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

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

• isoxazolo[4,5-b]pyridines 12 were obtained in pure form, however, cyclization of hydrazone 11a provided an inseparable mixture of two compounds which could be attributed to the target isoxazolo[4,5-b]pyridine 12a and triazole 13a formed as a result of Boulton–Katritzky rearrangement (Scheme 5). When this

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• esterification of alcohol (±)-5 gave redox active ester (±)-6, which was itself shown to be a suitable substrate for nickel-catalysed decarboxylative cross coupling reactions to aryl-substituted BCPs (±)-7. Oxidation of alcohol (±)-8 gave acid (±)-9 which yielded amine (±)-10 after a Curtius rearrangement

• rearrangement, amine (±)-27 was then accessible in one additional step. Formation of redox active ester (±)-28 from acid (±)-26 allowed photochemical Minisci reaction to 1,2-BCH (±)-29 and borylation to boronic ester (±)-30. Synthesis of phenol isostere (±)-31 was possible through oxidation of boronic ester

• nitrile group (to (±)-35 and (±)-37), Baeyer–Villiger oxidation (to (±)-38 and (±)-39), reduction of the nitrile group (to (±)-36) and Beckman rearrangement (to (±)-40). A mechanistically related synthesis of 1,2-BCHs was published recently by Wang and co-workers (not shown) [39]. They employed a

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• hand, the originally proposed cyclization mechanism (Scheme 1B) involves a 3,6-cyclization of cation IM-1 through a conformation shown as IM-1A to generate cation IM-5, which was proposed to undergo a dyotropic rearrangement, followed by a 1,2-alkyl shift of cation IM-6 to yield the spirocyclic cation

• either IM-9 or IM-11 cations. A direct dyotropic rearrangement, or two stepwise 1,2-alkyl migrations of IM-9, are possible pathways en route to cation IM-10. The presence of these intermediates IM-9, -10, -11 could be inferred by the identification of GJ1012B/D (5/6, Scheme 1D) [11], cattleyene (7) [19

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

• 10.3762/bjoc.20.74 Abstract A skeletal rearrangement of a series of 6,8-dioxabicyclo[3.2.1]octan-4-ols has been developed using SOCl2 in the presence of pyridine. An oxygen migration from C5 to C4 was observed when the C4 alcohols were treated with SOCl2/pyridine, giving a 2-chloro-3,8-dioxabicyclo[3.2.1

• ]octane ring-system via the chlorosulfite intermediate. Analogous allylic alcohols with endocyclic and exocyclic unsaturations underwent chlorination without rearrangement due to formation of allylic cations. The rearrangement was also demonstrated using Appel conditions, which gave similar results via

• the alkoxytriphenylphosphonium intermediate. Several reactions of the products were investigated to show the utility of the rearrangement. Keywords: bicyclic ring; cyrene; levoglucosenone; rearrangement; thionyl chloride; Introduction The 6,8-dioxabicyclo[3.2.1]octane derivative levoglucosenone (1

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• (Scheme 10). α-Branched alkenes are particularly prone to alkyl migrations which lead to more stabilized cations (Scheme 11). Thus, the hydrochlorination of tert-butylethylene (70) produces a mixture of 73 and the rearranged product 74. The rearrangement of 70 was previously reported by Stevens and Fahey