Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• Kingdom 10.3762/bjoc.20.82 Abstract 2-(Trifluoromethylthio)benzothiazolium triflate (BT-SCF3) was used as deoxyfluorinating reagent for the synthesis of versatile acyl fluorides directly from the corresponding carboxylic acids. These acyl fluorides were reacted with amines in a one-pot protocol to form

• unreliable isolation of acyl fluoride intermediates, we next considered whether BT-SCF3-mediated deoxyfluorination of carboxylic acids could be coupled with a subsequent acylation in an overall one-pot process. Selecting amines as nucleophilic coupling partners, a short optimisation study was carried out to

• amides. Scope of the BT-SCF3-mediated deoxygenative fluorination of carboxylic acids 1. Reactions were performed on a 0.2 mmol scale. 19F NMR yields using α,α,α-trifluorotoluene as the internal standard. Scope of the one-pot BT-SCF3-mediated deoxygenative coupling of carboxylic acids and amines via acyl

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• 109 (Scheme 12A) [58]. The formed products all contained a pendant primary iodide group and the synthesis was additionally shown to be tolerant of functional groups including protected amines (in 110c), protected alcohols (in 110d) and nitriles (in 110e). Grygorenko and co-workers accessed fluorine

• , respectively (Scheme 12B) [58]. Saponification of the ester moieties in these species followed by Curtius rearrangements then led to amines 114 and 116. Non-natural amino acid derivatives 113 and 117 are intermediates prepared using these methods that could be of interest to medicinal chemistry. Alcohol 111

• nitrogen-substituted 1,5-BCHeps 141a–d through a photoredox-catalysed aminoalkylation with amines 140 and iodonium dicarboxylates 139 (Scheme 15A) [27]. Both Anderson and Uchiyama also reported the synthesis of chalcogen- and tin-substituted 1,5-BCHeps 145a–f from [3.1.1]propellane (Scheme 15B) [27][47][60

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• of hydrophilic oligopeptide anchors (oligo-Lys, oligo-Glu, and oligo-Arg) were synthesized. A previously reported Prato reaction adduct of a biscarboxylic acid-substituted C60 derivative was subjected to a solid phase synthesis for amide formation with N-terminal amines of peptides on resin to

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• biomolecules via the nucleophilic aromatic (SNAr) substitution reactions [15][16]. A variety of nucleophiles such as amines [17][18], alcohols [18][19][20], thiols [17][19][21][22][23], and carboranes [17][24][25][26][27] have been studied in selective SNAr substitution reactions of the p-fluorine atoms in

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• pristinamycin I NRPS. This TE domain showed activity for hydroxy groups and amines to form either lactone or lactam, and the broad substrate scope made this strategy potent for modifying the bioactivity of streptogramin antibiotics. In 2007, the same laboratory identified the interactive TE domain of the

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• building blocks bearing two of the most versatile functional groups, allowing a rich panel of functionalization. They have been used as intermediates in numerous syntheses to access bioactive compounds [1][2][3][4] or materials [5][6][7]. In addition, azide reduction affords homopropargylic amines, which

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• of quinazolines. A scope of 2-amino-4-azido-6,7-dimetoxyquinazolines 17 was synthesized. For pyrrolidine, selective C2 substitution was achieved in a non-polar solvent such as CHCl3. Less nucleophilic amines gave C2-selective SNAr in MeCN. To apply the developed technique to the synthesis of

• pharmaceutically active substances such as terazosin and prazosin, nucleophilic substitution at the C2 position was carried out with the corresponding amines – piperazin-1-yl(tetrahydrofuran-2-yl)methanone and furan-2-yl(piperazin-1-yl)methanone to give products 17e and 17f. Products 17e,f can be obtained through

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• -light-mediated palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines, affording unsaturated γ- and ε-amino acid derivatives with diverse structures. In this methodology, the diazo compound readily transforms into a hybrid α-ester

• be difficult to achieve using either radical or polar chemistry alone. In recent years, Gevorgyan, Glorius, Huang and their co-workers reported elegant examples of the carboamination of 1,3-dienes with unactivated alkyl halides and amines under photoinduced palladium catalysis via a radical-polar

• reactant ratio produced the desired product 4a in 84% yield as optimal conditions for this protocol (Table 1, entry 13). With the optimized conditions obtained, we examined the generality of our palladium-catalyzed regioselective carboamination of 1,3-dienes with diazo esters and amines (Scheme 2). First

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

• ], to 3–5 [22][73][74]. The lack of KIE measured here for deuterated 1a thus presumes fast protodeauration. Deuterium KIE’s for intramolecular alkene hydroamination with N-protected amines such as the ones in this study, had not previously been quantified, but in Michon’s study of carbamate

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

• reactive enolate 1a-enolate. Nitrogen-centered bases react with fluorine gas to form N-fluoroammonium fluorides and fluoride ion [49]. Thus, on addition of tertiary amines, fluorine can react to generate basic fluoride ions and deliver reactive, electrophilic N–F species. Given that Selectfluor is

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• 1b. Wherein various alkyl and aryl olefins, including those that contain Lewis basic esters, carbamates and amines or α-branched moieties, may be used in efficient and exceptionally Z-selective cross-metathesis reactions [6][7][8]. A few years ago, some publications devoted to the cleavage of the C–F

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• nucleophilic substitution takes place to afford products of the type 155 (Scheme 31B). Representative examples of the substrate scope are shown in Scheme 31C. The in situ-generated phthalimidyl anion (–Nphth) is a competent nucleophile and gives rise to primary protected amines such as 156. Additionally

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

• probes, organic light-emitting diodes, and organic solar cells [2][7][8][9]. The principal way for the preparation of these heterocycles involves the coupling of 3H-phenoxazin-3-ones with variously functionalized aromatic amines. This is followed by the cyclization of the initially formed adducts [10][11

• highly basic amines (Scheme 1) [6]. The choice for one of the other two possible reaction pathways (nucleophilic additions to either the C(1) or C(2) center) critically depends on the electrophilicity. Figure 1 shows the distribution of electronic density in 6,8-di-tert-butyl-3H-phenoxazin-3-one (1

• amines, the direction of which is controlled by the large positive charge at the C(2) center of the p-quinone imine moiety of the heterocycle. With this in mind, we turned our attention to solid-state organic reactions. Numerous examples of nucleophilic substitutions at carbon centers are discussed in

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• (Na2S) to afford dinaphthothiepinetetracarboxylic anhydride 12 as key precursor of a series of thiepine bisimides bearing diverse substituents. Due to its very low solubility, the tetracarboxylic anhydride 12 was not isolated and was directly reacted with a variety of amines to yield the target soluble

• precursors 3a–f. Diverse primary alkylamines were well tolerated, also when an electron-withdrawing polyfluoroalkyl group (3d) was included, and bulkier amines, such as 3-pentylamine (3e) or trimethylaniline (3f), could also be inserted. As a matter of fact, the choice of amines was limited by the

Nucleophilic functionalization of thianthrenium salts under basic conditions

• Xinting Fan,
• Duo Zhang,
• Xiangchuan Xiu,
• Bin Xu,
• Yu Yuan,
• Feng Chen and
• Pan Gao

Beilstein J. Org. Chem. 2024, 20, 257–263, doi:10.3762/bjoc.20.26

• reaction system, yielding product 3ak in good yield. Furthermore, heteroaromatic rings, such as pyridine (2l), thiophene (2m), benzoxazole (2n), and benzimidazole (2o) all afforded the desired products (3al–ao) in satisfactory yields. Subsequently, we investigated the substrate scope of amines, which is

• outlined in Scheme 3. To our delight, various amines (2p–r), including aniline, N-methylaniline, and naphthylmethylamine are also compatible under the optimal conditions to give the corresponding amination products (3ap–ar) in moderate to high yields. For this amination method, it was necessary to

• engage in reactions with electrophilic reagents like thiophenol or amines under alkaline conditions, facilitating the formation of respective C–N/O bonds. The synthesis of alkylthianthrenium salts requires alkyl trifluoromethanesulfonate as a precursor, which can also act as an electrophile. However

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

• effect of functional groups on the further chemistry and basicity of the newly synthesized derivatives is also considered. Results and Discussion Amination, dehydrogenation, and supramolecular aggregation Direct amination of quinoquinoline 5 could potentially lead to 2(11)-substituted amines 6 (Figure 1

• ), the basicity of which must obviously be higher than that of the starting heterocycle 5. To this end, we conducted a series of experiments on its oxidative amination by varying the reaction conditions (time, temperature, addition of n-butyllithium to increase the nucleophilicity of amines), and

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

• crystalline form [55]. It was found that the aliphatic substituents (diacetyl- and distearoyl-) supported faster relaxation rates than the aryl-containing substituents (dibenzoyl- and bis(3,5-dinitrobenzoyl)-). Moreover, addition of catalytic amounts of amines accelerated the backward Z–E isomerization of Z

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

• system to produce the expected product (4p). In addition, the β-trifluoromethyl β-amino benzyl ester substrates 1 with different ester groups were tried to react with benzoic acid (3a) to further extend the substrate range. To our delight, both the amines with electron-donating groups (4q and 4r) and

• General procedure for copper-catalyzed multicomponent reaction of β-amino esters Into a flask were added amines 1 (0.4 mmol), acids 3 (0.1 mmol), CuI (20 mol %), and CH3CN (2 mL). Then, the mixture was stirred at room temperature under a nitrogen atmosphere and t-BuONO (0.4 mmol) was added dropwise

Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• ethyl 2-cyanoacetimidate and corresponding amines according to the literature procedure [17] and compounds 1a,c–e,h–j are commercially available. Azides 2a–d,f,g were synthesized according to the literature procedures [18][19][20][21][22][23], and azide 2e is commercially available. Preparation of

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• diaryliodonium salts [29][31], as well as Pd-catalysed methods for synthesizing N-aryl carbazoles [32]. Similar procedures were published for the Cu-catalysed synthesis of aryl carbazoles from amines as well as other heterocycles such as N-acyl acridanes with nitriles using cyclic iodonium salts by Wen and Chen

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

• to C60 fullerenes [12]. These amines function as bases, their position next to the aromatic surface is essential to turn on anion–π interactions as soon as substrate 4 is deprotonated. Fullerene derivatization with the Bingel reaction installs a cyclopropane that continues with one or two acid

• introduced explicitly in 2019 [13]. Already in the presence of pristine SWCNTs 2, the ability of TEA 23 to catalyze enolate addition with 4 increased to A/D48/23 = 1.2 for a virtual catalytic complex 48 between the two (Figure 8). Covalent modification of SWCNTs with tertiary amines as in 49 further

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

• -mediated domino reaction of chromone-3-carboxaldehydes and amines [41], Pd-catalyzed redox-neutral C–N coupling reaction of iminoquinones with electron-deficient alkenes [42], NH3 insertion into o‑haloarylynones [43], gold(III)-catalyzed azide-yne cyclization [44], Michael/Truce-Smiles rearrangement

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• the ability to be readily transformed into various valuable functional molecules, including amines, hydrazines, and nitrogen-containing heterocycles [13]. In a significant advancement in 2021, Lopchuk et al. revealed a novel method for the photodecarboxylative alkylation of diazirines 12 using the

• route for the synthesis of unnatural amino acids and amines. Remarkably, the procedure exhibited excellent compatibility with a wide range of alkyl radicals, including primary, secondary, tertiary, and α-heterosubstituted radicals generated from corresponding redox-active esters 3. Concurrently, Shang

• novel metallaphotoredox catalysis by combining the NaI/PPh3 photoredox catalyst with a Cu(I) catalyst to accomplish diverse C–O/N cross-couplings of alkyl N-hydroxyphthalimide esters 3 with various phenols/secondary amines 30 (Scheme 13) [24]. It was anticipated the utilization of computational methods

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

• (such as C60/C70 fullerenes) [56][57][58]. Other than amino esters and amino acids shown in Scheme 1, cyclic amines can also react with arylaldehydes to form B1-type semi-stabilized AMYs. In this context, the Seidel group reported the reactions of pyrrolidines 5 with arylaldehydes for the formation of

• AMYs B1 which then were reacted with nucleophiles to form C–H-functionalized pyrrolidines or subjected to the 1,3-dipolar cycloaddition with olefins to afford bicyclic compounds (Scheme 2A and B) [59][60]. We employed cyclic amines for the synthesis of spirooxindole-pyrrolidines 7a or 7b in good

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

• File 1 for amine syntheses). These amines were each carried through the protocols outlined in Scheme 2 to arrive at the deconjugated olefin substrates shown in Table 2. The cinnamylamine derivative 13 underwent the Heck cyclization in 50% yield, while the prenylamine derivative 15 proceeded to give