Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• . Key to the successful development of this two-step process is the identification of a benzhydryl-protecting group, which orchestrates the photochemical Norrish–Yang cyclization and facilitates the subsequent ring opening. Keywords: azetidine; Norrish–Yang cyclization; ring-opening reaction; ring

• , endergonic transformations can be realized [3]. A promising strategy for the synthesis of complex products lies in the combination of photochemical cyclization and strain-release reaction (Scheme 1a) [4]. In this ‘build and release approach’, a simple precursor is cyclized upon irradiation. Subsequently, a

• by Norrish–Yang cyclization, which employs easily accessible α-aminoacetophenones as starting materials [11][12][13][14][15]. Furthermore, ring-opening reactions of azetidines have been recently achieved using sulfur and oxygen nucleophiles [16][17][18][19][20][21][22][23][24][25]. However, methods

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• . arabica, and Coffea eugenioides (Eugenioides coffee plant) all contained >30 unique transcripts for potential precursor peptides. The core sequences themselves were typically 4 or 5 amino acids in length and most often contained a tyrosine for cyclization. However, a few sequences appeared to have a

• tryptophan at the position for cyclization, indicating they may correspond to the stephanotic acid-type burpitides like moroidin (Trp-indole-C to carbon crosslink, Figure 3) [4]. Amaranthaceae family The Amaranthaceae family is home to the known moroidin producer, Celosia argentea var. cristata (Cockscomb

Predicting bond dissociation energies of cyclic hypervalent halogen reagents using DFT calculations and graph attention network model

• Yingbo Shao,
• Zhiyuan Ren,
• Zhihui Han,
• Li Chen,
• Yao Li and
• Xiao-Song Xue

Beilstein J. Org. Chem. 2024, 20, 1444–1452, doi:10.3762/bjoc.20.127

• ][22], unsaturated alkane addition [23][24], and cyclization [25][26]. Despite the rapid development of hypervalent iodine(III) reagents, the exploration of isoelectronic hypervalent bromine(III) and chlorine(III) reagents has been comparatively limited despite their demonstrated potential for unique

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• heteroring closure, positioning appropriate functions both at N-3 and C-4 of the (thio)hydantoin frameworks 4a–r (30–81%) broadening their usable decorations (Scheme 2). Recently, we reported that compounds 4a, 4f, and 4m undergo an intramolecular cyclization process through the involvement of the restored

• -hydrazino form [17][24][25], we conceived the idea of reversing the reactivity of 4a–r in the six-membered cyclization process (N- vs O-annulation) through the generation of an electrophilic oxocarbenium [26][27] cation intermediate from the acetal residue at N-3 of the (thio)hydantoin core. To pursue our

• (entries 1–7, Table 1). Similarly to what was observed by Yu and co-workers for the intramolecular cyclization of alkynyl aldehyde acetals [28][29], it was found that the use of FeCl3 provided the better result in terms of overall yield (entry 3, Table 1). Moreover, the choice of iron(III) seemed to have

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• position and subsequent cyclization will furnish the desired oxazoline. Conclusion We have developed a hypervalent iodine-catalyzed amide and alkene coupling reaction. This reaction protocol furnished useful oxazoline products and introduced the use of lithium salts to activate hypervalent iodine catalysts

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

• , presumably due to the increased stability of isomer 18 towards acids. This corresponds with the results for the previously reported triazene cleavage to diazonium intermediates and subsequent cyclization to triazine derivatives [3]. In the next step, the obtained pyrazolyl azides were reacted with different

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• organic dye Mes–Acr–MeClO4 as photocatalyst (Scheme 5). They demonstrated intermolecular radical cyclization of o-hydroxybenzoic acid derivatives with terminal alkynes to afford flavone derivatives. Here, functionally diverse flavonoids were synthesized in moderate to excellent yield by reacting various

• iodide leads to the formation of 23, which further undergoes 5-endo-trig cyclization, followed by fragmentation to produce an alkyl radical and a cyclic thiocarbonate 25. These alkyl radicals then interact with B2cat2 (19) to produce a variety of structurally intricate boronic esters. The reaction occurs

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

• cyclization with participation of hydrazine and carbonyl functions leads to pyrazolylisoxazole D. Finally, condensation with second equivalent of hydrazine results in the target hydrazone 6. The synthetic utility of obtained 1,2,3-triazoles is demonstrated by its further derivatization. So, alkylation by MeI

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• by preventing overreduction [39]. While the metal-catalyst-free radical cyclization of alkene-tethered aryl halides has been well documented in the literature [40][41][42][43], the efficient intermolecular hydroarylation of alkenes still relies on the use of transition-metal catalysts, including Pd

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

• (1) [6]. In 1, the C2–C3 and C6–C7 alkenes are E-configured, with the latter alkene configuration being conserved in all known eunicellane cyclization mechanisms. The first trans-eunicellane synthase, AlbS from the biosynthesis of albireticulone in Streptomyces albireticuli [10], was also identified

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• second step of this reaction, regio- and stereochemically controlled intramolecular cyclization leads to the formation of versatile nitrogen-containing tricyclic systems. However, these useful organic transformations are usually carried out in highly toxic organic solvents such as benzene, toluene

• (Figure 3, path I) [132]. Similarly, Tomberg et al., note that in such reactions, amide is formed rapidly by opening the maleic anhydride ring first, followed by a slower cyclization [133]. On the other hand, according to the results of some DFT calculations, Naguib et al., state that [4 + 2

Phenotellurazine redox catalysts: elements of design for radical cross-dehydrogenative coupling reactions

• Alina Paffen,
• Christopher Cremer and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2024, 20, 1292–1297, doi:10.3762/bjoc.20.112

• enabling the activation of small yet highly relevant organic substrates. For example, Huber and co-authors recently designed a Te-based catalyst in an indole Michael addition reaction [1][2][3][4][5]. Pale and Mamane utilized another Te-based catalyst in an electrophilic bromine-mediated cyclization

• reaction [6][7], and Gabbaï yet another in a different cyclization reaction [8][9], among other catalytic chalcogen bonding activation examples [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. In contrast, we have reported recently some redox-active Te-based catalysts

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• undergo cyclization reactions under mild conditions. In case of 1,3-diphenylacetone (4a) some activation of the methylene group is observed as well, because of benzylic stabilization. Dianions of 1,3-dicarbonyl compounds follow a different regioselectivity as compared to simple monoanions [6][7][8][9][10

• , we studied also cyclization reactions of chromones with heterocyclic enamines [30][31]. The present review aims to provide a personalized account of our work related to domino reactions of various types of chromones with carbonyl compounds, such as 3 and 4, and with 1,3-bis(silyloxy)-1,3-butadienes

• cyclization can be explained by the higher electrophilicity of the aldehyde as compared to the ketone. The yields were in general quite good (51–65%). Relatively low yields (51–52%) were obtained for chromones containing methyl substituents, presumably due to the lower electrophilicity of the chromone based

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• -bromoaniline (1a) and ethyl trifluoroacetoacetate (2), adapting a known procedure from Schlosser and Marull (Scheme 1) [17]. The cyclization of 1a with 2a chemoselectively afforded 8-bromo-2-trifluoromethyl-4-quinolone (3) rather than 8-bromo-4-trifluoromethyl-2-quinolone. Bromination of 3 with phosphoryl

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• with a quantum yield of 0.34. The pronounced triplet formation was exploited for the isomerization reaction of (E)-stilbene to the Z-isomer and the cyclization of cinnamyl chloride. Catalyst degradation mainly occurs through the long-lived Aza-H triplet (28 µs), but the photostability is greatly

• with its relatively high formation quantum yield and an energy of 2.32 eV can be used for isomerizing photoswitches like stilbene and for the cyclization of cinnamyl chloride. Our goal was not only to clarify the reaction pathway but also to provide a clear method for distinguishing between singlet and

• Information File 1). A remarkable turnover number of 4440 was achieved when 1 M stilbene was used (see Supporting Information File 1 for more information). Furthermore, the photocatalyst was utilized in a photosensitized cyclization reaction of cinnamyl chloride [84]. This photoreaction was originally

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

• isoprenoid allylic carbocation has the capability to engage in standard carbocation reactions, including cyclization via intramolecular olefin attack at the positively charged center, Wagner–Meerwein rearrangements, and hydride or proton shifts. This sequence concludes either through deprotonation, resulting

• insecticidal activities [11], and are bio-fuel alternatives [12][13]. Sesquiterpene synthase can convert FPP to various terpenoids via different initial cyclization processes: 1,6-cyclization to yield the bisabolyl cation, 1,7-cyclization to form the cycloheptanyl cation, 1,10-cyclization lead to the

• germacradienyl cation, and 1,11-cyclization resulting in the humulyl cation [14][15]. Deprotonation of the intermediate germacradienyl cation yields germacrene A, a doorway towards the synthesis of many eudesmane and guaiane sesquiterpene hydrocarbons through its reprotonation-induced transannular reactions

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

• ][8][9][10][11][12]. The interest in the preparation of functionalized indanone derivatives has increased enormously, and many synthetic methods have been developed, including Friedel–Crafts cyclization reactions [13], cyclization of acetylenic derivatives [14], ring contractions and ring expansions

• [15], and the Nazarov reaction [16][17][18][19][20]. The Nazarov cyclization is one of the most versatile and simple methods for preparing indanones from aryl vinyl ketone derivatives [16][17][18][19][20]. The Nazarov reaction is classically formulated as a 4π conrotatory electrocyclization of a

• electrocyclization reaction could be mediated by weaker Lewis acids, and consequently a catalytic amount of them could be used. The first example of a catalytic version of the Nazarov cyclization was reported by Denmark and Jones [25][26][27][28][29][30][31]. They found that a substoichiometric amount of FeCl3 (40

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• compound E. Cyclization occurred via dehydrogenation and intramolecular aldol condensation and in the last step hydrogen transfer provided the desired cyclic product H (Scheme 35). In 2020, Maji and Adhikari reported a phosphine-free N,N-amine–manganese complex-catalyzed stereoselective intermolecular and

• control studies with Hg and TEMPO indicated that the reactions were homogeneous and did not proceed through a radical pathway. Synthesis of heterocycles via C–C and C–N bond formation In 2016, Beller and co-workers reported an intramolecular cyclization using 2-(2-aminophenyl)ethanol for the synthesis of

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

• for the cyclization. Alternatively (Scheme 1B), isoxazolo[4,5-b]pyridines can be constructed via intramolecular cyclization of 4-(propargylamino)isoxazoles [21] or through reactions of 4-amino-5-benzoylisoxazoles with ketones or 1,3-dicarbonyl compounds [10][13]. These and some additional examples of

• . Cyclization of the latter under the action of K2CO3 in MeCN at room temperature gave previously unknown ethyl isoxazolo[4,5-b]pyridine-3-carboxylates 4a–c (Scheme 2). To the best of our knowledge only one compound (ethyl 5,7-dimethylisoxazolo[4,5-b]pyridine-3-carboxylate) has been synthesized using a similar

• method, however, the cyclization occurred under drastic conditions (NaH, DMF, 130 °C) as it was reported in patent literature [23]. We assumed that a similar synthetic route (nitrosation/SNAr) would be applicable for the synthesis of isoxazolo[4,5-b]pyridine derivatives bearing other EWG in position 3

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• undergo a [4 + 2] Diels–Alder cycloaddition to identify furan moieties within complex cell supernatants. Results and Discussion When designing the reactive group of the furan probe 6, we chose to focus on a well-known reaction with furans, the Diels–Alder cyclization. While the Diels–Alder cyclization

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• of amides from 2-alkynylanilines by using TFBen (benzene-1,3,5-triyl triformate) as a CO source, Pd(OAc)2, DPEPhos (bis[(2-diphenylphosphino)phenyl] ether), and DIPEA (N,N-diisopropylethylamine) in MeCN. After 24 h, Pd(OAc)2 and AlCl3 were added to promote a selective cyclization reaction [14]. The

• selective cyclization to the indole derivative in the presence of Pd(OAc)2 and AlCl3. A variety of indole derivatives were synthetized in good isolated yields (Scheme 3). Synthesis of indoles by Pd(II)-catalyzed carbonylation reaction Oxidative carbonylation reactions, as well as all other types of

• carbonylative double cyclization process was developed obtaining 3,4-dihydro-1H-furo[3,4-b]indol-1-ones from suitably functionalized 2-alkynylanilines [20]. The reaction occurs in the presence of PdI2 (1 mol %) as catalyst and KI (10 mol %) as co-catalyst in MeCN at 120 °C for 24 h. At the end of the process

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• generate diverse terpene skeletons via sophisticated cyclization cascades. In addition to the many highly selective TSs, there are many promiscuous TSs that accept multiple prenyl substrates, or even noncanonical ones, with 6, 7, 8, 11, and 16 carbon atoms, synthesized via chemical approaches, C

• they often synthesize multiple products from a single substrate through complex cyclization cascades [4][5][6][7][8][9][10]. Based on the mechanism of initial carbocation generation, TSs generally fall into two main classes. Class I TSs generate an allylic cation from a prenyl substrate by

• . Classically, these prenyl analogs have been used as co-crystallization ligands [38], inhibitors of specific TSs [39], and tools to study the reaction mechanisms of cyclization cascades [40][41] which have been comprehensively addressed in important previous reviews [8][13]. Currently, noncanonical prenyl

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• and Heck cyclization reactions. The integration of the multicomponent and post-condensation reactions in one-pot maximizes the pot-, atom-, and step-economy (PASE). Keywords: Heck reaction; one-pot; tetrahydroisoquinoline; tetrazolo-pyrazino[2,1-a]isoquinolin-6(5H)-ones; tetrazole; Ugi-azide reaction

• oxidative cycloisomerization reactions for the synthesis of 2-tetrazolyl-substituted 3-acylpyrroles (Scheme 2C) [42]. The Ding group also reported sequential Ugi-azide/Staudinger/aza-Wittig/addition/Ag-catalyzed cyclization reactions for obtaining 12-tetrazolyl-substituted (E)-5H-quinazolino[3,2-a

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• ][42][43][44][45][46][47]. The remaining known methods use only both positions to induce cyclization [25][31][32][33][48][49][50][51][52][53][54][55][56]. Therefore, to the best of our knowledge, there are no known methods that allow the selective reaction of both positions of uracil (Figure 2). In

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

• cyclization mechanism of spiroviolene. Keywords: boron migration; diterpene; spiroviolene; stereochemistry; Introduction Terpenes represent one of the most fascinating families of natural products due to their structural complexity and diversity, as well as their indispensable biological functions that

• stereoselective process to form complex terpene skeletons, normally with multiple stereocenters. In this context, the 3D-defined cyclization products retain the rich information of the complex cyclization process. Thus, assignment of the stereochemistry of the terpene skeleton with high confidence is crucial for

• proposing a reasonable cyclization mechanism [5]. Spiroviolene (1, Figure 1) was identified by Dickschat and co-workers as a nascent cyclization product of spiroviolene synthase (SvS), the coding gene of which was cloned from Streptomyces violens NRRL ISP-5597 [6]. Its unique spiro-fused linear triquinane