Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• used as nucleophiles. First, optimization experiments were carried out for fluoroalkoxy reactions with benzonorbornadiene (1a, Table 1). As a result of experiments conducted in six different solvents at room temperature with 1.0 equivalent of selectflor and 1.0 equivalent of methanol, it was observed

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

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

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• generated by addition reaction of isocyanides to electron-deficient alkynes, which were sequentially trapped by various electrophiles and nucleophiles to give versatile acyclic and heterocyclic compounds [15][16][17][18][19][20][21][22][23][24][25][26]. In recent years, many multicomponent reactions based

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• .20.122 Abstract Hypervalent iodine catalysis has been widely utilized in olefin functionalization reactions. Intermolecularly, the regioselective addition of two distinct nucleophiles across the olefin is a challenging process in hypervalent iodine catalysis. We introduce here a unique strategy using

• simple lithium salts for hypervalent iodine catalyst activation. The activated hypervalent iodine catalyst allows the intermolecular coupling of soft nucleophiles such as amides onto electronically activated olefins with high regioselectivity. Keywords: amide coupling; hypervalent iodine catalysis

• nucleophiles were incorporated (Scheme 1b) [29][30][31][32][33][34][35][36][37][38][39][40]. Intermolecular hypervalent iodine catalysis with the regioselective additions of two distinct nucleophilic functionalities across an olefin, however, remains challenging with limited solutions [41][42][43][44][45][46

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• derivatives were 8h and 8k. The former is an α,β-unsaturated amide, which could react with nucleophiles inside the cell and thus explain its relative potency. The latter bears a long aliphatic side chain (thirteen carbon atoms), which could allow anchoring to cell membranes, representing a potential target

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

• to the scientific community [10][11][12]. In this process, first, the metal-catalyzed dehydrogenation of the alcohol provides a reactive substrate for coupling with nucleophiles and the active metal hydride species. Later, the borrowed hydrogen is used in the final step to reduce unsaturated

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• phosphinamide Vb inhibited hCDA similarly to dZ (IIc) at pH 7.4, whereas negatively charged phosphinic acid Va showed some inhibition of hCDA only at pH 4.7. Unfortunately, due to the low stability of charge-neutral phosphinamide Vb towards nucleophiles, we could not incorporate it into DNA. Synthesis of a DMT

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• , ethanol, ethylene glycol, and diethylene glycol in the presence of excess triethylamine (Scheme 2). These products provide evidence for the in situ formation of DCPQ 7a and demonstrate its ability to undergo trapping with various nucleophiles through an SNAr mechanism. An alternate strategy was employed

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• attractive class of reagents due to their stability, accessibility, and diverse chemical reactivity [1]. Diaryliodonium(III) salts, in particular, have been widely recognized as efficient arylating reagents for a range of carbon, nitrogen, oxygen, sulfur, and other nucleophiles, and can be employed in the

• 1,3,5-trimethoxybenzene are highly recommended for chemoselective arylation processes. Aryl(TMP)iodonium(III) salts have been successfully used as transition metal-free arylating reagents for various nucleophiles such as nitrogen- [23][24][25][26], oxygen- [13][27][28][29], sulfur- [30], and carbon- [31

• ] nucleophiles due to their excellent reactivity and aryl group selectivity over aryl(anisyl)iodonium(III) salts [32] and aryl(mesityl)iodonium(III) salts [33]. Based on our previously reported conditions for the synthesis of diaryliodonium(III) salts [21], we designed a more practical synthetic protocol for the

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

• %, respectively) in methanol under 90 bar of CO at 100 °C for two hours (Scheme 6). As already seen, triple bonds can be activated by Pd(II) catalysts towards the addition of nucleophiles in the right position, leading to heterocyclization reactions. Taking advantage of this possibility, in the Della Cá group, a

• alcohols were used as the nucleophiles (Scheme 32). About three years later, the same group developed a simple and efficient method to access CO-linked heterocyclic scaffolds by a Pd-catalyzed carbonylative cyclization of alkene–indole derivatives with 2-alkynylanilines and 2-alkynylphenols, in the

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

• employed as acylation reagents [1][2][3]. The strong C–F bond makes acyl fluorides relatively stable towards hydrolysis and easier to handle than other acyl halides [4][5][6][7][8]. Their reactions with nucleophiles are typically less violent than for the corresponding acyl chlorides with acyl fluorides

• − to another molecule of thioester 3 thus sets off a chain process, delivering acyl fluoride 2 and regenerating the fluoride nucleophile. A series of experiments conducted with thioester 3a suggest a number of nucleophiles feasibly present in the reaction mixture can initiate the chain process [34

• . Mechanistic experiments. (a) Conversion of thioester 3a into acyl fluoride 2a in the presence of DIPEA. (b) Conversion of thioester 3a into acyl fluoride 2a in the presence of carboxylate and fluoride nucleophiles. (c) Two-stage deoxyfluorination reaction using 0.5 equiv of BT-SCF3. 19F NMR yields using α,α,α

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• difunctionalization of alkynes with various heteroatom and carbon nucleophiles [27][28][29][30][31][32][33][34]. Specifically, intermolecular trans-iodo(III)functionalization of alkynes has been achieved using oxygen nucleophiles such as alcohols [28][32], ethers [33], carboxylic acids [31], phosphate esters [31

• ], and sulfonic acids [31]. On the other hand, nitrogen-based nucleophiles amenable to this reaction manifold have thus far been limited to nitriles in the context of Ritter-type iodo(III)amidation [29]. In light of the significance of vinylated azoles, our attention was attracted to the feasibility of

• various azole nucleophiles including pyrazole, indazole, 1,2,3-triazole, benzotriazole, and tetrazole. The follow-up transformation of the iodanyl group provides a means to prepare hitherto inaccessible types of alkenylated azoles. Further exploration of the three-component alkenylation of nitrogen and

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• -benzocoumarin skeletons in the presence of palladium catalysts (Scheme 1b). Furthermore, Olofsson and colleagues described an unprecedented reaction pathway using ortho-fluoro-substituted diaryliodonium salts bearing strong electron-withdrawing groups, leading to novel diarylations of N-, O-, and S-nucleophiles

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• at C4 determined the resultant ring system, as the σ* orbital is not accessible to external nucleophiles due to steric hindrance and the rigid conformation of the bicyclic ring system. When the C4–OH was equatorial, O8 migrated as it was aligned with the σ* orbital giving a 3,8-dioxabicyclo[3.2.1

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• conclusion we wish to point out that this reaction provides a convenient procedure to achieve anti Markovnikov addition of alcohols to olefins which can presumably be extended to other systems. Furthermore, the addition of other nucleophiles to photochemically generated cation radicals would make this type

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

• next studied the modification of the pentafluorophenyl substituents with carborane clusters via the SNAr substitution reaction with carborane nucleophiles [17][24][25][26][27]. These reactions are well studied for porphyrin 1 [17][24][25][26][27] to afford the corresponding carborane derivatives

• the SNAr substitution reactions with 9-mercapto-m-carborane. As a result, tris(carboranyl)-substituted porphyrins containing pentafluorophenyl- or p-aminotetrafluorophenyl-substituents were synthesized and used in the reactions with a variety of thio- or amino-nucleophiles to form functionalized

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

• polyketides or peptides, and form an ester bond. Then, they catalyze either intramolecular macrocyclization to give macrolactones or macrolactams with attacking of internal nucleophiles (alcohols or amine), or hydrolysis to release linear acids or peptides (Scheme 1b). Although TE domains may display

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

• explanation for the present tetrazole form in the solutions. Surprisingly, FTIR and X-ray analyses of 12a in the solid state indicated the existence of 12a in the azide form. In subsequent experiments it was discovered that for less nucleophilic N-nucleophiles (piperidine, morpholine, N-methylpiperazine) C2

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

• electrophilic trapping of onium ylides generated from metal carbenes with nucleophiles, providing an ingenious difunctionalization strategy for diazo compounds to access structurally complex and diverse molecules (Scheme 1b, top) [28][29]. In recent years, radical-mediated MCRs with diazo compounds have become

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

(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

• the corresponding =CF2 containing products [10]. In addition to complexes of aluminum and boron, several magnesium and lithium silyl reagents were prepared and proved to be good nucleophiles in reactions with (Z)-1,1,1,4,4,4-hexafluorobut-2-ene, as a result of which the corresponding

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

• activation of NHPI esters under a photocatalytic oxidative quenching mechanism was reported for the first time by Glorius and co-workers in 2017 [46]. This activation mode was applied in the functionalization of styrenes using an Ir-photocatalyst and a diverse range of nucleophiles that are H-bond donors

• oxyalkylation product 28. Li and co-workers described the activation of NHPI esters towards SET using a Lewis acid catalyst, allowing for the functionalization of styrene radical acceptors with nucleophiles that do not necessarily engage in hydrogen-bonding interactions, such as electron-rich (hetero)arenes [47

• . Intramolecular radical addition into the radical cation of the furan ring would then form cation 50 before nucleophilic capture by H2O leads to product 45. In 2020, the Wang group reported the functionalization of enamides employing radicals derived from NHPI esters in combination with indole nucleophiles [57

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

• ]. Recently, Ritter and co-workers reported that alkylthianthrenium salts can be employed to undergo reactions with N/O-nucleophiles under photocatalytic conditions [46]. Nevertheless, additional transition metal catalysts, visible light, or electrochemical devices are required for the reported works

• . Therefore, developing a green method to functionalize alkylthianthrenium salts is still highly desirable. Considering the highly polarized C(sp3)–S bond in alkylthianthrenium salts, alkylthianthrenium salts have the potential to serve as alkyl electrophiles to react with nucleophiles directly in the absence

• using nucleophiles directly, without the need for an external metal catalyst. Synthetic application of thianthrenium salts. Substrate scope. Reaction conditions: alkylthianthrenium salts 1 (0.3 mmol), thiophenols 2 (0.2 mmol), DIPEA (0.4 mmol) in 2.0 mL of MeCN at room temperature for 16 h under air

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

• equilibrium) under the action of an excess of nucleophiles as bases. Such dianions are characteristic of acenaphthene and have been repeatedly detected in subsequent transformations [18][19]. In our case, the CH-acidity of the CH2CH2 bridge should be even higher under the action of pyridine rings, and, if

• dianion 7 forms (resonance form 7b will prevail in this case, Figure 1), it will be inactive to attack by nucleophiles. The behavior of acenaphthene 5 could be clarified further using its naphthalene analog 3, which lacks benzylic CH2 protons, but there is no information in the literature about its

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• are excellent substrates for such reactions, affording electrophilic carbonyl derivatives susceptible to react with nucleophiles in the acidic reaction mixture [4][5][6][7][8]. Consequently, the Hock rearrangement is likely to be part of tandem processes involving this carbonyl function [9][10][11

• podophyllotoxin structure [26]. However, other nucleophiles like 20–27 (Scheme 5) were unsuccessful, only leading to complex mixtures or occasionally to small amounts of 4 (<10%). Finally, other homologous substrates were tested. While the tandem reaction with a phenylethyl substituent (n = 2, not shown) only led

• surrogate of the aldehyde function when it is engaged in a tandem photooxygenation and Hock rearrangement, involving allylic hydroperoxide intermediates in an acidic medium. In the presence of aromatic nucleophiles, the aldehyde intermediate of the Hock rearrangement can be involved in tandem Friedel–Crafts

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• positioning of the [2 + 2] CA or RE step as the rate-determining step may depend upon the structural attributes of the electrophiles and nucleophiles. In 2023, Nielsen et al. conducted an exhaustive kinetic analysis of the [2 + 2] CA–RE reaction involving 4-trimethylsilylethynylaniline and TCNE by leveraging