Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• as Meldrum’s acid and 1,3-dimethylbarbituric acid were used as the nucleophiles, the yne-allylic substitution products underwent further intramolecular cyclizations to give the spiro-cyclic products in high yields (Scheme 31, 30a–f). The generation of products likely begins with an α-attack on the

• formal [4 + 1] and [4 + 2] cyclizations were carried out through substitution by an alkynyl copper-driven dearomatization/rearomatization/cyclization/isomerization process (Scheme 40). Li, Yu and Liu et al. [78] achieved the asymmetric catalyzed dearomative [4 + 1] spiroannulation of nonfunctionalized 1

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

• performance. In their contribution “Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs”, Moutayakine and Burke described a new synthetic route for the synthesis of 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepinone (DBDAP

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• research [11][12], particularly focusing on innovative approaches to synthesize natural or bioactive compounds [13]. In the carboamination of alkenes, amides are used in photoredox cyclizations under proton-coupled electron transfer (PCET) conditions [14][15][16][17]. An alternative method to generate N

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• previous report on N-alkenylamide cyclizations. B) An overview of the present work. Calculated mechanism for the cyclization of amide 3a optimized at the B3LYP/ 6-31+G(d,p) level of theory with SDDall used for iodine. Solvent effects were considered using the CPCM model. All ΔG values are in kcal·mol−1

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

• aza-Wacker cyclizations under acidic conditions, which are expected to proceed via radical cations generated by single-electron oxidation of alkenes. Keywords: alkene; aza-Wacker cyclization; electrochemistry; radical cation; sulfonamide; Introduction Activating bench-stable substrates is the first

• the difference in such reactivities are intramolecular cyclizations (Scheme 1). A radical cyclization generates a five-membered ring with a less-stable primary radical, while a six-membered ring with a secondary cation is obtained through ionic cyclization. When such intramolecular cyclizations are

• expected to proceed via radical cations, there are several interpretations of the mechanisms involved, since radical and ionic cyclizations are both possible. In this context, electrochemical and photochemical aza-Wacker cyclizations have provided interesting models for mechanistic discussion (Scheme 2

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

• . Iterative Pictet–Spengler cyclizations: saframycin A and jorunnamycin A Saframycin A (5) was isolated from Streptomyces lavendulae, and a number of related alkaloid families such as safracins and renieramycins have been identified from both soil and marine microorganisms [89][90]. These natural product

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

• ). The corresponding protecting group (PG) was thought to control the conformation of the 1,4-biradical 2, which is known to be important for efficient Norrish–Yang cyclizations [27][28]. Furthermore, the PG was deemed crucial for the development of further functionalizations of the azetidinols (vide

• chosen as a preferred solvent because it is known to facilitate Norrish–Yang-cyclizations and allows simple analysis by nuclear magnetic resonance (NMR) spectroscopy [10]. Our results are summarized in Table 1. When p-toluenesulfonyl (Ts) was used as a PG at nitrogen, azetidine 3a was obtained in 81

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

• transformations in a single reactor, reducing the number of steps and the amount of waste with consequent benefits of cost and environmental impact [42][43]. Representative examples of relevant N-fused heterocycles. Different acid-catalyzed six-membered ring cyclizations. Substrate scope for the assembly of

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

• recent discovery of the aridacins, which transforms a 2E-cis-eunicellane into a 6/7/5-tricyclic diterpene via a cytochrome P450 [12]. Coincidentally, these reactive skeletons also provide chemists the ability to access synthetically challenging scaffolds with simple electrophilic cyclizations. With

• epoxide 9, but the similar reaction with 2 yields gersemienol 8. Isolation yields are provided. (B and C) Results of DFT calculations on the protonation-induced cyclizations of 1 and 2. The energies of the cationic intermediates (italicized values) are not on the same energy scale as for the substrates

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

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

• of the substituent located at carbon C3 of the chromone moiety and also on the type of nucleophile employed. Keywords: cyclizations; 1,3-dicarbonyl compounds; domino reactions; heterocycles; regioselectivity; silyl enol ethers; Introduction Domino reactions (also called cascade or tandem reactions

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• -workers [22][23]. Recently, Jacobsen reported asymmetric Prins cyclizations with HCl solutions [24]. Hence, all the described hydrochlorinations are racemic or diastereoselective reactions. Review Polar hydrochlorination reactions To comprehend polar hydrochlorination reactions, a solid understanding of

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• of acyl-CoA: cholesterol acyltransferase [4]. In this mini-review, we focus on the fungal meroterpenoids biosynthesis, especially terpenonid cyclizations and post-cyclization modifications, which mostly contribute to the skeletal diversity. Several terpenoid cyclases and αKG-dependent dioxygenases

• Aspergillus oryzae, will be also introduced. Review Standard reactions of fungal meroterpenoid biosynthesis The skeletal diversity within this group of compounds arises from polyketide synthesis, prenyl transfer, terpenoid cyclizations, and post-cyclization modifications [5]. In these reactions, terpenoid

• cyclizations and post-cyclization modifications are especially important in fungal meroterpenoid biosynthesis, contributing to the structural diversity of this class of compounds. Fungal meroterpenoid cyclases (CYCs) are seven-membrane-spanning transporter-like enzymes that regulate the conformations of

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

• attack of the oxygen atom of the ester group on the benzyl bromide residue prevails, with the cleavage of the arylidene succinimide fragment involved in further non-selective processes. The causes of the failed cyclizations in the last two cases can be summarized as follows. The intermediates obtained

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• of parameters with which to control reactivity. In this perspective, we provide an overview of the different mechanisms for radical reactions involving NHPI esters, with an emphasis on recent applications in radical additions, cyclizations and decarboxylative cross-coupling reactions. Within these

• [119] (Scheme 37A). Recently, Lumb and co-workers showcased the use of NHPI esters in key radical cyclizations, allowing the synthesis of diverse dibenzocyclooctadiene lignans [55] (Scheme 37B). A Ru-catalyzed cyclization was employed to construct the quaternary stereocenter in taiwankadsurin A

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

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

• ], Friedel–Crafts acylation [12], radical cascade reactions [2][13], and photoinduced radical cyclizations [14][15][16][17]. However, these methods often suffer from drawbacks such as harsh reaction conditions and the requirement of transition-metal catalysts. Although photocatalyzed cyclization reactions

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• introduced in 2017, followed by carbon nanotubes in 2019. Consistent with expectations from theory, anion–π catalysis on carbon allotropes generally increases with polarizability. Realized examples reach from enolate addition chemistry to asymmetric Diels–Alder reactions and autocatalytic ether cyclizations

• catalysis; electromicrofluidics; enolate addition; ether cyclizations; fullerenes; Introduction Anion–π catalysis was introduced ten years ago [1]. The idea is to stabilize anionic transition states on electron-deficient, π-acidic aromatic surfaces (Figure 1A). The true beginning is arguably in 2015

• catalysis. Moreover, epoxide opening polyether cyclizations are among the most impressive cascade reactions in nature [71][72][73]. Best known is the hypothetical cascade XII in the biosynthesis of brevetoxin B [74]. It affords eleven fused ethers by violating the Eschenmoser–Dunitz–Baldwin guidelines [75

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

• reductive cyclizations of o-nitrobenzoyl ketones [57][58], enamines [59][60], or isoxazoles [61]. The scope of these reductive cyclizations is limited by the availability of the necessary intermediates and has remained largely underexplored, especially with regard to 4-quinolones with long-chain

Synthesis of 7-azabicyclo[4.3.1]decane ring systems from tricarbonyl(tropone)iron via intramolecular Heck reactions

• Aaron H. Shoemaker,
• Elizabeth A. Foker,
• Elena P. Uttaro,
• Sarah K. Beitel and
• Daniel R. Griffith

Beilstein J. Org. Chem. 2023, 19, 1615–1619, doi:10.3762/bjoc.19.118

• cyclized product 16 in 75% yield. These results suggest that these Heck cyclizations are quite sensitive to the identity of the alkene substituent that is cis to the halogen. We were also interested in engaging vinyl iodide 17 in a 7-exo-trig cyclization to form 18. Z-Iodoalkene 17 appeared to react

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

• . Several terpene cyclizations with an exomethylene group are known, such as with caryolene and crotinsulidane diterpenoids, and the reaction mechanisms have been analyzed [27][28][29][30]. It would be interesting to see how the exomethylene group reacts in the cyclization of variexenol B. In this study, we

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• phostams, phostones, and phostines are summarized. They include cyclizations and annulations. Cyclizations achieve ring construction through the formations of C–C, C–O, P–C, and P–O bonds in the rings, while annulations build the rings via [5 + 2], [6 + 1], and [7 + 1] fashions with the stepwise formation

• the catalytic antibody [24]. They are also potential chiral ligands in asymmetric catalysis [25] (Figure 1). Cyclizations and annulations are two major strategies for the synthesis of medium and large phostam, phostone, and phostine derivatives. The cyclizations have been applied in the construction

• developed for the synthesis of seven-membered phostone and phostine derivatives. Review 1 Synthesis via cyclizations Cyclizations are major strategies for the construction of medium and large phostams, phostones, and phostines via C–C, C–O, P–C, and P–O bond formations, respectively. These strategies can be

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

• to the PBTA scaffold is an annulation of benzothiazoles with a pyrrole moiety (Scheme 1). It includes intramolecular cyclizations of benzothiazoles bearing a 3'-chloro substituent at C2 position (Scheme 1, entries 1 and 2) [5][6][7], intramolecular catalytic carbene cascade reactions of propargyl 1,3

• 1-(2-thiophenyl)pyrroles (Scheme 4). It includes intramolecular cationic π-cyclizations in 3-hydroxy-2-(2-sulfanylphenyl)-2,3-dihydro-1H-isoindol-1-ones (Scheme 4, entry 14) [9] and intramolecular cyclizations of 1-(2-(methylsulfinyl)phenyl)-1H-pyrroles under «interrupted Pummerer rearrangement

• reaction in 1-(2-bromophenyl)-5-(butylsulfanyl)pyrrolidin-2-one. Approach to PBTAs via intramolecular cyclizations of 1-(2-thiophenyl)pyrroles. A new approach to PBTAs via nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines. Reaction of APBTT 1a with methanol (2a). Derivatization of

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• exo face of 30b, oxidative cyclization can afford the ruthenacycle 101. Unlike previous works studying Ru-catalyzed cyclizations involving bicyclic alkenes and alkynes [56][57][58][59], the reaction preferentially undergoes β-hydride elimination to generate 102 rather than reductive elimination which

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• parameters for transannular cyclizations illustrated in Scheme 1.a Calculated activation parameters for transannular cyclizations illustrated in Scheme 2.a Distortion–interaction analysis for fused cyclohexanes. Distortion-interaction analysis for fused cyclopentanes and system 7-8. Comparison of relative

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

• found multiple applications in natural product synthesis [65]. Employed in C–C bond-formation reactions, this single-electron reducing agent has been particularly useful for five- to eight-membered ring cyclizations [65]. Its tunable reactivity opens access to both radical and anionic processes, hence