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45 pages, 12731 KiB

Open AccessReview

Recent Developments in Stereoselective Reactions of Sulfoxonium Ylides

by Ciarán O’Shaughnessy, Mukulesh Mondal and Nessan J. Kerrigan

Molecules 2025, 30(3), 655; https://doi.org/10.3390/molecules30030655 - 1 Feb 2025

Viewed by 2564

This review probes the recent developments in stereoselective reactions within the area of sulfoxonium ylide chemistry since the early 2000s. An abundance of research has been applied to sulfoxonium ylide chemistry since its emergence in the early 1960s. There has been a continued effort since then with work in traditional areas, such as epoxidation, aziridination and cyclopropanation. Efforts have also been applied in novel areas, such as olefination and insertion reactions, to develop stereoselective methodologies using organocatalysis and transition metal catalysis. The growing research area of interrupted Johnson–Corey–Chaykovsky reactions is also described, whereby unexpected stereoselective cyclopropanation and epoxidation methodologies have been developed. In general, the most observed mechanistic pathway of sulfoxonium ylides is the formal cycloaddition: (2 + 1) (e.g., epoxides, cyclopropanes, aziridines), (3 + 1) (e.g., oxetanes, azetidines), (4 + 1) (e.g., indanones, indolines). This pathway involves the formation of a zwitterionic intermediate through nucleophilic addition of the carbanion to an electrophilic site. An intramolecular cyclization occurs, constructing the cyclic product. Insertion reactions of sulfoxonium ylides to X–H bonds (e.g., X = S, N or P) are also observed, whereby protonation of the carbanion is followed by a nucleophilic addition of X, to form the inserted product. Full article

(This article belongs to the Special Issue Featured Reviews in Organic Chemistry 2025)

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13 pages, 1730 KiB

Open AccessArticle

Total Synthesis and Biological Profiling of Putative (±)-Marinoaziridine B and (±)-N-Methyl Marinoaziridine A

by Anđela Buljan, Višnja Stepanić, Ana Čikoš, Sanja Babić Brčić, Krunoslav Bojanić and Marin Roje

Mar. Drugs 2024, 22(7), 310; https://doi.org/10.3390/md22070310 - 3 Jul 2024

Cited by 1 | Viewed by 2069

Abstract

The total synthesis of two new marine natural products, (±)-marinoaziridine B 7 and (±)-N-methyl marinoaziridine A 8, was accomplished. The (±)-marinoaziridine 7 was prepared in a six-step linear sequence with a 2% overall yield. The key steps in our strategy were the preparation of the chiral epoxide (±)-5 using the Johnson Corey Chaykovsky reaction, followed by the ring-opening reaction and the Staudinger reaction. The N,N-dimethylation of compound (±)-7 gives (±)-N-methyl marinoaziridine A 8. The NMR spectra of synthetized (±)-marinoaziridine B 7 and isolated natural product did not match. The compounds are biologically characterized using relevant in silico, in vitro and in vivo methods. In silico ADMET and bioactivity profiling predicted toxic and neuromodulatory effects. In vitro screening by MTT assay on three cell lines (MCF-7, H-460, HEK293T) showed that both compounds exhibited moderate to strong antiproliferative and cytotoxic effects. Antimicrobial tests on bacterial cultures of Escherichia coli and Staphylococcus aureus demonstrated the dose-dependent inhibition of the growth of both bacteria. In vivo toxicological tests were performed on zebrafish Danio rerio and showed a significant reduction of zebrafish mortality due to N-methylation in (±)-8. Full article

(This article belongs to the Special Issue Total Synthesis and Synthetic Approaches towards Marine Bioactive Natural Products and Analogues)

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8 pages, 788 KiB

Open AccessShort Note

(3-Methylene-2,3-dihydronaphtho[2,3-b][1,4]dioxin-2-yl)methanol

by Lorenzo Suigo, Giulia Lodigiani, Valentina Straniero and Ermanno Valoti

Molbank 2022, 2022(4), M1521; https://doi.org/10.3390/M1521 - 6 Dec 2022

Cited by 1 | Viewed by 2213

Abstract

(3-Methylene-2,3-dihydronaphtho[2,3-b][1,4]dioxin-2-yl)methanol was unexpectedly achieved as the main reaction product while applying a standard Johnson–Corey–Chaykovsky procedure to the 2,3-dihydronaphtho[2,3-b][1,4]dioxine-2-carbaldehyde, aiming at obtaining the corresponding epoxide. The structure of the recovered compound was confirmed through NMR and HRMS, the melting point was measured by DSC, and the organic purity was assessed using HPLC. We hypothesized the possible mechanism for the obtainment of this side product, which should involve the opening of the dioxane ring soon after the nucleophilic attack of the ylide to the carbonyl function. The consequent transfer of the negative charge allows the achievement of the phenolate function. The tautomer further rearranges, forming the unstable oxirane, which opening is favored by the acidic phenolic function, thus closing into the more stable six-membered ring compound. We confirmed the hypothesized reaction mechanism by applying the same reaction conditions while starting from the corresponding methyl ketone. This undesired compound, easily and quantitatively obtained by standard Johnson–Corey–Chaykovsky conditions, could pave the way to a new methodology for the obtainment of 2,3-disubstituted 1,4-naphthodioxanes, further derivatizable. Full article

(This article belongs to the Collection Molecules from Side Reactions)

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29 pages, 32575 KiB

Open AccessFeature PaperReview

Recent Developments in Vinylsulfonium and Vinylsulfoxonium Salt Chemistry

by Mukulesh Mondal, Shi Chen and Nessan J. Kerrigan

Molecules 2018, 23(4), 738; https://doi.org/10.3390/molecules23040738 - 23 Mar 2018

Cited by 57 | Viewed by 8900

Abstract

This review describes advances in the literature since 2000 in the area of reactions of vinylsulfonium and vinylsulfoxonium salts, with a particular emphasis on stereoselective examples. Although the chemistry of vinylsulfonium salts was first explored back in the 1950s, and that of vinylsulfoxonium salts in the early 1970s, there has been renewed interest in these compounds since the turn of the century. This has been largely due to an increased appreciation for the many synthetic possibilities associated with these valuable electrophiles. The development of improved routes to vinylsulfonium salts allowing for their in situ generation has played a part in accelerating their study. In general, reactions of the two sulfur salt classes follow a similar mechanistic pathway: initial conjugate addition of a nucleophile to the β-position, followed by protonation of an ylide intermediate, and cyclization of tethered anion to afford monocyclic or bicyclic product (e.g., cyclopropane, aziridine, oxazole, oxazolidinone, γ-lactam or γ-lactone). Alternatively, reactions involve formation of an ylide intermediate followed by intramolecular Johnson-Corey-Chaykovsky reaction (epoxidation or cyclopropanation), and subsequent cyclization to afford the desired bicyclic product (e.g., fused bicyclic epoxide or cyclopropane). Full article

(This article belongs to the Section Organic Chemistry)

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18 pages, 396 KiB

Open AccessArticle

Enantioselective Synthesis of 2,2-Disubstituted Terminal Epoxides via Catalytic Asymmetric Corey-Chaykovsky Epoxidation of Ketones

by Toshihiko Sone, Akitake Yamaguchi, Shigeki Matsunaga and Masakatsu Shibasaki

Molecules 2012, 17(2), 1617-1634; https://doi.org/10.3390/molecules17021617 - 7 Feb 2012

Cited by 28 | Viewed by 9512

Abstract

Catalytic asymmetric Corey-Chaykovsky epoxidation of various ketones with dimethyloxosulfonium methylide using a heterobimetallic La-Li₃-BINOL complex (LLB) is described. The reaction proceeded smoothly at room temperature in the presence of achiral phosphine oxide additives, and 2,2-disubstituted terminal epoxides were obtained in high enantioselectivity (97%–91% ee) and yield ( > 99%–88%) from a broad range of methyl ketones with 1–5 mol% catalyst loading. Enantioselectivity was strongly dependent on the steric hindrance, and other ketones, such as ethyl ketones and propyl ketones resulted in slightly lower enantioselectivity (88%–67% ee). Full article

(This article belongs to the Special Issue Asymmetric Catalysis)

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