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

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• bifunctional compounds 74 at the end, allowing the obtention of the 16- to 20-membered tetrazolic macrocycles 75 in only five steps (Scheme 14). A similar approach was used shortly afterwards by the same research group in the synthesis of macrocyclic depsipeptides containing a tetrazole nucleus [31]. The

• intramolecular Passerini reaction was performed using bifunctional isocyanocarboxylate (Scheme 15a). Scheme 15b shows three of the 21 depsipeptides macrocycles synthesized by the authors in this study. Ethyl isocyanoacetate (13b) has also been successfully used as starting material to allow consecutive Ugi

• step was attributed to difficulties during the purification step along with to some oligomerization that might have occurred. Repetitive IMCRs – multicomponent macrocyclizations through bifunctional building blocks A strategy that has been widely used for the synthesis of macroheterocycles is the

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• synthesis of a novel category of pseudo-peptides via intramolecular Ugi reaction of levulinic acid (4-oxopentanoic acid), aromatic and aliphatic amines, and amino acid-based isocyanides is reported. Levulinic acid was applied as a bifunctional substrate containing both carbonyl and acid moieties suitable

• peptidomimetics with potential pharmaceutical applications. Therefore, the development of innovative Ugi reactions is crucial for the synthesis of novel chemical libraries for various purposes [12]. In recent years, one of the modifications for Ugi reactions is the introduction of bifunctional substrates into the

• by acid catalysis from renewable resources, such as sugars, lignocellulosic biomass and waste materials [18]. It can be used as a bifunctional precursor for the synthesis of pharmaceuticals, plasticizers, and different additives [19]. Furthermore, it is recognized as an excellent starting material

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• polymerization of another monomer [53][54][55]. Synthesis from end-functionalized blocks Another strategy to multiblock copolymer preparation is to assemble them by using pre-synthesized telechelic polymers with α,ω-bifunctional end groups, which can be coupled in different ways. The classical technique for

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• used for the C–C coupling in the N-acyl Mannich reaction with activated isochinolin 10, 1-chloroisochroman (18) and chromone 21 with different silyl ketene acetals. Due to more efficient bifunctional Si(OH)2-hydrogen bonding, silandiol 9 tops chlorosilanol 8, also on catalytic application

Copolymerization of epoxides with cyclic anhydrides catalyzed by dinuclear cobalt complexes

• Yo Hiranoi and
• Koji Nakano

Beilstein J. Org. Chem. 2018, 14, 2779–2788, doi:10.3762/bjoc.14.255

• peak molecular weight of the higher molecular weight portion was twice as large as that of the lower molecular weight portion. Accordingly, trace amounts of diacid in PA and/or water contaminants would work as bifunctional chain-transfer agents and gave twice the molecular weight of the copolymer

• initiated by monofunctional pentafluorobenzoate from (R,R,S,S)-1 and [PPN][OCOC6F5] [19]. The formation of the alternating copolymers initiated by monofunctional pentafluorobenzoate and the bifunctional chain-transfer agents was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass

Dispersion-mediated steering of organic adsorbates on a precovered silicon surface

• Lisa Pecher,
• Sebastian Schmidt and
• Ralf Tonner

Beilstein J. Org. Chem. 2018, 14, 2715–2721, doi:10.3762/bjoc.14.249

• theory; dispersion; organic/inorganic interfaces; Introduction The creation of organic/inorganic interfaces is one of the main endeavours in enhancing the application range of modern electronic devices for silicon-based technology [1][2]. One way to achieve this is covalent attachment of bifunctional

• of the parent system 1 thus gives crucial insight that is expected to be transferable to the bifunctional derivatives. The adsorption of a molecule on a surface can proceed either via a direct pathway or via an intermediate species that is crucial for selectivity and the description of adsorption

Transition metal-free oxidative and deoxygenative C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyl lithium as an efficient synthetic approach to azaheterocyclic carboranes

• Lidia A. Smyshliaeva,
• Mikhail V. Varaksin,
• Pavel A. Slepukhin,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2018, 14, 2618–2626, doi:10.3762/bjoc.14.240

• the first examples of the SNH methodology for the synthesis of new heterocyclic carboranes by means of direct C–H/C–Li coupling of non-aromatic 2H-imidazole 1-oxides with carboranyllithium. A growing interest in bifunctional compounds, bearing both the pharmacoactive imidazole motif and a polyhedral

• organoelement bifunctional ensembles, bearing heterocyclic and carborane moieties, which are of particular interest in the design of advanced materials, have been obtained in good yields. The 1H NMR spectra of 1-(5-(4-bromophenyl)-2-ethyl-2-methyl-2H-imidazol-4-yl)-1,2-dicarba-closo-dodecaborane (4d) and 1-(4

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• a suitable target to prevent toxin secretion. The anti-PcrV antibody KB001 [68] and the bifunctional antibody MEDI3902 [69], which targets PcrV and the biofilm-associated exopolysaccharide psl, are both currently in phase II clinical trials. 6. Bacterial communication Quorum sensing (QS) is employed

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• -activated acylimidazole derivative was then converted to a β-ketoester containing a two carbon atom-elongated side chain than that of the starting material. A Knorr cyclization of the bifunctional 1,3-dicarbonyl compound with hydrazine and its monosubstituted derivatives in AcOH under microwave heating

• magnesium enolate of malonic acid half ester, prepared in situ from potassium methyl malonate, MgCl2 and triethylamine in acetonitrile, was added [24][25]. The acylation of magnesium methyl malonate by the preformed imidazole 3 led to the desired bifunctional starting material 4 in good yield (79

Nucleoside macrocycles formed by intramolecular click reaction: efficient cyclization of pyrimidine nucleosides decorated with 5'-azido residues and 5-octadiynyl side chains

• Jiang Liu,
• Peter Leonard,
• Sebastian L. Müller,
• Constantin Daniliuc and
• Frank Seela

Beilstein J. Org. Chem. 2018, 14, 2404–2410, doi:10.3762/bjoc.14.217

• . Conclusion The synthesis of a macrocycle is often described as an intramolecular cyclization of a bifunctional precursor molecule. However, in many cases competition exists with dimerization and polymerization. Therefore, we were delighted to see that the intramolecular cyclization, utilizing dU and dC