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

• Swing Road, Greensboro, North Carolina, NC 27409, USA 10.3762/bjoc.20.41 Abstract Solutions of 1,3-diketones and 1,3-ketoester derivatives react with fluorine to give the corresponding 2,2-difluoro-1,3-dicarbonyl derivatives in the presence of quinuclidine. Quinuclidine reacts with fluorine in situ to

• controller equipment described previously [35]. Our aim was to form a N–F system in situ and thus mimic the successful monofluorination observed between 1a-enol and Selectfluor. After purging the product mixture with nitrogen, a known quantity of α,α,α-trifluorotoluene was added to the product mixture and

• this base that accelerates enolization of 2a–i-keto to allow difluorination to occur. The fluoride ion is a relatively strong base (pKa(MeCN) of HF is ≈25 based on pKa(DMSO) [55][56]), especially when formed in situ under anhydrous conditions, where solvation of fluoride ion is not possible. Since the

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

• formation of α-amino radical 107 through photoinduced SET followed by fragmentation. Subsequent oxidation of 107 by radical cation q-Ac•+ afforded iminium ion 108 before nucleophilic addition of the in situ-generated tetrachlorophthalimyl anion (–TCPhth) led to the formation of aminal product 105. Of note

• , the aminodecarboxylation reaction proved unsuccessful when employing alternative photocatalysts such as Ru(bpy)3Cl2 or eosin Y, underscoring the distinctive ability of q-OAc to activate TCNHPI esters via EDA complex formation. Photoinduced transition metal-catalyzed mechanisms The in situ formation of

• form product 132 or by the in-situ-generated tetrachlorophthalimyl anion (–TCPhth) affording product 105. Stoichiometric reductants can facilitate certain radical-mediated transformations that involve NHPI esters, even without the presence of metal catalysts. Larionov and Sun have independently

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

• conversion in situ, triggered by thermal activation, photoirradiation or redox control. Beside well-established reactions involving the elimination of carbon-based small molecules, i.e., retro-Diels–Alder and decarbonylation processes, the late-stage extrusion of chalcogen fragments has emerged as a highly

• small volatile molecules. Importantly, this ultimate synthetic step, performed in situ, should be quantitative and should not require the addition of chemical reagents, since any non-volatile byproduct would be trapped in the material and thus impact its performances. The “precursor approach” was

• the “precursor approach”, a synthetic strategy has to be devised according to a multi-step route to prepare the soluble precursor, in turn specifically designed to deliver the target π-CPC after activation in situ. This is thus fundamentally different from the approach consisting in reacting a

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• ][20][21][22][23][24][25][26][27], which can be readily generated in situ from α-halogeno hydrazones, have been extensively applied in recent years as versatile building blocks in inverse-electron-demand Diels–Alder (IEDDA) reactions [28][29][30] to construct diverse nitrogen-containing heterocycles

Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process

• Kazuhiro Okamoto,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2024, 20, 264–271, doi:10.3762/bjoc.20.27

• potential than 1 (Figure 2C, grey line); thus, it was subsequently oxidized on the anode to afford the halonium ion (Cl+), which can react with 1 to form unstable N−Cl species (B) in situ (Figure 4). Although we cannot detect the chlorinated intermediate of 1, electrolysis of N-propylcarbamate derivative

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• acetaldehyde dimethyl acetal as a masked form of acetaldehyde, which is hydrolyzed in situ, allowing for a higher product yield and fewer byproducts [15]. The group of Müller describes an elegant consecutive four-component reaction involving an alkynylation–cyclization–iodination–alkylation sequence toward

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• , followed by in situ re-acetylation of the C2-amino group and C6-alcohol with acetic anhydride, resulting in the formation of disaccharide 4 in a one-pot fashion. The anomeric benzyl protecting group in disaccharide 4 was then removed via a Pd/C-catalyzed hydrogenation reaction, producing a mixture of α/β

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

• [42][43][44][45][46][47][48][49], we sought to develop reactions of the unexplored β-trifluoromethyl β-diazo esters. We hypothesized that nitrile ylides, in situ generated from nitriles and β-trifluoromethyl β-amino esters, could also react with carboxylic acids to give nitriliums, which then could

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

• , synthesized in situ from a chiral boron phosphate complex with water, for asymmetric indole reduction (Scheme 1b) [30]. The mild reaction conditions, low catalyst loading, and high enantioselectivity rendered this transformation an attractive approach to synthesize optically active indolines. However, these

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

• surrogate through the in situ formation of an o-(2-bromophenyl)aminoaniline intermediate (Scheme 1d). It should be noted these target compounds have been of great interest to our group and in 2015 we reported a proposed novel methodology for the synthesis of dibenzodiazepines [18], however, upon later

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

• organic solvents (78–20% in MeCN). The quinolizinium derivatives bind to DNA by intercalation with binding constants of 6–11 × 104 M−1, as shown by photometric and fluorimetric titrations as well as by CD- and LD-spectroscopic analyses. These ligand–DNA complexes can also be established in situ upon

• side-effects. Therefore, the search for a class of photosensitizers is still a topical research area in photobiology [60]. To this end, benzo[c]quinolizinium derivatives may be considered as feasible photosensitizers because they can be formed readily in situ in the presence of DNA and because the

• binding angle α = 59° between the ligand 3f and the DNA helix, thus indicating a tilted orientation of the ligand relative to the DNA base pairs within the binding site. The DNA-binding ligands were also generated in situ in the presence of DNA. For that purpose, solutions of the styrylpyridines 2d–g and

Electron-beam-promoted fullerene dimerization in nanotubes: insights from DFT computations

• Laura Abella,
• Gerard Novell-Leruth,
• Josep M. Ricart,
• Josep M. Poblet and
• Antonio Rodríguez-Fortea

Beilstein J. Org. Chem. 2024, 20, 92–100, doi:10.3762/bjoc.20.10

• molecules on surfaces like graphene or carbon nanotubes have allowed the scientific community to visualize at atomic resolution the structural changes of molecules in situ by single-molecule atomic-resolution real-time TEM imaging (SMART-TEM) [1][2][3][4][5]. Since the initial discovery [2], many movies

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

• possibility of obtaining the products of alkyne hydration with analogous or improved yields, using less hazardous precursors to generate the reactive species in situ. In particular, for terminal arylalkynes, the electrochemical route proved to be advantageous, yielding preferentially the hydration products vs

• commercially available BF3 diethyl etherate (BF3·Et2O), commonly used in organic synthesis. Indeed, the main advantages of the developed system are: 1) in situ generation of BF3, which avoids its storage and handling, 2) the possibility to control the amount of electrogenerated BF3 using current by simply

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• CACTUS, Campus Vida, 15782 Santiago de Compostela, Spain 10.3762/bjoc.19.145 Abstract The synthesis of zwitterionic dithiocarboxylate adducts was achieved by deprotonating various aldiminium or 1,2,3-triazolium salts with a strong base, followed by the nucleophilic addition of the in situ-generated

• mesitylamine with sodium nitrite and acetic acid followed by a substitution of the intermediate diazonium salt with sodium azide [68]. All our attempts to prepare 2-azido-1,3-diisopropylbenzene along the same lines failed. Nevertheless, its in situ formation in the presence of phenylacetylene led to the

• lack of conjugation between the heterocyclic core of the molecules and their peripherical decorations. Conclusion The synthesis of three CAAC·CS2 and six MIC·CS2 zwitterions derived from aldiminium or 1,2,3-triazolium salts was achieved via a two-step procedure involving the in situ generation of free

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

• and proceeds through a by base-promoted annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates. The reaction mechanism of this formal [4 + 3] annulation includes the in situ generated allylic ylide, nucleophilic substitution, Michael additon, and elimination processes

• efficient synthesis of spiro[azepine-4,3'-indoline] derivatives via the [4 + 3] cycloaddition reaction of bromo-substituted isatin-derived MBH adducts and N-(o-chloromethyl)arylamides. In this efficient protocol, the reactive allylic phosphonium ylides and aza-o-quinone methides were generated in situ and

• depicted in Scheme 5. At first, MBH carbonates of isatin 2 is attacked at the α-position by the Lewis base to give the ammonium salt A with elimination of carbon dioxide and a tert-butoxide ion. Secondly, the ammonium salt A is deprotonated by the in situ generated tert-butoxide ion to give the allylic

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides

• Kan Tang,
• Megan R. Brown,
• Chad Risko,
• Melissa K. Gish,
• Garry Rumbles,
• Phuc H. Pham,
• Oana R. Luca,
• Stephen Barlow and
• Seth R. Marder

Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142

• concert with sacrificial weak reductants (Figure 1b) [8][9][10][11]. Another approach is to add ambient-stable precursors to reaction mixtures: for example, reducing Wanzlick dimers and related species (Figure 1a, ii) have been formed from precursors through in situ decarboxylation [12] or deprotonation

• [4][5], while other reducing species have been formed from in situ reactions of simple diols or diamines [13]. Another approach is to utilize dimers formed by highly reducing radicals, such the bibenzoimidazoles (Y-DMBI)2 (Figure 1c). (Me-DMBI)2 was first reported in 1984 and used as a reductant in

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• approaches have gained popularity for synthesizing biphenylene derivatives [23]. The utilization of in-situ aryne synthesis to generate biphenylene through the dimerization of arynes 2 from diverse substrates has gained popularity. However, this approach occasionally gives rise to the production of high

• are in situ formed from 23, resulting in the formation of symmetric polycyclic structures 24a and 24b. These isomers obtained as a mixture are then subjected to treatment with p-TsOH in acetic acid, without the need for further purification, to yield the desired products 25a and 25b in 71 and 42

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

• under basic conditions, and expanded the synthetic method to N-substituted acylhydrazones [106][107] (Scheme 18). In the early development of 1,3-dipolar cycloadditions of azomethine imines, the acyclic azomethine imines were unstable and their in situ preparation required Brønsted acid or thermal

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

• elimination reactions between in situ generated 16-K2–19-K2 and MCl3(THF)3 yielding 16-Ti, 18a-Ti (structure not shown), 16-V (Scheme 7), 18a-V (structure not shown), and 19-Cr [67]. The Ti(III)-incorporated 16-Ti and 18a-Ti exhibited paramagnetic properties; their identity was confirmed through elemental

• nitrogen in the middle of the ether chain of 19-Cr. The reaction between in situ generated 17-K2 or 19-K2 and CoCl2 produced paramagnetic cobalt(II) complexes 17-Co or 19-Co [67]. The XRD analysis of 17-Co revealed a molecular structure with distorted octahedral Co(II) coordinating water and hydroxide

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• mostly used for the polymerization of fluorinated olefins. However, the C–I bond of iodoalkyl compounds used as chain-transfer agents is weak and unstable during storage [21]. Therefore, Lacroix-Desmazes et al. [72] used iodine molecules to synthesize iodine chain transfer agents in situ, a process known

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

• sulfenylation of yne-tethered ynamide 147 with N-thiosuccinimides 1 was possible in the presence of only methanesulfonic acid in dichloromethane at room temperature (Scheme 63) [93]. The electrophilic activation of propargylalkyne 147 generated in situ a sulfonium cation 1-I. Afterwards, 6-endo-dig cyclization

• of the phthalimide anion to the β-carbon of chalcone, followed by electrophilic sulfur attack and deprotonation. In the thiolation, in situ formation of thiophenol occurred, followed by thio-Michael addition of chalcone with thiophenol. N-Calcogenophthalimide also can be used to prepare

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

• atom to zinc enables this SH2 process which represents a rare example of alkylzinc-group transfer to a tertiary α-carbonyl radical. The zinc enolate thus formed readily undergoes β-fragmentation unless it is trapped by electrophiles in situ. Enolates of substrates having free N–H bonds undergo

• allylation of lithium (trimethylsilyl)amides prepared in situ from the parent amines by a lithiation/silylation/lithiation sequence (Table 1). Using this protocol, α-(aminomethyl)acrylates 5 and 6 derived from benzhydrylamine and aniline were prepared in high yields (Table 1, entries 1 and 2). The procedure

• is poised to undergo β-fragmentation, but this process can be outcompeted by in situ electrophilic substitution reactions which offer synthetically useful procedures: 1,4-addition (for substrates having N–H bonds) or tandem 1,4-addition–aldol reactions (in the presence of carbonyl electrophiles

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

• the synthesis and applications of NHC–Cu(I) complexes only. 1 Synthesis of NHC–Cu(I) complexes 1.1 Deprotonation of NHC precursors (in situ) with a base The N-alkylazolium salts 11 upon treatment with a base generate the corresponding NHCs which react with a Cu(I) salt to afford the corresponding NHC

• the earlier report [15], under these conditions, formation of [(NHC)2Cu]+ complexes was not observed. In the same year, César et al. [26] reported in situ-generated malonate-derived anionic carbenes which reacted with CuCl to afford the anionic [(maloNHC)CuCl]Li complexes. Furthermore, zwitterionic

• having a triisopropoxy(propyl)silyl ((-CH2)3Si(OiPr)3) substituent on the imidazole ring through in situ transmetallation. One of these complexes, 78a, was successfully anchored on mesoporous silica MCM-41 to afford a new heterogeneous catalyst (Scheme 27). Both compounds were subsequently used as

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

• nucleophilic substitutions employing sodium azide and organic substrates with potential leaving groups have been reported. The resulting organic azides were trapped in situ by a suitable alkyne to give the 1,2,3-triazoles [26][27][28][29][30][31][32][33][34][35][36]. Fairly recent review articles summarize

• aminopyrans [54], should be converted into divalent compounds via coupling of the terminal propynyl group with benzylic biazides. Since biazides are potentially explosive [22] it was very desirable to avoid their isolation and to generate these reactive species in situ from the corresponding benzylic halides

• benzyl azide 3 in situ from benzyl bromide (5) and sodium azide and to directly trap the intermediate with alkyne 2. Under conditions summarized in reaction 3 of Scheme 2 we obtained the desired 1,2,3-triazole derivative 3 in 82% yield. Copper(II) sulfate pentahydrate (0.07 equivalents based on 2) in the

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• complex between Hantzsch ester and N-trifluoroethoxyphthalimide was subsequently engaged in a nickel-catalyzed coupling reaction with in situ-activated alkyl carboxylic acids. This convenient protocol does not require photocatalysts and metal reductants, providing a straightforward and efficient access to

• elegant strategies on direct conversion of in situ-activated carboxylic acids for ketone synthesis [27][35][38], we chose dimethyl dicarbonate (DMDC, A1) as the activating reagent. To our delight, the reaction of 1a and 2 in the presence of NiBr2(dtbbpy) (10 mol %), Hantzsch ester (HE) and A1 in DMAc

• light-induced charge transfer event to give trifluoroethoxyl radical B, followed by a 1,2-hydrogen atom transfer (HAT), producing the stable radical C. For the nickel cycle, it is initiated by oxidative addition of Ni(0) catalyst E to acyl electrophile D formed in situ from carboxylic acid 1 with