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

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

• , 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

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

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

• 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

• mechanism for the reaction (Scheme 38) in which activation of the alkene and intramolecular attack of oxygen through a 6-exo-trig mechanism followed by SN2 reaction with bromide eliminates the chiral aryliodide to form the product 73. In 2018, Liu, Ling and co-workers reported bromoenol-cyclisation of

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

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

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

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

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• chromatography. Because 4.6 was obtained in better yields and in only 3 steps, the epimerization of 4.6 to 4.10 was also reported (Figure 4B). This epimerization is achieved in three-step sequence that starts with the double tosylation of 4.6 to produce 4.11. Then, the SN2 reaction with potassium acetate in DMSO

• mesylation produced 17.3. Then, the nucleophilic substitution (SN2) reaction of benzoate with 17.3 produced the benzoate ester 17.4 with an inversion of configuration. Then, the two protecting groups (ester and trityl) were removed to produce (S)-17.6. The modification of the sn-2 position is illustrated in

• Figure 17B starting from the mesylate derivative (S)-17.3. Its reaction with sodium azide produced, following a SN2 reaction, the azido derivative 17.7. The deprotection of the alcohol function produced 17.8 that subsequently reacted with 2-chloro-2-oxo-1,3,2-dioxaphospholane (17.9) in the presence of

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

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• changes observed as the water content increased were consistent with an SN2 reaction becoming a mixed SN2–SN1 situation and then, eventually, an essentially SN1 pathway was followed. It was concluded that nucleophilic attack at sulfur has many of the characteristics of attack at carbon, including the

• conveniently designated as “the molecularity of the rate-determining stage.” We personally favor the designation as bimolecular with or without general-base assistance from a second nucleophilic (basic) molecule. The SN2 reaction plot of log (k/ko) vs (1.26 NT + 0.65 YCl) for the solvolyses of benzesulfonyl

• ., distributed under the terms of the Creative Commons Attribution 3.0 International License, https://creativecommons.org/licenses/by/3.0). The SN2 reaction plot of log (k/ko) vs (1.35 NT + 0.70 YCl) for the solvolyses of 2-thiophenesulfonyl chloride (13) in pure and binary solvents at 25.0 °C. The specific rate

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• from the C6′-OH group (Scheme 6). The second inversion at the C5′ centre occurred when the C2′-OH attacked the same chiral centre and opened the epoxide ring by SN2 reaction and inverted the configuration of the centre into (R). In the chemical route for synthesis of bridged nucleosides 9a,b, an

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• carbon atom while maintaining α-configuration and simultaneous elimination of an acyl group as illustrated in intermediate IV. Further, attack of silylated cytosine on α-chloro-substituted derivative V in an SN2 reaction results in the formation of a glycosidic C–N bond in the β-configured nucleoside

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• our studies on a direct benzylic allylic reaction of 2-alkylpyridines with MBH carbonates as allylic precursors under base- and catalyst-free conditions. As depicted in Scheme 2, we envisioned that the MBH carbonate 2 can undergo the SN2’ reaction with the nucleophilic 2-picoline 1a, giving the

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• proved that the reaction mechanism proceeds via activation of the alkynyl group with Hg(OTf)2 salt and addition of 2-chloropyridine N-oxide. The resulting activated alkynyl complex was demercurated, followed by the SN2′ reaction thus formed undergoes demercuration to yield 3-coumaranone (Scheme 51) [111

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

Dirhamnolipid ester – formation of reverse wormlike micelles in a binary (primerless) system

• David Liese,
• Hans Henning Wenk,
• Xin Lu,
• Jochen Kleinen and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2020, 16, 2820–2830, doi:10.3762/bjoc.16.232

• chain length without the production of side products (Scheme 1). Under mild and basic conditions, with this SN2 reaction of the dirhamnolipid and any primary alkyl halide, the desired product was obtained with a high yield ranging from 70–85%. Also, a gemini-like structure 7 was synthesized. Solubility

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• instance, an MO picture of the SN2 reaction is attractive but less common than the compact and informative “curly arrow” picture. The Diels–Alder reaction or aromaticity, on the other hand, cannot really be treated adequately within the Lewis picture without resorting to the Dewar–Zimmerman rules [80][81

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• approach, the thietane ring was constructed more efficiently through a two-step displacement sequence from the D-xylose-derived dimesylate 114 (Scheme 24). The first step displacement involved the selective SN2 reaction of the primary mesylate with KSAc to yield a monothioacetate 115 in 80% yield. The

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• have been synthesized via solid-phase peptide synthesis and SN2’ reaction on a Morita–Baylis–Hillman (MBH) residue introduced at the N-terminal of a tetrapeptide. This last step takes advantage of the electrophilic feature of the MBH residue and represents a new cyclization strategy occurring. The

• solution of peptides 8 in dry THF/CH2Cl2 (1:1) containing Et3N was vigorously stirred for 48 h at room temperature (Scheme 4) as previously described in a similar procedure for the intermolecular SN2’ reaction between thiophenol and O-acetylated MBH adducts [39]. The solonamide analogues 9 were obtained

• adducts 2 and their carboxylic acids 3. Chemical synthesis of the linear peptidomimetics 8. Macrocyclization strategy based on SN2’ reaction to affords the solonamide analogues 9 and their overall yields based on the initial resin’s molarity. Halos of hemolysis or inhibition of hemolysis of S. aureus ATCC

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• thiophenols 14 through SN2 reaction with cyclopropyl bromide (15, Scheme 2a) [2][4] or by SNAr reaction between aryl fluorides 16 and cyclopropanethiol (17, (Scheme 2b) [6]. Although simple and attractive, these approaches usually require harsh conditions such as the presence of a strong base and high

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• formal syn-SN2’ reaction. This is an intriguing observation, since for other TSs a NPP-cyclisation by anti-SN2’ is usually described [40][45][46][47]. This cyclisation mechanism is thought to be the predominant case, giving rise to a more energetically favoured transition state, but occasionally also the

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• stereochemistry (anti-SN2’ reaction), which is favoured for a concerted process and is also discussed for other cyclisation mechanisms [24][25][26], the four theoretically possible options for the BbS cyclisation mechanism are narrowed down to two possibilities: Either the reaction takes place via (R)-NPP