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

• Figure 1 and Figure 2, it can be found that the C=C bond is located in the unit of the pyrrolidine-2,5-dione, while the scaffold of indolin-2-one is connected via a C–C single bond with the unit of the pyrrolidine-2,5-dione. Therefore, an allyl rearrangement must proceed in the reaction process, which is

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• directly to the alkene, then reacts with the nucleophile to afford product 7. The regioselective 1,2-difunctionalization of allyl alcohol has been developed as a three-component cascade reaction using arenes and sulfonamides as nucleophiles to achieve arylation/hydroamination processes. The reaction

• involves a Friedel–Crafts alkylation of the arene followed by hydroamination (Scheme 6) [5]. The mechanism plausibly starts with the in situ formation of triflic acid from Cu(OTf)2 which leads to protonation of the oxygen atom of the alcohol with generation of the activated allyl alcohol. This latter gives

• the allyl carbenium ion VI through the loss of a molecule of water, then undergoes a Friedel–Crafts alkylation by attack of the aromatic partner. The outcome of the reaction proceeds through a Markovnikov protonation of the allylated arene VII by triflic acid, which generates the carbocation

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

• instance, when the bulky tert-butyl ester sulfoxonium ylide was used, the fluoroalkyl product 3f was obtained in 82% yield. A 60% yield was obtained for 3g when the reaction was carried out with the cyclopentyl ester ylide derivative. The allyl sulfoxonium ylide reacted to produce 3h in an excellent 92

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• ] developed artificial, ‘natural-like’ polyphenols, using the Ugi reaction, since it leads to mixed polyphenol–peptidomimetic structures (Scheme 4). The procedure involved an Ugi reaction using phenolic building blocks protected as allyl ethers, followed by deprotection, acetylation, and high-yielding

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

• -workers (Scheme 16) [39]. p-TolIF2 is formed in situ from p-iodotoluene and Selectfluor in a 4.5:1 HF:amine solution, which is obtained by combining Et3N·3HF and pyridine·HF. A range of N-allyl carboxamides 31 were successfully cyclised forming fluoromethyl-2-oxazolines 32 in good yields. The synthesis of

• [30]. In 2015, Li and co-workers reported the synthesis of chloromethyloxazolines 49 [48] (Scheme 27). Using PhI(OAc)2 as an oxidant and TMSCl as a source of chloride and activator, a range of N-allyl carboxamides 31 were successfully cyclised, forming 5-chloromethyl-2-aryloxazolines 49 in good yields

• of a range of N-allyl carboxamides 31 with PhI(OAc)2 and TMSBr formed 5-bromomethyl-2-oxazolines 71 in excellent yields. In 2015, Wang and co-workers reported the bromocyclisation of allylamino alcohols 72 to give chiral morpholines 73 (Scheme 38) [56]. Using an amino acid-derived chiral HVI reagent

Tunable full-color dual-state (solution and solid) emission of push–pull molecules containing the 1-pyrindane moiety

• Anastasia I. Ershova,
• Sergey V. Fedoseev,
• Konstantin V. Lipin,
• Mikhail Yu. Ievlev,
• Oleg E. Nasakin and
• Oleg V. Ershov

Beilstein J. Org. Chem. 2024, 20, 3016–3025, doi:10.3762/bjoc.20.251

• configuration of the double bond was confirmed using 1H,1H-NOESY spectroscopy. As shown in Figure 2, a correlation between protons of the allyl moiety and the aryl substituent evidenced their spatial proximity in molecule 1c. The absence of a correlation between allyl and vinyl protons additionally supported

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

• tert-butylperoxy radical В. Fe(acac)3-catalyzed oxidation of benzyl, allyl and propargyl ethers 78 with TBHP led to the formation of tert-butylperoxyacetals 79 (Scheme 28) [75]. Probably, in the first step TBHP oxidizes Fe(II) to Fe(III) with the formation of tert-butoxy radical A. Then the second

• reaction of iodine and TBHP forms tert-butoxy radical and tert-butylperoxy radical A. Addition of tert-butylperoxy radical A to diene 220 results in the stable allyl radical B, which reacts with iodine radical to form iodoperoxide C. Elimination

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• ]. In this context, while significant contributions have highlighted the reliable use of diverse organometallic species in the three-component coupling, most examples of sp3-hybridized compounds have remained restricted to allyl [5] or benzyl [5][6] organometallic reagents. Conversely, examples of

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

• cation is formed by oxidation of the substrate at the anode. This radical cation is subsequently deprotonated to produce an allyl radical. The allyl radical is further oxidized to form the allyl cation, which is then attacked by the nucleophilic sulfonamide, leading to the formation of the desired C–N

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

• trifluoromethoxylations of (hetero)aromatics [47][48][49][50][51][52], enol carbonates [53] or silyl enol ethers and allyl silanes [54] have been reported. Most of the methods described have used the trifluoromethoxide anion (CF3O−) [45]. Many sources of the CF3O− anion have been described, but with certain drawbacks

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

• directly prepared by combining three readily accessible synthons: an amine, an allyl nucleophile, and a carbonyl compound (Scheme 1) [15][16]. A selection of structural motifs accessible via homoallylic amines is shown in Scheme 1. Despite several reviews on homoallylic amine syntheses being published [17

• two enantiotopic faces of acylimine 2, exposing only one face to the attack by the allyl group. The replacement of one isopropoxy (iPrO) group between allylboronate 1 with BINOL was confirmed by ESI-MS and NMR analysis of the reaction mixture. Interestingly, both (E)- and (Z)-crotyl boronates 6 and 8

• new methodology used bench-stable allyl-1,3,2-dioxaborinane (27) in the reaction with preformed crude N-aryl-, N-benzyl- and N-allylimines in the presence of 2–8 mol % of the relatively simple 3,3’-Ph2-BINOL catalyst 3 at 50 °C in a microwave reactor at 10 W irradiation for 1 hour to afford amines 26

Electrochemical allylations in a deep eutectic solvent

• Sophia Taylor and
• Scott T. Handy

Beilstein J. Org. Chem. 2024, 20, 2217–2224, doi:10.3762/bjoc.20.189

• 1:3 molar ratio of tetrabutylammonium bromide and ethylene glycol (TBAB/EG) [28]. Using the reaction of p-anisaldehyde with allyl bromide as a test case, reactions were performed using three sets of different sacrificial electrodes as well as non-sacrificial graphite. As can be seen in Table 1, tin

• product, although in this case, reduction of the nitro group to an amino group was observed and the resulting 4-aminobenzaldehyde is likely too electron-rich to undergo allylation. The use of other halides was also explored (Table 3). Switching to allyl chloride (Table 3, entry 2) did result in partial

• conversion, but the reaction was much less efficient than for allyl bromide. More substituted allyl bromides, such as crotyl and prenyl bromide (Table 3, entries 3 and 4) did react, although they afforded only partial conversion when using 2.5 F/mol of current. In terms of regiochemistry, addition at the

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

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

• the functionalized 1,3-dicarbonyl compound 33 after the first step. Instead of allyl, a cyano group can also be introduced at position 2 of the 1,3-dicarbonyl compound using TsCN [60]. Cyclization of the intermediates leads to the corresponding 4-cyanopyrazoles. Beyrati and Hasaninejad presented a

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

• reported a novel and straightforward method for synthesizing spiro 2,5-dihydrofuran derivatives starting from 17-ethynyl-17-hydroxysteroids such as lynestrenol (38) (Scheme 12) [25]. The 17-hydroxy group of steroids underwent allylation using allyl bromide and sodium hydride. After formation of the alkenyl

• -butylsulfinamide, leading to the formation of the imine 119. Subsequent reaction with allylmagnesium bromide yielded a mixture of 17-allyl 17-sulfonamido derivatives 120a,b in a 2.5:1 diastereomeric ratio (17S:17R), which were isolated and treated separately. Acid treatment of the sulfinamides 120a,b resulted in

• tert-butylsulfinyl cleavage, yielding the 17-allyl-17-amine hydrochlorides 121a,b diastereomers. These hydrochlorides were then acrylated with acryloyl chloride. When starting from 121a, the bis-acylated compound 122a1 was only detected in traces (3% yield), with the mono-acylated derivative 122a2

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

• on a decagram scale in five steps from (+)-limonene oxide (13), involving epoxide manipulation, oxidative cleavage, and intramolecular aldol condensation. Similarly, the right-half fragment, allyl chloride 16, was synthesized from limonene in five steps. Site-selective hydrogenation, oxidative

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

• ]. Furthermore, alternative alkyl groups such as ethyl, propargyl, allyl, benzyl, and nitrobenzyl groups can be transferred [31][138][139][140][141][142]. Such alkylation strategies have been successfully applied to small molecules such as coumarin [141], anthranilate [21], and pyrazole [24], as well as larger

• used for biocatalytic methylation reactions. If RiPP MTs, like many other MTs, also accept SAM-derivatives with larger alkyl groups as substrates, they can transfer various groups such as ethyl, allyl, propyl, and benzyl moieties. In vitro systems can be used to install specific modifications in

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

• electrophilic alkene and forms the target product. N-Alkoxyphthalimides: In 2019, Tang and co-workers [53] utilized N-alkoxyphthalimides for the generation of alkyl radicals by reacting photogenerated alkoxyl radicals with P(OMe)3 (Scheme 17). This strategy provided the alkylation of allyl and alkenyl sulfones

• the production of an alkyl radical. After that, this alkyl radical reacts with allyl and alkenyl sulfones in an addition–elimination cycle to produce the required product and a benzenesulfonyl radical. The benzenesulfonyl radical abstracts a hydrogen radical from the Hantzsch ester radical to form

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• , so various alkyl halides to replace the benzyl halides were investigated in this reaction (Table 1). Allyl bromide, propargyl bromide, and carbon tetrabromide did not work well as shown in entries 1, 2, and 6 in Table 1. On the other hand, other alkyl halides gave the product in moderate to good

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

• dehydrogenated secondary alcohols into ketone B and diol into aldehyde A. Further, aldol condensation occurred between the ketone and aldehyde and produced α,β-unsaturated ketone C, which was subsequently hydrogenated by complex Mn1-c, followed by allyl isomerization, which led to the formation of hydroxy ketone

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• insufficient evidence provided even by meticulous NMR analysis and eventually had to be confirmed by X-ray crystallography (Figure S1, Supporting Information File 1). Changing the ester function from an ethyl to an allyl group enabled a very mild cleavage using a Pd-mediated reaction with triethylsilane [28

• , DCM, rt, overnight, b) BnBr, NaH, DMF, 0 °C to rt, 1 h, c) (R = Et) diethyl carbonate, LiHMDS, THF, −78 to 0 °C, 1 h, d) (R = allyl) allyl chloroformate, LiHMDS, THF, −78 to 0 °C, 1 h, e) POCl3, DMF, 90 °C, 30 min, f) (BnCO)2O, 100 °C, 1.5 h, g) methanesulfonic acid, DCM, 0 °C to rt, 4 h, h) CyOH

• , PPh3, DIAD, 1,4-dioxane, 50 °C, overnight, i) (R = Et) NaOH, H2O, EtOH, 75 °C, 3 h, j) (R = allyl) Et3SiH, PPh3, Pd(OAc)2, ACN, rt, k) H–ʟ-Tyr–OMe, HOBt, EDCI, TEA, DCM, DMF, rt, 12 h, l) LiOH⋅H2O, H2O, 1,4-dioxane, rt, 45 min. Cy = cyclohexyl. Synthetic pathway to pyridone derivatives 3a–c of HeE1

(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

• itself accessible in good yields from allyl chloride 1 using a route based on that reported by Schlüter [28]. Bifunctional 1,2-BCP (±)-4 bearing orthogonally protected alcohol functionalities was obtained from 3a through a three-step sequence of strain-release radical ring-opening with iodochloromethane

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

• the displacement of the chloro substituent with the allyl group, affording 21 in good yield. Electrophilic aromatic substitution reactions at the chloroalkyl ether site were possible when promoted by aluminium chloride, with anisole and diphenyl ether giving addition products 22 and 23 containing

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

• % yield of the azido-arylated product, and using the more nucleophilic 13 only slightly improved the yield. Finally, a small amount of product resulting from the addition of allyl-BF3K 14 could be observed but decomposed during purification. Based on literature precedence [41][42][44] and experimental

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

• limitation of the photoinduced palladium-catalyzed carboamination reactions and the radical-mediated difunctionalization of alkenes with diazo compounds. We envisioned an interesting MCR strategy with mild conditions to access unsaturated γ- and ε-AA derivatives via a π-allyl Pd radical-polar crossover

• case of 1,3-cyclohexadiene 2e, the amine was expected to attack the π-allyl palladium from the exo side. Considering that substituent effects might affect the regioselectivity in this MCR, we further investigated the 1,4-/1,2-addition selectivity with 1-phenyl-substituted 1,3-dienes 2f–i. Interestingly

• [32][33][34][35][36][37][59][60][61][62], upon the loss of dinitrogen. The radical I further adds to the terminal position of 1,3-butadiene (2a) to produce hybrid allylPd radical II, which would exist in equilibrium with π-allyl complex III. Following the classical Tsuji–Trost reaction mechanism, a