Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• plausible pathways. Attractive elements include the regioselective and straightforward direct synthesis of fully substituted 1,2,3-triazoles, which are otherwise difficult to access, from readily available starting materials. Keywords: [3 + 2] cycloaddition; defluorination; fully decorated 1,2,3-triazoles

• defluorinative processes in gem-difluoroalkenes. NiCl2(PCy3)2 and NiCl2(dppp)2 were chosen for our initial investigations since they have been used in both the defluorination of gem-difluoroalkenes and the coordination with the azides to promote [3 + 2] cycloaddition reactions [2][31][32]. Based on our

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• was modified by Wang and co-workers [76]. It is also possible to remove the fluorine substituents from difluorocyclopropanes while preserving the three-membered ring. The reductive defluorination of the difluorocylopropane derivative 75 by the treatment with excess NaBH4 in hot DMSO (Scheme 31) gave

Activation of pentafluoropropane isomers at a nanoscopic aluminum chlorofluoride: hydrodefluorination versus dehydrofluorination

• Maëva-Charlotte Kervarec,
• Thomas Braun,
• Mike Ahrens and
• Erhard Kemnitz

Beilstein J. Org. Chem. 2020, 16, 2623–2635, doi:10.3762/bjoc.16.213

• –Crafts-like reactions to give with C6D6 11 or 3, which is consistent with previous studies [16]. The formation of the products described above (Scheme 4) involves consecutive reaction steps, such as dehydrofluorination, hydrodefluorination, hydrofluorination, allylic defluorination, hydroarylation, and

• (Scheme 7, bottom). Indeed, in C6D12, allylic defluorination to yield 5 was observed, together with 6 and traces of 2-chloro-1,1,1-trifluoropropene (15). The chlorinated product 15 could stem from a plausible HCl formation if the substrate is fluorinating ACF [41]. It should be noted that the synthesis of

• that the single C–F bond in 10a does not require the use of HSiEt3 as a hydrogen source to be activated via dehydrofluorination. However, when silane was introduced, further reactivity was observed, leading to the formation of subsequent defluorination products. In contrast, CF2, CHF2, and CF3 groups

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• olefination or defluorination reactions or a sigmatropic rearrangement, but these approaches are limited and do not allow the synthesis of tetrasubstituted fluoroalkenes with good control of their geometry [18][19][20][21]. In order to develop a selective synthesis for tetrasubstituted fluoroalkenes we

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• defluorination, presumably via a Tsuji–Trost-like elimination of the allylic fluoride [18][19]. This sequence represents a marked improvement from the Wittig-including route, lowering the number of synthetic steps and increasing the overall yield [2]. Furthermore, no problematic byproducts are formed, and good

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• high diastereoisomeric purity (Scheme 36). The subsequent deprotection of 151 had to be achieved with BrO3−, because hydrogenolysis resulted in defluorination [74]. Alternatively, a series of substituted anti-β-fluorophenylalanine derivatives 154a–d was obtained from the corresponding enantiopure α

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

• highly regioselective photoinduced hydro-defluorination of perfluoroarenes with RhIII(TSPP) [38]. The oxidative addition of the perfluoroarene to the metal complex furnished the active rhodium aryl complex intermediate, which led to the product after visible light irradiation. The hydro-defluorination

• RhIII(TSPP) under visible light irradiation. Regioselective photocatalytic hydro-defluorination of perfluoroarenes by RhIII(TSPP). Formation of 2-methyl-2,3-dihydrobenzofuran by intramolecular hydro-functionalization of allylphenol using RhIIITMPP under visible light irradiation. Photocatalytic

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

Fluorine-containing substituents: metabolism of the α,α-difluoroethyl thioether motif

• Andrea Rodil,
• Alexandra M. Z. Slawin,
• Nawaf Al-Maharik,
• Ren Tomita and
• David O’Hagan

Beilstein J. Org. Chem. 2019, 15, 1441–1447, doi:10.3762/bjoc.15.144

• evidence of defluorination, unlike the corresponding oxygen ether (p-OMe)PhOCF2CH3, which was converted to the (demethylated) phenol acetate ester during C. elegans incubation. We conclude that the aryl–S–CF2CH3 motif is metabolised in a similar manner to aryl–SCF3, a motif that is being widely explored in

• significantly more rapid than the second oxidation to the sulfone. The first oxidation gave enantiomerically enriched sulfoxides (Ar–S(O)CF2CH3) in the 54–60% ee range. This could arise by the action of more than one P450 enzyme. There was no evidence of defluorination, or hydroxylation at the terminal -CH3

• group. The corresponding oxygen ether 14 was susceptible to hydrolytic defluorination to generate an acetate ester. The α,α-difluoroethyl thioether (Ar–SCF2CH3) motif can be readily prepared from thiols and emerges as a potentially attractive substituent for consideration by medicinal chemists and for

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• defluorination of γ,γ-difluoro-α,β-enoylsilane 80 in the presence of 18-crown-6 followed by addition of camphorsultam 81 gave the corresponding monofluoroalkene 82. Then, α-alkylation of the amide with either allyl bromide or benzyl bromide provided the corresponding dipeptide isosteres 83a and 83b

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• view to its subsequent elaboration, e.g., via diazotization. However, a variety of reduction conditions resulted either in no observable reaction (Table 2, entries 1 and 2), or else in defluorination at the benzyl position (Table 2, entry 3). The latter proceess is precedented [41]. Since none of the

• to be successful. The reaction duration was another significant determinant of the yield of 43 (Table 2, entries 4−6), since the over-reduced (i.e., benzylic defluorination) product was still produced in varying amounts. The subsequent oxidation of 43 was successfully achieved using sodium

Carbon–carbon bond cleavage for Cu-mediated aromatic trifluoromethylations and pentafluoroethylations

• Tsuyuka Sugiishi,
• Hideki Amii,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2015, 11, 2661–2670, doi:10.3762/bjoc.11.286

• synthesis of 2,2-difluorostyrenes through Mg(0)-promoted defluorinative silylation followed by fluorine-ion-catalyzed 1,2-desilylative defluorination. Buchwald et al. demonstrated aromatic trifluoromethylation using potassium trifluoroacetate (CF3CO2K), CuI and pyridine under flow conditions. Increasing the

Highly selective electrochemical fluorination of dithioacetal derivatives bearing electron-withdrawing substituents at the position α to the sulfur atom using poly(HF) salts

• Bin Yin,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2015, 11, 85–91, doi:10.3762/bjoc.11.12

• in the solution, and consequently the C–S bond cleavage seems to take place more favorably than a deprotonation. A similar effect on the suppression of defluorination of CF3-enolate anion in the presence of a large amount of fluoride ions has been reported [38]. On the other hand, it is known that

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• synthesis and reactions of fluorine-containing molecules by the use of flow microreactor systems to overcome long-standing problems in fluorine chemistry. Keywords: defluorination; fluorine; fluorination; flow microreactor; organo-fluorine; perfluoroalkylation; Review Fluorine is a key element in the

• by nucleophilic substitution reactions using [18F]-fluoride ion (Scheme 7) [55][56][57][58][59][60][61][62][63][64][65][66][67]. For not only fluorination/fluoroalkylation, but also for defluorination, flow microreactor synthesis is quite effective. Defluorination involving a nucleophilic addition

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

• Reik Löser,
• Steffen Fischer,
• Achim Hiller,
• Martin Köckerling,
• Uta Funke,
• Aurélie Maisonial,
• Peter Brust and
• Jörg Steinbach

Beilstein J. Org. Chem. 2013, 9, 1002–1011, doi:10.3762/bjoc.9.115

• ][49]. Their fate seems to be different from their aromatic counterparts in the way that they undergo defluorination at the α-methylene group rather than hydrolytic cleavage of the amide bond [13]. The metabolic hydrolysis of sulfonamide bonds has not been reported so far. Thus, this type of chemical

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229