Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• Ruichen Lan Brock Yager Yoonsun Jee Cynthia S. Day Amanda C. Jones Chemistry, Wake Forest University, 1834 Gulley Rd., Winston-Salem, NC, 27109, USA 10.3762/bjoc.20.43 Abstract Kinetic studies on the intramolecular hydroamination of protected variants of 2,2-diphenylpent-4-en-1-amine were carried

• -order dependence on alkene, first-order dependence on catalyst, and second-order dependence on the imidazolidinone nucleophile [22]. They observed a primary kinetic isotope effect (k(H/D) = 3.14) when deuterated amine was used. The second order dependence is rationalized by a mechanism where a second

• molecule of amine delivers a proton to the alkylgold intermediate (for protodeauration). In a platinum-catalyzed hydroamination, a protodemetalation pathway is supported by kinetics and reactivity studies on generated platinum alkyl intermediates [46]. In a palladium-catalyzed hydroamination, a

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• -diketone 2a. Supplementation of the reaction mixture with either a tertiary amine or inorganic base led to varying mixtures of mono- and difluoro products 2a and 3a, respectively, with the tertiary amines proving most effective. Inorganic bases offer the possibility of deprotonating 1a-enol to form a more

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• ][12]. At the first stage, this reaction follows one of three possible reaction pathways, including Schiff base formation (attack at the C(3) center), Michael addition at C(1), or nucleophilic substitution (SNH) at the C(2) center [13][14][15]. Most readily used is the pathway involving carbonyl–amine

• conditions. The reactions proceed readily in refluxing acidified (pKa = 1–5) ethanol solutions of the amine hydrochlorides to give 2-monosubstituted derivatives of 3H-phenoxazin-3-ones in a moderate yield [10][17]. In the present work, we intended to explore the reaction of 3H-phenoxazin-3-ones with aromatic

• the crystalline samples, which is otherwise typical for solid-state reaction, was employed in this case. As seen in Scheme 2, the nucleophilic substitution reaction occured in good yield and with no restrictions in terms of amine basicity. The molecular structures of compounds 4c,d,f were determined

Spatial arrangements of cyclodextrin host–guest complexes in solution studied by ¹³C NMR and molecular modelling

• Konstantin Lebedinskiy,
• Ivan Barvík,
• Zdeněk Tošner,
• Ivana Císařová,
• Jindřich Jindřich and
• Radim Hrdina

Beilstein J. Org. Chem. 2024, 20, 331–335, doi:10.3762/bjoc.20.33

• anisotropy of the chiral cavity is expressed by differences in the magnetic shielding of prochiral atoms, resulting in signal splitting of the prochiral carbons of the guest molecule in 13C NMR spectra. Adamantan-2-amine hydrochloride was used as a model guest molecule containing three sets of prochiral

• -cyclodextrins. Compounds 1, 6 and 8 are commercial, compounds 2–5 [21] and 7 [22] were prepared according to published procedures. Compound 2 (as a free amine) crystallized in the supramolecular capsule of two α-cyclodextrins, and the mono-crystal was subjected to X-ray analysis. This experiment was performed

• arrangement in solution and extrapolated for compounds with similar size and bonding nature. Model system for the elucidation of the solution state conformations of the host–guest complexes. 13C NMR splits of prochiral carbons of the guest molecule 1 (adamantan-2-amine hydrochloride) in the anisotropic cavity

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• reagents (amine, oxidizing agent) (for details and literature sources, see Supporting Information File 1, Table S1). In most experiments, only starting compound 5 was isolated almost quantitatively from the reaction mixture. Azaarene 5 proved to be resistant to the action of reagents even in the presence

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• -9a and Z-9d in benzene solution. Interestingly, the order of acceleration was primarily dependent on the basicity of the catalyst, unless the steric hindrance of the amine became a significant factor, as is the case of diisopropylamine and trimethylamine. Compounds 9d and 9e are the first examples of

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• side reactions was carried out with benzyl 3-amino-4,4,4-trifluorobutanoate (1a) and benzoic acid (3a) as model substrates. The initial reaction of amine 1a and acid 3a in acetonitrile in the presence of diazotization reagent tert-butyl nitrite with CuI (10 mol %) as catalysts for 2.5 h at room

• bring any improvement on the reaction outcome (Table 1, entries 6 and 7). Further optimization of the reaction conditions focused on the variation of the amounts of amine 1a and tert-butyl nitrite (Table 1, entries 8–12). Considering the instability of the diazo structure generated from amine 1a, we

• increased the amount of amine 1a and tert-butyl nitrite to 4 equivalents. Pleasingly, the yield of product 4a was further increased to 74% (Table 1, entry 12). Furthermore, we optimized the reaction time and found that shortening the reaction time resulted in a decreased yield (Table 1, entry 13

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• mechanism of the CPA-catalyzed transfer hydrogenation reaction was proposed (Figure 2). The activation of 3,3-difluoro-substituted 3H-indole 1 by protonation through the Brønsted acid generates the iminium A. Subsequent hydrogen transfer from the Hantzsch ester gives the chiral amine 2 and pyridinium salt B

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• takes places to deliver palladium species III. Then the insertion of CO that is released by Mo(CO)6, should afford intermediate IV that undergoes a base-promoted intramolecular cyclization via nucleophilic attack of the amine [31]. Finally, the dibenzodiazepinone 4a would be obtained through reductive

Correction: Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2024, 20, 170–172, doi:10.3762/bjoc.20.16

• compound 24 to give the title compound 1d (275 mg, 1.14 mmol) was achieved in a percent yield of 26% over two steps. However, this does not match the amounts of substance given for amine 23 and nobilone (1d), respectively. The yield should be 58% instead of 26%. All required corrections for the original

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• amine functionalized substrate, because of competition of the reaction site during the synthesis of substrates. However, an amide-substituted indole furnished a clean product without competition; for example, product 3u was derived from melatonin with an amide functional group, whose reaction to the

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• the amine 2b gave the corresponding amide 2g in 28% yield. The chloro-substituted derivative 2e was synthesized in a Sandmeyer-reaction from 2b in 20% yield. The products 2a–g were identified and fully characterized by NMR spectroscopy (1H, 13C, COSY, HSQC, and HMBC), elemental analyses, and mass

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