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

• .21.96 Abstract Aerobic copper(II)-mediated phosphorylation of enol acetates with H-phosphonates leading to the formation of β-ketophosphonates was discovered. The proposed method is applicable to a wide range of H-phosphonates or phosphine oxides as PH-reagents and enol acetates. Unlike previous reports

• ) salts, including halides, nitrate, tetrafluoroborate, or perchlorate, were much less effective or completely inert. Keywords: C–P coupling; copper; enol acetates; β-ketophosphonates; phosphorylation; Introduction The construction of C–P bonds is a highly important task in key areas of modern chemistry

• leading to β-ketophosphonates have been reported [41][42][43][44][45][46][47][48][49][50][61], challenges in this area still exist primely in the search for new available synthetic equivalents of alkynes and alkenes for effective radical C–P bond formation. Enol acetates are potentially versatile

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• of enol acetates with aryldiazonium salts [93]. The excitation of the porphyrin macrocycles by light irradiation initiated the catalytic cycle, generating aryl radicals from the diazonium salts, similar to findings by Gryko and co-workers. They explored both batch and continuous-flow photocatalysis

Electrochemical vicinal oxyazidation of α-arylvinyl acetates

• Yi-Lun Li,
• Zhaojiang Shi,
• Tao Shen and
• Ke-Yin Ye

Beilstein J. Org. Chem. 2022, 18, 1026–1031, doi:10.3762/bjoc.18.103

• have reported a manganese dioxide-catalyzed radical azidation of enol acetates to afford the corresponding azidoketones using dioxygen as the oxidant (Scheme 1A) [14]. The adoption of electrosynthesis in green and sustainable redox transformations has been experiencing a dynamic renaissance [15][16][17

• substrate scope of this electrochemical oxyazidation reaction was investigated (Scheme 2). Enol acetates derived from various alkyl-substituted phenylacetones were generally well tolerated (3–9, 40–76% yields). The relatively low yield of the isopropyl-substituted one (7) was attributed to the competing

• ), and benzofuran (23) were all amenable in this transformation. In addition, various linear- (24, 25) and cyclic enol acetates (26, 27) also readily underwent the anticipated oxyazidation. Unfortunately, the current protocol was not applicable to the oxyazidation of enol acetate deriving from aliphatic

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• , SelectfluorTM, from a cost-effectiveness viewpoint. The fluorinating power of reagents 16-3 strengthened as the electronegativity of the R group increased in the order of CH3 < CH2Cl < CH2CF3. The reagents 16-3 were able to fluorinate enol and conjugated enol acetates of steroids, sodium malonates, enamines

• ], electron-rich alkenes (entry 3) [65][66], alkyl sulfides (entry 4) [65][67], 1,3-dicarbonyl compounds [65][68], phosphonate esters (entry 5) [65], steroidal silyl enol ethers and enol acetates (entry 6) [65], pyrimidine bases and nucleosides (entry 7) [67][69], phenylalkynes (entry 8) [70], anthraquinones

• . By using the bistetrafluoroborate salt 22-1d, many substrates such as aromatics, active methylene compounds and their salts, olefins, and enol acetates were efficiently fluorinated (Scheme 50). It was shown also that only one of the two N–F groups of 22-1 is used for C-fluorination, while the other N

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• work was extended to incorporate these modifications into oligonucleotides containing all four bases [202]. N-Iodosuccinimide promoted the alkoxylation of the 4'–5'-enol acetates yielded the corresponding 5'-acetoxy-5'-iodo-4'-methoxy intermediates [202]. These intermediates were hydrolyzed with a

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• applications of these compounds in photomedicine [23][25][26][27]. Recently we reported a porphyrin-photocatalyzed protocol for the arylation of enol acetates and elucidated the mechanism explaining why the electron-deficient porphyrin TPFPP is more efficient than TPP in the whole process (Scheme 4A). Briefly

• the diazonium salts, as well as the enol acetates are reported giving versatile α-aryl ketones/aldehydes in both batch and continuous-flow conditions (20 examples in 26–88% yields) [9]. A comparison between batch and flow conditions was performed showing that similar yields are obtained (batch 82% vs

• for the alkylation of aldehydes with diazo acetates in the presence of TPP. Arylation of heteroarenes with aryldiazonium salts using TPFPP as photocatalyst, and corresponding mechanism. A) Scope with different aryldiazonium salts and enol acetates. B) Photocatalytic cycles and comparison between TPP

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• , acrylates, enol acetates, and enamines. The functional group tolerance of the transformation was fairly decent and demonstrated the synthetic utility of this reaction manifold. To explain the reaction outcome, the authors suggested the following mechanism: The excited copper catalyst reduces the CF3SO2Cl

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• as an additional supporting electrolyte along with chiral 55c (Scheme 22) [42][57]. In 2003, Nishiguchi’s group explored the anodic oxidation of enol acetates 57 upon constant current electrolysis in an undivided cell at −78 ºC in a mixture of solvents containing (S)-tetraethylammonium

• supporting electrolyte. Asymmetric anodic oxidation of enol acetates using chiral supporting electrolytes. Kinetic resolution of primary amines using a chiral N-oxyl radical mediator

Thiol-free chemoenzymatic synthesis of β-ketosulfides

• Adrián A. Heredia,
• Martín G. López-Vidal,
• Marcela Kurina-Sanz,
• Fabricio R. Bisogno and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2019, 15, 378–387, doi:10.3762/bjoc.15.34

• -ketosulfides [44]. Results and Discussion In a first set of experiments, a series of commercially available hydrolases were screened in aqueous buffer containing 5% v/v of an organic cosolvent towards a β-thioalkyl-substituted enolester as model substrate 1a (Table 1). As enol acetates, (e.g., vinyl acetate

Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• . Interestingly, the reaction of dialdehyde 16 with Ac2O/pyridine only afforded decomposition products, failing to give 18. The electrophilic reactivity of model dialdehydes 11 and 15 and enol acetates 13 and 17 towards 1-pentanethiol and 1-pentylamine were then studied. As found for onchidal, no reaction (NMR

• each of cyclohexylmethyl dialdehyde 15, and enol acetates 13 and 17, with no reactivity towards 1-pentanethiol being detected, but with rapid reaction with 1-pentyamine to form pyrrole adducts. In the case of dialdehyde 15, the reaction product was determined to be 31 (12% plus 18% as the salt, 32

• . Next, the reactivity of dialdehydes 11, 12, 15 and 16 and enol acetates 13 and 17 with lysozyme were examined in a similar manner with mass spectrometry identifying varying degrees of modification. Of the dialdehydes, 11 was the most reactive leading to rapid formation of a white precipitate

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• all components in air, the environmentally friendly nature, and the recycling of the aqueous medium. Subsequently, the group of Li and Duan [58] reported an efficient method for the synthesis of α-trifluoromethyl ketones via addition of CF3 to aryl(heteroaryl)enol acetates using readily available

• CF3SO2Na as a trifluoromethyl source. Trifluoromethylation of aryl(heteroaryl)enol acetates

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• ) cyclic enamides, different N-vinyllactams and enecarbamates. Short time later, they applied this concept for the sulfonylation of enol acetates and observed the formation of β-ketosulfones (Scheme 52b) [90]. Again electron-rich, neutral and electron-deficient (hetero)arylsulfonyl chlorides were tolerated

• under the reported conditions. The scope of enol acetates includes electron-rich and deficient derivatives as well. In addition, also branched enol acetates yield β-ketosulfones. A different approach was reported by Zheng and co-workers in 2014: They applied [Ru(bpy)3](PF6)2 as photoredox catalyst and

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• review. The direct introduction of CF3S and CF3S(O) motifs also occupies a prime position in this review. 1 Trifluoromethylation Csp3–CF3 bond-forming reactions Trifluoromethylation of silyl enol ethers and enol acetates: After their original reports on the trifluoromethylation of aromatics in 1990 (Csp2

• , consequently resulting in higher yields indifferently of the substrate. Enol acetates as another type of masked enol(ates) also proved to be appropriate substrates to access α-trifluoromethylated ketones (Scheme 3) [10]. In the presence of 1 mol % of (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridinyl)phenyl

• ]iridium(III) hexafluorophosphate, Ir(ppy)2(dtbbpy)PF6, various aryl enol acetates carrying electron-donating or electron-withdrawing groups were converted into the corresponding products in high yields. Moreover, the reaction was compatible with cyclic and acyclic branched enol acetates. Quite

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

•  69) [20], Langlois and co-workers demonstrated that enol acetates 1a–c were converted into the corresponding α-trifluoromethyl ketones upon treatment with CF3SO2Na with tert-butyl hydroperoxide (TBHP) and a catalytic amount of copper(II) triflate (Scheme 1) [21]. The scope was rather narrow and

• yields were moderate to poor. In particular, enol acetate 1b, prepared from symmetrical undecan-6-one, gave a mixture of the desired α-CF3 ketone and two isomeric enol acetates 1b'. In 2014, Li, Duan and co-workers applied the conditions described by Langlois to a series of enol acetates 3 derived from

Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines

• Alexander Penger,
• Cortney N. von Hahmann,
• Alexander S. Filatov and
• John T. Welch

Beilstein J. Org. Chem. 2013, 9, 2675–2680, doi:10.3762/bjoc.9.303

• pentafluorosulfanylated compounds is constantly increasing [2], this expansion has not generally been accompanied by applications of these materials. Among aliphatic SF5-substituted compounds α-pentafluorosulfanylated aliphatic carbonyl compounds [16], readily prepared from the corresponding enol acetates or enol ethers

• of SF5Cl to the enol ether 2 instead of the previously described additions to enol acetates [16] (Scheme 1). In earlier studies, it was found that the yield of SF5Cl addition to enol acetates was highly dependent upon the purity of the enol acetate substrate, compounds surprisingly difficult to