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

• preparation of biologically active compounds [15]. The synthesis was achieved via a sulfonyl group rearrangement driven by the azide–tetrazole equilibrium in quinazolines. The researchers utilized two synthetic pathways to prepare the target compounds. The first pathway involved a nucleophilic aromatic

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• -hydroxybenzophenones are conventionally prepared via Fries rearrangement of a phenyl ester [10]. Organocatalytic methods have also been reported for the synthesis of 2-hydroxybenzophenones [11]. In addition, several metal-mediated methods for their synthesis have been reported. For example, the Rh-catalyzed

• rearrangement of 2-aryloxybenzaldehydes yielded 2-hydroxybenzophenone [12]. Pd-catalyzed o-hydroxylation of benzophenones gave moderate yield of the title compound, and Br-substituted substrates were found to be not compatible with this method [13]. Various metals (Rh, Cu, Ir etc.) were applied to catalyze the

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• alternative to the harsh Pummerer rearrangement. Methanol played a crucial role in achieving the desired transformation and it was suggested to promote the self-assembly of reagents 24 and 25 for the formation of 27, which allows the selective abstraction of H+ from the less sterically hindered side

Visible-light-mediated flow protocol for Achmatowicz rearrangement

• Joachyutharayalu Oja,
• Sanjeev Kumar and
• Srihari Pabbaraja

Beilstein J. Org. Chem. 2024, 20, 2493–2499, doi:10.3762/bjoc.20.213

• platform developed with an integrated system enabling a downstream process in a time and labor-efficient manner which facilitates the Achmatowicz rearrangement, resulting in a fast (10 min) formation of the dihydropyranone products. Keywords: Achmatowicz reaction; flow chemistry; furfuryl alcohols

• Achmatowicz rearrangement substrates for accessing highly decorated dihydropyranones [5]. In recent years, several groundbreaking approaches for the synthesis of dihydropyranones have been described by diverse groups of researchers [6]. These techniques do not require any pre-functionalization of non

• -prefunctionalized materials in order to proceed with the rearrangement. However, the Achmatowicz reaction or similar methodologies involve a catalytic to stoichiometric amount of oxidants such as m-CPBA [7], PCC [8], Br2 [9], NBS [10], DMDO [11], KBr/Oxone [12], Na2S2O8 [13], photosensitizers/O21 [14], or Me2S [15

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

• ; rearrangement; Introduction Nitrogen-containing organic compounds (sometimes referred to as alkaloids due to their basic properties) are of critical importance in medicinal chemistry because of their unique binding properties to biomolecules [1]. Out of 55 drug candidates, approved by the FDA in 2023, 28 (51

• diaziridine 110 with 88% ee albeit with a modest 42% yield. Overall, this is an interesting example of dearomative allylation of Ν-acylquinolinium salts, though enantioselectivity currently is too low to ensure wider practical application of the method. Enantioselective 2-aza-Cope rearrangement In 2008, a

• conceptually different methodology was reported by Rueping and co-workers [41] that was based on the aza-Cope rearrangement of in situ-formed N-α,α’-diphenyl-(α’’-allyl)methyliminium cations catalysed by the BINOL-derived chiral phosphoric acid 112 (Scheme 23). The amine 113 acting as the allyl donor source

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

• enantioselectivities of a kinetic resolution of benzyl alcohols and an enantiodivergent fluorination of allylic alcohols, observing good correlations for both reactions. Since then, the proposed NCI descriptors have been successfully applied to multiple different reactions, such as an allenoate Claisen rearrangement

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

From perfluoroalkyl aryl sulfoxides to ortho thioethers

• Yang Li,
• Guillaume Dagousset,
• Emmanuel Magnier and
• Bruce Pégot

Beilstein J. Org. Chem. 2024, 20, 2108–2113, doi:10.3762/bjoc.20.181

• Yang Li Guillaume Dagousset Emmanuel Magnier Bruce Pegot Université Paris-Saclay, UVSQ, CNRS, UMR 8180, Institut Lavoisier de Versailles, 78035 Versailles Cedex, France 10.3762/bjoc.20.181 Abstract Access to original ortho thioether derivatives was achieved through a [3,3]-rearrangement in a one

• -pot two-step protocol. Several aryl-SCF3 compounds are reported by variation of the nitrile or of the trifluoroalkyl sulfoxide starting material. The variation of the perfluoroalkyl chain was also possible. Keywords: ortho functionalization; rearrangement; sulfoxide; Introduction Since decades

• their ability to be engaged in such a rearrangement [4][5]. Upon activation with trifluoromethanesulfonic anhydride and under heating, we showed their transformation to ortho thioethers with a fairly acceptable selectivity towards the pathway of sulfilimine synthesis (Scheme 1b). Following our seminal

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

• iodoalkanes 89. Subsequent reaction with acylsilanes 90 leads to alcohols, which react by Brook rearrangement to enoxysilanes and form the intermediate 92. Following a Michael addition/cyclocondensation with methylhydrazine, 4-fluoropyrazoles 91 are regioselectively formed (Scheme 32) [115]. Bouillon

• . An advantage of this method for preparing 1,3,5-substituted pyrazoles is its tolerance towards a wide range of substituents. Trimethyl phosphite can be added to acetylene dicarboxylates 95 to generate a zwitterion that readily reacts with electrophiles. This zwitterion undergoes a rearrangement

• preparation of these pyrazoles involves the cycloaddition of diazo compounds generated in situ with (Z)-2-arylidene-2H-benzofuran-3-ones. This reaction yields intermediate spiropyrazolines, which react undergo 1,3-prototropic rearrangement to form the corresponding pyrazoles [175]. Aggarwal's method was also

Understanding X-ray-induced isomerisation in photoswitchable surfactant assemblies

• Beatrice E. Jones,
• Camille Blayo,
• Jake L. Greenfield,
• Matthew J. Fuchter,
• Nathan Cowieson and
• Rachel C. Evans

Beilstein J. Org. Chem. 2024, 20, 2005–2015, doi:10.3762/bjoc.20.176

• decreased rate of diffusion in the more viscous D2O could lead to slower rearrangement after reverse isomerisation into the E isomer morphology. This demonstrates that the solvent plays a crucial role in X-ray-induced reverse isomerisation in these systems, not only due to catalysis from the radiolysis

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

• ’-dimethoxybenzilhydrazone (X = H, Cl). In these cases, the diazo compounds directly underwent both Wolff rearrangement and overoxidations to yield a mixture of the corresponding diphenyl acetal and benzil dimethyl acetal (akin to the conversion of 132 into 133 in Scheme 27), respectively (Scheme 29) [78]. Using a similar

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• 191036, Russian Federation 10.3762/bjoc.20.164 Abstract In this work, we report an efficient approach to 2-oxoazetidine-3-carboxylic acid derivatives based on a thermally promoted Wolff rearrangement of diazotetramic acids in the presence of nucleophiles. The method allows easy variation of the

• well as a wide range of nucleophiles provides access to a structural diversity of medically relevant 2-oxoazetidine-3-carboxylic acid amides and esters. Keywords: β-lactams; diazotetramic acids; nucleophiles; spirocycles; thermolysis; Wolff rearrangement; Introduction The importance of the β-lactam

• ketenes 2 generated by a thermally promoted Wolff rearrangement [3]. The interaction of such ketenes with nucleophiles of different nature could serve as a source of libraries of structurally diverse 2-oxoazetidine-3-carboxylic acid derivatives 3 (Scheme 1). The 2-oxoazetidine-3-carboxylic acid

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

• reaction can be considered the third in importance after Ugi [3] and Passerini [4] ones, and, as the two venerable reactions, is an α-addition of an electrophile and a nucleophile to an isocyanide, followed by a suitable rearrangement, as depicted in Scheme 1. Compared with the Passerini and Ugi reactions

• provide the ammonium 77. The intermediate 77 underwent Steven rearrangement to give a bridged polyheterocycle 78 in 28% yield. Unlike the previous examples, Jeong et al. [60] developed a cascade reaction by installing the additional ring prior to the GBB reaction (Scheme 26). The bifunctional 2-(2

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• different competitive reactions triggered by it, such as the interrupted Ugi reaction resulting from the competitive addition over the nitrilium intermediate [9][10] or the split-Ugi reaction arising from a competitive O,N-acyl transference on the imidate intermediate, through a remote Mumm rearrangement

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• hybrid syntheses of cotylenol (1) and brassicicenes [19]. The key oxidative allylic rearrangement was conducted enzymatically, while the skeletal rearrangement originally mediated by P450 enzymes in the biosynthetic pathway was achieved through chemical transformation. Hence, this strategy can be

• of scaffold 6 yield a series of intermediates and natural products, including cotylenol (1) and brassicicenes I and B (9 and 10), as well as brassicicene O (12), which possesses a distinct scaffold resulting from a skeletal rearrangement. To the core scaffold 6, the P450 enzymes, BscB and BscC

• , introduce hydroxy groups at C8 and C16 to produce FD-8β,16-diol (7), and BscE-catalyzed O-methylation generates the putative intermediate 8. The subsequent oxidative allylic rearrangement (8→9), catalyzed by the nonheme iron(II) and 2-oxoglutarate (Fe(II)/2OG)-dependent dioxygenase BscD, was a key step

A fiber-optic spectroscopic setup for isomerization quantum yield determination

• Anouk Volker,
• Jorn D. Steen and
• Stefano Crespi

Beilstein J. Org. Chem. 2024, 20, 1684–1692, doi:10.3762/bjoc.20.150

• actinometry, thus demonstrating the reliability of our setup. Keywords: isomerization; molecular photoswitches; photochemistry; photon flux; UV–vis spectroscopy; Introduction Photoswitches are molecules that can undergo a light-driven structural rearrangement to populate a metastable state of the initial

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• rearrangement between a barbiturate–furan adduct 4 and compound 3n under ambient conditions in dichloromethane and hexafluoro-2-propanol (HFIP). The synthetic procedures and characterization of all newly synthesized compounds, including DA11, DA7, and DA6, are summarized in Supporting Information File 1

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• excess NFSI, the heterobenzyl fluoride is obtained. In the case of product 3, the authors suggested that the absence of radical clock rearrangement products supported a polar mechanism. Conveniently, when both benzylic and heterobenzylic C–H bonds were present in a substrate, the reaction was selective

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• and 30). In these cases, a carbocation-involved pathway may be operative to yield the product. The successful and exclusive observation of product 29, however, provided a piece of evidence to the objection of this possibility, as no carbocation-based rearrangement product was observed in our reaction

• system [48]. To probe the radical intermediate in the reaction, a radical rearrangement experiment with cyclopropane-derived acid 31 was subjected to the standard conditions, leading to the expected ring opening, alkene-containing nitrile product 32 in 62% isolated yield (Figure 3A). Moreover

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

• rearrangement using benzonorbornadiene and the chiral natural compound (+)-camphene as bicyclic alkenes, selectfluor as an electrophilic fluorine source, and water and various alcohols as nucleophile sources. The structure of bicyclic oxy- and alkoxyfluorine compounds was determined by NMR and QTOF-MS analyses

• . Keywords: alkoxyfluorine compounds; bicyclic alkene; oxyfluorination; selectfluor; Wagner–Meerwein rearrangement; Introduction Organofluorines are of great importance in the pharmaceutical and agrochemical industries, as the presence of fluorine has a serious effect on the biological activities of organic

• compounds 4a–j were also obtained in very good yields (60–98%, Scheme 2). Since the reaction mechanism proceeding with a Wagner–Meerwein rearrangement does not cause racemization or a diastereomeric mixture and preserves the initial enantiomeric excess in the camphene's fluoroalkoxy derivatives (Scheme 4

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• oxidation of the aryl methyl ketones 5 to the corresponding aryl glyoxal with concomitant rearrangement of the aryl glyoxal to the target α-hydroxycarboxylic acid derivatives 6, catalyzed by Yb(OTf)3. The simple process reflects the generality of the methodology with yields ranging from 78–99% as

Synthesis of 1,2,3-triazoles containing an allomaltol moiety from substituted pyrano[2,3-d]isoxazolones via base-promoted Boulton–Katritzky rearrangement

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 1334–1340, doi:10.3762/bjoc.20.117

• ]isoxazolone derivatives with various hydrazines was studied. It was shown that the considered process includes formation of corresponding hydrazones followed by Boulton–Katritzky rearrangement. As a result, the general method for the synthesis of substituted 1,2,3-triazoles bearing an allomaltol fragment was

• types of aforementioned structures were proved by X-ray analysis. Keywords: allomaltol; Boulton–Katritzky rearrangement; hydrazones; pyrano[2,3-d]isoxazolones; recyclization; 1,2,3-triazoles; Introduction The Boulton–Katritzky rearrangement (BKR) also known as mononuclear heterocyclic rearrangement is

• reaction of hydrazones of 1,2,4-oxadiazoles leads to the corresponding 1,2,3-triazoles containing an amide fragment. Generally, the considered rearrangement proceeds under action of acidic or basic reagents [3][4][5][6][7]. Other options for this process are based on the application of copper salts or

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• intrinsic properties, which result in protonation-initiated cyclization, Cope rearrangement, and atropisomerism. Finally, we exploited the reactivity of the trans-eunicellane skeleton to generate a series of 6/6/6 gersemiane-type diterpenes via electrophilic cyclization. Keywords: atropisomer; Cope

• rearrangement; DFT calculations; diterpene; electrophilic cyclization; eunicellane; Introduction The eunicellane diterpenoids are a family of nearly 400 natural products that present a conserved 6/10-bicyclic hydrocarbon framework [1][2][3]. Mostly known from soft corals [2], but with a growing number of

• never isolated, gave a similar estimated C2–C7 distance of 3.57 Å, suggesting that a factor other than distance controls any subsequent or concomitant cyclization. Cope rearrangement is facile for trans-eunicellanes During our study of the albireticulene (2) biosynthetic gene cluster, we found that 2

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• cleavage and rearrangement reactions, which are catalyzed by AlpJ-family oxygenases, including AlpJ, JadG, and GilOII. Prior investigations established the essential requirement for FADH2/FMNH2 as cofactors when utilizing the quinone intermediate dehydrorabelomycin as a substrate. In this study, we unveil

• a previously unrecognized facet of these enzymes as cofactor-independent oxygenases when employing the hydroquinone intermediate CR1 as a substrate. The enzymes autonomously drive oxidative ring cleavage and rearrangement reactions of CR1, yielding products identical to those observed in cofactor

• cofactor-independent manner. Keywords: angucyclines; aromatic polyketide; biosynthesis; cofactor-independent oxygenase; oxidative rearrangement reaction; Introduction The angucyclines represent a large class of natural products biosynthesized by type II polyketide synthases. Within this category, a

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• ], Reformatsky reaction [65], azalactone synthesis [66], nitro reduction [67][68], epoxide rearrangement, thiourea guanylation, and others [69][70]. In this article, we describe a simple and direct protocol for the preparation of indanones through a classical Nazarov reaction catalyzed by bismuth(III) triflate