Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• t-BuO2Li reagent [31], we speculated that NaClO·5H2O would similarly work for the corresponding Z-1 with retention of stereochemistry. The procedure found here was also applied to the three representative CF3-containing α,β-unsaturated esters,1h–j [42] with different substitution patterns (Scheme 2

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• synthesized from 1,1-diphenylethanol (1i) and phenyl(thiophen-2-yl)methanol (1l), respectively, in one step by this electrochemical method. Notably, synthesis of xanthene-9-carboxylic acid (2k) and dibenzocycloheptene-5-carbocylic acid 2j was conducted with excellent yield. Direct substitution of a hydroxy by

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

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• -substitution (CO2Me, OCH2, Br) showing excellent enantioselectivity, the 3-methoxyphenyl-substituted substrate afforded the homoallylic amine in only 85% ee. The bulky 2-cyclohexylallyltrimethylsilane showed only moderate yield and enantioselectivity (55%, 76% ee). In 2022, Mancheño and co-workers [40

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• the shortened version described in the previous paragraph (Figure 13) [112][113][114][115]. As an interesting feature, the DADPS-linker with dibromo substitution takes advantage of the naturally occurring stable isotopes 79Br and 81Br in almost stoichiometric ratio. The predictable isotopic pattern

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• , changes in the epi-amino alkaloid core of the two-component catalytic system were investigated. Introduction of the 2’-substitution to the quinine core as in AQ-2 and AQ-4 (Scheme 2) resulted in the decrease of chirality transfer providing the product with 50% and 72% ee, respectively. A similar trend was

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• with the stability of the relevant iminoiodinane reagent, with higher yields attributed to more electron-rich sulfonamide substitution such as 2a. Relatively electron-deficient iminoiodinanes are less efficient but are also more prone to decomposition (see Supporting Information File 1, Figure S2 for

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• effect studies and isotopic substitution experiments revealed multiple different mechanisms of enantioinduction for the respective combinations. To rationalise relevant interactions, MLR models were trained on subsets of the data set. For each different mechanism of enantioinduction previously elucidated

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

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

• the possible substitution patterns, meta-substituted anilines hold a special place. These compounds are difficult to access due to the inherent ortho-/para-directional reactivity of the amino group, at the same time they are widely used in medicinal chemistry, resulting in several marketed drugs

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

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

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

• -methoxymethylpyrrolidine)hydrazones could be also key intermediates for the asymmetric synthesis of α-substituted aldehydes and ketones [18][19]. Interestingly, depending on the substitution pattern, the C=N bond can feature different electronic properties [20]. For instance, various hydrazones have been employed for the

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• and carboxyl functionalities. Furthermore, a β-alkyl substitution is not very common in pyrrolic secondary metabolites. The most related metabolites to 1–5 are the reported alkylpyrroles from a marine sponge Oscarella lobularis [7] and pyrroloterpenes from Streptomyces [12][13][14][15], although the

• substitution patterns are different (Figure 1). Natural alkylpyrroles were shown to have cytotoxicity [27], antidiabetic activity [28], anti-lipid peroxidation [12], in vivo antihypoxic activity [12], and antibacterial activity [15]. Though not impressive in cytotoxicity and tyrosinase-inhibitory evaluations

Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate

• Masahiro Terada,
• Zen Iwasaki,
• Ryohei Yazaki,
• Shigenobu Umemiya and
• Jun Kikuchi

Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173

• ]. As expected, the use of the flow reaction system significantly increased yields, although the yields obtained in the reactions of substrates having an electron-donating methoxy group were low to moderate regardless of the substitution pattern (Table 2, entries 1, 2, and 6). Indeed, when a methoxy

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• for 24 h. Careful investigation of the product structures by 1H and 19F NMR as well as GC–MS revealed exclusive substitution of fluorine rather than hydrogen, leading to a mixture of products in the ratio 0.15:1:1:0.15 (Scheme 25), with a combined yield of 50% for 4-iodotoluene and 75% for methyl 4

• ], while S-nucleophiles, namely thiophenolates, led to products upon fluorine atom substitution, which were isolated in low yield. Corresponding disulfides were isolated as major products, even when the reaction was carried out under inert atmosphere, suggesting a radical process. In summary, we compiled

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• compounds 6, 18, and 21 via natural bond orbital (NBO) analyses which further support the suggested reaction pathways. Keywords: DFT; indazole; indazole substitution; mechanism; N1-substituted indazole; N2-substituted indazole; regioselectivity; Introduction Indazoles constitute an important class of

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

• synthesis of highly fluorescent DPP derivatives through straightforward nucleophilic aromatic substitution reactions with thiols and phenols. These nucleophilic substitutions occur at room temperature and manifest a remarkable selectivity for the 4-position of the pentafluorophenyl groups. Both symmetrical

• aromatic substitution; phenol; thiol; Introduction Diketopyrrolopyrroles (DPPs) are a class of organic pigments discovered by serendipity in the 1970s [1][2]. Generally, N-unsubstituted DPP derivatives exhibit high melting points, low solubility in most solvents, and strong absorption in the visible

• pentafluorobenzyl bromide, followed by a nucleophilic aromatic substitution (SNAr) with thiols and phenols. This approach is based on the well-established reactivity of perfluoroaromatic compounds in nucleophilic aromatic substitutions [32][33][34][35]. By varying the reaction conditions and the number of

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

• cyclophanyl-imidazole-based library of ligands. The synthesis of ligands based on the [2.2]paracyclophane (PCP) moiety, thanks to its structural features and inherent planar chirality upon selective substitution, has been recently reviewed by the same author [46]. Starting from 4-formylcyclophane 37, a GBB

• 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

• diversification points. The scope of the reaction was limited: alkyl aldehydes and aryl/benzyl isocyanides could not be used, and 4 distinct compounds were obtained in yields of 23–40%. Nevertheless, these results represent an improvement compared to previous studies where substitution on C4 of the 2

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• ): UPGMA, and minimum diagnostic length (lambda): 24. Additionally, in MEGA X, phylogenetic trees were made using Neighbor-joining [43]. Evolutionary distances were calculated employing the Poisson correction method, measured in amino acid substitution units per site. Ambiguous positions were removed for

• each sequence pair using the pairwise deletion option. Bootstrap phylogeny testing was conducted with 1000 replicates, utilizing the Poisson model for amino acid substitution and uniform rates between sites while handling gaps and missing data through pairwise deletion. The genomes associated with LanM

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

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• reported before [26][27][28], we developed a new synthetic route which is shown in Scheme 5. In the first step trifluoromethylketone 17 was prepared by a nucleophilic acyl substitution of methyl 2-iodobenzoate 16 with Ruppert’s reagent. Ketone 17 was then reacted with an excess of Ruppert’s reagent and

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

• of acid also led to the formation of amides 10b–d as main products and the corresponding ketobisamides 12d–e as minor products (Table 2, entries 10, 11, 18, 23, and 24). This can be explained by the formation of HCl in the reaction mixture due to the substitution of chlorine in the vinyl chloride