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Search for "fluorine effect" in Full Text gives 4 result(s) in Beilstein Journal of Organic Chemistry.
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
- selection of the reagents and catalysts. These have an influence on the mechanism and regioselectivity of the C–C bond cleavage. Although there are several different mechanisms for ring-opening reactions, in most cases there is a cleavage of the most weakened C–C bond due to the fluorine effect. This C–C
Graphical Abstract
Scheme 1: Synthesis of 1,1-difluoro-2,3-dimethylcyclopropane (2).
Scheme 2: Cyclopropanation via dehydrohalogenation of chlorodifluoromethane.
Scheme 3: Difluorocyclopropanation of methylstyrene 7 using dibromodifluoromethane and zinc.
Scheme 4: Synthesis of difluorocyclopropanes from the reaction of dibromodifluoromethane and triphenylphosphi...
Scheme 5: Generation of difluorocarbene in a catalytic two-phase system and its addition to tetramethylethyle...
Scheme 6: The reaction of methylstyrene 7 with chlorodifluoromethane (11) in the presence of a tetraarylarson...
Scheme 7: Pyrolysis of sodium chlorodifluoroacetate (12) in refluxing diglyme in the presence of alkene 13.
Scheme 8: Synthesis of boron-substituted gem-difluorocyclopropanes 16.
Scheme 9: Addition of sodium bromodifluoroacetate (17) to alkenes.
Scheme 10: Addition of sodium bromodifluoroacetate (17) to silyloxy-substituted cyclopropanes 20.
Scheme 11: Synthesis of difluorinated nucleosides.
Scheme 12: Addition of butyl acrylate (26) to difluorocarbene generated from TFDA (25).
Scheme 13: Addition of difluorocarbene to propargyl esters 27 and conversion of the difluorocyclopropenes 28 t...
Scheme 14: The generation of difluorocyclopropanes using MDFA 30.
Scheme 15: gem-Difluorocyclopropanation of styrene (32) using difluorocarbene generated from TMSCF3 (31) under...
Scheme 16: Synthesis of a gem-difluorocyclopropane derivative using HFPO (41) as a source of difluorocarbene.
Scheme 17: Cyclopropanation of (Z)-2-butene in the presence of difluorodiazirine (44).
Scheme 18: The cyclopropanation of 1-octene (46) using Seyferth's reagent (45) as a source of difluorocarbene.
Scheme 19: Alternative approaches for the difluorocarbene synthesis from trimethyl(trifluoromethyl)tin (48).
Scheme 20: Difluorocyclopropanation of cyclohexene (49).
Scheme 21: Synthesis of difluorocyclopropane derivative 53 using bis(trifluoromethyl)cadmium (51) as the diflu...
Scheme 22: Addition of difluorocarbene generated from tris(trifluoromethyl)bismuth (54).
Scheme 23: Addition of a stable (trifluoromethyl)zinc reagent to styrenes.
Scheme 24: The preparation of 2,2-difluorocyclopropanecarboxylic acids of type 58.
Scheme 25: Difluorocyclopropanation via Michael cyclization.
Scheme 26: Difluorocyclopropanation using N-acylimidazolidinone 60.
Scheme 27: Difluorocyclopropanation through the cyclization of phenylacetonitrile (61) and 1,2-dibromo-1,1-dif...
Scheme 28: gem-Difluoroolefins 64 for the synthesis of functionalized cyclopropanes 65.
Scheme 29: Preparation of aminocyclopropanes 70.
Scheme 30: Synthesis of fluorinated methylenecyclopropane 74 via selenoxide elimination.
Scheme 31: Reductive dehalogenation of (1R,3R)-75.
Scheme 32: Synthesis of chiral monoacetates by lipase catalysis.
Scheme 33: Transformation of (±)-trans-81 using Rhodococcus sp. AJ270.
Scheme 34: Transformation of (±)-trans-83 using Rhodococcus sp. AJ270.
Scheme 35: Hydrogenation of difluorocyclopropenes through enantioselective hydrocupration.
Scheme 36: Enantioselective transfer hydrogenation of difluorocyclopropenes with a Ru-based catalyst.
Scheme 37: The thermal transformation of trans-1,2-dichloro-3,3-difluorocyclopropane (84).
Scheme 38: cis–trans-Epimerization of 1,1-difluoro-2,3-dimethylcyclopropane.
Scheme 39: 2,2-Difluorotrimethylene diradical intermediate.
Scheme 40: Ring opening of stereoisomers 88 and 89.
Scheme 41: [1,3]-Rearrangement of alkenylcyclopropanes 90–92.
Scheme 42: Thermolytic rearrangement of 2,2-difluoro-1-vinylcyclopropane (90).
Scheme 43: Thermal rearrangement for ethyl 3-(2,2-difluoro)-3-phenylcyclopropyl)acrylates 93 and 95.
Scheme 44: Possible pathways of the ring opening of 1,1-difluoro-2-vinylcyclopropane.
Scheme 45: Equilibrium between 1,1-difluoro-2-methylenecyclopropane (96) and (difluoromethylene)cyclopropane 97...
Scheme 46: Ring opening of substituted 1,1-difluoro-2,2-dimethyl-3-methylenecyclopropane 98.
Scheme 47: 1,1-Difluorospiropentane rearrangement.
Scheme 48: Acetolysis of (2,2-difluorocyclopropyl)methyl tosylate (104) and (1,1-difluoro-2-methylcyclopropyl)...
Scheme 49: Ring opening of gem-difluorocyclopropyl ketones 106 and 108 by thiolate nucleophiles.
Scheme 50: Hydrolysis of gem-difluorocyclopropyl acetals 110.
Scheme 51: Ring-opening reaction of 2,2-difluorocyclopropyl ketones 113 in the presence of ionic liquid as a s...
Scheme 52: Ring opening of gem-difluorocyclopropyl ketones 113a by MgI2-initiated reaction with diarylimines 1...
Scheme 53: Ring-opening reaction of gem-difluorocyclopropylstannanes 117.
Scheme 54: Preparation of 1-fluorovinyl vinyl ketone 123 and the synthesis of 2-fluorocyclopentenone 124. TBAT...
Scheme 55: Iodine atom-transfer ring opening of 1,1-difluoro-2-(1-iodoalkyl)cyclopropanes 125a–c.
Scheme 56: Ring opening of bromomethyl gem-difluorocyclopropanes 130 and formation of gem-difluoromethylene-co...
Scheme 57: Ring-opening aerobic oxidation reaction of gem-difluorocyclopropanes 132.
Scheme 58: Dibrominative ring-opening functionalization of gem-difluorocyclopropanes 134.
Scheme 59: The selective formation of (E,E)- and (E,Z)-fluorodienals 136 and 137 from difluorocyclopropyl acet...
Scheme 60: Proposed mechanism for the reaction of difluoro(methylene)cyclopropane 139 with Br2.
Scheme 61: Thermal rearrangement of F2MCP 139 and iodine by CuI catalysis.
Scheme 62: Synthesis of 2-fluoropyrroles 142.
Scheme 63: Ring opening of gem-difluorocyclopropyl ketones 143 mediated by BX3.
Scheme 64: Lewis acid-promoted ring-opening reaction of 2,2-difluorocyclopropanecarbonyl chloride (148).
Scheme 65: Ring-opening reaction of the gem-difluorocyclopropyl ketone 106 by methanolic KOH.
Scheme 66: Hydrogenolysis of 1,1-difluoro-3-methyl-2-phenylcyclopropane (151).
Scheme 67: Synthesis of monofluoroalkenes 157.
Scheme 68: The stereoselective Ag-catalyzed defluorinative ring-opening diarylation of 1-trimethylsiloxy-2,2-d...
Scheme 69: Synthesis of 2-fluorinated allylic compounds 162.
Scheme 70: Pd-catalyzed cross-coupling reactions of gem-difluorinated cyclopropanes 161.
Scheme 71: The (Z)-selective Pd-catalyzed ring-opening sulfonylation of 2-(2,2-difluorocyclopropyl)naphthalene...
Figure 1: Structures of zosuquidar hydrochloride and PF-06700841.
Scheme 72: Synthesis of methylene-gem-difluorocyclopropane analogs of nucleosides.
Figure 2: Anthracene-difluorocyclopropane hybrid derivatives.
Figure 3: Further examples of difluorcyclopropanes in modern drug discovery.
Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose
- Danny Lainé,
- Vincent Denavit,
- Olivier Lessard,
- Laurie Carrier,
- Charles-Émile Fecteau,
- Paul A. Johnson and
- Denis Giguère
Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237
- at C4 could contribute to a new fluorine effect in nucleophilic substitution. Finally, with the continuous objective of synthesizing novel multi-vicinal fluorosugars, we prepared one difluorinated and one trifluorinated alditol analogue. Keywords: deoxyfluorination; Et3N·3HF; fluorine effect
- simple Et3N·3HF with or without addition of triethylamine. The role of the reagent and the remote influence of the fluorine atom at C2 on reactivity at C4 could concomitantly contribute to a new fluorine effect in nucleophilic substitution [49]. Finally, the synthesis of two distinct polyfluorinated
Graphical Abstract
Figure 1: Previously described synthesis of 2,3,4-trifluorinated analogues of galactose 6, glucose 7, mannose ...
Figure 2: Typical 19F NMR spectrum (470 MHz, CDCl3) of the crude reaction mixture using Et3N·3HF/Et3N (entry ...
Figure 3: Fluorination at C4 of 1,6-anhydro-2,3-difluorohexopyranose analogues. a) Reactions on triflates 13, ...
Scheme 1: Synthesis of polyfluorinated alditols from levoglucosan 1: a) difluoroglucitol analogue 22; b) trif...
Asymmetric synthesis of CF2-functionalized aziridines by combined strong Brønsted acid catalysis
- Xing-Fa Tan,
- Fa-Guang Zhang and
- Jun-An Ma
Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60
- or fluoroalkyl groups into three-membered N-heterocycles has emerged as an attractive direction due to the unique fluorine effect in pharmaceuticals and biology [7][8][9][10][11]. In this context, it is not surprising that the syntheses of trifluoromethylaziridines have been pursued from versatile
Graphical Abstract
Scheme 1: Preparation of chiral aziridines from fluorinated diazo reagents.
Scheme 2: Substrate scope of chiral CF2-substituted aziridines from PhSO2CF2CHN2. General reaction conditions...
Scheme 3: Scale-up experiment to 4a and further synthetic transformations.
The C–F bond as a conformational tool in organic and biological chemistry
- Luke Hunter
Beilstein J. Org. Chem. 2010, 6, No. 38, doi:10.3762/bjoc.6.38
- this fluorine effect is ongoing. Fluorine atoms are known to influence the conformation of pyrrolidine rings through the F–C–C–N gauche effect (see this review’s section on collagen for a further discussion of this effect in the context of fluorinated peptides). It is interesting to speculate whether a
Graphical Abstract
Figure 1: Conformational effects associated with C–F bonds.
Figure 2: HIV protease inhibitor Indinavir (17) and fluorinated analogues 18 and 19. In analogue 18 the gauche...
Figure 3: Cholesteryl ester transfer protein inhibitors 20 and 21. In the fluorinated analogue 21, nO→σ*CF hy...
Figure 4: HIV reverse transcriptase inhibitor 22 and acid-stable fluorinated analogues 23–25. The F–C–C–O gau...
Figure 5: Dihydroquinidine (26) and fluorinated analogues 27 and 28. Newman projections along the C9–C8 bonds...
Figure 6: The neurotransmitter GABA (29) and fluorinated analogues (R)-30 and (S)-30. Newman projections of (R...
Figure 7: The insect pheromone 31 and fluorinated analogues (S)-32 and (R)-32. The proposed bioactive conform...
Figure 8: Capsaicin (33) and fluorinated analogues (R)-34 and (S)-34.
Figure 9: Asymmetric epoxidation reaction catalysed by pyrrolidine 35. Inset: the geometry of the activated i...
Figure 10: The asymmetric transannular aldol reaction catalysed by trans-4-fluoroproline (41), and its applica...
Figure 11: The asymmetric Stetter reaction catalysed by chiral NHC catalysts 49–52. The ring conformations of ...
Figure 12: A multi-vicinal fluoroalkane.
Figure 13: X-ray crystal structures of diastereoisomeric multi-vicinal fluoroalkanes 55 and 56. The different ...
Figure 14: Examples of fluorinated liquid crystal molecules. Arrows indicate the orientation of the molecular ...
Figure 15: Di-, tri- and tetra-fluoro liquid crystal molecules 60–62.
Figure 16: Collagen mimics of general formula (Pro-Yaa-Gly)10 where Yaa is either 4(R)-hydroxyproline (63) or ...
Figure 17: Enkephalin-related peptide 64 and the fluorinated analogue 65. The electron-withdrawing trifluorome...
Figure 18: The C–F bond influences the conformation of β-peptides. β-Heptapeptide 66 adopts a helical conforma...
Figure 19: The conformations of pseudopeptides 69 and 70 are influenced by the α-fluoroamide effect and the fl...
