Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• alcohol was then protected as a PMB ether. After deprotecting the THP group, the resulting secondary alcohol was converted to a tosyl ester, which underwent an SN2 reaction with sodium cyanide in DMSO, yielding compound 109 with stereochemical inversion. Interestingly, reduction of the cyanide group with

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• (Scheme 21C) [55]. Kawabata and co-workers (2020) prepared the β-glycoside 66 from α-ᴅ-glucose and cinnamic acid (7) in good yield through the Mitsunobu reaction (Scheme 22) [56]. The 13C kinetic isotope effect experiment (KIE = 1.028) showed that the glycosylation proceeded via SN2 substitution (67). Sun

Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• ring was opened in a diastereoselective (SN2 type) and exo-selective manner by a trifluoroacetate anion. The trifluoroacetate anion was conveniently derived from (bis(trifluoroacetoxy)iodo)benzene (PIFA), which was used as the stoichiometric oxidant in the reaction. Overall, this amounted to a highly

• , which attacks the pendant olefin to form an aziridinium cation (Scheme 2). A sulfonate counter-anion then opens this aziridinium ring in an exo-selective, SN2 reaction. We were successful in scaling the reaction from 0.3 mmol to 11.5 mmol (38-fold increase) without any erosion in yield or selectivity

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• organoboron compound with CuOt-Bu and subsequent SN2’-selective allylic alkylation of 1. The densely functionalized structure of these dimerization products offers a versatile synthetic handle for further chemoselective functionalization. Considering the presence of two enolizable esters together with the

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• (Scheme 3) [46]. Their methodology involves a stereoretentive I/Li exchange at −100 °C, followed by transmetalation with CuBr·P(OEt)3 to generate the secondary alkylcopper species 14. These organocopper species demonstrated remarkable reactivity in SN2-type additions to allylic bromides with exceptional

• regioselectivity (SN2/SN2' = >99:1). The reaction with 3-methylbut-2-en-1-yl bromide (15) was particularly noteworthy, as it exhibited superior selectivity compared to the corresponding phosphates. The high efficiency of this protocol was demonstrated through the synthesis of various functionalized alkenes with

• complete stereocontrol. For example, the reaction of syn-alkylcopper species 14 with 3-methylbut-2-en-1-yl bromide (15) provided the corresponding SN2 product 16 in excellent yield and stereoselectivity (SN2/SN2' = >99:1, dr = 97:3). Remarkably, the regioselectivity of these reactions could be completely

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• ignored [26][27][28]. However, recent experimental, kinetic, and physical data reveal the incidence of more associative mechanisms [29][30][31] wherein the mechanistic pathway of glycosylation seems to lie at an interface of SN1–SN2 reaction (Scheme 1) [29]. The continuum mechanism expands in two

• directions away from the central oxocarbenium ion intermediate in the limiting dissociative process involving diastereomeric ion pairs. Destabilisation and greater reactivity of the oxocarbenium intermediate causes the nucleophilic acceptor moiety to attack in a concerted process following a classical SN2

• pathway through an associative transition state to form the equatorial glycoside, 7. Surprisingly, recent evidences show that typical homogeneous glycosylation reactions in organic solution shift more towards the SN2 end of the mechanistic spectrum [32][33][34], with some exceptions [35]. The kinetic

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• diastereomeric ratios. The relative configurations of the various polycyclic compounds were clearly elucidated by determination of several single crystal structures. Keywords: allylic SN2 reaction; dimerization; isatin; MBH carbonate; 3-methyleneoxindole; Introduction Isatins (indoline-2,3-diones) possessing

• conditions in hands, the scope of the reaction was investigated by using various MBH nitriles of isatins and aromatic amines in the reaction. The results are summarized in Scheme 1. All reactions proceeded smoothly to give the expected allylic SN2-substituted products 3a–i in satisfactory yields. Aromatic

• triphenylphosphine with MBH nitriles of isatins in acetonitrile at room temperature quickly gave red solid products 6a–d in high yields (Scheme 3). In this reaction, triphenylphosphine acted as a nucleophile to finish an allylic SN2 reaction. The obtained triphenylphosphaneylidenes are stable, which can be isolated

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• reactants. Finally, DFT calculations provided insights about the mechanism of this transformation, which strongly suggest that an SN2 reaction is operative. Keywords: alkylation; DFT calculations; fluorine chemistry; hypervalent iodine; sulfoxonium ylide; sulphur ylides; Introduction Introducing fluorine

• those that lead to α-alkyl-substituted compounds, is still challenging [27]. For example, in the SN2 reaction of alkyl halides with sulfoxonium ylides, the initially formed α-alkyl-substituted ylide reacts further with the halide to expel the sulfoxide and ultimately generate an α-halogenated product

• deprotonation would complete the pathway. The alternative mechanistic proposal is an SN2 reaction [40][41][42] between 1a and the iodonium ion 2a’, which directly furnishes B without invoking halogen bonded adducts. To assess which of these mechanistic possibilities was more probable, we turned to computational

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• in poor yield with α preference for 7-membered rings 7 in a ratio of 1:9.3. The authors proposed two mechanisms for the reaction (Scheme 1). In pathway A (top), the alkene-activated iodonium is formed, intramolecular attack of nitrogen forms the 6-membered ring A before an SN2 reaction with the

• products or stabilised by the tosyl group and subsequently attacked to form only the cis product in an SN2 reaction. Liu and co-workers reported a palladium-catalysed intramolecular aminofluorination of unactivated alkenes [27] (Scheme 2) in the presence of PhI(OPiv)2, AgF and MgSO4 as an oxidant, source

• ring A (Scheme 2). The Pd(II) intermediate is oxidised by PhI(OPiv)2/AgF, forming Pd(IV). Formation of the product can occur either by reductive elimination by Pd(IV) or SN2 nucleophilic attack by fluorine with concomitant palladium reduction. Reductive elimination of the Pd(II) intermediate forms the

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• styrenes 217, oxygen sources (water or alcohol), and TBHP mediated by ammonium iodine has been developed (Scheme 68) [137]. Addition of the tert-butylperoxy radical to alkene 217 followed by SN2 nucleophilic substitution with O-source was considered as a possible pathway to the formation of products 218

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• fluorine-containing building blocks have been developed [21][22][23][24][25]. Jubault and Poisson et al. reported SN2’ reactions of hydride or alcohols to electrophilic fluorine-containing alkenes gave the corresponding fluoroalkenes (Scheme 1B) [21]. In recent years, many fluorine-containing coupling

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• scaffolds. During the reaction, the arylcyclopropane is oxidized at the anode to form a radical cation, causing the weakening of the Cα–Cβ bond. The radical cation then undergoes a three-electron SN2 reaction to generate a benzylic radical, which loses an electron at the anode to form a benzylic carbocation

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

• , the iodane moiety in 12 is eliminated by an intramolecular attack by the amide nitrogen to form the aziridinium 13. Finally, ring-opening by SN2 attack of trifluoroacetate leads to the final product 14 [20]. In this case, the kinetic pyrrolidine product is obtained due to the electron-withdrawing

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• -to-handle reagent, NaOCl·5H2O. Because very little has been disclosed about the reactivity of such 2,3-epoxyesters, their epoxy ring opening by a variety of nucleophiles was carried out and we succeeded in clarifying these chemo- as well as regioselective processes proceeding via the SN2 mechanism to

• is the high regio- and stereoselectivities of its epoxy ring opening specifically occurring at the 2 position in an SN2 manner, when it is treated with appropriate nucleophiles (Nu), leading to the formation of the 2-substituted 3-hydroxyesters with 2,3-anti stereochemistry. These characteristic

• outcomes would stem from a result of the electronically repulsive interaction between the incoming nucleophiles and an electronically strongly negative CF3 group, and the anticipated clean SN2 mechanism of epoxides in general, respectively. This is interestingly compared with the case of 2a with

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

• concerted SN2 mechanism or SN1 mechanism with the allyl nucleophile addition step as rate-determining. Interestingly, the authors observed a 0.55 order in the catalyst, which indicates that a substantial part of the catalyst forms a hydrogen-bonded dimer with Kdiss ≈ 1000 M−1 when not in the catalytic cycle

• , an observation that is in good agreement with previously obtained data on bisurea catalysts [36]. To further distinguish between the SN1 and SN2 mechanisms, the authors performed an in silico simulation of the non-catalysed reaction to determine the possible potential energy surface and found that

• concerted SN2-key intermediate 60 must be at least 18.9 kcal/mol more favoured than a separated imine–chloride ion pair 61 attacked by the free allylsilane (Figure 3). Altogether, the developed methodology can be formally viewed as a useful tool for the enantioselective synthesis of chiral α-carboxyl-2,3

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• (Mg2+-dependent, metal-independent, cobalamin-dependent), common structural folds (class I–V, with class I being the largest group, characterised by the Rossmann fold) [58], or catalytic mechanism (SN2 mechanism, radical mechanism, Figure 3) [59]. This review categorises RiPP MTs based on the acceptor

• broad range of reactions [60]. There are different rSAM MT classes, description of the classes follows below in the C-MT section. Unlike conventional MTs, which follow an SN2 mechanism, rSAM MTs can methylate non-activated carbons. O-Methyltransferases The predominant group of MTs are O-MTs, which

• binding domain (CBD) at the N-terminus and an rSAM domain at the C-terminus (Figure 9) [119]. In addition to its different enzyme structure, a distinct mechanism of methylation than the classical SN2 mechanism is employed. Reductive cleavage of SAM generates a 5'-deoxyadenosyl (dAdo) radical, which

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• reference. At this stage, the PIDA–AlBr3 adduct undergoes ionization, giving rise to the corresponding ion pair I-1–Br (ΔG = −31.3 kcal/mol) in a highly exergonic and energetically favorable process. Next, an intramolecular SN2 reaction of the formed aluminum anion transfers a bromine atom to the

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• bond formation to afford the acyloxylation product was observed, and favoured when using directing groups with less steric bulk. This product had the opposite stereochemistry to the fluorination product suggesting it occurred via a competitive SN2 pathway. This is supported by the selectivity for C–O

• bond formation for substrates bearing primary benzylic positions, attributed to the faster rate of SN2 at the less hindered carbon. The scope was limited to substrates bearing secondary benzylic sites, with various functional groups tolerated. However, substrates bearing electron-donating substituents

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• formation of the 1,2-anhydro sugar through intramolecular attack of the 2-hydroxy group of the DMC-activated β-intermediate, followed by dihydroxyazobenzene attacking the anomeric center in an SN2 manner, or by direct nucleophilic SN2 attack on the DMC-activated α-intermediate, to produce the corresponding

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• exchange and transmetalation to the organocuprate 83. The latter undergoes an SN2’ addition to the propargyl chloride 84 and the resulting allene intermediate 85 undergoes an intramolecular Cannizzaro-type hydride transfer via 86 to produce the 8-membered cyclized target 87 in good yield (70%) (Scheme 24

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• (Scheme 3). No α-tosyloxy ketone products were observed in the crude reaction mixtures, either with catalytic or stoichiometric use of TsOH·H2O, even when the reactions were incomplete. These observations ruled out the possibility of double SN2 attack by tosylate followed by bromide. TsOH·H2O accelerates

• the iodonium intermediate C. Liberation of PhI serves as the driving force for subsequent SN2 attack by the bromide anion to give the dialkyl α-bromoketone 2. m-CPBA then regenerates the hypervalent iodine (HTIB) catalyst by oxidizing PhI in the presence of TsOH·H2O. The formation of the Ritter-type

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• desired reactivity. Substitution of a hydrogen atom with a halogen atom within an organic skeleton significantly increases the electrophilicity of the linked carbon centre, enhancing concerted (SN2) as well as carbenium ion-mediated (SN1) substitutions, common – for instance – on benzylic positions

Comparison of glycosyl donors: a supramer approach

• Anna V. Orlova,
• Nelly N. Malysheva,
• Maria V. Panova,
• Nikita M. Podvalnyy,
• Michael G. Medvedev and
• Leonid O. Kononov

Beilstein J. Org. Chem. 2024, 20, 181–192, doi:10.3762/bjoc.20.18

• the presentation [39] (i.e., microenvironment) of glycosyl donor molecules, which are incorporated in supramers, hence their chemical properties [35], thus making possible a shift of a fragile and not well-understood borderline between different reaction pathways at the SN1–SN2 interface [22][24][25

• concentration on stereoselectivity achieved with different glycosyl donors are currently missing. A putative cross-over from one reaction pathway to another one within the SN1–SN2 continuum [22][24][25] would require a sensible explanation why this happens differently for the two glycosyl donors under study

• the SN1-like mechanism to a more SN2-like mechanism occurs only (or mainly) for sialyl donor 2. Although this hypothesis can explain why the glycosylation with sialyl donor 2 exhibits substantial concentration dependence, it does not allow one even to guess why such SN1-to-SN2 cross-over did not occur

Controlling the reactivity of La@C₈₂ by reduction: reaction of the La@C₈₂ anion with alkyl halide with high regioselectivity

• Yutaka Maeda,
• Saeka Akita,
• Mitsuaki Suzuki,
• Michio Yamada,
• Takeshi Akasaka,
• Kaoru Kobayashi and
• Shigeru Nagase

Beilstein J. Org. Chem. 2023, 19, 1858–1866, doi:10.3762/bjoc.19.138

• transfer, followed by bimolecular nucleophilic substitution (SN2) reaction [8]. Endohedral metallofullerenes, wherein one or more metal atoms are encapsulated inside a fullerene cage, have garnered research interest [12][13][14][15]. The encapsulation of metal atoms can result in electron transfer from the

• derivatives followed by the radical coupling reaction is more plausible for the formation of the corresponding adducts rather than the SN2 reaction mechanism of the La@C2v-C82 anion with benzyl bromide derivatives. Conclusion The reaction of La@C2v-C82 anion with benzyl bromide derivatives 1 at 110 °C