nanoparticles to TiO2 and ceria (CeO2) as a bifunctional heterogeneous photoredox Lewis acid catalyst for reductive cyclisation reactions, previously reported with ruthenium transition metal complex photocatalysts [157]. Both electrochemical and photochemical deposition

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• reactions, should be used with caution, as they themselves may promote side reactions. Results and Discussion Our objective was to subject selected bifunctional compounds to the McKenna reaction conditions. In order to simplify the design of the study, in most cases the reaction mixture contained two model

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

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

• intermolecular alkene 1,2-aminopyridylation to give the difunctionalized products 32.3 (Scheme 32) [148]. Eosin Y (OD13) was an efficient dye for the SET reduction of the N-aminopyridinium salts, which act as bifunctional reagents as the released pyridine later added to the olefin 32.1. The generation of amidyl

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• amides (71–99% yields) and with 5–66% ee (Scheme 42). In 2018, Meng and co-workers developed a bifunctional photo-organocatalyst combining both the photosensitizer and the chirality inducer. Relevant enantiomeric excesses were observed (up to 86% ee) in the oxidation of both β-keto esters and β-keto

• esters and β-keto amides by singlet oxygen using PTC-2 as a chiral organocatalyst. Bifunctional photo-organocatalyst used for the asymmetric oxidation of β-keto esters and β-keto amides by singlet oxygen. Mechanism of singlet oxygen oxidation of sulfides to sulfoxides. Controlled oxidation of sulfides to

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• proceeded well with heterocycle-containing chlorides such as 2-chloro-5-(chloromethyl)thiophene (4e), leading to 2-aminoethyl acetate product 3k in 66% yield which has potential as bifunctional monomer for polymerization. Furthermore, oxazole derivative 2,4,4-trimethyl-4,5-dihydrooxazole (2b) was also

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 yield. In 2019, Collins and co-workers reported the synthesis of a new bifunctional copper photocatalyst for the reductive pinacol coupling of ketones and aldehydes (Scheme 33) [50]. This new catalyst was designed to activate the ketones or aldehydes due to an acidic proton present on the

Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt

• Tobias Lucas,
• Jule-Philipp Dietz and
• Till Opatz

Beilstein J. Org. Chem. 2020, 16, 445–450, doi:10.3762/bjoc.16.41

• arginine, where the desired pyrimidine 10q was also only observed in trace amounts while the majority of the starting material remained unchanged. Synthesis of fluorinated aminopyrazoles As in the cyclocondensation with amidines, the reaction of 8 with other bifunctional nucleophiles could also result in

Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• % overall yield. Installation of the cationic head was performed in two steps: first bromination of 11 via Appel reaction, followed by treatment with trimethylamine to give 2 in 35% overall yield. Photoswitch 2 is the first example of a bifunctional, asymmetrically substituted 4FAB chromophore that actually

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• ], conjugated additions to enones [7], and allylic alkylations [8][9]. Another direction of research is the use of phosphines in organocatalysis [10][11] and bifunctional catalysis [12]. Several methods were developed to introduce the phosphine functionality to organic molecules. The reaction of organometallics

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• kinetic resolution of epoxides with CO2 remains a big challenge. Recently, Ema and co-workers described a chiral binaphthyl strapped Zn(II) porphyrin with triazolium halide units as a bifunctional catalyst for the kinetic resolution of epoxides with CO2 [63]. The condensation of click-reaction-derived

• reaction with the highest enantioselectivity. The importance of the bifunctional system for the catalytic activity and enantioselectivity was demonstrated by performing a series of reactions with lower activity and selectivity, utilizing free-base porphyrin 16h with triazolium moieties and the two

Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• [27]. Then, the bifunctional P450c17 acts as a 17α-hydroxylase and 17,20-lyase to give rise to androstanes [27]. Related enzymes have not been reported from plants. We searched transcriptome data of P. peruviana for putative homologues of these enzymes [28]. The best hits only had amino acid sequence

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• has been demonstrated by Alonso et. al. [26] with the development of a multicomponent approach to obtain 4-azasteroids using an intramolecular Ugi-4CR between a bifunctional steroidal ketoacid and different amines and isocyanides. Because of the poor reactivity of the steroidal ketone, the Ugi-4CR had

• line. A very recent example of a highly diastereoselective Ugi-type MCR was reported by Rivera, Paixão and co-workers using a steroidal isocyanide [31]. As shown in Scheme 9, the procedure comprised the organocatalytic asymmetric synthesis of the chiral bifunctional substrate 30 bearing an masked

• organocatalytic multicomponent approaches [32] not only the chiral steroidal isocyanide but also the bifunctional component 30, used in enantiomerically enriched form, plays a crucial role in the high stereoselection. The mechanistic insights of this class of MCR were disclosed in the original publication [31

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• Leon Buschbeck Aleksandra Markovic Gunther Wittstock Jens Christoffers Institut für Chemie, Universität Oldenburg, Carl von Ossietzky-Str. 9–11, D-26129 Oldenburg, Germany 10.3762/bjoc.15.96 Abstract Two bifunctional diaminoterephthalate (DAT) fluorescence dyes were prepared in a three-step

• suitability for molecular surface labeling. Conclusion Two bifunctional diaminoterephthalate (DAT) fluorescence dyes have been prepared. One functional unit is α-lipoic acid (ALA) for binding the dye to gold surfaces. The other carries a trifluoromethyl group for facile detection of the surface-bound material

• . Bifunctional DAT as a cross-linker for proteins. The compound is a turn-on-probe, i.e., the fluorescence quantum yield Φ = 2% increased upon reaction with the target to Φ = 41%. High-resolution XPS of SAM 3. High-resolution XPS of SAM 7. Preparation of DAT–ALA conjugate 3 with fluorinated benzyl residue