Transition-Metal-Free Addition of Dialkyl Phosphites to Phthalazin-2-ium Bromide: Synthesis of α-Aminophosphonate Analogues

Chen, Qian; Zheng, Xiaofeng; Guo, Fang; Liang, Kun; Zhou, Fanrui

doi:10.1021/acs.joc.1c02024

Cited by 6 publications

(3 citation statements)

References 80 publications

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“…Scheme 3 Formation of bis-sulfide 5a from thiol 1a in DMSO Therefore, according to literature reports, 37,38 the reaction proceeds by formation of a known intermediate of disulfide 5a via the oxidation of thiols, followed by nucleophilic substitution of diethyl phosphite with the disulfide intermediate to give phosphorothioate 3 (Scheme 4).…”

Section: Letter Synlettmentioning

confidence: 95%

Catalyst-Free Synthesis of Phosphorothioates via P–S Coupling Reaction of Dialkyl Phosphites with Thiols

Kaboudin¹,

Daliri²,

Esfandiari³

et al. 2022

Synlett

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A catalyst-free synthesis of phosphorothioates via a P-S cross coupling reaction of thiols with dialkyl phosphites has been studied. By presented method, various phosphoroatioates are obtained by the reaction of thiols with H-dialkyl phosphites in the presence of DMSO as a solvent and oxidant under transition metal-free conditions. Mechanistic studies showed that the reaction is proceeded with formation of a known disulfide intermediate via the oxidation of thiols in the presence of DMSO. Nucleophilic substitution of dialkylphosphite with the disulfide intermediate gave phos-phorothioate. The presented method is a convenient process for the synthesis of phosphorothioates under catalyst-free condition.

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Section: Letter Synlettmentioning

confidence: 95%

Catalyst-Free Synthesis of Phosphorothioates via P–S Coupling Reaction of Dialkyl Phosphites with Thiols

Kaboudin¹,

Daliri²,

Esfandiari³

et al. 2022

Synlett

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“…To obtain phosphonylated phthalazine derivatives 843 , Chen and co-workers have developed an addition reaction of H-phosphites 842 to phthalazin-2-ium bromides 841 (Scheme ). This metal-free methodology needs the presence of a base, such as Li 2 CO 3 , to afford the phosphonylated derivatives by nucleophilic addition of dialkyl phosphites, which are favored to undergo phosphonate–phosphite tautomerism in the presence of a base …”

Section: Six-membered Rings: Nonaromatic Aromatic and Benzo-fused Het...mentioning

confidence: 99%

“…This metal-free methodology needs the presence of a base, such as Li 2 CO 3 , to afford the phosphonylated derivatives by nucleophilic addition of dialkyl phosphites, which are favored to undergo phosphonate−phosphite tautomerism in the presence of a base. 424 Trofimov and collaborators have reported that acridines 844 can undergo a nucleophilic addition of secondary phosphine oxides and dialkylphosphites 845 under catalyst-free conditions to obtain the corresponding 9-phosphoryl-9,10dihydroacridines 846 in good yields (Scheme 154). This reaction was applied to the addition of other secondary phosphine chalcogenides with similar results.…”

Section: Tetrahydroisoquinolines and Tetrahydroquinolinesmentioning

confidence: 99%

Synthetic Methods for Azaheterocyclic Phosphonates and Their Biological Activity: An Update 2004–2024

Mayorquín-Torres,

Simoens,

Bonneure

et al. 2024

Chem. Rev.

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The increasing importance of azaheterocyclic phosphonates in the agrochemical, synthetic, and medicinal field has provoked an intense search in the development of synthetic routes for obtaining novel members of this family of compounds. This updated review covers methodologies established since 2004, focusing on the synthesis of azaheterocyclic phosphonates, of which the phosphonate moiety is directly substituted onto to the azaheterocyclic structure. Emphasizing recent advances, this review classifies newly developed synthetic approaches according to the ring size and providing information on biological activities whenever available. Furthermore, this review summarizes information on various methods for the formation of C–P bonds, examining sustainable approaches such as the Michaelis–Arbuzov reaction, the Michaelis–Becker reaction, the Pudovik reaction, the Hirao coupling, and the Kabachnik–Fields reaction. After analyzing the biological activities and applications of azaheterocyclic phosphonates investigated in recent years, a predominant focus on the evaluation of these compounds as anticancer agents is evident. Furthermore, emerging applications underline the versatility and potential of these compounds, highlighting the need for continued research on synthetic methods to expand this interesting family.

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Mechanistic Studies on the Bidentate Lewis Acid Catalyzed Domino Inverse Electron‐Demand Diels‐Alder/Thiol Transfer Reaction

Beeck

Wegner

2022

Eur J Org Chem

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Recently, we presented a novel enantioselective multicomponent reaction of phthalazines, aldehydes and thiols accessing thioether‐substituted 1,2‐dihydronaphthalenes. Herein, a comprehensive investigation on the mechanism of this domino inverse electron‐demand (IEDDA)/thiol transfer reaction is disclosed. In particular, the origin of the stereochemical outcome has been rationalized, as well as structural requirement of the thiol component for an efficient transfer step. Detailed NMR spectroscopy studies uncover a competing reaction pathway resulting in N,S‐acetals. In addition, DFT computations illuminate the mechanism of the group transfer process and enable an explanation for the formation of the most dominant by‐product. The insights allow a direct prediction of suitable substrates for the reaction and provide the basis for further developments of novel stereoselective domino reactions.

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Transition-Metal-Free Addition of Dialkyl Phosphites to Phthalazin-2-ium Bromide: Synthesis of α-Aminophosphonate Analogues

Cited by 6 publications

References 80 publications

Catalyst-Free Synthesis of Phosphorothioates via P–S Coupling Reaction of Dialkyl Phosphites with Thiols

Catalyst-Free Synthesis of Phosphorothioates via P–S Coupling Reaction of Dialkyl Phosphites with Thiols

Synthetic Methods for Azaheterocyclic Phosphonates and Their Biological Activity: An Update 2004–2024

Mechanistic Studies on the Bidentate Lewis Acid Catalyzed Domino Inverse Electron‐Demand Diels‐Alder/Thiol Transfer Reaction

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Transition-Metal-Free Addition of Dialkyl Phosphites to Phthalazin-2-ium Bromide: Synthesis of α-Aminophosphonate Analogues

Cited by 6 publications

References 80 publications

Catalyst-Free Synthesis of Phosphorothioates via P–S Coupling ­Reaction of Dialkyl Phosphites with Thiols

Catalyst-Free Synthesis of Phosphorothioates via P–S Coupling ­Reaction of Dialkyl Phosphites with Thiols

Synthetic Methods for Azaheterocyclic Phosphonates and Their Biological Activity: An Update 2004–2024

Mechanistic Studies on the Bidentate Lewis Acid Catalyzed Domino Inverse Electron‐Demand Diels‐Alder/Thiol Transfer Reaction

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Product

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Catalyst-Free Synthesis of Phosphorothioates via P–S Coupling Reaction of Dialkyl Phosphites with Thiols

Catalyst-Free Synthesis of Phosphorothioates via P–S Coupling Reaction of Dialkyl Phosphites with Thiols