Fluorine ChemistryFluorine Chemistry
How to make and to break C-F bonds?How to make and to break C-F bonds?
Fluorine HistoryFluorine History
• F2 gaz isolated in 1886 by Henri Moissan (Nobel Prize 1906)
• Green-yellow gaz, very toxic, very strong oxidant, inflames organic materials by contact, makes bonds violently with almost every elements
• Electrochemical method Uses melted KHF2 to increase the conductivity of the bath(HF too weak electrical conductivity)Platinium electrolyser, lower reaction temperature of the electrolyte bath (HF/KHF2) to avoid corrosion: observation of gaz emission at the anode
• Moissan solved a major issue of the mineral chemistry at this time
• F2 gaz isolated in 1886 by Henri Moissan (Nobel Prize 1906)
• Green-yellow gaz, very toxic, very strong oxidant, inflames organic materials by contact, makes bonds violently with almost every elements
• Electrochemical method Uses melted KHF2 to increase the conductivity of the bath(HF too weak electrical conductivity)Platinium electrolyser, lower reaction temperature of the electrolyte bath (HF/KHF2) to avoid corrosion: observation of gaz emission at the anode
• Moissan solved a major issue of the mineral chemistry at this time
Modifications Introduce by a Fluorine in Organic Compounds
Modifications Introduce by a Fluorine in Organic Compounds
• increases thermal and oxidative stability
• alters electronic effects
• increases lipophilicity
• closely mimics hydrogen steric requirements
• increases thermal and oxidative stability
• alters electronic effects
• increases lipophilicity
• closely mimics hydrogen steric requirements
Common Uses of FluorineCommon Uses of Fluorine
• surfaces treatement: Teflon®, Gore Tex®, UV absorbent, anti burned meal, anti graffitti, anti reflect, anti flammable materials, biocompatible materials....
• nanotechnology: nanocomposites, gaz filtration systems, silicium composant cleaning
• agronomy: herbicide, fongicide, insecticide
• medicine: active molecules in drugs, blood substitutes, diagnosis by PET (18F-fluorodesoxyglucose)
• surfaces treatement: Teflon®, Gore Tex®, UV absorbent, anti burned meal, anti graffitti, anti reflect, anti flammable materials, biocompatible materials....
• nanotechnology: nanocomposites, gaz filtration systems, silicium composant cleaning
• agronomy: herbicide, fongicide, insecticide
• medicine: active molecules in drugs, blood substitutes, diagnosis by PET (18F-fluorodesoxyglucose)
Fluoride “this friend who wants you evil”
Fluoride “this friend who wants you evil”
★ < 1 mg/day : prevents cavities★ 2 mg/day : dental fluorosis risk
★ < 1 mg/day : prevents cavities★ 2 mg/day : dental fluorosis risk
Fluoride “this friend who wants you evil”
Fluoride “this friend who wants you evil”
★< 1 mg/day : prevents cavities★ 2 mg/day : dental fluorosis risk★10 to 40 mg/day : skeletal fluorosis★ 20 to 80 mg/day : ankylosing fluorosis★100 mg/day : growth retardation★125 mg/day : alteration of kidney function★200 to 500 mg/day : lethal dose
★< 1 mg/day : prevents cavities★ 2 mg/day : dental fluorosis risk★10 to 40 mg/day : skeletal fluorosis★ 20 to 80 mg/day : ankylosing fluorosis★100 mg/day : growth retardation★125 mg/day : alteration of kidney function★200 to 500 mg/day : lethal dose
Do not swallow your toothpaste !!!
Montreal : 0,15 mg/lMontreal : 0,15 mg/l
C-F Bond FormationC-F Bond Formation
Fluorine chemistry can be more difficult because of the great reactivity of the fluorine itself. The problem is enhanced when a specific incorporation is required. (regio- or stereoselectivity)
“F” as a nucleophile
“F” as an electrophile
Fluorine chemistry can be more difficult because of the great reactivity of the fluorine itself. The problem is enhanced when a specific incorporation is required. (regio- or stereoselectivity)
“F” as a nucleophile
“F” as an electrophile
“F” as a Nucleophile“F” as a Nucleophile
• Small size of the atom and low polarisability encourages F- to act more like a base rather than a nucleophile
• C-F bond: 107 kcal/mol (strongest bond with carbon, driving force)
Metal Fluorides
Non metallic compounds
• Small size of the atom and low polarisability encourages F- to act more like a base rather than a nucleophile
• C-F bond: 107 kcal/mol (strongest bond with carbon, driving force)
Metal Fluorides
Non metallic compounds
Metal FluorideMetal Fluoride
• KF, CsF, AgF, CuF2...
• boiling and anhydrous polar solvents
• crown ethers are used to make ionic fluoride soluble in non polar solvents.
• KF, CsF, AgF, CuF2...
• boiling and anhydrous polar solvents
• crown ethers are used to make ionic fluoride soluble in non polar solvents.
O OMe
OBnBnOOBn
TsOO OMe
OBnBnO
OBn
FKF / polyethylene glycol 400
44hrs, 70°C
63%
Chem. Rev. Chem. Rev. 19921992, 505., 505.
Metal Fluoride Utilisation Example:Halex Reaction
Metal Fluoride Utilisation Example:Halex Reaction
Angew. Chem. Int. Ed.Angew. Chem. Int. Ed.,, 2006 2006, , 4949, 2720., 2720.
Using TBAF in DMSO at rt :Using TBAF in DMSO at rt :
conversionconversion between 80 and >95% (mainly > 90%) between 80 and >95% (mainly > 90%)
activating groupementactivating groupement : NO : NO2,2, CF CF3,3, Cl, CN, N intra cyclic, ketone Cl, CN, N intra cyclic, ketone must be in ortho or para position except for NOmust be in ortho or para position except for NO22
leaving group: -leaving group: -NONO22, -Cl, -Cl
reaction timereaction time from 20 min to 14 days from 20 min to 14 days
from 1.3 to 4 equiv. of TBAFfrom 1.3 to 4 equiv. of TBAF
Cl
CN
spray-dried KFPh4PBr
1,1-dimethyl-2-imidazolidinone
290°C
C
N
Cl F F
CN
+ KCl
N
F
TASF: Ley’s synthesis of fluoroinositolTASF: Ley’s synthesis of fluoroinositol
TASF, THF, reflux
4 days
BnO
O
O
O
OBnBnO
O
O
OBn
OH
F
74%
tris(dimethylamino)sulfonium difluorotrimethylsilicatetris(dimethylamino)sulfonium difluorotrimethylsilicatewhite solidwhite solid
Middelton 1976Middelton 1976
S
N
NNSi
F
F
BnOOCOPh
OHBnOBnO
BnO
BnOOCOPh
BnOBnO
BnO F
DAST / Toluene80°C
(−)-1L-1-desoxy-1-fluoro-myo-inositol
NS
F
F
F
DAST:diethylaminosulfur trifluoride
1. 1. Tet. Lett. Tet. Lett. 19891989,, 30 30, 3557, 3557..2.2. J. Chem. Soc., Chem. Commun. J. Chem. Soc., Chem. Commun. 19881988, 1301, 1301
Baltz Schiemann ReactionExample of Metalloid Fluoride:
Baltz Schiemann ReactionExample of Metalloid Fluoride:
NN
BF4
NH2
diazotisationreaction Δ
F BF3
F
BF3
OMe
MeO NH2
COOEt
H3COCHN
COOEt
OMe
MeO NO2
OH
nitro-vanillin
1. NaNO2 / 5N HCl -5°C to 0°C
2. HBF4, Et2O 85%
OMe
MeO N
COOEt
H3COCHN
COOEt
N
BF4
xylene, reflux, 2h26%
OMe
MeO
COOEt
H3COCHN
COOEt
F
48% HBrreflux85%
OH
HO
COOH
H3N
F
Br
5-fluoro-D/L-dopa hydrobromideJ. Fluorine ChemJ. Fluorine Chem 19941994,, 68 68, 141., 141.
“F” as an Electrophile“F” as an Electrophile
Not easily achieved at a first glance because ‘F’ is the most electronegative element.
F2
N-O reagents
N-F reagents
Not easily achieved at a first glance because ‘F’ is the most electronegative element.
F2
N-O reagents
N-F reagents
F2 itself F2 itself
• reacts violently with alkenes giving mixture of products including degradation of the carbon chain....
• few industrial processes (diluted fluorine, low temperature...)
• upon addition of alkenes, syn stereochemistry observed
• formation of β-fluorocarbocation
• mainly used to synthesize O-F and N-F reagents
• reacts violently with alkenes giving mixture of products including degradation of the carbon chain....
• few industrial processes (diluted fluorine, low temperature...)
• upon addition of alkenes, syn stereochemistry observed
• formation of β-fluorocarbocation
• mainly used to synthesize O-F and N-F reagents
O-F ReagentsO-F Reagents
• Less used than N-F reagent because of their price
Main O-F Reagent :
• Less used than N-F reagent because of their price
Main O-F Reagent :
depending on Rdepending on Ryields from 37-60%yields from 37-60%
NR
H
NR
HO
F
CF3
NR
HHF
OCF3
F
NRH
F2CO HF
F3CO F
CO + F2 + CsF CF3OCsF2
CF3O• + F• + CsF
Chem. Rev.Chem. Rev. 19961996, 1717., 1717.
O-F ReagentsO-F Reagents
In the case of concentrated reaction or neat olefin (usually electron-depleted) the radical In the case of concentrated reaction or neat olefin (usually electron-depleted) the radical pathway is observed : less regioselective reaction.pathway is observed : less regioselective reaction.
Can be overcome with a radical inhibitorCan be overcome with a radical inhibitor
Chem. Rev.Chem. Rev. 19961996, 1717., 1717.
H
Ph
Ph
HCF3OF
H
F
Ph
HPh
CF3O H
F PhOCF3
HPh
H
F
Ph
HPh
CF2O F H
F PhF
HPh
O-F ReagentsO-F Reagents
Chem. Rev.Chem. Rev. 19961996, 1717., 1717.
CH3COONa ROH
R = H, Ac
F2CFCl3 (-78°C)
CH3COOF
AcOF
half life of 2h at rthalf life of 2h at rt
OOR
OR
RO
AcO18F OOR
OR
RO
18FOAc
deprotection OOH
OH
HO
18FOH
[18F]-fluorodeoxyglucose
N-F ReagentsN-F Reagents
• said to be safer, easier to handle, selective source of electrophilic fluorine.
• Can be R2NF or R3N+FA- where A- is a non-nucleophilic anion.
• said to be safer, easier to handle, selective source of electrophilic fluorine.
• Can be R2NF or R3N+FA- where A- is a non-nucleophilic anion.
Chem. Rev.Chem. Rev. 19961996, 1737., 1737.
R3N F + Nu- R3N F Nu R3N F-Nu
N-F ReagentsN-F Reagents
Chem. Rev.Chem. Rev. 19961996, 1737., 1737.
N
F
N
F
CF3COO
N
F
Tf
NN
F BF4
Cl
BF4
UmemotoBanks
F NS
OO
NSO2PhPhO2S
F NFSO2
N-fluorobenzenesulfonimide"NFSI"
Selectfluor
F
FF
FF
F
F
F
F
F
chiral N-Fluorosultams
N-F Reagents: How They Are MadeN-F Reagents: How They Are Made
Chem. Rev.Chem. Rev. 19961996, 1737., 1737.
(SelectFluor)(SelectFluor)
NSO2PhPhO2S
H
F2, RT, 1570 TorrN
SO2PhPhO2S
F
"NFSI"
N
F
Tf
N
+ 10% F2 + Na+Tf-- 40°C, MeCN
N
F
F
F
F
FF
F
FF
F
F
N
CoF3 fluorination
HF anhydrousSimmons Cellelectrochemical
Electrophilic aromatic substitutionElectrophilic aromatic substitution
Various compounds were fluorinated by electrophilic aromatic substitution. Various compounds were fluorinated by electrophilic aromatic substitution. Pb: Need activated fluorinating agent, if too activated: polyfluorinationPb: Need activated fluorinating agent, if too activated: polyfluorination
Me
MeMe
Me
F
Me
Me
F
MeF
Me
Me
Me
Me
MeF
Me
Me
Me
Me
Me
Me
F
FF
SelectFluor
SelectFluor
SelectFluor
Chem. Rev.Chem. Rev. 19961996, 1737., 1737.
Fluorination of carbanionFluorination of carbanion
Easy access to mono or difluoro-olefinsEasy access to mono or difluoro-olefins
Chem. Rev.Chem. Rev. 19961996, 1737., 1737.
SO2PhPEtO
OEtO
OMet
R3
R2
R1OSiX3
R3
R2
R1O
R3
R2
R1 R1
R3
R2
NR2
R1
O
R2
O
R3 R1
O
R2
OMet
R3
Fluorination: OrganocatalysisFluorination: Organocatalysis
Angew. Chem. Int. Ed.Angew. Chem. Int. Ed. 20052005, 3706., 3706.
HR1
R2
O
+ R1
FR2
H
O30mol%
0.5M in DMF4°C, 4h
NH
OH
O
very good yieldbut ee ~ 50%
NFSI
HR1
O
+ R1
F
H
O
NH
NO
Ph30mol%
0.5M in DMF4°C, 4h
8 examplesfrom 40 to 94% yieldfrom 86 to 96% ee
NFSI
Fluorination: Organocatalysis(in presence of 6 equiv of an alkaloid)
Fluorination: Organocatalysis(in presence of 6 equiv of an alkaloid)
Org. Lett.Org. Lett. 20022002, 545., 545.Angew.Angew. 20082008 ASAP ASAP
OR3R1
O
R2
O
NtBu
tBuOMe
HO
N
Br
10mol%
NFSI (100mol%)base (600mol%)
toluene, rt
OR3R1
O
R2
O
F
5 examples74-94% yield
40-69% ee
(CH2)nR
X SiMe3
n = 1,2
X = O, CH2
NFSI (1.2 equiv.)bis-cinchona alkaloïd(10mol%)
K2CO3 (6 equiv.)CH3CN (CH2)n
X
RF
20 examplesyieds between 58% and 95%
X = CH2 ee up to 95%X = O ee up to 86%
Fluorination: Metal-catalysedFluorination: Metal-catalysed
Angew. Chem. Int. EdAngew. Chem. Int. Ed 20052005, 4276., 4276.Angew. Chem. Int. EdAngew. Chem. Int. Ed 20052005, 4204., 4204.
COOR
O
OO
N NO
Ph Ph
NiOH2
2 ClO4
2 +
10 mol%
NSFI (120mol%)CH2Cl2, 4Å MS, RT
n
n = 1, 2
COOR
O
n
n = 1, 2
F 6 examples66-84% yield93-99% ee
J. Am. Chem. Soc.J. Am. Chem. Soc. 20062006, 7134., 7134.
Metal induced Formation of C-F bondsMetal induced Formation of C-F bonds
Fluorination of organometallic compoundsFluorination of organometallic compounds
Metal catalysed fluorinationMetal catalysed fluorination
Fluorination organometallic compoundsFluorination organometallic compounds
Chem. Rev.Chem. Rev. 19961996, 1743., 1743.Perkin, Trans. 1Perkin, Trans. 1, , 19921992, 1891, 1891
Organometallic = nucleophile, F = electrophileOrganometallic = nucleophile, F = electrophilelot of examples with differents metals: organolithium, stannanes...lot of examples with differents metals: organolithium, stannanes...
Tl
SelectFluor , 0°C to rt
dimethylacetylenedicarboxylate
HF
COOMe
COOMe52%
F
Poorly stable
Diels Alder
synsyn product product
J. Am. Chem. Soc.J. Am. Chem. Soc. 20062006, 7134., 7134.
Palladium catalysed Fluorination of C-H bondsPalladium catalysed Fluorination of C-H bonds
N
H
10mol% Pd(OAc)2
1.5 equiv.
MW, 110°C, 1h, 200W, benzene
NF
BF4
N
F
N
Ph
N
OAc
97% conv.75% yield of 1
1 2 3
N
F
N
F
F57% 49%
N
Br
F53%
N
F
F
62%69%
from mono-fluorated
N
F
N
F
OMe
N
F
Cl
N
F
CF3
50% 59%33%52%
N
F
CF3 N
F
COOEt
N
O
F
N
F
F
MeO
52%
60%54%75%
C-F Bond cleavageC-F Bond cleavage
• Fluorocarbon really stable (cf. ozone layer problem), resistant to chemical attack, high thermal stability, reluctant to coordinate to metal centers but fluorocarbon-transition metal complexes are extremely robust compared to hydrocarbon-transition metal complexes
• C-F activation bond challenge compared to C-H activation bond one.
• C-F bond: 107 kcal/mol
• π-donnor, σ-acceptor
• interactions between lone pair of fluorine and π orbitals of adjacent unsaturated carbon: had rather to form bonds with sp3 than with sp2 carbon centers.
• Fluorocarbon really stable (cf. ozone layer problem), resistant to chemical attack, high thermal stability, reluctant to coordinate to metal centers but fluorocarbon-transition metal complexes are extremely robust compared to hydrocarbon-transition metal complexes
• C-F activation bond challenge compared to C-H activation bond one.
• C-F bond: 107 kcal/mol
• π-donnor, σ-acceptor
• interactions between lone pair of fluorine and π orbitals of adjacent unsaturated carbon: had rather to form bonds with sp3 than with sp2 carbon centers.
Unsaturated Fluorinated compoundsUnsaturated Fluorinated compounds
• π-framework subject to nucleophilic attack and fluorine is a good leaving group... depending on the solvent...
• π-framework subject to nucleophilic attack and fluorine is a good leaving group... depending on the solvent...
NO2
O2N
FHN 22°C, THF
N
NO2O2N
+ HF
Kinectic isotope effect 1.0262 ± 0.0007 in THF Kinectic isotope effect 1.0262 ± 0.0007 in THF 0.9982 ± 0.0004 in Acetonitrile0.9982 ± 0.0004 in Acetonitrile
J. Am.Chem. SocJ. Am.Chem. Soc, , 19961996, , 118118, , 20.20.
Activation by a proximal carbocationActivation by a proximal carbocation
FF
F
F
O
F
FF
COOEtF
Et2OHCO3
- C6F6HCO3
-
J. Am. Chem. Soc.J. Am. Chem. Soc. 19971997, 4319., 4319.
C-F Activation by a MetalloidC-F Activation by a Metalloid
Me2Si SiMe2F
Me2Si SiHMe2F
R3Si-H
R3Si
R3SiF
Me2Si SiMe2H
Me2Si SiHMe2F
RH
R-F
R
J. Am. Chem. Soc.J. Am. Chem. Soc. 20062006, 9676., 9676.
R = CR = C1010HH2121
R= CR= C66HH55CFCF22
C-F Bond Cleavage Activated by a MetalC-F Bond Cleavage Activated by a Metal
• Fluorocarbon are reluctant to coordinate metal centers
★Need an activation
• But fluorocarbon-transition-metal complexes are extremely robust compared to hydrocarbon-transition-metal complexes.
★Will be problematic for catalytic systems
• Fluorocarbon are reluctant to coordinate metal centers
★Need an activation
• But fluorocarbon-transition-metal complexes are extremely robust compared to hydrocarbon-transition-metal complexes.
★Will be problematic for catalytic systems
Insertion of alkali in C-F bondInsertion of alkali in C-F bond
• Intrinsic difficulty to insert Mg or Li in C-F bonds (longer reaction time) and can trigger explosive decomposition of the metalation product via α or β elimination
• Intrinsic difficulty to insert Mg or Li in C-F bonds (longer reaction time) and can trigger explosive decomposition of the metalation product via α or β elimination
F
1. KI - MgCl2-K-THF, reflux THF, 1h
2. CO2
COOH
65%
J. Chem. Soc., Chem. Commun.J. Chem. Soc., Chem. Commun. 19731973, , 7179.7179.
Nucleophilic attackNucleophilic attack
FF
F
F
F F
F
FMn(CO)5
-THF
RT
F F
Mn(CO)5
F
F
FF
FF
F
F
F
FF F
Mn(CO)5
OrganometallicsOrganometallics, , 19901990, , 99, 2732., 2732.
Achieved by numerous electron rich metals but Achieved by numerous electron rich metals but used almost only for stoechiometric dehalogenationused almost only for stoechiometric dehalogenation
α Activationα Activation
J. Am. Chem. Soc.J. Am. Chem. Soc. 20012001, 10973., 10973.
F
ZrCp*2
H
HgF
F
Cp*2ZrH2
- Hg0, - H2
Cp*2Zr
H
FZrCp*2
FΔ
Activation of the C-F in Activation of the C-F in αα of the metal center is observed in many case of the metal center is observed in many case (elongation of the C-F bond)(elongation of the C-F bond)
However mecanism of activation is not well known...However mecanism of activation is not well known...
Attempt with less activated substratesAttempt with less activated substrates
F HCp*2ZrH2 + Cp*2ZrHF +C6D12, rt, 2d
F
HCp*2ZrF2 + 2
10 days
Cp*2ZrH2 + Cp*2ZrBuHC6D12, 30°C, 15min
Cp*2ZrHFF
+
J. Am. Chem. Soc.J. Am. Chem. Soc. 20012001, 10973., 10973.
Further Activation with PtFurther Activation with Pt
F
F
F
F
F
Ph2P Ph2P
F
F
F
F
OH
F
Ph2P
F
F
F
F
F
Ph2P
O
F
F
F
Pt
Pt
Pt Pt
PC6F5Ph2
H3C
PC6F5Ph2
FH3C
PC6F5Ph2
H3C
Pt THFH3C
PC6F5Ph2
PC6F5Ph2
OH-
OH-
PC6F5Ph2
H3C OH
- HF
- HF
J. Am. Chem. Soc.J. Am. Chem. Soc. 19891989, 3101., 3101.
Activation with PtActivation with Pt
Organometallics,Organometallics, 19931993, 4297., 4297.Org. Lett.Org. Lett. 20072007, 5629., 5629.
F
Cl
N Ph
F
99%
F
F
N Ph
Br
85%
F
F
N Ph
Pt
N
F
F
SMe2Me
MePh
Pt
Me2SMe
Me SMe2
PtMe
Me
F
F
F
N Ph
[Me2Pt(μ-SMe2)]25mol%Me2Zn 0.6 equiv.CH3CN, 35°C, 24h
F
F
CH3
N Ph
95%
Cross coupling using C-F bondCross coupling using C-F bond
J. Am. Chem. Soc.J. Am. Chem. Soc. 20032003, 1696., 1696.
NH2+
F
NO2
Pd(PPh3)4 (10mol%)Cs2CO3,
DMF, 65°C
HN
NO2
65%
B(OH)2
+
R1
F
NO2
Pd(PPh3)4 10mol%Cs2CO3
DMF, 80°C
NO2R1
R1 = CN, 64%R1 = CHO, 86%
(nBu)3SnR1
F
NO2
R2Pd(PPh3)4, 10mol%
DMF, 65°C
R1
NO2
R2 R1 = phenyl, R2 = CN, 56%R1 = phenyl, R2 = CHO, 65%R1=vinyl, R2 = CN, 28%R1=vinyl, R2 = CHO, 45%
Pd PPh3Ph3P
NO O
R
F SNAr
NO O
R
F
Pd
PPh3
Ph3PPd
Ph3P
PPh3
FNO2
RR = CHO, CN
C-C bond Formation using C-F bondC-C bond Formation using C-F bond
J. Am. Chem. Soc.J. Am. Chem. Soc. 20032003, 5646., 5646.
Ph
Ph
F + nPr MgBr
NiCl2, 1,3-butadiene (100mol%)72%
CuCl2, 1,3-butadiene (10mol%)98%
Ph
Ph
n-Pr
C-C bond Formation using C-F bondC-C bond Formation using C-F bond
J. Am. Chem. Soc.J. Am. Chem. Soc. 20032003, 5646., 5646.
nC5H11-MgBr + nC9H19-F (1.5 equiv.)
nC8H17-Cl (1.5 equiv.)
nC10H21-Br (1.5 equiv.)
cat 3mol%THF, 25°C, 30min NiCl2, (100mol%) 8% 0% 39%
CuCl2, (10mol%) 16% 0% 40%
nC13H28nC14H30 nC15H32
Ph-MgBr + nC9H19-F (1.5 equiv.)
nC8H17-Cl (1.5 equiv.)
nC10H21-Br (1.5 equiv.)
CuCl2 3mol%THF, 25°C, 30min
Ph-nC8H17 0% <1%
Ph-nC9H19 8% 44%
Ph-nC10H21 2% 17%
25°C reflux
C-C bond Formation using C-F bondC-C bond Formation using C-F bond
Angew. Chem., Int. Ed.Angew. Chem., Int. Ed. 20012001, 3387., 3387.
N
N
iPr
iPr
iPr
iPr
Ni
2
F+ BrMg Ar
5mol% [Ni]THF, RT, 18h
ArR1
R1
R1= Ar yield
4-CF3 Ph 95
4-Me Ph 82
2-Me Ph 38
4-CF3 4-tBuC6H4 95
H 4-tBuC6H4 83
According to the authors, kinetics study suggest oxidative insertion...According to the authors, kinetics study suggest oxidative insertion...
ConclusionConclusion
Do not swallow your toothpaste !!Do not swallow your toothpaste !!
Usefull reagents have been developped to achieve the regio-, stereo- and Usefull reagents have been developped to achieve the regio-, stereo- and enantioselective formation of C-F bonds.enantioselective formation of C-F bonds.
Mild conditions has been developped to activate C-F bondsMild conditions has been developped to activate C-F bonds
Reactivity of perfluoroalkanes is still problematicReactivity of perfluoroalkanes is still problematic