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

• imidazolium ring formation. The resulting carbene was metalated at the C2 position with Au(I), Cu(I), and Ir(I), obtaining an L-shaped NHC ligand scaffold. Līpiņš et al. introduced a new method for synthesizing 4-azido-6,7-dimethoxy-2-alkyl/arylsulfonylquinazolines, which are key intermediates in the

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

• ring formation via benzannulative inter- or intramolecular condensation of acyclic precursors [27][32][33][34][35][36][37]. Within the latter strategy, [3 + 3] condensations are gaining much attention due to the availability of starting materials and the straightforward installation of the aryl(hetaryl

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

• base in the Knoevenagel reaction and as a component for ring formation. Cyclization is completely regioselective when arylhydrazines are used; with methylhydrazine, the ratio is greater than 10:1. In addition to malononitrile, derivatives with reduced nucleophilicity (X = CO2R) are also tolerated in

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

• ester) was positioned in the aldehyde precursors 86 (Scheme 28). Various 2-aminothiazoles 87 and tert-butyl isocyanide (5) were reacted with 86 in the presence of Yb(OTf)3, affording 88. Addition of a new aliquot of Yb(OTf)3 (30 mol %) allowed the new ring formation through a 7-exo-trig intramolecular

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

• activity of nisin, a lanthipeptide produced by certain strains of Lactococcus lactis, is dependent on thioether-ring formation [14]. Additional post-translational modifications contributing to their distinct biological activities were identified [15][16]. Intermolecular disulfide bridges were proved to

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

• mesylate 1, whose basic treatment promoted the substitution of the mesylate group at C-21 by the 17α-hydroxy group and the oxetane ring formation in a 16% yield (Scheme 1) [10]. Winkler et al. developed the synthesis of alkylated derivatives of 17-spirooxetanosteroids from non-alkylated frameworks (Scheme

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• the minimum geometries are reported, as no transition states were obtained because the carbocation ring formation is a spontaneous process. Moreover, it is noteworthy that for each cation optimized, we examined several other conformers (specifically rotamers), but these were of higher energy than the

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

• group of compounds 7 should be protected prior to the attempted isoxazole ring formation. Indeed, reactions of 7a–c with ethylene glycol gave dioxolane derivatives 9a–c which were converted into isoxazolo[4,5-b]pyridines 10a–c in high yields under mild conditions (Scheme 4). The obtained result prompted

A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• -step ynamide annulation and imidazolium ring-formation sequence. Metalation with Au(I), Cu(I) and Ir(I) at the C2 position provides an L-shaped NHC ligand scaffold that has been validated in gold-catalysed alkyne hydration and arylative cyclisation reactions. Keywords: annulation; carbene; gold

• [20][21] that should facilitate access to different groups at the oxazole C-2 position allowing a range of imidazolium-forming cyclisation strategies to be explored. Glorius and co-workers reported the formation of symmetrical NHCs by imidazolium ring formation from bisoxazoline motifs [22] but

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

• also performed theoretical calculations, unveiling that the ring-opening step presented a higher energy barrier compared with the ring-formation step, particularly when the DCV compounds lacked aryl substituents. Subsequently, they successfully isolated the corresponding cyclobutene intermediate 13

• yield for the ring-formation process was modest at 5% (see Scheme 16) [121][122]. The macrocycle in 46 was observed to engage with the peptide segment in low-polarity solvents. In contrast, 1H NMR analysis suggested that the macrocycle disengaged from the peptide segment and relocated along the alkyl

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• possibility of through-space interactions with prenyl side chains using DFT calculations. Our calculations show that (i) the unstable secondary carbocation is stabilized by the cation–π interaction from prenyl side chains, thereby lowering the activation energy, (ii) the four-membered ring formation is

• formation, the C2–C10 bond in IM3a is 1.73 Å long, which is hard to recognize as a single bond. However, it is well consistent with the previously reported hyperconjugation in 4-membered ring formation [7]. Then, the C2–C10 bond became 1.56 Å and the 4-membered ring bond is completed (Figure 3B) when the

• stabilization of the secondary carbocation by the prenyl side chain of the intermediate, (ii) the four-membered ring formation is completed by the bridging reaction, and (iii) the annulation from the exomethylene group is a barrier-free process. To date, when constructing the computational model, we have

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• : 1) it functions as the central intermediate in the biosynthetic pathways leading to numerous prenylated indole alkaloids, such as ergot alkaloids in normal biosynthesis and clavicipitic acid in derailment biosynthesis [68][69][70][71]; and 2) the mechanism of the fundamental central C-ring formation

• -aminoalkyl radicals from free carboxylic acids of 8 and 10 under mild conditions would make the approach even more efficient and more biosimilar; nevertheless, issues regarding the regioselectivity of the ring formation could be raised, since both the 6-exo-trig and 7-endo-trig cyclization are both favorable

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• Gibbs activation energy of enantiomer 53 for the racemization process was determined as 33.0 kcal mol−1 at 298 K. The CPL spectra of M-53 and P-53 showed an emission maximum at 560 nm with glum value of 2.3 × 10−4. Instead of helicene formation in the final Scholl-type ring formation step, Martín and co

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• following criteria: position/stage of the key cyclooctane ring formation in the synthesis plan, the selectivity, and the opportunity for late-stage functionalization. Review 1 Metathesis: ring-closing metathesis and related methods The metathesis reaction, first discovered by serendipity in the 1950s, has

• were necessary to give compound 38 as a precursor for the late-stage RCM cyclization. This ring formation was very challenging and necessitated extended optimization. Indeed, during the course of the RCM a dramatic effect of the OH-protecting group on the cyclopentane unit was observed. The presence of

• steric hindrance, alcohol 47 was converted into triene 48 upon dehydration, and further engaged in the RCM reaction. In this case, the use of HG-II catalyst proved to be the best choice to achieve cyclooctene ring formation giving rise to intermediate 49, providing entries for further functionalization

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• limonoid biosynthesis were recently explored by functional characterisation in heterologous hosts [29][105][106][107]. There, CYP enzymes MaCYP71CD2 and MaCYP71BQ5 from Melia azedarach initiate the ring formation on the side chain of the triterpene precursor tirucalla-7,24-dien-3β-ol (19) in a sequential

• manner. MaCYP71CD2 is a bifunctional CYP that hydroxylates C23 and additionally introduces a C24–C25 epoxide on the side chain of tirucalla-7,24-dien-3β-ol (19), yielding dihydroniloticin (20). MaCYP71BQ5 then oxidises the methyl group C21 to a formyl group, leading to spontaneous hemiacetal ring

• formation in the product melianol (21). It is believed that these transformations are the starting point for formation of the characteristic furan ring of limonoids [29]. Taken together, these case studies not only represent impressive examples how CYPs create chemical complexity in plant triterpenoid and

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• (see Scheme 1C) [10]. Appropriately 2-functionalized quinazolinones of type 5 might be good starting materials for the intramolecular cyclization providing the target compounds (see Scheme 1D); however, this approach was rarely used [33][34][35][36], possibly due to low regioselectivity of the ring

• formation at the two competing nucleophilic centers. Results and Discussion In this work, we propose a regioselective approach to the synthesis of 2,3-dihydropyrroloquinazolin-5(1H)-ones 6 functionalized with a hydroxymethyl group by oxidative cyclization of hereto unknown 2-(buten-3-yl)quinazolin-4(3H

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• desired epoxide 5 in an acceptable 70% yield with excellent stereoselectivity as the sole syn isomer (dr > 95:5). It is worth noting that a small quantity of pyridine was added to prevent unwanted acid-catalyzed epoxide hydrolysis [31]. The stereochemistry of 5 was assigned later after pyrrolidine ring

• formation. Since the aqueous tungstic acid-catalyzed hydrogen peroxide epoxidations of monosubstituted allylic alcohols usually proceed in anti (erythro) stereoselective fashion [32], we propose that the high syn selectivity can be attributed to the presence of the unprotected hydroxy group in the

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• acids are widely used in stereoselective oxidative/cross-coupling of two aryl counterparts, asymmetric control of aromatic ring formation, atroposelective functionalization of biaryl compounds, and so on [17][29][30]. In this context, Akiyama (2004) described that chiral phosphoric acids (CPAs) have

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• give the 1,3-oxathiolane sugar ring. Herein, the research on 1,3-oxathiolane sugar ring formation strategies, mainly starting from oxygen- and sulfur-containing substrates, is summarized. In 1989, Belleau and co-workers [38] produced the first oxathiolane nucleoside as a racemic mixture, popularly

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• total syntheses of many natural products [34]. Despite its wide application in ring formation reactions, only a few review articles on Hg(II)-salt-mediated cyclization reactions are available in the literature [35]. This review describes the intramolecular cyclization of unsaturated compounds in the

• -ribose derivative 16 at room temperature (Scheme 7). They had confirmed the formation of the α-isomer of ᴅ-C-ribofuranosyl 16 predominantly over the β-isomer (α/β 95:5) [44]. In contrast, when Reitz and co-workers carried out a ring formation of benzylated C-arabinofuranoside derivative 17 in presence of

• in a diastereomeric pair of cyclized products 69 and 71, respectively. It was observed that the cis-isomer was predominant in the case of the five-membered ring while the trans-isomer was predominant in the case of the six-membered ring formation (Scheme 24) [72]. Cyclization involving alkynes (-C≡C

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• of this kind of reaction is the catalytic use of the hydride donor, in this case phenylsilane (PhSiH3), due to the regeneration of the active metal hydride species in the cycloisomerization mechanism pathway (Scheme 18). The lower cyclization constant for the six-membered ring formation, in

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• ion intermediate in a stereoselective manner for THP ring formation as shown in Scheme 3. The outcome of exclusive cis-stereoselectivity in the Prins cyclization might be attributed to the most favorable conformation adopted by 12 with equatorial orientation of the 2,6-substituents (R1 and R2). Alder

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• conversion of oxanorbornene (rac)-13 to heterotricycle (rac)-16 through the eight-membered-ring formation would be owing to the cis-relationships of the pentenyl and vinyl groups on the ring B of (rac)-15, which allows the proximal arrangement of the reacting sites in the RCM. The N-Boc derivatization of

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25