Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• the optimized conditions, unprotected amine 9 was not compatible. Although gem-dimethyl groups installed at the tether should have a positive impact on intramolecular cyclization, they were not essential for the reaction (10). In order to obtain mechanistic insight into the aza-Wacker cyclization

• -electron oxidation of the alkenes. Although a drop in oxidation potential for the alkene was observed when tethered to an aryl sulfonamide, as detailed by Moeller, rapid intramolecular cyclization would be the key [26][27][28]. We also measured cyclic voltammograms for aryl sulfonamides with and without

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

• -substituted products 60 underwent TFA-promoted deprotection which triggered the intramolecular cyclization to furnish the indole moiety in the desired products 61. A control experiment showed that the GBB product 60 was obtained as the sole product in the absence of acid catalyst. Another group developed the

• elimination of III, underwent intramolecular cyclization to deliver the desired products 85. The scope of reaction showed that higher yield (57–90%) of 85 were obtained when benzaldehydes 83 were equipped with electron-donating groups (R1) and when bulky groups, such as 1-adamantyl or t-Bu (R4), were

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

• component, after the formation of the expected Ugi bisamide products, subsequent post-transformations allow the synthesis of products of intramolecular cyclization [19][20][21][22] and/or products of a tandem combination of several reactions (Scheme 1) [22][23][24][25][26]. At the same time, the use of so

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

• -Spirofuran steroids Intramolecular cyclization of alcohols with allenes is a common method for obtaining 17-spirodihydro-(2H)-furan-3-ones. In 2006, Jiang et al. utilized a known reaction sequence to construct the 17-spiro heterocycle 27 from the commercially available ethylene deltenone 24 [20][21]. In this

• of the primary alcohols under Jones oxidation conditions, led to the corresponding carboxylic acids. These carboxylic acids underwent intramolecular cyclization with the 17β-hydroxy group to provide the spirolactones 112 and 113. The ADT-lactone 113 was further methylated and oxidized to yield a

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

• cleavage, and intramolecular cyclization provided 15, followed by functional group manipulation to yield 16. The two segments 14 and 16 were assembled by Nozaki–Hiyama–Kishi (NHK) coupling while controlling the regio- and diastereoselectivities to afford intermediate 17 [25]. Site-selective hydroboration

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

• (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

• formation of N,O-aminals 5 and hemiaminals 6. Control mechanistic experiments. Optimization conditions for the Lewis acid-catalyzed intramolecular cyclization of 4a. Supporting Information Supporting Information File 16: General experimental information, synthetic procedures, analytical data and NMR

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

• recyclization is depicted at Scheme 8. Initially, hydrazine molecule is added to double bond of the pyranone ring leading to zwitter-ion A. Further, cleavage of dihydropyranone fragment results in intermediate B. Next, enehydrazine C is formed from compound B through migration of a proton. Then, intramolecular

• 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

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

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

• 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

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• have been employed in benzocyclization and arylocyclization reactions, enabling intramolecular cyclization by forming aromatic or heterocyclic rings as a part of cyclic structures [8]. In these reactions, the dual activation of a C–I bond and vicinal C–H bonds/functional groups features a distinct

• diaryliodonium salts in a cascade cyclization, the cyclization features a copper-catalyzed activation strategy involving the cleavage of the C–I bond and esterification. The resulting cascade of selective arylation/intramolecular cyclization facilitated the synthesis of 3,4-benzocoumarin derivatives. The

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• can be found in bioactive molecules and have been tested in structure–activity relationship studies (Scheme 1A) [8][9][10]. Moreover, transformations have been developed to exploit the two functional groups simultaneously, for example through their intramolecular cyclization to form pyrroles in the

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• alcohols, followed by base-promoted cyclization to afford the target spirocyclic compounds in good to high yields. Keywords: diazoarylidene succinimides; intramolecular cyclization; rhodium(II) carbene O–H insertion; spirocycles; Introduction Spirocyclic motifs have emerged as auspicious frameworks for

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• Tsvelikhovsky introduced an efficient synthetic strategy to construct diverse dibenzodiazepinones through a sequential methodology consisting of a B–H coupling between o-carbonylanilines and 1,2-dihaloarene derivatives providing access to key precursors that undergo a tandem amination–intramolecular cyclization

• carbonylative intramolecular cyclization of the intermediate 3a using different catalytic systems. To elucidate the role of the palladium catalyst in this process, we carried out the initial attempt under metal free-conditions using molybdenum hexacarbonyl (Mo(CO)6) as CO surrogate, in the presence of Et3N in

• . The reactivity of Co2CO8 as CO surrogate was also explored, in this case the reaction afforded the DBDAP product 4a in 55% yield (entry 6, Table 3). Molybdenum hexacarbonyl (Mo(CO)6), was shown to be a powerful CO surrogate in this carbonylative intramolecular cyclization. The efficacy of Mo(CO)6 is

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• , Umemoto’s reagent undergoes a homolysis process to generate the trifluoromethyl radical species. The trifluoromethyl radical is trapped by the terminal alkene and forms a relayed radical intermediate 6, which is intercepted by the indole ring realizing an intramolecular cyclization (6-exo-trig). The newly

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• aromatic nitro derivatives 3 and 6 proceeds through the corresponding hydroxylamines, capable of intramolecular cyclization to products 4 or 7. Fortunately, under Zn/AcOH reductive conditions this was resolved by extending the duration of the reaction to 18–24 h, providing enough time for compounds 4/7 to

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• Nef reaction in MeNO2 under acidic conditions. In the meantime, 1 was activated by AlCl3 to form sulfenium cation I, which induced an intramolecular cyclization of 60 to produce pyrroline 62. In MeCN solvent, 3-thiolated pyrroline 62 was stable and could be isolated, but in MeNO2, in the presence of

• first thiolation and intramolecular cyclization of propargyl azides the removal of N2 and a proton. Subsequently, monothiolated perroles were subjected to the second thiolation process to prepare 3,4-bisthiolated pyrroles. Cyclic voltammetry and DFT calculations revealed that the 3,4-bisthiolated

• formation of three-membered cyclic sulfonium ion II followed by ring-opening of sulfonium ion and intramolecular cyclization. The use of a Lewis base/Brønsted acid catalysis system for the sulfenylation of aromatic substrates 4 was reported by Gustafson et al. (Scheme 55) [87]. In the method, catalyst P

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• calculations, and to study their intramolecular cyclization in triflic acid into the synthetically and medicinally relevant (see recent reviews [12][13][14][15][16][17][18]) indan-1-ones. Results and Discussion The synthesis of 1-aryl-4,4,4-trichloro-3-hydroxybutan-1-ones (CCl3-hydroxy ketones) 1a–o was

• electron-donating substituents in the aromatic ring gave oligomeric materials. Presumably, in these cases, after dehydration and formation of the corresponding enone 2, the latter underwent subsequent cationic oligomerization. Next we studied the intramolecular cyclization of compounds 1 and 2 in TfOH. It

• C1 (0.60 e). This carbon atom gives 14.9% contribution to the LUMO. Contrary to that, the carbon C3 bears no positive charge (−0.13 e) and contributes 12.1% to the LUMO. The intramolecular cyclization of cation Ba takes place between the atom C3 and the ortho-carbons of the phenyl ring. Thus

Unravelling a trichloroacetic acid-catalyzed cascade access to benzo[f]chromeno[2,3-h]quinoxalinoporphyrins

• Chandra Sekhar Tekuri,
• Pargat Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2023, 19, 1216–1224, doi:10.3762/bjoc.19.89

• beginning of the reaction, copper(II) 2,3-diamino-5,10,15,20-tetraarylporphyrins 1 react with 2-hydroxynaphthalene-1,4-dione (2) in the presence of trichloroacetic acid to form an imine intermediate which on intramolecular cyclization affords a key benzo[f]quinoxalinoporphyrin intermediate 17. Further, a

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• guanidine C. Finally, the intramolecular cyclization of the guanidine moiety and the carbonyl group leads to the target pyrimidine 9. After the general synthetic method for pyrimidines containing the allomaltol fragment had been established, the photochemical behavior of the obtained compounds 9 was

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• deliver N-arylsulfonylimines under mild reaction conditions is highly desirable. Previously, we reported a tandem oxidative intramolecular cyclization of N-aryl(benzyl)amines, having an internal nucleophile substituted at the ortho-position in the aniline ring, to nitrogen heterocycles using potassium

• persulfate (K2S2O8) as the exclusive reagent [14]. The mechanistic study revealed that an initial oxidation to an iminium ion could be the key intermediate in the intramolecular cyclization step. In sharp contrast, when N-aryl(benzyl)amines that do not have an ortho-substituted nucleophile in aniline ring

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• ) [32]. The third group of approaches to the PBTA scaffold includes only one example, the intramolecular radical substitution reaction in 1-(2-bromophenyl)-5-(butylsulfanyl)pyrrolidin-2-one (Scheme 3, entry 13) [8]. The fourth group of approaches to the PBTA scaffold is the intramolecular cyclization of

• approaches from Scheme 4). Then, intermediate A underwent an intramolecular cyclization by the attack of the SH group on the C5 atom of the pyrrole-2,3-dione moiety to afford intermediate B that underwent a 1,3-prototropic shift to give product 3aa. Next, the conditions (Table 1) of the model reaction of

• the cleavage of the S–C bond of the 1,4-benzothiazine moiety under the action of the nucleophile to form in situ a 1-(2-thiophenyl)pyrrole derivative that undergoes an intramolecular cyclization to give the target pyrrolobenzothiazoles 3, 7, and 12. The developed approach works well with alkanols 2

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44