Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• situ-generated acetone imines in a (3 + 3) manner to afford meta-substituted anilines (Scheme 1C) [53][54]. Various EWGs (ester, carbamoyl, ketone, trifluoromethyl) have been successfully employed which motivated us to evaluate other possible EWGs. Results and Discussion Based on the fact, that many

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• agrochemical industries. The (3 + 2)-cycloaddition between nitrile imines and alkenes represents one of the most efficient strategies to prepare these azacycles. However, conventional methods for the generation of the nitrile imine involved the use of unstable hydrazonoyl halides or the oxidation of aldehyde

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• reported in the literature are based on the construction of the β-lactam ring (Scheme 1). The main methods include the [2 + 2] cycloaddition of acyl ketenes, generated by various methods, with imines [11][12][13][14] and the Wolff rearrangement of γ-amino-α-diazo-β-ketoesters followed by intramolecular

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• combination of reactants was studied, but a major hurdle was found to be the imine formation step in aqueous media. Consequently, imines were first prepared as metastable adducts (with benzotriazole or p-TSA as stabilizers) and then tested with isocyanides in the presence of the template protein, involving

• metastable imines, could serve as a starting point for the development of other TGS projects involving imine-based multicomponent reactions. 1.4 In situ generation of reactants and use of enabling technologies Despite their high versatility, isocyanides have some drawbacks, such as their repellent smell (but

• a variation of the GBB reaction employing benzothiazole acetonitrile 104 (X = S) in place of the amidine component (Scheme 33). Knoevenagel condensation with an aldehyde in the presence of 2-(hydroxymethyl)pyrrolidinium acetate produced conjugated imines 105 as the reaction intermediates. Once

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• readily converted into a myriad of functional groups including carbonyls, amines, imines, and a variety of heterocyclic scaffolds with well-established procedures [4][5][6][7][8][9]. In particular, tertiary nitriles are common structural motifs in many bioactive compounds and are widely used as

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• aldehydes or ketones, undergo base-assisted condensation reactions with amines providing the corresponding imines. In the last step, the active manganese hydride complexes reduce the imine compounds and afford the desired alkylated amine products (Scheme 2B). Several well-defined manganese complexes have

• synthesis of amines and imines using Mn-pincer catalyst [37]. When t-BuOK (1 equiv) was used as a base, alkylated amine products were observed selectively using alcohol as an alkylating agent, whereas when t-BuONa (1.5 equiv) was used as base, alkylated imine products were isolated (Scheme 6). This

• indicates that the cation-coordinative interaction with the catalyst plays a significant role. Moreover, the mechanistic investigation suggested that the observed selectivity is due to the more reactive potassium manganate hydride towards the hydrogenation of imines to amines than the sodium manganate

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• ., in two different periods, reported two paradigmatic examples for indole syntheses. In 2010, they developed the synthesis of 1-(alkoxyarylmethyl)indole-3-carboxylic esters from 2-alkynylaniline imines by using PdI2/KI as catalyst system and oxygen as oxidant [15]. In particular, the reaction was

• )-catalyzed heterocyclization/alkoxycarbonylation of 2-alkynylaniline imines. Pd(II)-catalyzed heterocyclization/alkoxycarbonylation of 2-alkynylanilines to N-substituted indole-3-carboxylic esters and indole-3-carboxylic esters (top). Pd(II)-catalyzed selective carbonylation of 2-alkynylaniline to methyl 1

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• , Supporting Information File 1). Notably, the YjgF protein previously proposed to aid in deamination of imines – a proposed direct product of NNG degradation by NnlA – is absent [20]. This observation suggests this protein is not needed to aid in glyoxylate formation. Therefore, imine hydrolysis to glyoxylate

Synthesis of photo- and ionochromic N-acylated 2-(aminomethylene)benzo[b]thiophene-3(2Н)-ones with a terminal phenanthroline group

• Vladimir P. Rybalkin,
• Sofiya Yu. Zmeeva,
• Lidiya L. Popova,
• Irina V. Dubonosova,
• Olga Yu. Karlutova,
• Oleg P. Demidov,
• Alexander D. Dubonosov and
• Vladimir A. Bren

Beilstein J. Org. Chem. 2024, 20, 552–560, doi:10.3762/bjoc.20.47

• inverse photochromism), such as merocyanine forms of spiropyrans and spirooxazines, azomethine imines, thioindigoid dyes and N→O acylotropic systems [12][13][14][15]. Recently, they have been actively used to create next-generation molecular switches, materials with new properties (in particular, color

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• quinolines and indoles [24], pyridines [25], and imines [26], the reactions of 5 and 15c with ammonia borane (3 equiv) in the presence of a catalytic amount of B(C6F5)3 in toluene as an aprotic solvent at a temperature of 80 °C afforded aminoboranes 17b (R1 = F) and 17c (R1 = CH3) as main products along with

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

• enolization of the monofluoro-diketone intermediates. In addition, imines and α-diboryl ketone derivatives can also be transformed to 2,2-difluoroketones using an N–F electrophilic fluorinating reagent [18]. Alternatively, building blocks containing CF2 units such as ethyl bromodifluoroacetate and

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

• structure, 3H-phenoxazin-3-ones can easily be accessed through oxidative couplings of o-aminophenols [3][4] or N-aryl-o-benzoquinone imines [5][6]. Further, they can serve as efficient precursors of pentacyclic N,O-heterocyclic compounds that possess promising properties for application in fluorescent

• condensation and Schiff base formation, which is then cyclized [12][16]. The reaction of 1 with arylamines 2a is performed in toluene solution in the presence of a catalytic amount of p-toluenesulfonic acid. This readily affords 6,8-di-tert-butyl-N-aryl-3H-phenoxazin-3-imines 3 but proceeds smoothly only with

• obtained via treatment of 6,8-di-tert-butyl-N-aryl-3H-phenoxazin-3-imines with various arylamines in the presence of an excess of trifluoroacetic acid [9]. The structure of the newly synthesized compounds 5, which are derivatives of a previously unknown 14Н-quinoxaline[2,3-b]phenoxazine system 7a, was

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• . Hydrazones can be regarded as electrophilic and nucleophilic imine equivalents, and thus they represent valuable and versatile building blocks in synthetic chemistry [32][33][34][35][36]. Trifluoroacetaldehyde hydrazones can be regarded as an equivalent of fluorine-containing azomethine imines in the

• -withdrawing property of the trifluoromethyl group is key to this coupling reaction [45] (Scheme 7). Trifluoromethylated hydrazonoyl halides Hydrazonoyl halides, which offer a reactive 1,3-dipole, can easily be transformed to nitrile imines in the presence of a base, and they have shown to be useful building

• , 1,4-naphthoquinones, o-trimethylsilylphenyl triflate and chalcones have all been reacted with fluorinated nitrile imines to give a series of fluoroalkylated pyrazoles by Jasiński’s team [67][68][69][70][71][72] (Scheme 11a). Subsequently, Hu et al., Nie et al., and Ma et al. have all independently

Benzoimidazolium-derived dimeric and hydride n-dopants for organic electron-transport materials: impact of substitution on structures, electrochemistry, and reactivity

• Swagat K. Mohapatra,
• Khaled Al Kurdi,
• Samik Jhulki,
• Georgii Bogdanov,
• John Bacsa,
• Maxwell Conte,
• Tatiana V. Timofeeva,
• Seth R. Marder and
• Stephen Barlow

Beilstein J. Org. Chem. 2023, 19, 1651–1663, doi:10.3762/bjoc.19.121

• in the presence of sodium metabisulfite (Na2S2O5) [29] to obtain the corresponding substituted benzimidazoles (III) in essentially quantitative yield (Scheme 1). In the absence of Na2S2O5, but under otherwise similar conditions, we obtained in some cases the imines in which one of the amino groups

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

• , have also been employed in conjugate addition reactions. These reagents are less reactive than organolithium and Grignard reagents but can still add to a range of α,β-unsaturated carbonyl compounds, including enones, acrylates, and imines. In 2011 Sakaguchi and co-worker [64] accomplished the conjugate

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

• -light photons [77]. In their previous work, the Polyzos group discovered the capability of [Ir1]+ to reduce diarylimines via SET in presence of Et3N albeit the large difference in the oxidation potential of [Ir1]0 (E1/2 = −1.47 V vs SCE) and the reduction potentials of imines (e.g., Epred = −2.18 V vs

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• -fused tetrahydroquinolines (reaction 1 in Scheme 1) [41][42]. Menéndez and co-workers reported a Yb(OTf)3-mediated Povarov reaction of imines and N-alkyl-1,4-dihydropyridines for the synthesis of hexahydrobenzo[h][1,6]naphthyridines (reaction 2 in Scheme 1) [43]. Khan and co-workers employed a one-pot

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

• Anup Biswas Department of Chemistry, Hooghly Women’s College, Vivekananda Road, Pipulpati, Hooghly - 712103, WB, India 10.3762/bjoc.19.72 Abstract The aza-Friedel–Crafts reaction allows an efficient coupling of electron-rich aromatic systems with imines for the facile incorporation of aminoalkyl

• replaced by 2-substituted furans 1 as the aromatic reacting partner with imines 12 to execute the asymmetric aza-Friedel–Crafts process modulated by the chiral phosphoric acid P5 as the catalyst. A major concern of this process was the reduced aromatic character of the furan ring and the C2 methoxy

• -substituted substrate was exclusively employed to make the aromatic ring sufficiently electron rich. The substrate scope was mainly attributed to alterations of the substituents on the benzene ring of imines 12 (Scheme 4b) [28]. In 2018, Morimoto, Ohshima and co-workers reported an aza-Friedel–Crafts process

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• , imines, other Michael acceptors, or alkyl halides. Our group is developing trapping of metal enolates with stabilized carbocations and could show that magnesium enolates generated from enones [22], unsaturated amides [23], or heterocycles reacted with tropylium, dithiolylium or flavylium cations [24

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• imines 25 (Scheme 6). The authors also demonstrated the enantioselective aminoalkylation, using chiral diamines as ligands. The introduction of chiral diamines in the metal complex produced the aminoalkylated products enantioselectivity with good ratio of enantiomeric excess. The plausible mechanism

• ] described the catalytic ortho-C(sp2)–H functionalization of pyridines with polar imines 35 and nonpolar alkenes 37 by using mono(phosphinoamido)-ligated rare earth complexes (NP2-Gd and NP1-Sc) as shown in Scheme 8. Complex NP2-Gd was found to be effective in the functionalization of pyridines with imines

• the pyridine ring in bipyridine ring systems. In early 2009 Miura and co-workers [111] reported the rhodium-catalyzed regioselective reaction of aryl-N-heterocycles and aromatic imines with terminal silylacetylenes 209 to synthesize C–H-alkenylated products 210. The terminal silylacetylenes were

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• chosen as the best conditions for further evaluating the substrate scope. Unlike the oxidation of N-aryl(benzyl)amines to N-arylimines using K2S2O8 in the presence or absence of a base is unsuccessful, the oxidation of N-arylsulfonyl(benzyl)amines 1a to imines 2a was achieved under the optimized

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• -methoxyphenyl (PMP)-protected imines 21 (Scheme 6A). By varying the reaction conditions, the syn-anti and the syn-syn diastereomers can be prepared with good yields and excellent stereoselectivity. Using nitroacrylate 23, the authors have also demonstrated a tandem conjugate addition/nitro-Mannich/lactamization

• imines or their synthetic equivalents. Furthermore, we wanted to develop an enantioselective and diastereoselective process without adding chirality elements within the reagents. For our initial studies, we have selected the well-studied cyclic enones as substrates and the Taniaphos ligand (L14) that has

• up to 97:3 er (Scheme 15) [47]. These experiments showed that the concept of interception of magnesium enolates, derived from Cu-ACA, with imines can be realized. As it could have been predicted, chiral enolates reacted with high diastereoselectivity with their Si-face (attack anti to the R group

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• common reaction conditions. The reaction has been defined by Houk and Rueping as a (3+ + 2) monopolar cycloaddition [33] pointing out the protonated state of the imino nitrogen of the hydrazone in contrast to the well-known 1,3-dipolar cycloaddition of azomethine imines in which the terminal nitrogen has

• inversion of the reagents and whereas in the classical cycloadditions with azomethine imines, they act as a nucleophile (involving their HOMO, interacting with the LUMO of the alkene), in our case, the protonated hydrazone acts as an electrophile (involving their LUMO, interacting now with the HOMO of the

• alkene) (Figure 2). Thus, we can consider the reaction of hydrazones with alkenes an inverse-demand cycloaddition with respect to that of azomethine imines (Figure 2). In fact, we monitored the global electron density transfer (GEDT) [34] between the reagents along the reaction coordinate (Figure 3) and