1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• electrogeneration of BF3 in BMIm-BF4 Electrolyses were performed as reported above and stopped after the passage of 60 C. At the end of the electrolysis the cathodic compartment was removed and 0.6 mmol of the appropriate tertiary amine (DIPEA or DBU) were added to the anolyte. The mixture was stirred at room

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• sequentially underwent a [4 + 3] cycloaddition reaction (reaction 1 in Scheme 1) [54]. Recently, Chen and co-workers reported a chiral tertiary amine-catalyzed asymmetric γ-regioselective [4 + 3] annulation reaction of isatin-derived MBH carbonates and cyclic 2-benzylidenebenzo[b]thiophen-3-ylidene

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• derivatives. In fullerene 8, this is an amide with a short ethylene tether for the tertiary amine (Figure 3). Fullerene 8 catalyzed the formation of the addition product 6 with high selectivity over the decarboxylation product 7 [12]. The experimental product ratio A/D8 was divided by the product ratio A/D9

• intermediates and anionic transition states on top of fullerenes dimers should thus induce a larger macrodipole which should in turn strengthen their binding to the expanded π system and thus increase anion–π catalysis (Figure 1B). Fullerene dimer 37 was equipped with the tethered tertiary amine needed to

• /23 = 4.6 of the respective monomer 22, which was already best among fullerene monomers. In computational simulations, the positive maximum of the MEP surface next to the amine base was the same for dimer 37 (+13.9 kJ mol−1) and monomer 22 (+13.8 kJ mol−1), supporting that the dramatic increase in

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• ). The cinchona amine 3 was prepared starting from the naturally occurring quinine [31]. The gained catalyst was demethylated using BBr3 to give alcohol 4. The demethylated cinchona amine was reacted with half-squaramide [9] 5, resulting in demethylated squaramide 6. A short and flexible linker was

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• experiments we used a set of β-keto amides 1. One of these compounds (1g) was acquired from a commercial supplier, others (1h and 1i) were prepared by acetoacetylation of the corresponding amine [64], and the remaining ones (1a–f) were prepared according to our previously published method [65][66]. The

• intermediate β-enamino amides 2 are easily available by condensation of the corresponding β-keto amide 1 and an amine (Scheme 1, conditions i). As the amine here plays only an auxiliary role, for the purpose of this research we opted for inexpensive ethylamine. Compounds 2 were obtained by simply stirring a

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• -pyrazolo[3,4-d]pyrimidin-5-amine followed by dimerization to give the final macrocycle. A convenient synthesis of the latter starting from 4-imino-2-methyl-2,4-dihydro-5H-pyrazolo[3,4-d]pyrimidin-5-amine was developed. A plausible pathway for the macrocycle self-assembly is discussed. Some features of the

• -2-methyl-2,4-dihydro-5H-pyrazolo[3,4-d]pyrimidin-5-amine described by Baraldi et al. [41] using the reaction of 3-[(ethoxymethylene)amino]-1-methyl-1H-pyrazole-4-carbonitrile with excess hydrazine hydrate in EtOH under reflux. However, a pyrazole-fused 1,2,4,8,9,11-hexaazamacrocycle was unexpectedly

• the detailed studies of the hydrazine-promoted transformation of 3-[(ethoxymethylene)amino]-1-methyl-1H-pyrazole-4-carbonitrile (4) or 4-imino-2-methyl-2,4-dihydro-5H-pyrazolo[3,4-d]pyrimidin-5-amine (8) into 2,10-dimethyl-2,8,10,16-tetrahydrodipyrazolo[3,4-e:3',4'-l][1,2,4,8,9,11

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• pyrrolo[2,1-a]isoquinolines and hexahydropyrrolo[2,1-a]isoquinolines. Bioactive tetrahydropyrrolothiazoles. Aminoester- and amino acid-based AMYs for single and double [3+2] cycloadditions. Formation of semi-stabilized AMYs B1 from pyrrolidines. Cyclic amine-based AMYs A3 and B1 for [3 + 2] cycloadditions

A deep-red fluorophore based on naphthothiadiazole as emitter with hybridized local and charge transfer and ambipolar transporting properties for electroluminescent devices

• Suangsiri Arunlimsawat,
• Patteera Funchien,
• Pongsakorn Chasing,
• Atthapon Saenubol,
• Taweesak Sudyoadsuk and
• Vinich Promarak

Beilstein J. Org. Chem. 2023, 19, 1664–1676, doi:10.3762/bjoc.19.122

• ) (30 nm)/tris(4-carbazoyl-9-ylphenyl)amine (TCTA) (10 nm)/TPECNZ (60 nm)/1,3,5-tris(1-phenyl-1H-benzimidazol-2-yl)benzene (TPBi) (40 nm)/LiF (1 nm)/Al (100 nm), in which ITO and Al served as anode and cathode, respectively (Figure 7a). Herein, HAT-CN and LiF were used as the hole- and electron

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• commercially available. Regarding the molecular design and their properties, porphyrins and crown ethers are like water and fire – they constitute the opposite elements (Figure 1). Porphyrins are built of four pyrrole rings, two of which are considered amine-like due to the presence of NH groups, whereas the

• complexes, the fragment originating from the porphyrinoid could form hydrogen bonds with a carboxyl group, while the crown ether cavity would allow interaction with the protonated amine group of an amino acid molecule. The choice of macrocycle size could enable the recognition of different biomolecules

Synthesis of 7-azabicyclo[4.3.1]decane ring systems from tricarbonyl(tropone)iron via intramolecular Heck reactions

• Aaron H. Shoemaker,
• Elizabeth A. Foker,
• Elena P. Uttaro,
• Sarah K. Beitel and
• Daniel R. Griffith

Beilstein J. Org. Chem. 2023, 19, 1615–1619, doi:10.3762/bjoc.19.118

• accessed from tropone (via its η4-diene complex with Fe(CO)3) in a short sequence of steps: 1) nucleophilic amine addition and subsequent Boc-protection, 2) photochemical demetallation of the iron complex, and 3) an intramolecular Heck reaction. Minor modifications to the protocol enabled access to the

• ervitsine [10][11] (Figure 1). We reasoned that, with an appropriately functionalized amine side chain and properly disposed unsaturation on the seven-membered ring, an intramolecular Heck reaction could give rise to skeleton 4 in just a few steps from tricarbonyl(tropone)iron (Scheme 1). Herein, we report

• our successful efforts to access this bridged bicyclic ring system. Results and Discussion As shown in Scheme 2a, the synthesis of the requisite Heck reaction precursor began with the addition of the known allylic amine 5 to tricarbonyl(tropone)iron, immediately followed by Boc-protection of the crude

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• azido amine intermediate INT-3 can be formed via vinylic substitution of INT-1 with an azide which can cyclize to form INT-4 that subsequently aromatizes to afford product 3 (route B). To demonstrate the applicability of this method, a scale-up reaction was performed using 150 mg of the limiting reagent

Complexes of resorcin[4]arene with secondary amines: synthesis, solvent influence on “in-out” structure, and theoretical calculations of non-covalent interactions

• Waldemar Iwanek

Beilstein J. Org. Chem. 2023, 19, 1525–1536, doi:10.3762/bjoc.19.109

• also found that the stoichiometry of the formed complexes depends on the size of the amine molecule. The automated interaction sites screening (aISS) made it possible to generate molecular ensembles of complexes. The geometry of the ensembles was first optimized with the r2scan-3c functional and

• exchange and dispersion interactions in CHCl3 in relation to DMSO are the driving forces behind the placement of sec-amine molecules into the R[4]A cavity and the formation of “in” type complexes. Keywords: complexes; DFT calculations; hydrogen bond; resorcin[4]arene; supramolecular chemistry

• the amine nitrogen of the guest molecule. In addition to hydrogen bonding, other interactions such as π–π stacking and electrostatic interactions also play a role in the complexation process. These interactions can be modulated by changing the pH, solvent, and temperature of the solution. The binding

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• determined to be significantly more potent than the methanol negative control. General route to berberine variants, displaying the numbering system for the berberine ring. Synthesis of new berberine variants. Reductive amination to a secondary amine was followed by cyclization with glyoxal to provide the

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• the presence of N-(2-bromophenylthio)succinimide 1’ and copper catalyst led to intermolecular sulfenoamination of alkenes and subsequent C–N coupling to produce dihydrobenzothiazine structures 27 in a one-pot manner. Furthermore, deprotection of the amine unit by K2CO3 and Na metal was performed in

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• of primary amines and tert-butylsulfinamide (preparation of compounds 5–7 and 8a–c). In a round-bottomed flask under argon, n-BuLi (1.0 equiv, soln. in heptane) was added dropwise to a THF (0.2 mol·L−1) solution of the appropriate primary amine or tert-butylsulfinamide (1.0 equiv) at −55 °C. The

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• . Two complexes, 61 and 65 (see Scheme 21), were found equally efficient. The products were obtained in 95 to 99% yield and the range of functionalities tolerated included nitro, nitrile, ether, carbonyl, alcohol, and amine [35]. Gautier and co-workers studied the effect of the addition of aromatic N

• , generated from the tetranuclear complex, as the catalytically active species. 2.4 A3 reactions In recent years, the three component reaction of an aldehyde, a secondary amine and a terminal alkyne, known as A3 reaction to afford chiral propargylamines 140 has received much attention. The latter compounds

• multifunctional catalytic system 142 incorporating ruthenium nanoparticles (RuNPS) and an NHC–Cu–Cl complex supported on silica (Scheme 56). The catalyst, Ru@SiO2–[Cu(NHC)] was successfully applied to a one-pot tandem A3 reaction of an aldehyde, alkyne, and secondary amine followed by hydrogenation of the

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• (bromomethyl)benzene furnished geometrically differing bis(1,2,3-triazole) derivatives. The use of tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA) as ligand for the click step turned out to be very advantageous. The compounds with 1,2-oxazinyl end groups can potentially serve as precursors of divalent

• converted into several multivalent compounds B by amine or amide bond formations [44][45][46][47]. The transformation of the corresponding azidopyrans and azidooxepanes C or E into multivalent 1,2,3-triazole derivatives D and F by Meldal–Sharpless cycloadditions with suitable alkynes proceeded generally in

• we examined the influence of the ligand tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA) which has been identified by Sharpless et al. [58] as a very beneficial component in CuAAC reactions. After comprehensive optimization, we found that the addition of 0.2 equiv of this ligand not only

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• indeed much more stable than PAF in serum, increases the formation of prostaglandin E2 from astrocyte cortical cell culture [103] and affect memory [104]. Ponpipom et al. have reported the synthesis of PAF-analogues featuring in sn-2 position either an azide, amine or acetamide group [79]. In each case

• trimethylamine to yield the phosphate 17.10 as an intermediate. Then, its reaction with trimethylamine produced the phosphocholine moiety and compound N3-PAF (17.11). Then, the amine (NH2-PAF) 17.12 was formed by catalytic hydrogenation and subsequently the (acetamido-PAF) 17.13 was formed by acetylation of the

• amine with acetic anhydride. It is worth noticing that acetamido-PAF 17.13 was previously reported following a different synthesis scheme starting from serine as chiral precursor [96][105]. Recently, is was reported that the acetamido-PAF 17.13 is an activator of the TRPV2 channel leading to

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• reaction for the synthesis of polyfunctionalized cyclohexenes bearing multiple stereocenters. The reaction is promoted by a chiral secondary amine, which is capable of catalyzing each step of the process activating the substrates through enamine and iminium ion catalysis towards a Michael/Michael/aldol

Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors

• Grace A. Lowe

Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88

• -workers published a study in which they used a cyclic tertiary amine sacrificial donor that they had designed to be regenerated [32]. This was significant because instead of replacing amine sacrificial donors with redox mediators, this paper proposed an alternate strategy of an ex-situ regeneration of

• organic donors. The authors designed and synthesized a tertiary amine that could be oxidized and rehydrogenated. They used their amine to successfully replace triethylamine in a photocatalytic carbon dioxide reduction reaction from the literature and proved that the recyclable byproduct was formed. In

• . Carpenter and co-workers also proposed, but did not test, recycling their amine with electrochemistry and light [32]. They cited a work by Itoh et al. who modified a proton exchange membrane electrolyzer with a Rh–Pt catalyst to generate hydrogen from water to hydrogenate benzene to cyclohexane in one

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• ]. They disclosed a reaction between acyclic iodonium ylides (e.g., 31/ I-10) and tertiary amines 32, which produced indoline rings 33 by forging two new C–C bonds between the ylidic carbon and unactivated positions on the amine (Scheme 5). In 2020, they disclosed a more complex variant of this reaction

• leading to malonate, the second equivalent of 31 coupled with the activated amine and cyclized to produce 33. The formation of 35 in their latter study was mechanistically analogous to this proposal; however, a third equivalent of ylide 31 was necessary to facilitate an additional series of PT and SET

• gave 33a in 32% yield, significantly lower than the previously obtained 56%, when the ortho-anisyl ylide 39 was used it gave 33a in a much improved 72% yield. The yields of other reactions that employed various amine and ylide derivatives were consistent with those previously obtained (Scheme 5

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• ). Nucleophilic addition of the amine to the acyl radical and amine-assisted intermolecular proton transfer [84] generates the α-hydroxy radical 24 from which formation of the amide 25 proceeds either via i) oxidation by [Ir2]+ and deprotonation or ii) radical chain propagation [85]. Electron-deficient, electron

• . Notably, carbonylative amidation of a borylated aryl bromide to 26d proceeded well, where a Pd-catalyzed carbonylative amidation reaction would be plagued by undesired Suzuki coupling. Several secondary cyclic and acyclic amines, as well as primary amines were successfully employed as amine coupling

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• amines smoothly proceeded N-arylation to give the corresponding tertiary amine derivatives with moderate yields after 6–8 hours. The results are summarised in Scheme 3. The reaction of N-methylaniline with iodonium ylide 2a in the presence of 10 mol % of catalyst delivered N-methyl-N-phenylaniline (3r

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• of indole 9 through aza-Friedel–Crafts reaction with aryl-α-ketimino esters 26/29. They also utilized unsubstituted and 2,3-disubstituted pyrroles 9 as π-nucleophile towards the same electrophiles to incorporate an amine-substituted quaternary stereocenter at the C2’ position (Scheme 8b) [33]. In

• stereocenter bearing primary amine and trifluoromethyl functionalities associated with appreciable enantiocontrol. The substrate scope was investigated by the variation of sterically and electronically divergent aryl substituents in the ketimines but the enantioselectivity was markedly lowered with sterically

• in 83 and the enantioregulation was achieved by BINOL-derived chiral phosphoric acid P22. An amine functionality was crucial in the isoxazole ring to enhance the nucleophilicity of the adjacent carbon atom. In addition, the amine hydrogen forms an H-bond with the catalyst along with another hydrogen

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• proposed by Wang [55] (Scheme 2b), 2,5-dimethoxytetrahydrofuran (2) is first protonated with acetic acid, followed by ring opening to form carbocation B. In the following step, primary amine 1 nucleophilically attacks carbocation B to produce intermediate C, which, after proton rearrangement and the

• reactivity of the aromatic amine depends on the electron density of the amino compounds. In addition, the authors also performed the reaction of aliphatic amines with 2,5-DMTHF (2), and found that aliphatic amines are inert in the presence of MgI2 etherate. The proposed mechanism shown in Scheme 9b suggests

• and forms an unstable intermediate that easily forms activated dialdehyde B. The amine 24 reacts with activated dialdehyde and provides the corresponding pyrrole 25 through the removal of water molecules. Smith and co-workers [65] reported a modified one-pot, two-step Clauson–Kaas procedure for the