Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• (Scheme 1). It should be noted that the reaction with styrene gave low yields and the resulting products appeared very unstable. Finally, the tri-substituted alkene 1-methylcyclohexene did not give the expected products. Finally, some more elaborated molecules such as the macrolactone 2j, the clofibrate

• addition of DNTFB and quickly turns yellow). Then, the tube is opened and PhSeBr (118 mg, 0.5 mmol, 1 equiv) is added in one portion. The resulting reaction mixture is stirred in the same ice bath for 15 minutes. Then, the tube is opened and the alkene (1, 0.5 mmol, 1 equiv) is added. The reaction is

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• transfer reagents; (iv) direct metal-free imine carbanion addition to electrophilic alkene. Class (i) underwent an evolution from catalysis by covalent interaction to chiral hydrogen-bonded catalysis, which allowed the expansion of the allyl component scope from simple allyl to substituted allyl groups

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• can react with BF4− to give fluorinated alkene B [57][58][59][60]. In the next step, B can undergo the second addition of H+, followed by the incorporation of F− into the carbocation intermediate C, forming the difluorinated compound 2a. The carbocation adjacent to the F atom might be stabilized by

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

• condensation by introducing additional functional groups into the amine moiety (Figure 3). Substituted arylamines bearing alcohol (3ae), phenol (3ad), alkene (3bi), dimethyl acetal (3bj) functionality can be accessed in good yields. Reaction of 1,3-diketone 1a with a non-amidine type heterocyclic amine, 3

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

• -position of the nitrile is also detrimental to the reaction, resulting in less than 30% yield of the desired product 3d. Nevertheless, the reaction is compatible with halogens elsewhere in longer nitrile alkyl chains (3e,g). Finally, it was possible to obtain the terminal alkene 3f with a yield of 58

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

• toluene [173]. N-Vinylimidazole, an alkene with a leaving group, was used to synthesize the 3-substituted pyrazoles 169 because, unlike acetylene, it is not gaseous and, therefore, easier to handle. Instead of vinylimidazole, vinyl azides 170 can also be used as alkyne surrogates. After the 1,3-dipolar

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

• electron donor to furnish the olefin product 148. In the cathodic chamber, reduction of the acidic proton of TFA counterbalance the overall transformation. A wide range of carbonyl compounds including aromatic and aliphatic aldehydes and ketones as well as various alkene partners were compatible. Of note

Radical reactivity of antiaromatic Ni(II) norcorroles with azo radical initiators

• Siham Asyiqin Shafie,
• Ryo Nozawa,
• Hideaki Takano and
• Hiroshi Shinokubo

Beilstein J. Org. Chem. 2024, 20, 1967–1972, doi:10.3762/bjoc.20.172

• the electrophile [16][17][18]. In addition, C–C double bonds of the norcorrole skeleton outside the π-delocalization pathway exhibit a reactivity similar to an alkene to afford hydrogenated norcorroles by hydrogenation [19] or reduction with hydrazine [20] and [3 + 2]-cycloadducts with 1,3-dipoles [21

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

• cyclization using the alkene 1 as a model (Table 1). Based on the conditions reported by Yoon and Moeller, the initial screening was carried out using tetrabutylammonium triflate (Bu4NOTf)/1,2-dichloroethane (1,2-DCE) solution. Carbon felt (CF) was used as an anode instead of reticulated vitreous carbon (RVC

• , differently substituted alkenes 11, 14 were prepared and subjected to the reaction under electrochemical and non-electrochemical conditions (Scheme 4). In the case of the trisubstituted alkene 11, the six-membered anti-Markovnikov product 12 was selectively obtained under electrochemical conditions, while the

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

• protecting group yielded the corresponding hydroxyalkynyl derivative 4. Subsequent Lindlar reduction resulted in the (Z)-alkene and a chemoselective tosylation of the primary alcohol led to the formation of tosylate 5. This intermediate underwent a stereospecific 4-exo cyclization upon exposure to iodine

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

• size of the alkyl side chain at the alpha position of arylacetic acids (9–16). These features offer great opportunities for the introduction of a wide range of functional groups, including bromide (9), boron (12), ether (13), nitrile (14), ester (15), and alkene (16) moieties, which are versatile

• 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

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• elongated growing chain may undergo further processing by KR, DH, and ER domains, generating β-hydroxy, α,β-alkene, and saturated β-methylene groups, respectively (Figure 1a). KR domains have garnered significant attention from researchers due to their ability to control the stereochemistry at the α- and β

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

• . 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

• (Scheme 1). The configurations of fluoroalkoxy compounds 3a–j were confirmed by the COSY 2D-NMR spectrum of compound 3a (Supporting Information File 1). Additionally, (+)-camphene (1b), a chiral natural product, was used as another alkene for fluoroalkoxy reactions. From (+)-camphene (1b), fluoroalkoxy

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

• applications [27][28][29][30]. For example, hypervalent bromine(III) reagents enable C–H amination and alkene aziridination reactions without the need for additional Lewis acid activation [31][32][33]. However, challenges in the synthesis and stabilization of cyclic hypervalent bromine and chlorine reagents

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

• bifunctional amide nucleophiles (Scheme 1e). Results and Discussion Our studies here focused on the development of hypervalent iodine-catalyzed amide and alkene coupling reaction [53][54][55]. In this case, we started with styrene (1) and benzamide (2) as the standard substrates. Using iodotoluene A as the

• benzamides provided a significant yield boost to provide the oxazoline structures 14 and 15. Finally, sterically encumbered tertiary amides participated in the reaction to afford the respective regioisomeric product 16. Encouraged by these results, we then turned our attention to explore the extent of alkene

• difluorinated iodotoluene B. Then, LiBF4 can perform a salt metathesis with B to produce LiF along with the active hypervalent iodoarene catalyst C. The activated hypervalent iodine catalyst C can coordinate to the alkene to form complex D. The nucleophilic oxygen of the amide will attack in the internal

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

• . Appropriate selection of the phosphine reagent was the key to success in the process. Due to the lower oxidation potential, electron-rich PMe2Ph preferentially transferred a single electron to the excited state of the photocatalyst rather than the alkene, which was essential for obtaining the desired product

• presence of alkene, alkyne, halogen, and ether moieties. N-Boc-protected amines and esters also provided a good to excellent yield. Unfortunately, α,β-unsaturated carboxylic acids and aliphatic carboxylic acids were ineffective using this method. In 2024, Liu and co-workers [31] introduced a photocatalytic

• excited-state photocatalyst oxidizes the cesium alkyl oxalate via SET, followed by elimination of two carbon dioxide molecules, generating a tertiary alkyl radical that easily combines with an electron-deficient alkene, providing the product. This protocol was well compatible with a wide range of acceptor

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

• that a reductive radical-polar crossover pathway is likely to be involved in this transformation. Keywords: aryl halides; C–C bond formation; electroreduction; radicals; visible light; Introduction Alkene hydroarylation is an attractive method for the construction of alkylarenes, which serve as

• -light-mediated alkene hydroarylation commonly requires external reductants and/or hydrogen atom sources to complete the catalytic cycle [21][22][23][24][25]. Over the past few decades, electrochemistry has proven to be an environmentally benign and convenient approach for accessing open-shell

• 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

• system and the C2–C3 alkene, are instilled by these terpene synthases. Four types of eunicellane synthases are known (Figure 1B). The first eunicellane synthase identified, Bnd4 from the biosynthesis of benditerpenoic acid in Streptomyces sp. (CL12-4) [5], forms a cis-eunicellane named benditerpetriene

• (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

• from bacteria and forms albireticulene (2), a C1 diastereomer of 1 that also features the 2E alkene [7]. Two coral enzymes, BaTC-2 and EcTPS1, were found to form klysimplexin R (3), a 2Z-cis-eunicellane [8][9]. Recently, a third bacterial version, MicA, was identified as producing the 2Z-trans

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• alkene 2j carboxylic acids were used successfully in this MCR, demonstrating a great reaction scope (Scheme 2 and Figure 2). Remarkably, the best yields were obtained when heterocyclic carboxylic acid components like 1H-pyrrole-3-carboxylic acid (2n), 2-furoic acid (2o) and 5-nitrofuran-2-carboxylic acid

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

• alcohols were used as the nucleophiles (Scheme 32). About three years later, the same group developed a simple and efficient method to access CO-linked heterocyclic scaffolds by a Pd-catalyzed carbonylative cyclization of alkene–indole derivatives with 2-alkynylanilines and 2-alkynylphenols, in the

• )-catalyzed synthesis of CO-linked heterocyclic scaffolds from alkene-indole derivatives and 2-alkynylanilines (top) and 2-alkynylphenols (bottom). Proposed mechanism for the Pd(0)-catalyzed synthesis of CO-linked heterocyclic scaffolds. Pd-catalyzed C–H and N–H alkoxycarbonylation of indole derivatives to

(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

• were rare, but a number of practical approaches have been disclosed in recent years. Many of these utilise the ability of bicyclo[1.1.0]butanes (BCBs) to undergo [2σ-2π]-type cycloadditions with alkene reaction partners [37]. Brown and co-workers used this approach to synthesise a variety of 1,2-BCHs

• (±)-30. In a related strategy, Procter and co-workers prepared 1,2-BCHs (±)-33a–e from BCBs 32 via a SmI2-catalysed radical relay alkene insertion (Scheme 3C) [35]. This approach relied on single-electron reduction of the ketone moiety and ring-expansion from the ketyl radical anion. Electron-deficient

• homologation and hydrolysis led to aldehyde (±)-46 which could then be oxidised to acid (±)-47 using a Pinnick oxidation. BCH 42b also led to ester (±)-48 via a Horner–Wadsworth–Emmons reaction followed by hydrogenation of the formed alkene. 1,2-BCH 44 could be turned into amine (±)-49 by oxime formation and

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

• 18 containing an exocyclic alkene was subjected to the reaction conditions, a mixture of benzylic chlorides (20) was formed in low yields, and trace amounts of the allylic chloride 19 was also isolated, the materials differentiated on the basis of the coupling of the acetal H5 with the respective

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• provide a better overall understanding. The hydrochlorination of alkenes can be categorized into three main classes (Scheme 1; only a terminal alkene is shown as a substrate, although polysubstituted and conjugated alkenes can also serve as substrates). 1) Polar reactions: These involve the protonation of

• the alkene in the first step, providing a carbocation that subsequently reacts with a chloride anion to yield the Markovnikov product. While this ionic mechanism is commonly illustrated in textbooks by showing “naked” cations as intermediates, several recent studies suggest a molecular concerted or

• alkene reactivity is essential. Two reactivity scales for alkenes are available in the literature, one considering the reactivity of the alkene itself (Mayr scale) [25] and the other the stability of the corresponding cation after protonation (hydride affinities) [26]. In the polar hydrochlorination

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

• , greatly increasing the molecular complexity of the starting substrate. Using radical chemistry would lead to a regioselective addition of azide radicals to the alkene, forming selectively the most stabilized C-centered radical. A prominent method for the generation of azide radicals relies on hypervalent

• would initially involve the addition of azide radicals to an alkene, generating a carbon-centered radical. Then, different trapping of this intermediate could be performed (Scheme 1B). First, C-centered radicals are known to recombine with metal-acetylides, in particular copper [27]. Reductive

• ]. On the other hand, the nature of the alkene might be limited as it would strongly influence the oxidation potential of the carbon radical and the stability of the resulting carbocation. Recently, we reported the first successful application of an RPC strategy for the azido-alkynylation of styrenes

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• alkene followed by a nucleophilic addition, is unknown (Scheme 1b, bottom). The radical-polar crossover strategy has been steadily emerging in synthetic organic chemistry during the last few years [43][44][45][46]. This strategy allows complex chemicals to be assembled with high step economy that would