Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• -derived azadiene by H-bonding. This dual activation promotes a stereoselective addition of 3-chlorooxindole to the azadiene leading to intermediate A. The latter is also activated by the chiral guanidine and undergoes an intramolecular nucleophilic substitution which delivers the product 19b with the

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• structure in the early days. Rotaxane bearing a dumbbell comprising only covalent bonds was first reported by Harada and co-workers in 1997 (Scheme 1B) [38]. In this system, the end-capping reaction was based on the nucleophilic substitution of the amino groups on the axle ends. Afterward, such nucleophilic

• synthesis, Harada and co-workers reported the end-capping reaction based on nucleophilic substitution by the amino groups on axle ends (Scheme 2) [43]. Similarly, other highly efficient reactions have been performed as end-capping reactions to produce polyrotaxane [13][14][15]. In addition to the simple

• substitution/addition reactions became the standard for end-capping reactions, although a transition metal–catalyzed cross-coupling reaction has also been used to synthesize CD-based rotaxane. Typically, water-soluble components are prepared, after which the Suzuki coupling reaction in water is used to

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• mainly include: nucleophilic addition or nucleophilic substitution with H2O2 or ROOH [17][18], autoxidation with O2, pericyclic reactions of unsaturated bonds with O3 or O2, and metal-catalyzed peroxidation (Isayama–Mukaiyama hydrosilylperoxidation [19][20], for example) [21][22][23]. As the topic is

• styrenes 217, oxygen sources (water or alcohol), and TBHP mediated by ammonium iodine has been developed (Scheme 68) [137]. Addition of the tert-butylperoxy radical to alkene 217 followed by SN2 nucleophilic substitution with O-source was considered as a possible pathway to the formation of products 218

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• 20 in a yield of 89% [13]. To convert the iodo to an OH group, compound 20 was reacted with Cu2O, 2-pyridinaldoxime and CsOH to give 2-hydroxy-3,4,5-trimethoxybenzaldehyde (21, 65%) [13]. In a subsequent nucleophilic substitution, the fluorinated alkyl chains of 16, 17, and 18 were linked via a

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• compounds (Scheme 16) [68]. The novel iodine(III) intermediate was generated through nucleophilic substitution of a heteroatom nucleophile, which initiated the reaction. A subsequent aryl migration from the iodine to the heteroatom resulted in the formation of the arylated nucleophile. In addition to

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• ). Preliminary mechanistic studies have ruled out the 1,3-sigmatropic shift, indicating that the reaction proceeds through a nucleophilic substitution–annulation process of a reactive π-extended copper-allenylidene intermediate (Scheme 43). At the same time, Qi and Xu et al. [79] also realized the dearomative

• spiroannulation of 2-naphthols or electron-enriched phenols under mild conditions with excellent regioselectivities, enantioselectivities and diastereoselectivities (Scheme 44, 43a–g, 44a–q). In addition, the nucleophilic substitution–dearomative cyclization process between indoles and yne-allylic esters can also

• and rearomatization. Arylation by alkynylcopper driven dearomatization and rearomatization. Remote substitution/cyclization/1,5-H shift process. Proposed mechanism. Arylation or amination by alkynylcopper driven dearomatization and rearomatization. Remote nucleophilic substitution of 5

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• nucleophilic substitution reaction between cyanuric chloride and 4-aminophenylphosphonate or 4-hydroxyphenylphosphonate derivatives. These synthesized dopants were used to prepare the modified Nafion membranes using a casting methodology. Almodovar and Tomé reported the synthesis and characterization of nine

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• reactions was made. It has been suggested that a nucleophilic substitution of the peroxide oxygen atom occurs in peroxydisulfate [32]. Regarding phenols (Elbs reaction), there is also a nucleophilic substitution of the phenolate ion. For aromatic amines (Boyland–Sims reaction), a neutral nitrogen atom of

Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• trifluoromethoxylation by nucleophilic substitution, using an excess of DNTFB as a reservoir of CF3O− [68]. Thus, by adding cyclohexene (1a) to the preformed mixture of DNTFB (2 equiv) and DMAP (1 equiv), followed by the addition of PhSeCl, only a low yield of the expected α-trifluoromethoxylated,β-phenylselenylated

• are difficult to synthesize by nucleophilic substitution, such as products 5a and 5b [68]. Conclusion In this work, an efficient phenylseleno trifluoromethoxylation of alkenes has been developed to readily obtain β-selenylated trifluoromethoxylated compounds. These compounds can also undergo radical

• deselenylation to provide trifluoromethoxylated molecules that can be difficult to access by nucleophilic substitution. These results contribute to the further valorization of the DDPyOCF3 salt (arising from DNTFB/DMAP) as an efficient tool in organic fluorine chemistry. Experimental Typical procedure: Synthesis

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• corresponding thiol [35][36][37][38], in the nucleophilic substitution reaction in the aromatic ring of catechol [39][40] or under electrochemical conditions [41][42][43]. An anodic activation of catechols in the presence of a thiol leads to S-functionalized catechols with triazole, triazine, pyrimidine

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• thioesters and acyl chlorides (Scheme 1a, path 7) [30]. For β-keto amides, they could be efficiently synthesized from the nucleophilic substitution reactions of amines with β-keto acids (Scheme 1b, path 1) [31][32][33], β-keto esters (Scheme 1b, path 2) [34] and the nucleophilic addition reactions of amines

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

• . The α,β-unsaturated carbonyl compounds 60 can undergo cyclization with tosylhydrazine in situ to form pyrazoles 61 under alkaline conditions, with the tosyl group acting as a leaving group. Upon deprotonation at position 1 by a base, followed by nucleophilic substitution of halides, N-functionalized

A new platform for the synthesis of diketopyrrolopyrrole derivatives via nucleophilic aromatic substitution reactions

• Vitor A. S. Almodovar and
• Augusto C. Tomé

Beilstein J. Org. Chem. 2024, 20, 1933–1939, doi:10.3762/bjoc.20.169

• equivalents of the nucleophile, it is possible to promote the substitution of one or more fluorine atoms. Nucleophilic substitution of fluorine atoms often necessitates harsh conditions such as elevated temperatures, strong bases, or strong nucleophiles, but our findings demonstrate that this process can be

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• for our needs [52][53]. Benzylic bromination followed by nucleophilic substitution offers a general approach for the introduction of the nitrogen atom [54][55][56]. Consequently, the continuous flow Wohl–Ziegler bromination of 2b was attempted [57]. Even though we could observe excellent LCMS

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• cyclization of perfluorinated phenylpyrilium salts using arylhydrazine [12]; the process is based on the fluorine nucleophilic substitution thus limiting its applicability to a wider range of substrates. Pyridyl-substituted diarylamines may be considered as the possible precursors for N-arylpyridoindazolium

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

• instead, the authors synthesized a series of 2-amino-protected compound 41 through an aromatic nucleophilic substitution on 2-chloropyrimidin-4-amines. Derivatives 41 were then reacted under the optimized conditions, leading to the formation of a series of GBB adducts 42, finally deprotected with TFA to

• limited to methanol due to solubility problems, and HClO4 was selected because other Brønsted acids caused amine deprotection. The GBB adducts 58 could be further elaborated through a Buchwald intramolecular nucleophilic substitution/cyclization, as it will be described in section 3.3. 3 Novel scaffolds

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• product 3a for further transformations. Comparable yield and enantioselectivity were observed relative to those of the smaller-scale reaction (0.1 mmol scale, Scheme 4). The bromomethyl group in 3a readily undergoes nucleophilic substitution reactions, leading to the formation of optically active δ

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• case of bisamides 5d, 6a, 6c, 7b, 8a, and 8c (Table 2), additional transformation products were also isolated from the reaction mixture. According to 1H and 13C NMR, MS, and X-ray diffraction studies these were the corresponding ketobisamides 12, which are products of a nucleophilic substitution of the

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• reactions. To increase the molecular diversity at the morpholine ring, tertiary amines were formed by nucleophilic substitution. A final removal of the cyclic ketal group in aq sulfuric acid provided spiromorpholinone derivatives 134a–e, 136a–e, and 138 (Scheme 37). Spiromorpholinones were evaluated as

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• nucleophilic substitution using hydrobromic acid, as a 33% solution in acetic acid, to afford the corresponding bromide derivative 9 [54] (Scheme 2). Subsequently 1-(benzyloxy)-4-(bromomethyl)benzene (9) underwent Michaelis–Arbuzov reaction with triethyl phosphite to afford diethyl [4-(benzyloxy)phenyl

• , purification of the crude product by column chromatography led to the decomposition of compound TP7. Another strategy was devised to obtain the desired triazinephosphonate TP7: The first step was the nucleophilic substitution of the chlorine atoms of triazine 1 by 4-hydroxybenzaldehyde (12), followed by the

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• an ammonium hypoiodite species which first facilitates the α-iodination of the pronucleophile, followed by a phase-transfer-catalyzed nucleophilic substitution by the azide. Furthermore, we also show that an analogous α-nitration by using NaNO2 under otherwise identical conditions is possible as well

• first, which then facilitates the α-iodination of 1a (hereby either the formed benzoate or the hypoiodite itself may serve as a base). Intermediate 3 then undergoes a phase-transfer-catalyzed nucleophilic substitution with NaN3 thus delivering the final product 2a. With optimized conditions and a

• pronucleophile, followed by a phase-transfer-catalyzed nucleophilic substitution by the azide. Furthermore, we also obtained a first proof-of-concept for the conceptually analogous α-nitration by using NaNO2 under otherwise identical conditions. Experimental General details 1H, 13C and 19F NMR spectra were

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• followed by the addition of diisopropylamine, either in a one-pot synthesis or in two consecutive steps (Table 1). Subsequently, different aliphatic and aromatic substituents were attached to the pyrazole nitrogen by nucleophilic substitution with suitable organohalides 16 and cesium carbonate [3]. Due to

• 25 was carried out using the nucleophilic substitution procedure reported above with yields of 63–76%. The anticipated formation of a second regioisomer could not be confirmed due to the limited analytical methods available for compounds on solid supports. The cleavage to obtain azidopyrazole 19g was

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• interest [12][13]. The various approaches used for selenation of aromatic compounds include directed lithiation [14][15], copper-catalyzed selenation [16][17][18], and aromatic nucleophilic substitution reactions [19][20][21][22]. Electrophilic selenium reagents (e.g., phenylselenenyl bromide) have often

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

• corresponding Ugi adduct 5aa in 42% yield (Scheme 2 and Figure 2). Interestingly, N-benzyl-2-(N-(1-benzyl-3,3-dimethoxy-2-oxoindolin-5-yl)acetamido)-3-hydroxy-2-methylpropanamide (5aa) was obtained rather than the predictable compound with a 3-chloro-2-methylpropanamide group. We believe that a nucleophilic

• substitution occurs due to the presence of acetic acid (2a) as reaction component. Aliphatic aldehydes with small chains (3b and 3c) were used successfully in the reaction approach, as expected. Also, aromatic 2-chlorobenzaldehyde (3d) was used and the desired compound 5ad was obtained in 36% yield (Scheme 2

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• the basis of readily available 2-chloro-3-nitropyridines via the intramolecular nucleophilic substitution of the nitro group as a key step. The previously unknown base-promoted Boulton–Katritzky rearrangement of isoxazolo[4,5-b]pyridine-3-carbaldehyde arylhydrazones into 3-hydroxy-2-(2-aryl[1,2,3

• ]triazol-4-yl)pyridines was observed. Keywords: aromatic nitro compounds; Boulton–Katritzky rearrangement; isoxazolo[4,5-b]pyridines; nucleophilic substitution; 1,2,3-triazoles; Introduction Nitrogen heterocycles represent a very important class of organic compounds that has found application in various

• shown in Scheme 1C. Since the key step of the synthesis is the intramolecular nucleophilic substitution of the aromatic nitro group, we assumed that the presence of an electron-withdrawing substituent at the pyridine ring would facilitate this transformation. Results and Discussion According to the