Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• contraction of six-membered cycles in the synthesis of functionalized cyclopentane/enones, which are biologically active compounds. The main synthetic methods of ring contraction (ozonolysis–aldol condensation, ozonolysis–Dieckmann reaction, Baeyer–Villiger cleavage–Dieckmann reaction) and rearrangements

• [7]. Syntheses of cyclopentanoids usually are based on cyclopentaannelation reactions: transformations accompanied by cyclization [8]; transformation of compounds containing a cyclopentane ring [9]; contraction of large cycles to cyclopentane derivatives. Ring contraction reactions are among the most

• cyclohexane/ene ring contraction. The structure of the review includes examples of simple transformations (ozonolysis–aldol condensation, ozonolysis–Dieckmann reaction, and Baeyer–Villiger cleavage–Dieckmann reaction) and rearrangements (photochemical, benzil, semi-pinacol, Wolff, Meinwald, Wagner–Meerwein

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• cascade to give enone 21 in 42% yield. Baeyer–Villiger oxidation of this highly activated alkene promoted an epoxidation/Baeyer–Villiger oxidation cascade to yield lactone 22 in 67% yield (dr 2:1). The low diastereoselectivity suggested that the epoxidation happened subsequent to the ring contraction, as

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

• 112 in 33% overall yield, which was then used in a 4-step sequence to produce PF-06878031 in >99% purity and a combined yield of 1,500 kg across multiple facilities. 1.5 Ring contractions Another strategy for oxetane synthesis is a ring contraction of 5-membered rings. There are two main approaches

• 113a–d, which are valuable precursors of oxetane nucleosides (Scheme 29) [77]. The triflates were prepared from the corresponding 1,2-O-isopropylidenepentofuranose sugars in 4 steps and then treatment with methanolic K2CO3 smoothly induced the ring contraction, affording the oxetane products in 70–82

• less reactive mesyl almost completely shut down the ring contraction. In 2024, Twiddle et al. showed that this ring contraction can also be effected from lactones containing bromine as the leaving group and used this approach to develop a 2nd generation industrial synthesis of PF-06878031 (Scheme 30

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

• intermediates Int-53 or Int-53'. Reductive elimination of Int-53 or Int-53' regenerates Pd(0) and produces intermediate 55. With the assistance of the base K2CO3, the ten-membered silacycle 55 undergoes rapid ring contraction via cleavage of two Si–O bonds and formation of one Si–O bond, leading to 56 and Int

• -55. Concurrently, Int-55 dimerizes to form 54, which is further transformed into cyclosiloxanes under K2CO3 and DMA conditions. Intermediate 56 undergoes additional ring contraction through cleavage of Si–O/Si–C bonds and formation of a Si–C bond, yielding 57 and Int-56, with Int-56 polymerizing to

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• interaction of 2,3,3-trimethylindolenine with 3,5-di(tert-butyl)-1,2-benzoquinone leads to the formation of indolo[1,2-a]indoline derivatives [23], while the presence of a nitro group in 4,6-di(tert-butyl)-3-nitro-1,2-benzoquinone the reaction with 2,3,3-trimethylindolenine leads to an o-quinone ring

• contraction and the formation of 2-azabicyclic products and pyridino[1,2-a]benzo[e]indol-10,11-diones [24]. o-Chloranil was found to be the most efficient 1,2-benzoquinone, which engages in o-quinone ring-expansion reactions with 2,3,3-trimethylindolenines to form hard-to-reach polychlorinated derivatives of

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• the exocyclic carbonyl group by preformed ring contraction and interaction of the intermediate ketene with the selected nucleophile. Various aromatic and aliphatic amines as well as alcohols and thiols can be used as nucleophiles. 5-Monosubstituted diazotetramic acids give exclusively trans

• organic synthesis as a route to generate ketenes is being actively investigated, involving both acyclic and carbocyclic diazocarbonyl compounds [26]. At the same time, the use of diazoheterocyclic reagents (including diazotetramic acids) in this transformation, with the formation of heterocyclic ring

• contraction products, is represented in the literature only by isolated examples [27][28][29][30][31]. In addition, photoinitiation is mainly used, while the possibilities of thermolysis remain virtually unexplored. Herein, we report our findings obtained while investigating a synthetic approach to 2

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• 2 via Baeyer–Villiger oxidation, followed by hydrolysis to yield another crucial aldehyde/acid intermediate 3 [11][15]. Commencing from 3, diverse ring rearrangement reactions can occur, leading to the formation of distinct products. In the AlpJ-catalyzed reaction, compound 3 undergoes ring

• contraction reactions, yielding a benzofluorene intermediate 4 and the dimer 5, both featuring a kinamycin skeleton (Scheme 1) [11][12]. Recent investigations unveiled the catalytic activity of the O-methyltransferase-like protein AlpH, which catalyzes a unique SAM-independent coupling of ʟ-glutamylhydrazine

(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

• ), deprotection, decarboxylation, oxidation, nitrogen extrusion (to cyclobutadiene) and Diels–Alder reaction yielded annulated tricycle 164. Further intramolecular [2 + 2] cycloaddition formed cubane precursor 165. From diketone 165, 1,3-cubane 166 was obtained by Favorskii ring contraction followed by

• oxidation of alcohol 175 with Dess–Martin periodinane. Synthesis of cubane 166 was then achieved by [2 + 2] cycloaddition of enone 176 using acetone as the photosensitiser (to 177), the first Favorskii ring contraction (to 178), deketalisation, the second Favorskii ring contraction and esterification (to

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• strategies in line with the “precursor approach” have been recently reported, in which chalcogen-containing precursors undergo a ring contraction combined with the extrusion of a chalcogen fragment in the ultimate step. In view of the diversity of π-conjugated polycyclic structures potentially accessible via

• can be ascribed to a redox-driven S-extrusion (Scheme 6). This behavior of extended thiepines upon oxidation was further confirmed by investigating the corresponding sulfoxide, which appeared labile and readily underwent ring contraction. Since thiepine precursors (such as 15) and the corresponding

• -doped triphenylene derivative 22. In the same year, An et al. reported their investigations regarding chalcogen-doped hexa-peri-benzocoronene (HBC) derivatives and their controllable conversion into hydrocarbon nanographenes by ring contraction of the heteropine moiety [65]. The authors first tackled

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• a surrogate of acetylene reacted with trifluoroacetonitrile imine to form 1-aryl-3-trifluoromethylpyrazoles, followed by a series of cascade annulation/dehydration/ring contraction reactions when treated with p-TsCl [65] (Scheme 10b). The chemistry of pyrazoles with a fluorine or a fluoroalkylated

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• structure and reactivity of the obtained macrocycle are outlined. Keywords: amidrazones; hexaazamacrocycles; pyrazolo[3,4-d]pyrimidines; ring contraction; self-assembly; Introduction The chemistry of polyazamacrocycles (PAMs) is currently one of the most rapidly developing areas of heterocyclic chemistry

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• ]. These non-traditional electrophiles allow access to structurally highly interesting motifs. In addition, they are amenable to valuable synthetic transformations such as oxidative ring contraction of the cycloheptatrienyl ring or reduction of the benzodithiolyl group. In this context, we decided to study

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• -containing heterocycles intensively studied in medicinal chemistry and pharmacology. In the present paper, a new synthetic approach to pyrrolobenzothiazoles is developed based on 1,4-thiazine ring contraction in 3-aroylpyrrolo[2,1-c][1,4]benzothiazine-1,2,4-triones under the action of nucleophiles. The

• » conditions (Scheme 4, entry 15) [10][11]. This work reports a new approach to PBTA derivatives via nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines 1 (Scheme 5, entry 16), which can generally be attributed as a new entry to the fourth group of approaches to the PBTA scaffold (Scheme

• , recently, we have reported a new class of FPDs, aroylpyrrolobenzothiazinetriones (APBTTs) 1 (Figure 2) [37][38], whose structural features allowed us to assume a possibility of the development of a new approach to PBTAs via a nucleophile-induced ring contraction in the 1,4-benzothiazine moiety of compounds

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• substituents on the chromenone or piperidinone core (Scheme 28). Furthermore, cycloheptatrienyl and benzodithiolyl substituents can be further modified, thus, expanding the synthetic possibilities of this methodology. The cycloheptatrienyl substituent allows oxidative ring contraction to form a phenyl ring

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• reported for vinyl sulfides, including dihydrodithiin 13 (Scheme 5a) [36]. In fact, Parham has found that fully unsaturated dithiins can undergo this electrophilic formylation, but at the same time also undergo a ring contraction and an aromatizing desulfurization to yield thiophenes as the main formylated

Isolation and biosynthesis of daturamycins from Streptomyces sp. KIB-H1544

• Yin Chen,
• Jinqiu Ren,
• Ruimin Yang,
• Jie Li,
• Sheng-Xiong Huang and
• Yijun Yan

Beilstein J. Org. Chem. 2022, 18, 1009–1016, doi:10.3762/bjoc.18.101

• via the terphenylquinone atromentin (Figure 1), followed by oxidative ring contraction [17]. However, the details of cyclopentenone formation involving ring contraction have remained unclear. In this study, two novel diarylcyclopentenones daturamycins A amd B (1 and 2), one new p-terphenyl daturamycin

• molecules of phenylpyruvic acid (7) undergo direct condensation to form a five-membered ring intermediate or (path b) polyporic acid (8) undergoes oxidative ring contraction or conversion to generate the cyclopentenone skeleton. To verify which pathway was responsible for the biosynthesis of daturamycins in

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• conditions. In sharp contrast, the corresponding six-membered α-bromo-δ-valerolactone has a more-distorted ring and is extremely unstable, even at room temperature [39][40][41]. In fact, it must be stored in a freezer because ring-opening polymerization and ring-contraction reactions occur readily at room

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• Serusi et al. in a tandem reaction to synthesize functionalized tryptamines from 2-hydroxycyclobutanones 107 with a primary aniline [30]. Notably, the α‑iminol rearrangement results in a ring contraction to give the 2-aminocyclopropyl ketone intermediate 109, which upon condensation with a second

• silica gel on 38 and the other by NaOMe on both 38 and 39, part of the total synthesis of silvestrol (34) and episilvestrol (35). PMP = p-methoxyphenyl. α-Ketol rearrangement of triumphalone (41) to isotriumphalone (42) via ring contraction. Tandem reaction of strophasterol A synthetic intermediate 43 to

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• 1,6-anhydro derivative 10, we were able to isolate one of the side-products in sufficient purity and quantity to assign the structure of C-furanoside 20 (Scheme 2). This compound resulted from pyranose ring contraction probably caused by intramolecular displacement of the C2 azide aided by

• coordination of ZnI2. When the α-anomer of thioglycoside 17 was separately subjected to the reaction conditions, the byproduct 20 started to form in trace amounts in accordance with the suggested mechanism. The ring contraction may involve formation of a transient oxiranium cation as suggested in Scheme 2 [42

• ][43][44][45]. Analogous ring-contraction reactions have been described for substrates possessing a good C2 leaving group [42][46][47][48][49][50]. We initially considered converting thioglycosides 14–19 to benzyl glycosides because thioglycosides give glycosyl fluorides on reaction with diethylamino

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• ring contraction under reductive conditions in presence of zinc dust in acetic acid according to the Boger procedure, which is a highly reliable synthetic approach [66][67][68]. For pyrrole conversions, methoxycarbonyl- and 2-pyridylpyridazine derivatives 4a and 4b were used. When

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• fluorine electron density to attack equatorially. Although we propose an oxiranium intermediate for the C4 deoxyfluorination of 13, we did not observe any ring rearrangement, typically as a result of ring contraction (for example, compound 19, step d) [26][29][38]. Also, we did not observe any 1,2-alkyl

Recent synthesis of thietanes

• Jiaxi Xu

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

• thietane backbones developed during 1966 to 2019. Keywords: cycloaddition; cyclization; ring contraction; ring expansion; thietane; thiotherification; Review 1. Introduction Thietanes are a class of important aliphatic four-membered thiaheterocycles. Some simple alkyl and dialkyl thietanes are components

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• potassium selenocyanate proceeded via a rearrangement with ring expansion, leading to a six-membered 2,3-dihydro-1,4-thiaselenin-2-yl selenocyanate (kinetic product) which in turn underwent rearrangement with ring contraction to a 1,3-thiaselenol-2-ylmethyl selenocyanate (thermodynamic product). These

• -dihydro-1,4-thiaselenines (up to 96% yields) – products of rearrangement with ring expansion, which in turn underwent rearrangement with ring contraction, forming a new family of 1,3-thiaselenoles in up to 99% yield. The article was included in the RSC themed web collection "The chemistry of Selenium

• temperature underwent rearrangement and ring contraction to 1,3-thiaselenol-2-ylmethyl selenocyanate 4. These rearrangements proceeded via a seleniranium cation 2 that is attacked by the nucleophilic selenocyanate anion at two different carbon atoms of the three-membered ring. The regio- and stereoselective

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• further oxidation to carbonyls or carboxylates. Other reactions, such as epoxidation, ether bond formation, and structural rearrangement have also been reported (Figure 7). CYP114 in gibberellin (5) biosynthesis, for example, catalyzes the unique oxidation/six-membered to five-membered ring contraction of

• examples of terpene modification by bacterial CYPs. a) Hydroxylation [89]. b) Carboxylation, hydroxylation, and ring contraction [41]. c) Ether formation [90]. d) Rearrangement [91]. Off-target effects observed during heterologous expression of terpenoid BGCs. Unexpected oxidation of 34b by an

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• MCR is due to the ring contraction of the 7-membered ring cyclic intermediate by transannular acyl transfer, which leads to the β-lactam derivative. Despite the chiral nature of the steroidal substrate, no significant stereoselective induction was observed, probably because the 7-membered ring