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

• tetrafluoro-Phe derivatives via chiral auxiliary 31. Synthesis of 2,5-difluoro-Phe and 2,4,5-trifluoro-Phe via Schöllkopf reagent 34. Synthesis of 2-fluoro- and 2,6-difluoro Fmoc-Phe derivatives starting from chiral auxiliary 39. Synthesis of 2-[18F]FPhe via chiral auxiliary 43. Synthesis of FPhe 49a via

• photooxidative cyanation. Synthesis of FPhe derivatives via Erlenmeyer azalactone synthesis. Synthesis of (R)- and (S)-2,5-difluoro Phe via the azalactone method. Synthesis of 3-bromo-4-fluoro-(S)-Phe (65). Synthesis of [18F]FPhe via radiofluorination of phenylalanine with [18F]F2 or [18F]AcOF. Synthesis of 4

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• the reactants was explored by subjecting the reaction of 2,2-difluoro-1-phenylethan-1-one (2i) with 1a. The desired product 3i was obtained in 63% yield. However, no product was formed when the reaction was carried out with 2-fluoro-1-phenylethan-1-one (2j) or acetophenone (2k). The reason could be

• scope of ketones was further extended with mixed halogen-substituted, pentafluoro or heptafluoro ketones such as 2-chloro-2,2-difluoro-1-phenylethan-1-one (2m), 2,2,3,3,3-pentafluoro-1-phenylpropan-1-one (2n) and 2,2,3,3,4,4,4-heptafluoro-1-phenylbutan-1-one (2o). All these reactions provided the

Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• . Since the latter has an oxygen atom para to the azo group we tested the feasibility of adding such a strong electron donor to an analog of a difluoro-(2F)AB Hecht photochrome [13] by making "MeO-2FAB" (Figure 1, see Supporting Information File 1 for synthesis). Since 2FAB and 4FAB photochromes with

• absorption spectra of these compounds (left). Note, the analogous difluoro-ABs have similar spectra to 4FABs [13]. Effect of electron donation on the fluoro-AB absorption spectra, the cis-MeO-2FAB (pink dots) is the green photostationary state of the photochrome (right). Structure of the photochrome core of

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

• fluorination of α,α-difluoro- and α-fluoroarylacetic acids with a wide functional group compatibility in the presence of AgNO3 as catalyst in good yields (Scheme 40). Further, this approach was efficiently applied to the preparation of [18F]-labelled tri- and difluoromethylarenes using [18F]Selectfluor bis

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

• Sara Peeters,
• Linn Neerbye Berntsen,
• Pål Rongved and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2019, 15, 2156–2160, doi:10.3762/bjoc.15.212

• 6,7-difluoro-4-quinolone-3-carboxylate building block 10 was accessed in high yield in only three steps from commercially available substrates. The nature of the cyclopropanation–ring expansion makes the 4-chloro-3-carboxy-quinoline structure with perfect positioning of the carboxylate and chlorine

• substituents for the subsequent reaction to form the quinolone. The current work shows that the key cyclopropanation–ring expansion reaction works well with 3-chloroindole and 6,7-difluoro-3-chloro-indole, consistent with our previous work where substituents in positions 3–7 are well tolerated. Experimental

Synthesis of dipolar molecular rotors as linkers for metal-organic frameworks

• Sebastian Hamer,
• Fynn Röhricht,
• Marius Jakoby,
• Ian A. Howard,
• Xianghui Zhang,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1331–1338, doi:10.3762/bjoc.15.132

• leave rotational freedom in solids with confined free volumes. The dipole moments are generated by electron-donating substituents (benzo-1,3-dioxole, benzo-1,4-dioxane, or benzo-2,1,3-thiadiazole annelation) and withdrawing substituents (difluoro, or dicyano substitution) at the opposite positions of

• cross coupling. Using this method, dicarboxylic acids could be obtained from simple aqueous work-up and extraction. Difluoro compound 1 Difluorobenzenes have been employed as dipolar rotors by Garcia-Garibay in crystals [10], as an elongated MOF linker by Blight and Forgan [25] and for the investigation

• acid 1 using cesium fluoride under a carbon dioxide atmosphere. Difluoro- and dicyanobenzothiadiazole compounds 2 and 3 Substituted benzothiadiazole derivatives are well studied in the literature and are of great interest in organic photovoltaics and electronics. As there are no reports of such

Conformational signature of Ishikawa´s reagent using NMR information from diastereotopic fluorines

• Laize A. F. Andrade,
• Lucas A. Zeoly,
• Rodrigo A. Cormanich and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2019, 15, 506–512, doi:10.3762/bjoc.15.44

• NMR spin–spin coupling constants (SSCCs), such as in methyl 2-fluoroesters [2], 3-fluoro-1,2-propanediol [3], 1-halo-2-propanols [4], enflurane [5], and 1-chloro-1,1-difluoro-2-pentanol [6]. This is possible due to an analogy with the Karplus curve that correlates the magnitude of vicinal 3JH,H SSCCs

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• substituent at C1. Whereas conjugation with the phenyl group (R = Ph) provides the driving force for the base-promoted isomerization of 1-benzyl-3,3-difluorocyclopropene (A’, R = Ph) into the corresponding benzylidene(gem-difluoro-cyclopropane) (B’) [18], methylene(gem-difluorocyclopropane) (B’’, R = H) is

• afford alkylidenecyclopropane 63 (92%, Scheme 22) [61]. The Ireland–Claisen rearrangement was then extended to a challenging class of cyclopropylcarbinyl glycolates possessing gem-difluoro substitution at C3 [65]. Gem-difluorocyclopropenes are accessible by difluorocyclopropenation of alkynes with

Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• of substrates bearing either two or four methylene groups between the alkene and sulfonamide failed to provide the fluoroheterocycles. Difluorination of alkenes Hara and co-workers reported a vicinal difluorination of unactivated alkenes in the presence of stoichiometric amounts of difluoro

Investigations of alkynylbenziodoxole derivatives for radical alkynylations in photoredox catalysis

• Yue Pan,
• Kunfang Jia,
• Yali Chen and
• Yiyun Chen

Beilstein J. Org. Chem. 2018, 14, 1215–1221, doi:10.3762/bjoc.14.103

• catalysis reactions. Herein we report the synthesis of alkynylbenziodoxole derivatives with difluoro, monofluoro, monomethoxy, and dimethoxy substitution on the benziodoxole moiety, and investigated their radical alkynylation reactivity for the first time. A series of mechanistic experiments were conducted

• synthetic advantages in some cases (Scheme 1). Results and Discussion We started the synthesis of BI-alkyne derivatives with substituted o-iodobenzoic acids 1 bearing 3,4-difluoro, 4-fluoro, 3-methoxy, 4-methoxy, or 3,4-dimethoxy substitutions (Scheme 2). Using a slightly modified Ochiai procedure [11], the

• NMR spectra of BI-alkynes 3a–f were studied with the focus on the α-carbon, which position directly underwent α-radical addition [19]. The electron density of the α-carbon was decreased in 3a with electron-deficient 3,4-difluoro groups on the benziodoxole, and was increased for 3f with electron

Copper-catalyzed asymmetric methylation of fluoroalkylated pyruvates with dimethylzinc

• Kohsuke Aikawa,
• Kohei Yabuuchi,
• Kota Torii and
• Koichi Mikami

Beilstein J. Org. Chem. 2018, 14, 576–582, doi:10.3762/bjoc.14.44

• isomer 23.8 min. (S)-1-Ethoxy-3,3-difluoro-2-methyl-1-oxopropan-2-yl benzoate (2g’) Reaction temperature was −78 °C. The yield of alcohol 2g (89%) was determined by 19F NMR analysis. In the protection of alcohol, benzoyl chloride was used instead of p-nitrobenzoyl chloride. Benzoylated alcohol 2g’ was

• mL/min, 20 °C detection UV 220 nm) tR of major isomer 21.2 min, tR of minor isomer 22.6 min. (S)-1-Bromo-3-ethoxy-1,1-difluoro-2-methyl-3-oxopropan-2-yl 4-nitrobenzoate (2h’) Reaction temperature was −78 °C. The yield of alcohol 2h (53%) was determined by 19F NMR analysis. p-Nitrobenzoylated alcohol

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• trifluoromethyl group. It must be noted that this methodology represented the first efficient and general preparation of chiral β-trifluoromethyl β-amino acid derivatives containing a quaternary stereocenter adjacent to the amine function. In 2014, Linclau and Poisson reported the synthesis of chiral α,α-difluoro

• -mediated aza-Reformatsky reactions of chiral N-tert-butylsulfinyl imines (R)-25h–t with bromodifluoromethyl ketones 31a–d in the presence of CuBr [29]. The reactions were performed in acetonitrile at room temperature, leading to the corresponding chiral α,α-difluoro-β-(N-tert-butylsulfinyl)amino ketones (R

• required to achieve at room temperature the corresponding chiral α,α-difluoro-β-lactams (R)-63a–h in moderate to good yields (45–76%) and high to excellent enantioselectivities (86–99% ee), as shown in Scheme 24. Using enantiomeric ligand (1S,2R)-59 under the same reaction conditions allowed the opposite

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• ·TLR4 complex, such that the full TLR4-mediated activity would be preserved. Accordingly, the 6’-O-glycine-linked BODIPY (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene)-labeled lipid A was previously synthesized [79]. However, this compound revealed only a weak fluorescence in aqueous solution

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

• authors also realised the same chemical transformation under visible light irradiation at 450 nm by means of the iridium photocatalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6 ([4,4’-bis(tert-butyl)-2,2’-bipyridine]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl]phenyl]iridium(III) hexafluorophosphate), which

Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes

• Takeshi Fujita,
• Ryo Kinoshita,
• Tsuyoshi Takanohashi,
• Naoto Suzuki and
• Junji Ichikawa

Beilstein J. Org. Chem. 2017, 13, 2682–2689, doi:10.3762/bjoc.13.266

• Takeshi Fujita Ryo Kinoshita Tsuyoshi Takanohashi Naoto Suzuki Junji Ichikawa Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8571, Japan 10.3762/bjoc.13.266 Abstract 1,1-Difluoro-1-alkenes bearing a biaryl-2-yl group effectively underwent

• ; Introduction As 1,1-difluoro-1-alkenes have an electron-deficient carbon–carbon double bond, they readily undergo intramolecular substitution of nucleophiles through an addition–elimination mechanism [1][2]. Thus, under basic conditions, they serve as useful precursors for ring-fluorinated heterocycles and

• carbocycles that are promising candidates for pharmaceuticals, agrochemicals, and functional materials. In contrast, the cationic cyclization of 1,1-difluoro-1-alkenes using electrophilic reagents (under acidic conditions) has been quite limited because of their low electron densities caused by fluorine

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

• -heterocyclic carbenes (NHCs, Scheme 11) [40]. The reaction was first performed on the γ,γ-difluoro-α,β-enal 52 which was synthesized via a Wittig olefination of 50. The resulting monofluoroalkene Boc-Val-ψ[(Z)-CF=CH]-Gly-OEt was obtained in good yield. Afterwards, the γ,γ-difluoro-α,β-enoylsilane 55, obtained

• with Boc-Asp(OBn)-OH gave the final tripeptide isostere Boc-Asp(OBn)-Pro-ψ[(Z)-CF=CH)-Val-CH2OH (72). In the last years, Taguchi and co-workers described the synthesis of the monofluoroalkenes 74 by SN2’ reaction between 4,4-difluoro-5-hydroxyallylic alcohols 73 and Gilman reagent prepared in situ from

• in 2011 a new synthetic route using Grignard reagents, which are widely available or can be easily synthetized in the laboratory (Scheme 14B) [46]. Unfortunately, these reagents did not react with the 4,4-difluoro-5-hydroxyallylic alcohols 73. Terminal 3,3-difluoropropenes 76 were then prepared

Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides

• Tao Fan,
• Wei-Dong Meng and
• Xingang Zhang

Beilstein J. Org. Chem. 2017, 13, 2610–2616, doi:10.3762/bjoc.13.258

• successfully employed to couple with a conjugated alkene and afforded the corresponding products 4d and 4h in good yields. The current cross coupling was also applicable to the secondary difluoroalkylated alkyl halides as demonstrated by the representative reaction of secondary ethyl 2,2-difluoro-2-iodoacetate

• carried out in 0.2 mmol scale. bEthyl 2,2-difluoro-2-iodoacetate was used. Radical clock experiment for mechanistic studies. Proposed mechanism. Representative results for the optimization of Pd-catalyzed cross-coupling between 1a and 2-bromo-1,1,1-trifluorohexane (2a)a. Radical inhibition experiments of

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• accessible from gem-difluoropropargylic alcohols C through a base-mediated isomerization process (Scheme 1) [26][27]. Results and Discussion The required propargylic alcohols 5a–e (type C, Scheme 1) were obtained in 27–73% yields by reaction of the lithium salt of the easily accessible gem-difluoro

• of 4,4-difluoro-1,6-diphenylhex-2-yn-1-ol (5a) To a solution of gem-difluoro intermediate 4 [28] (500 mg, 2.77 mmol, 1 equiv) in anhydrous THF (6 mL) cooled at −80 °C was added dropwise under nitrogen a 2.5 M solution of n-BuLi in hexanes (1.3 mL, 3.30 mmol, 1.2 equiv). The mixture was stirred for 1

• + Na]+: calcd. for C18H16OF2Na, 309.10614; found, 309.1060 (0 ppm); m/z [M – HF + Na]+: calcd. for C18H15OFNa, 289.09991; found, 289.0992 (2 ppm). Synthesis of (E)-4,4-difluoro-1,6-diphenylhex-2-en-1-one (6a) The previous difluoropropargylic alcohol 5a (540 mg, 1.88 mmol, 1 equiv) was dissolved in THF

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• , sensitivity and good spatio-temporal resolution altogether [5]. From the plethora of known fluorescent compounds, there are widely used small organic fluorophores, such as BODIPY dyes. BODIPYs are fluorescent dyes based on the 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene scaffold, which have recently

Synthesis and characterization of benzodithiophene and benzotriazole-based polymers for photovoltaic applications

• Desta Gedefaw,
• Marta Tessarolo,
• Margherita Bolognesi,
• Mario Prosa,
• Renee Kroon,
• Wenliu Zhuang,
• Patrik Henriksson,
• Kim Bini,
• Ergang Wang,
• Michele Muccini,
• Mirko Seri and
• Mats R. Andersson

Beilstein J. Org. Chem. 2016, 12, 1629–1637, doi:10.3762/bjoc.12.160

• -difluoro-2H-benzo[d][1,2,3]triazole (Tz) have attracted much attention and effectively employed in BHJ PSCs due to their intrinsic advantages, potentials and versatility [14][15]. Thanks to the desirable properties such as structural rigidity, planarity, extended π-conjugation length and favorable

• , 0.23 mmol) and 4,7-bis(5-bromothiophen-2-yl)-2-(2-butyloctyl)-5,6-difluoro-2H-benzo[d][1,2,3]triazole (3, 0.15 g, 0.23 mmol) were dissolved in toluene (10 mL) and degassed with N2 gas for 10 minutes. Pd2(dba)3 (4.2 mg, 2 mol %) and P(o-tolyl)3 (6.3 mg, 9 mol %) were added and purged with nitrogen gas

• black solid (149 mg). Synthesis of PTzBDT-2 (4,8-Bis(4,5-dihexylthiophen-2-yl)benzo[1,2-b:4,5-b']dithiophene-2,6-diyl)bis(trimethylstannane) (2, 0.095 g, 0.147 mmol) and 4,7-bis(5-bromothiophen-2-yl)-2-(4-((2-butyloctyl)oxy)butyl)-5,6-difluoro-2H-benzo[d][1,2,3]triazole (3, 0.15 g, 0.147 mmol) were

From N-vinylpyrrolidone anions to modified paraffin-like oligomers via double alkylation with 1,8-dibromooctane: access to covalent networks and oligomeric amines for dye attachment

• Daniela Obels,
• Melanie Lievenbrück and
• Helmut Ritter

Beilstein J. Org. Chem. 2016, 12, 1395–1400, doi:10.3762/bjoc.12.133

• reactive amino-functionalized oligomers. Further modification of the free amino groups with 1,4-difluoro-9,10-anthraquinone (DFA) yields red-colored oligomeric anthraquinone dyes. The final reaction of DFA-substituted N-VP oligomers with Jeffamine® M 600 leads to blue-colored and branched oligomers with

• bonds of 2a were subjected to further modification through a thiol–ene [40][41][42] click reaction with 2-aminoethanethiol hydrochloride yielding oligomer 4 (Scheme 2). Subsequently, the reactivity of the primary amino groups in 4 was proven by the attachment of 1,4-difluoro-9,10-anthraquinone (DFA

• primary amino groups. The reactivity of the latter functionalities was exemplarily demonstrated by the reaction with the dye 1,4-difluoro-9,10-anthraquinone resulting in the red-colored derivative 5. Further reaction of 5 with Jeffamine® M 600 yielded the blue-colored branched oligomer 6. Both reactions

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• ,8E,12E,16E)-N-{1-[(2R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxo-1,2-dihydropyrimidin-4-yl}-21-(2H3)methyl-4,8,13,17-tetramethyl(22,22,22-2H3)docosa-4,8,12,16,20-pentaenamide (3): To a solution cooled at −5 °C of trisnorsqualenic acid-d6 (1) (31.5 mg, 0.077 mmol) in dry THF (0.6

Syntheses of dibenzo[d,d']benzo[2,1-b:3,4-b']difuran derivatives and their application to organic field-effect transistors

• Minh Anh Truong and
• Koji Nakano

Beilstein J. Org. Chem. 2016, 12, 805–812, doi:10.3762/bjoc.12.79

• -isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (iPrO-Bpin) gave boronate ester 7 in 57% yield. Then, terphenyl 9 was synthesized via palladium-catalyzed Suzuki–Miyaura cross coupling of boronate ester 7 with 2,3-difluoro-1,4-diiodobenzene (96% yield) and subsequent demethylation (95% yield). Finally, the

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• focused on the synthesis of acetylated 3-deoxy-3-fluoro, 4-deoxy-4-fluoro and 3,4-dideoxy-3,4-difluoro analogs of D-glucosamine and D-galactosamine via 1,6-anhydrohexopyranose chemistry. Moreover, the cytotoxicity of the target compounds towards selected cancer cells is determined. Results: Introduction

• more than cisplatin and 5-fluorouracil (IC50 28 ± 3 μM and 54 ± 5 μM, respectively). Conclusion: A complete series of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine is now accessible by 1,6-anhydrohexopyranose chemistry. Intermediate fluorinated 1,6-anhydro

• -difluoro analogs 1, 4–8 (Figure 1) including previously unknown members of this class of hexosamine mimics: acetylated 3-fluoro-D-GalNAc 6, 3,4-difluoro-D-GlcNAc 7 and 3,4-difluoro-D-GalNAc 8, as well as 3-fluoro-D-GlcNAc 5, in which case the reported synthesis was troublesome and low-yielding [20]. To