Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• generate a fluoride ion that facilitates limiting enolization processes, and an electrophilic N–F fluorinating agent that is reactive towards neutral enol species. Keywords: difluorination; difluoromethylene; direct fluorination; electrophilic fluorination; organofluorine; Introduction Fluorine is

Decarboxylative trifluoromethylthiolation of pyridylacetates

• Ryouta Kawanishi,
• Kosuke Nakada and
• Kazutaka Shibatomi

Beilstein J. Org. Chem. 2021, 17, 229–233, doi:10.3762/bjoc.17.23

• lithium pyridylacetates undergo decarboxylative fluorination upon treatment with an electrophilic fluorination reagent to afford fluoromethylpyridines under catalyst-free conditions. Furthermore, we demonstrated the one-pot synthesis of fluoromethylpyridines from methyl pyridylacetates by saponification

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• ][178][179], renders their employment in synthesis problematic. The high demand for a safe, stable and highly reactive electrophilic fluorinating reagent prompted researchers to synthesize the first generation of electrophilic fluorination reagents, including fluoroxytrifluoromethane [180], fluorine

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• alkaloid-promoted electrophilic fluorination producing enantioenriched post-Ugi adducts fluorinated at the peptidyl position. Keywords: cinchona alkaloids; electrophilic fluorination; enantioselective synthesis; 2-oxo-aldehydes; Ugi reaction; Introduction Multicomponent reactions (MCRs) [1][2][3][4][5][6

• previously tested the reactivity of 8 in the intermolecular aldol addition to ethyl glyoxalate [62]. As these attempts met with failure, we have turned our attention to enantioselective fluorination reactions [63][64][65]. Specifically, we decided to explore the enantioselective electrophilic fluorination of

• asymmetric electrophilic fluorination for derivatizing the 2-oxo-aldehyde-derived Ugi adducts. This allowed us to obtain the post-Ugi products fluorinated at the peptidyl position with the enantiomeric excess values in several instances reaching more than 70%. Molecular representation of the X-ray crystal

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

• other hand, when the quinoline-based ligand 162 was used, it was shown to promote the palladium-catalyzed direct electrophilic fluorination of β-methylene C(sp3)–H bonds. Thus, fluorinations of ʟ-phenylalanine 4-trifluoromethylphenylamides 161a–l carrying a range of functional groups such as fluoro

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

• source and behaves as a nucleophile. The electrophile, such as an alkyl chain or an aryl ring with halides or sulfonates, reacts with the fluoride source (Scheme 1a). On the other hand, in the electrophilic fluorination, the nucleophile may be a carbon anion (e.g., Grignard reagent), a compound with

• electron-rich unsaturated bonds (arene, alkene, or alkyne), or a substrate having a nucleophilic and labile bond (e.g., C−Si, C−Sn, and C−B), while the electrophile is the fluorination reagent (Scheme 1b). As shown in Scheme 1d, many nucleophilic and electrophilic fluorination reagents have been developed

• a palladium catalyst (Scheme 9). Under these conditions, the fluorination of ethyl 2-cyano-2-phenylacetate afforded the product with highest enantiomeric excess (93%). In 2013, Kim’s group [46] described an enantioselective electrophilic fluorination of α-chloro-β-keto phosphonates with up to 95% ee

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

• ]-Gly isosteres with control of the stereochemistry at the side chain will be discussed in this section. In particular, olefination reaction, defluorinative reduction of 3,3-difluoropropene derivatives and electrophilic fluorination of alkenylstannanes are presented. Pannecoucke’s group described the

• final saponification gave the monofluoroalkene-based dipeptide isostere 61. Finally, Fürstner’s group developed the silver-mediated fluorination of functionalized alkenylstannanes to access monofluoroalkenes [42]. Hydrostannation of the N-protected ynamines 62 followed by electrophilic fluorination with

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

• the repeating (CHF)n motif within the target molecule via an iterative synthetic approach (Scheme 1, boxed). We reasoned that an aldehyde such as 7 could undergo electrophilic fluorination, mediated by a chiral organocatalyst [18][19][20], to generate the fluorinated aldehyde 8 as a single

• the electrophilic fluorination reagent NFSI (compared with nucleophilic fluorination reagents such as DeoxoFluor). Accordingly, two aldehyde substrates (7a and 7b) were prepared [21][22], containing either a phthalimide or a Boc protecting group. Electrophilic fluorination was attempted according to

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• derivatives 123 via the Nazarov cyclization followed by electrophilic fluorination, has been described in 2007 by Ma et al. [65]. This reaction was catalyzed by Cu(II) triflate and proceeded in the presence of N-fluorobenzenesulfonimide (NFSI) 122 as a fluorinating reagent (Scheme 39). Scientists are

Copper-catalyzed aminooxygenation of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives

• Yan Li,
• Xue Zhou,
• Guangfan Zheng and
• Qian Zhang

Beilstein J. Org. Chem. 2015, 11, 2721–2726, doi:10.3762/bjoc.11.293

• -tetramethylpiperidine-N-oxyl (TEMPO) [36]. NFSI is a very interesting reagent. Besides classic electrophilic fluorination reagent [37], it has been used not only as fluoride-atom transfer reagent [38][39][40] but also as nucleophilic/radical amination reagent [41]. We are highly interested in the multiple reaction

Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

• Antal Harsanyi,
• Graham Sandford,
• Dmitri S. Yufit and
• Judith A.K. Howard

Beilstein J. Org. Chem. 2014, 10, 1213–1219, doi:10.3762/bjoc.10.119

• prepared using electrophilic fluorination of enolate esters [64][65][66], deoxofluorination [67][68][69] nucleophilic [70] and electrochemical fluorination [71][72] strategies. Attempts to prepare 2-fluoro-2-(2,4-dinitrophenyl)acetic acid by an analogous process led to the isolation of a benzyl fluoride

Organocatalytic asymmetric fluorination of α-chloroaldehydes involving kinetic resolution

• Kazutaka Shibatomi,
• Takuya Okimi,
• Yoshiyuki Abe,
• Akira Narayama,
• Nami Nakamura and
• Seiji Iwasa

Beilstein J. Org. Chem. 2014, 10, 323–331, doi:10.3762/bjoc.10.30

• enantiofacial selection during electrophilic fluorination of the enamine intermediates, but also a high level of kinetic resolution of the starting aldehydes. From these results, we proposed a reaction mechanism for the fluorination of α-chloroaldehydes, as shown in Scheme 4. Catalyst (S)-1 reacts with (R)-2a

Recyclable fluorous cinchona alkaloid ester as a chiral promoter for asymmetric fluorination of β-ketoesters

• Wen-Bin Yi,
• Xin Huang,
• Zijuan Zhang,
• Dian-Rong Zhu,
• Chun Cai and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 1233–1240, doi:10.3762/bjoc.8.138

• supported cinchona alkaloids have been developed as recyclable chiral promoters or organocatalysts. Among them, the Cahard group developed soluble polymer- and ionic-liquid-supported cinchona alkaloids for electrophilic fluorination [21][22]. The Fache and Soόs groups developed fluorous tag-attached

Development of the titanium–TADDOLate-catalyzed asymmetric fluorination of β-ketoesters

• Lukas Hintermann,
• Mauro Perseghini and
• Antonio Togni

Beilstein J. Org. Chem. 2011, 7, 1421–1435, doi:10.3762/bjoc.7.166

• -catalyzed asymmetric fluorinations were discovered by others and ourselves, based on complexes of Pd(II) [46], Cu(II) [47][48][49], Ni(II) [48][50] and Ru(II) [51] as catalysts [4][51]. In parallel, organocatalytic asymmetric electrophilic fluorination of carbonyl compounds by means of phase-transfer

• ][64][65]. Preparative halogenations of 1,3-dicarbonyl substrates at ambient temperatures are relatively slow and it is more common to halogenate their alkali enolates instead [58]. From studies on the electrophilic fluorination with N–F reagents, it is known that some β-carbonyl compounds are α

• solutions were formed within few minutes, which implies that a β-diketonate complex was formed. We therefore assume that the catalytic acceleration of the electrophilic fluorination reaction with F–TEDA by Lewis acidic titanium complexes is due to the intermediacy of chelating titanium–enolate complexes B

Combination of gold catalysis and Selectfluor for the synthesis of fluorinated nitrogen heterocycles

• Antoine Simonneau,
• Pierre Garcia,
• Jean-Philippe Goddard,
• Virginie Mouriès-Mansuy,
• Max Malacria and
• Louis Fensterbank

Beilstein J. Org. Chem. 2011, 7, 1379–1386, doi:10.3762/bjoc.7.162

• the elucidation of the mechanism and Selectfluor was suggested to play the double role of promoting the oxidation of gold(I) to a gold(III) active species and also the electrophilic fluorination of the enamine intermediates. Keywords: cycloisomerization reactions; fluorinated pyrrolidines; gold

DBFOX- Ph/metal complexes: Evaluation as catalysts for enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones

• Takehisa Ishimaru,
• Norio Shibata,
• Dhande Sudhakar Reddy,
• Takao Horikawa,
• Shuichi Nakamura and
• Takeshi Toru

Beilstein J. Org. Chem. 2008, 4, No. 16, doi:10.3762/bjoc.4.16

• electrophilic fluorination represents an important and straightforward strategy for C-F bond formation at a carbon stereocenter, providing easy access to chiral fluoro-organic compounds [1][2]. Due to the significance of chiral fluoro-organic compounds, such as fluorinated quinolones [3][4] and liquid crystals

• [5], in pharmaceutical and material sciences considerable effort has been dedicated to this issue for decades [6][7][8][9][10][11][12][13][14][15][16][17]. As a consequence, a variety of procedures have been developed to increase the yields and enantioselectivities of electrophilic fluorination

• ][59][60][61][62][63][64] procedures for enantioselective fluorination are major advances in recent years. The discovery that chiral ligands/metals can catalyze electrophilic fluorination with conventional fluorinating reagents has had a large impact on synthetic organic chemistry, because of the

Single and double stereoselective fluorination of (E)-allylsilanes

• Marcin Sawicki,
• Angela Kwok,
• Matthew Tredwell and
• Véronique Gouverneur

Beilstein J. Org. Chem. 2007, 3, No. 34, doi:10.1186/1860-5397-3-34

• Marcin Sawicki Angela Kwok Matthew Tredwell Veronique Gouverneur University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK 10.1186/1860-5397-3-34 Abstract Acyclic allylic monofluorides were prepared by electrophilic fluorination of branched (E)-allylsilanes with

• highly efficient diastereoselective fluorodesilylation. We encountered more difficulties with the fluorination of acyclic allylsilanes A constructed by metathetic coupling of allyltrimethysilane with chiral olefinic partners (eq. 1, Scheme 1). Although high yielding, the electrophilic fluorination of

• highly efficient and stereoselective synthesis of alkenes featuring bis-allylic stereocentres, one of them being fluorinated, emerged from this study. Significantly, alkenes flanked by two allylic fluorinated stereogenic centres are also accessible upon double electrophilic fluorination of (E

Stereoselective α-fluoroamide and α-fluoro- γ-lactone synthesis by an asymmetric zwitterionic aza-Claisen rearrangement

• Kenny Tenza,
• Julian S. Northen,
• David O'Hagan and
• Alexandra M. Z. Slawin

Beilstein J. Org. Chem. 2005, 1, No. 13, doi:10.1186/1860-5397-1-13

• are finding increasing utility in pharmaceutical, fine chemicals and materials research. The zwitterionic aza-Claisen rearrangement proved to be an effective and competitive complement to asymmetric electrophilic fluorination strategies and provides access to versatile synthetic intermediates with

• iodolactonisation to generate α-fluoro-γ-butyrolactones, with good diastereoselectivities (~80–100% de). These molecules are useful intermediates for further derivatisation in the area of nucleoside analogue synthesis and the method is complementary to asymmetric electrophilic fluorination strategies for the