Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• formation between carbonyl and alkene units. Keywords: bathtub; chirality; cyclobisbiphenylenecarbonyl; figure-eight; Wittig reaction; Introduction Figure-eight π-conjugated molecules represent chiral macrocycles with a twisted crossover structure [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15

• conformation (Sa,Sa)-A is feasible with a small activation barrier of 9.9 kcal mol−1. The figure-eight conformer (M,M)-B untwists to adopt an achiral conformation C with the exo-alkene units rotated inwards in opposite directions. These conformational changes are almost identical to those of CBBC 1. However

• conditions. Mono-olefin 3 undergoes a reductive carbon–carbon-bond formation between carbonyl and alkene units upon treatment with TiCl4. The current study demonstrates that the transformation of the carbonyl groups of CBBC results in products with altered physical and chemical properties which may be

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• of the resulting alkene [36]. In addition, this intramolecular etherification corresponds to the 4-exo-tet cyclisation which, in terms of kinetics, is the least favoured n-exo-tet cyclisation mode where n ≤ 7 [37]. Nevertheless, the Williamson etherification still remains one of the most common

• /RPC mechanism starts with a single-electron oxidation of the cobalt catalyst followed by a reaction with the siloxane to generate a cobalt–hydride complex. Subsequent hydride transfer to the alkene produces radical pair 23 which collapses to alkylcobalt intermediate 24. Another single-electron

• butyraldehyde in a mercury vapour illuminator and since then, the reaction has become known as the Paternò–Büchi reaction. Throughout the years after the report, investigations in this field were focused on identifying new reactive alkene and carbonyl components, developing photosensitisers that would allow

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• subsequently adds to the activated alkene of N-arylacrylamide, followed by intramolecular cyclization, ultimately leading to the formation of the hydroxy-containing oxindole via the loss of a hydrogen radical. In 2016, Han and colleagues developed a novel methodology in which TBHP served dual roles as both

• to generate t-BuO and OH radicals. The t-BuO radical then abstracts a hydrogen atom from the β,γ-unsaturated ketoxime, forming the iminoxyl radical 10. This is followed by a 5-exo-trig cyclization, yielding a C-centered radical 11, which then adds to the alkene moiety of the N-arylacrylamide, forming

• from N-cyanamide alkenes (Scheme 27) [16]. This approach is notable for its alignment with the principles of green chemistry, utilizing the metal-free photocatalyst 4CzIPN under visible light conditions. In this system, N-cyanamide alkene 54 and BrCF2CO2Et 55 were used as model substrates, with 4CzIPN

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• various synthetically useful transformations, including alkene synthesis via Horner–Wadsworth–Emmons reaction [14][15], heterocycle construction [16][17], and the synthesis of chiral β-amino and β-hydroxy phosphonic acids [18][19]. Furthermore, they exhibit metal-complexing abilities [20], and anti

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

• stereoselectivity. The authors emphasized that, as the alkene moiety in 54 was in a terminal position, the stereoselectivity of the products was determined solely by the chiral environment of the catalysts. The application of this method to construct the C3–C11 fragment 60 of borrelidin is summarized in Scheme 8

• compound 84 through a series of sequential steps, including chemoenzymatic (ω-1)-hydroxylation, regioselective dehydration of the resulting alcohol to form a terminal alkene, ozonolysis of the alkene to yield an aldehyde, reduction of the aldehyde product to a primary alcohol, and protection of the alcohol

• subsequently dehydrated using Martin’s sulfurane to produce terminal alkene 90 in 97% yield. A sequence of ozonolysis, reduction with sodium borohydride, and PMB protection using camphorsulfonic acid and PMB-trichloroacetimidate reagents followed, yielding compound 87 in 62% yield. Next, the ester

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• first report by Stork in the 1950s [1][2][3]. Compared with enols, enamines benefit from the lone pair of electrons on the nitrogen atom, which enhances the nucleophilicity of the alkene, enabling it to react with a broad range of electrophiles. This activation mode of carbonyl compounds has been so

• , the terminal alkene remains intact during this process, and the initial protonation proceeds with full stereocontrol, rendering this transformation both highly chemo- and diastereoselective. From the cyclization result, it is presumed that the higher nucleophilicity of the alkyne functionality over

• the terminal alkene and the conformational strain of forming a bridge[3.2.1]bicycle might be responsible for a selective 6-exo-trig cyclization. From tricyclic compound 4, anti-Markovnikov oxidation catalyzed by palladium led to the formation of aldehyde 5. When treated with p-TsOH, the intramolecular

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

• Abstract We present the first examples of alkene amino-sulfonoxylation reactions that leverage the unique reactivity of carbamate tethered N-alkoxy nitrenium ions. In almost all cases examined, the reactions deliver product with exquisite regioselectivity and diastereoselectivity. The protocols followed

• are operationally very simple and only use commercial I(III) reagents and sulfonic acids, amounting to a metal-free protocol for alkene amino-oxygenation. No special precautions need be taken to exclude air or ambient moisture, and the products are amenable to further transformations. Keywords

• : alkene; amino-sulfonoxylation; metal-free; tethered nitrenium; Introduction Our laboratory has a programmatic focus on the development of metal-free oxidation reactions that avoid the use of toxic reagents such as osmium and chromium [1][2][3]. In line with this agenda, we recently explored a mild amino

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• at C10 was then introduced via a Michael addition (MeMgBr, CuI) to afford 22 in a yield of 65% (4:1 dr at C10). Initial attempts on the carbonyl 1,2-transposition protocol reported by Dong and co-workers were ineffective [45], leading to premature hydride termination and the formation of alkene 23

• . As an alternative solution, by treating 22 with KHMDS and PhNTf2, enol triflation took place successfully. The resultant triflate was coupled with n-Bu3SnH to afford Δ1,29-alkene 23 in 83% yield over two steps. Subsequent hydroboration–oxidation by employing BH3·THF proceeded smoothly, providing a

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• scaffolds (Scheme 6) [64][65]. First, we attempted heterogeneous hydrogenation of the alkene functionality in compound 16a under 1 atm hydrogen pressure using Pd/C as a catalyst. Although the reaction proved sluggish, we were able to drive it to completion over a prolonged reaction time of 14 days

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• , the Shu group developed a catalyst-controlled regioselective and enantioselective hydroamination reaction of electron-deficient alkenes (Scheme 7) [30]. By efficiently regulating the regioselectivity and enantioselectivity of alkene 23 hydrometallation through catalytic systems, they overcame the

• C(sp3)–C(sp3) coupling via distal stereocontrol, efficiently producing C3-alkylated pyrrolidines, while the nickel catalytic system afforded C2-alkylated pyrrolidines through a tandem alkene isomerization/hydroalkylation process. This method utilized readily accessible catalysts, chiral BOX ligands

• insertion to achieve C3 selectivity, whereas nickel catalysis involved alkene isomerization to generate a (2,3-dihydropyrrolyl) intermediate Int-35, followed by C2-selective coupling. In 2024, the Zheng group reported a catalyst-controlled cyclization reaction of bicyclo[1.1.0]butanes (BCBs) 32 with α

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• energy sensitizers, would represent an attractive platform for future reaction design. Here, we disclose the photoactivation of simple alkenylboronic esters established using alkene scrambling as a rapid reaction probe to identify a suitable catalyst and boron motif. Cyclic voltammetry, UV–vis analysis

• facilitated landmark organic transformations, such as the venerable Paternò–Büchi [6][7][8], Norrish–Yang [9][10][11], and enone–alkene cycloadditions [12][13][14], that proceed via the generation of a singlet or triplet diradical through the activation of an unsaturated bond [2][14]. While these seminal

• contributions have enabled the efficient activation of carbonyl and alkene moieties, the inability of most organic molecules to efficiently absorb photons at longer wavelengths often preclude their use in direct excitation strategies, requiring unique experimental set ups and light sources that are

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• % yield under basic conditions using sodium hydroxide and tert-butanol. The reduction of nitrile 3q with lithium aluminum hydride generated amine 7 in an 85% yield, whereas the selective hydrogenation of the alkene moiety of 3q using a Pd/C catalyst in a H2 gas environment smoothly produced product 8 in a

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

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

• wide range of 1,1-diborylalkanes bearing an N-tosyl-protected amine as well as alkene and alkyne moieties underwent efficient coupling with allylic bromides. A notable advantage of this synthetic approach is that it provides a distinct alternative to traditional CuH-catalyzed allylic alkylation

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• , the cyclization of the amino acid fragment-containing monoesters 9l,m afforded dipeptides 6l,m in 36% and 50% yield, respectively. Notably, the decarboxylative cyclization is compatible with the alkene moiety (product 6m). Both dipeptides 6l,m were obtained as a 67:33 mixture of diastereomers. In the

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• –Alder reaction between an imine and an alkene (Scheme 6). Very successfully, the multicomponent version of the Povarov reaction using aldehydes, anilines, and alkenes has been explored in a three-component cascade reaction to quinolines [28][29][30][31] (Scheme 6). Furthermore, protocols have been

• developed in which the alkene compound has been replaced with other surrogates for electrophilic addition, such as ketones [32][33][34]. In the case of the carbonyl component, it is generally an aromatic aldehyde [30][33][34] and there are not many reports on using formaldehyde in the Povarov reaction. In a

• the alkene moiety of the amine. The resulting stabilized carbocation 15 is then captured by formaldehyde (generated in situ from DMSO) leading to an intermediate oxocarbenium 16 that undergoes a cyclization to obtain the sulfenylated oxazinane derivative 13. In isotope labelling experiments using DMSO

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• containing a dimethylamino motif did not require an additional protecting group, ring closure was performed through alkene cross metathesis, which has been accomplished reliably and with good yields for other cryptophycins [11][26][27]. However, for the synthesis of a cryptophycin with a monomethylated amino

• group in unit B a suitable protecting group, i.e., allyloxycarbonyl (Alloc), must be used. Since the presence of this allylic double bond would most likely interfere with a clean reaction outcome after alkene cross metathesis, we decided for a more classical ring-closure strategy through

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• of our ongoing interest in radical cyclization reactions [22][23][24][25][26], we report here a sustainable and efficient protocol for synthesizing difluoromethylated and aryldifluoromethylated polycyclic imidazoles via visible-light-promoted cyclization of unactivated alkene-containing imidazoles

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• bearing linear alkyl groups were transformed into N-acyl amidines 10a–c by copper catalysis. Moreover, good functional group tolerance was observed with a terminal alkene motif (10d). The cyclohexyl-substituted dioxazolone successfully provided the corresponding N-acyl amidine 10e. However, the

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• an alkene to generate a radical intermediate, followed by oxidation, which enables radical-polar crossover (RPC) and the subsequent nucleophilic attack of the cationic intermediate [67]. Alternatively, the initial radical intermediate can be trapped by a transition-metal catalyst, followed by a cross

• enantioselective radical cyanation. In the proposed catalytic cycle, Co(III)–H species 92 are initially formed from the anodically oxidized Co(III) complex 91 and hydrosilane 88 (Figure 15). Subsequently, the HAT between the Co(III)–H catalyst 92 and the alkene 27 generates a carbon-centered radical species 93

• reacts with the alkene 97 to produce an alkyl radical 104, which undergoes ligand transfer from Cu(II)(N3)2 (102) to yield the diazidation product 99 and Cu(I)(N3) (100). The Cu(I)(N3) (100) is reoxidized to Cu(III)(N3)3 (101) on the anode in the presence of N3- to complete the catalytic cycle. In 2024

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

• , respectively. The latter interacts with the alkene generating an alkyl radical IV that converts to the cationic intermediate V by single-electron oxidation by the Cu(II) species. Finally, the attack of the nucleophile leads to the desired products 6. Starting from aryl carbazates, intermediate II, adds

• 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

• begins with a nucleophilic attack of hydrazine on the aldehyde, activated by the copper salt, to give the corresponding hydrazone XXVIII. Subsequently, the formation of a Mannich-type intermediate XXIX was hypothesized by interaction between the hydrazone and the alkene mediated by Cu(OTf)2 coordination

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• ) cyclization of alkynylindolylmethanols 170 and 2-naphthols 171 mediated by chiral phosphoric acid C37 leading to axially chiral aryl-alkene-indoles 172 (Scheme 50) [78]. Very high enantioselectivities and E/Z ratios, along with, on average, decent yields, were reported. Slow racemization was observed at 40 or

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• cycloadducts 29e and 31e in good yields (Scheme 12). Further derivatizations were also carried out: The treatment of 29e with SOCl2 led to interesting unsaturated derivative 32 in a 54% yield. The acetylation of 31e provided 33 in 76% yield. Next, an alkene metathesis of 33 with styrene led to product 34 in 72

• stepwise mechanism could be also feasible (path b). In the latter, the addition of the alkene to the azadiene is occurring first and leads to an intermediate which then undergoes an intramolecular cyclization to yield product 62f. In both pathways, the hydrogen-bonding interaction between the substrate and

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• established as a powerful approach for molecule synthesis. Strategies within click chemistry include several widely used reactions such as the (hetero-)Diels–Alder reaction [1][2], alkene hydrothiolation [3], and an array of amide-bond-forming chemistries [4]. However, by virtue of the access to alkyne and

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

• firstly through the coordination of an alkene by the HVI reagent, which activates it toward intramolecular attack by an internal nucleophile. Following this, substitution of the iodane(III) can occur from the nucleophilic halide in solution to reveal the halo-cyclised product (Figure 2). In this review

• this review aims to fill. The synthetic uses of HVI reagents [14][15][16], their involvement in heterocycle synthesis [17][18][19], and alkene functionalisation [20][21], have each been well-reviewed elsewhere. Review Hypervalent iodine-mediated fluorocyclisation Fluorine can substantially improve the

• fluoride and BF3·OEt2 as activator. A range of unsaturated amines 5 were cyclised to racemic β-fluorinated piperidines 6. Good yields were reported for all compounds except those with substituents present on the alkene. Homologation of the carbon chain from 5 to 6 carbons gave both 6- and 7-membered rings