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CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
Fro
mT
rifl
uo
roaceti
cacid
to t
rifl
icd
eri
vati
ves
:
RH
OD
IA’s
Flu
ori
nati
on
tree
Fra
nç
ois
ME
TZ
Rh
od
ia R
esearc
h C
en
tre L
yo
n -
Fra
nce
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
2
F. M
ET
Z C
hem
Sp
ec
2006
Flu
ori
nati
on
: a
key t
ech
no
log
y f
or
Rh
od
ia
•F
or
the p
ast 20 y
ears
, flu
orin
ate
d in
term
ed
iate
shave k
now
n a
g
rea
t success in L
ife S
cie
nce a
ctives, as t
he intr
oduction o
f one
or
se
vera
l fluorine a
tom
s c
an in
cre
ase
th
e a
ctive
’s b
iolo
gic
al
activity.
•A
s a
result, flu
orin
atio
n is a
te
ch
no
log
yin
dem
and w
ith 2
0%
of
Life
Scie
nce
active
s c
on
tain
ing
on
e o
r se
ve
ral flu
orin
e a
tom
s
(C&
EN
,84
(23
), 2
00
6, p
p1
5-2
3)
•R
ho
dia
is r
eco
gn
ise
d a
s a
wo
rld
wid
e le
ad
er,
with a
n e
xte
nsiv
e
ind
ustr
ial e
xp
erie
nce
an
d in
no
va
tive
ch
em
istr
y in
se
ve
ral
flu
orin
atio
n t
ech
no
log
ies, to
pro
duce b
oth
flu
oro
alip
ha
tic
an
dflu
oro
aro
ma
tic
co
mp
ou
nd
s.
Rh
od
ia’s
Flu
ori
na
tio
nT
ec
hn
olo
gie
s
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
3
F. M
ET
Z C
hem
Sp
ec
2006
(X)C
F3
F
R
RC
F2X
R =
H,
Cl,
F
HA
LE
X r
eacti
on
HF
liq
uid
tech
no
log
yH
F g
as
tech
no
log
yD
ire
ct
trif
luo
rom
eth
yla
tio
n
Facilit
ies
Lab
ora
tory
Ind
us
tria
lP
ilo
t
Flu
ori
na
tio
n s
ite
s lo
ca
tio
n
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
4
F. M
ET
Z C
hem
Sp
ec
2006
•In
du
str
ial scale
flu
ori
nati
on
reacti
on
s a
re p
erf
orm
ed
on
de
dic
ate
dan
dfu
lly-i
nte
gra
ted
sit
es
,d
esig
ned
fo
r m
ult
i-p
rod
ucts
man
ufa
ctu
rin
g.
•Researc
h &
Develo
pm
en
t te
am
s a
re b
ased
in
ou
r cen
tral R
esearc
h C
en
ter
in L
yo
n.
Sa
lin
dre
s
Avo
nm
ou
th
Lyo
n
Main
Researc
h
Cen
ter
Pro
du
cti
on
sit
es
Flu
oro
-ali
ph
ati
cin
term
ed
iate
str
ee
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
5
F. M
ET
Z C
hem
Sp
ec
2006
A s
oli
d a
nd
sta
ble
tru
nk
:
TF
A
F3C
CO
2H
all
ow
ing
a v
igo
rou
s t
ree
to
gro
w
TF
A :
a t
hre
e s
tag
es
pro
ce
ss
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
6
F. M
ET
Z C
hem
Sp
ec
2006
•P
ho
to-o
xid
ati
on
:
CC
l 2=
CC
l 2+
1/2
O2
CC
l 3–
CO
Cl
PE
RT
CA
C
•F
luo
rin
ati
on
:
CC
l 3-
CO
Cl+
4H
F
CF
3-
CO
F +
4H
Cl
TF
AF
•H
yd
roly
sis
:
CF
3-
CO
F +
H
2O
C
F3-
CO
OH
+
H
F
TF
A
h
Un
iqu
e
CF
C-f
ree
pro
ce
ss
TF
A :
a t
hre
e s
tag
es
pro
ce
ss
pro
ce
ss
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
7
F. M
ET
Z C
hem
Sp
ec
2006
Cl Cl
ClCl
Cl
ClCl
+C
l..
h
O2 C
l
ClCl
O-O.
Cl Cl
ClCl
Cl
ClCl
O-O
.C
l
Cl
Cl
Cl
Cl
ClCl
OO
Cl
Cl
ClCl
Cl
O
CT
CA
by-p
rod
ucts
by-p
rod
ucts
Cl
ClCl
O.
Ph
oto
-ox
ida
tio
n :
Reacti
on
mech
an
ism
(su
pp
osed
)
Initiation
pro
paga
tion
To
flu
ori
nati
on
TF
A :
a t
hre
e s
tag
es
pro
ce
ss
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
8
F. M
ET
Z C
hem
Sp
ec
2006
Flu
ori
na
tio
n :
su
ccess
ive C
l-F
exch
an
ges
HF
HF
CC
l 3C
OC
lC
Cl 2
FC
OF
CC
l 3C
OF
-HC
l-H
Cl
(T
CA
F)
(D
CF
AF
)(T
CA
C)
HF
HF
CF
3C
OF
CC
lF2C
OF
CC
l 2F
CO
F-H
Cl
-HC
l
(T
FA
F)
(C
DF
AF
)
TF
A :
a t
hre
e s
tag
es
pro
ce
ss
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
9
F. M
ET
Z C
hem
Sp
ec
2006
Hy
dro
lys
is :
access
to b
oth
TF
A &
CD
FA
+
trif
luo
roaceti
c a
cid
(TF
A)
ch
loro
dif
luo
roaceti
c a
cid
(C
DF
A)
O
FC
F3
O
FC
F2C
l
O
OH
CF
3
O
OH
CF
2C
l
H2O
H2O
TF
A a
nd
CD
FA
are
key
sta
rtin
gra
wm
ate
rials
, w
hic
hopen t
he w
ay
to a
exte
nsiv
e r
ange o
f alip
hatic
fluorinate
dcom
pounds.
TF
A :
sp
ec
ific
itie
s
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
10
F. M
ET
Z C
hem
Sp
ec
2006
Rh
od
ia’s
ad
va
nta
ge
s :
•L
arg
e c
ap
acity
•U
niq
ue
an
d c
om
pe
titive
pro
ce
ss
•E
nviro
nm
en
tally
frie
nd
ly p
roce
ss :
CF
C f
ree
•E
xp
eri
en
ce
in
ha
nd
ling
ha
za
rdo
us r
ea
ge
nts
•R
ho
dia
’s in
teg
ratio
n in
o
the
r te
ch
no
log
ies
Cos
tco
mpeti
tive
pro
cess
Sus
tainable
tech
nology
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
11
F. M
ET
Z C
hem
Sp
ec
2006
TF
A :
ap
plicati
on
s
So
me e
xam
ple
s :
•P
rote
cti
on
an
d d
ep
rote
cti
on
re
ac
tio
ns
(of
alc
oh
ols
, a
mid
es, n
ucle
osid
es, p
ep
tid
es
, p
hen
ols
, su
gars
, cle
avag
e
of
dit
hio
aceta
ls…
.)
•C
ata
lyst
an
d s
olv
en
t
( Rin
g s
ub
sti
tuti
on
, aro
mati
c n
itra
tio
n, re
arr
an
gem
en
ts, is
om
eri
zati
on
…)
•H
ete
roc
yc
liza
tio
nre
ac
tio
ns
•R
ea
cti
on
wit
h h
alo
ge
na
ted
co
mp
ou
nd
s
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
12
F. M
ET
Z C
hem
Sp
ec
2006
F3C
OH
O
F3C
O
O
CF
3
O
F3C
OH
F3C
H
O
F3C
OE
t
O
F3C
OE
t
OO
CF
3S
O3H
TF
ET
FA
A
ET
FA
ET
FA
A
Flu
ora
l
triflic
acid
chain
TF
A
TF
A c
ha
in
Sta
rtin
g f
rom
th
ese b
uild
ing
blo
cks a
nd
th
an
ks t
o a
n e
xte
nsiv
e p
ort
folio
of
tech
no
log
ies,
Rh
od
ia
off
ers
th
e w
idest
ran
ge o
f T
FA
deri
vati
ves a
nd
ad
van
ced
d
ow
nstr
eam
in
term
ed
iate
s .
An
esth
eti
cs
Ce
lec
ox
ib(P
fize
r)
Efa
vir
en
z(B
MS
)
Dit
hio
pyr
(Do
w)
CD
FA
ch
ain
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
13
F. M
ET
Z C
hem
Sp
ec
2006
O
FC
lF2C
O
OH
CF
2C
l
H2O
CD
FA
FC
DF
AM
eC
DF
A
MeO
H
- H
2O
O
OC
F2C
l-H
F
Eli
Lill
yG
em
citabin
e(a
nticancer)
O
OH
OH
N
FF
N
O
H2N
F
O
O
F
Cl
Me
CD
FA
Activate
d Z
n
OO
CH
O
FO
O
FOH
O O
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
14
F. M
ET
Z C
hem
Sp
ec
2006
Tri
flic
ac
id (
TA
) :
a u
niq
ue
ch
em
ica
l p
ath
wa
y
F3C
OH
O
CF
3S
O3H
SO
2
CF
3C
OO
K[C
F3K
]C
F3SO
2K
EP
0735023
-C
O2
Dire
ct n
ucle
op
hili
ctr
iflu
oro
me
thyla
tio
n: a n
ew
pro
cess u
sin
g C
FC
fre
ein
no
va
tive
te
ch
no
log
y
cation
effect: K
>N
a>
Li
Influence ofte
mpera
ture
and
choic
eofsolv
entare
key
Pro
ce
ss
op
tim
isa
tio
n a
llow
sfo
rre
liab
lea
nd
co
mp
etitive
ma
nu
factu
rin
gco
nd
itio
ns.
An
ion
ic t
rifl
uo
rom
eth
yla
tio
n:
sc
op
e &
lim
ita
tio
ns
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
15
F. M
ET
Z C
hem
Sp
ec
2006
CH
O+
C
F3C
O2K
C6H
5C
F3
OH
40
-60
%
C6H
5
SC
6H
5
SC
6H
5
+
CF
3C
O2K
SC
6H
5
CF
3
80
%
C6H
5S
CN
+
CF
3C
O2K
C6H
5S
CF
3
40%
EP
0733614
An
ion
ic t
rifl
uo
rom
eth
yla
tio
n:
sc
op
e &
lim
ita
tio
ns
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
16
F. M
ET
Z C
hem
Sp
ec
2006
C6H
5O
O
+
CF
3C
O2K
2C
6H
5C
F3
O
C6H
5C
F3
OH
F3C
+
10
%20
%
C6H
5C
F3
O
+
CF
3C
O2K
C6H
5C
F3
OH
F3C 2
5%
O
10
%
OH
CF
3+
C
F3C
O2K
+ c
roto
nis
ati
on
EP
0733614
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
17
F. M
ET
Z C
hem
Sp
ec
2006
Acilys
Acilys
™ T
A™
TA
Tri
flic
Tri
flic
Ac
idT
rifl
uoro
meth
anesu
lfon
ic
acid
, al
so
kno
wn
astr
iflic
acid,
is
the
mos
t acidic
of
all
the
com
merc
ial
chem
ical
s av
aila
ble
at
the i
ndus
tria
lsc
ale.
Its
uni
que c
hem
ical
str
uctu
re g
ives
trif
lic
acid
an o
utst
andin
g ac
id s
treng
th a
s w
ell a
s ch
em
ical
stab
ilit
y.
It
is extr
emely re
sist
ant
tow
ards
therm
al
degr
adat
ion,
ox
idat
ion
and
reduc
tion
,an
d is
also
non
-oxid
izin
g.
Tri
flic
aci
d i
s w
idel
y us
ed f
or s
peci
alty
and
fin
ech
emic
al
prod
ucti
ons,
fo
r ac
id
cata
lyze
d
reac
tion
ssu
ch a
s :
Cat
ionic
polymer
izat
ions
Aro
mat
ic a
lkylat
ions
Est
erificat
ions
Acy
lation
s
Ac
id
MW
150 g
.mol
150 g
.mol-- 11
BP
162°C
162°C
De
ns
ity
1.7
kg.l
1.7
kg.l
-- 11
Inven
tori
es
All
All
CA
S #
1
493
CA
S #
1
493
-- 13
13
-- 66
SO
CO
H
OFF
F
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
18
F. M
ET
Z C
hem
Sp
ec
2006
OH
OH
+
SO
OH
OFF
F
OM
e
OO
O
OM
e
O
SO
OH
OFF
F
+
Ex
am
ple
so
f re
ac
tio
ns
us
ing
Ac
ily
s-T
A
Rhod
ia
com
merc
ializes
trif
lic
acid
under
the
trad
ena
me
Acilys-
TA
. It
isre
adily
avai
lable
from
few
kilog
ram
sto
mul
tito
nssc
ale.
Mor
eov
er,
a larg
e r
ang
e o
f tr
iflic
acid
deriva
tive
ssu
ch
as
trif
lic
anhyd
ride,
orga
nic
and s
ilyl
est
ers
as
well a
s m
eta
l tr
ifla
tes,
ar
e
also
av
aila
ble
fr
om
Rhod
ia.
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
19
F. M
ET
Z C
hem
Sp
ec
2006
CF
3C
O2H
CF
3S
O2K
CF
3S
O2C
l (B
r)(C
F3S
O2) 2
NH
Ph
arm
a
(CF
3S
O2) 2
O
Cata
lysis
(CF
3S
O3) 3
M
Cata
lysis
[(C
F3S
O2) 2
N] 3
M
H2O
2
Tri
flic
acid
ch
ain
:A
n e
xte
nsiv
e r
an
ge o
f p
rod
ucts
fo
r a w
ide r
an
ge o
f ap
plicati
on
s
Batt
ery
salt
(CF
3S
O2) 2
NL
i
In b
lue :
develo
pm
en
t p
rod
ucts
M :
ra
re e
art
hs
e.g
. Y
b,
La
CF
3C
O2K
F3C
OA
c
Ph
arm
a
Ion
icliq
uid
s
Ph
arm
aC
F3S
O3C
H2C
F3
N. R
oques F
R 2
804 9
55(2
000)
Ph
arm
a b
uid
ing
blo
cks
Cata
lysis
CF
3S
O3H
CF
3S
O3S
iMe
3
CF
3S
O3S
iMe
2t-
Bu
Ph
arm
a
Ele
ctr
on
ics
CF
3S
O3R
(Me,
Et,
…)
Ne
w t
ec
hn
olo
gy
: ra
dic
al
trif
luo
rom
eth
yla
tio
nN
ew
te
ch
no
log
y:
rad
ica
l tr
iflu
oro
me
thy
lati
on
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
20
F. M
ET
Z C
hem
Sp
ec
2006
•A
ne
w r
an
ge
of
bu
ildin
g b
locks
OA
cF
3C
Cl
OA
cF
3C
Cl
OH
OA
c
F3C
F3C
O*
*
CF
3SO
2X
Lab
scale
K
ilo
Lab
OA
cF
3C
O CH
3
OA
cF
3C
Cl
OA
cF
3C
O OH
CF
3°
Rh
od
ia O
rga
nic
s :
a k
ey
pla
ye
r in
flu
ori
na
tio
n
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
21
F. M
ET
Z C
hem
Sp
ec
2006
•R
ho
dia
asso
cia
tes a
ll th
ese
flu
oro
alip
ha
tic
bu
ildin
g b
locks w
ith
an
exte
nsiv
e p
ort
folio
of
technolo
gie
s.
•W
e a
re y
our
innovative p
art
ner
in d
evelo
pin
g m
ore
advanced
do
wn
str
ea
m in
term
ed
iate
s.
Bu
ild
ing
blo
ck
s
+
ou
r te
ch
no
log
ies
po
rtfo
lio
Ad
van
ced
flu
ori
nate
d in
term
ed
iate
s
•W
ith
yo
u,
let
Rh
od
ia’s
flu
oro
alip
ha
tics
tre
e g
row
an
d b
losso
m !
•F
or
more
info
rmation,
com
e a
nd s
ee u
s o
n B
ooth
C11
Ac
kn
ow
led
gm
en
ts
CH
AL
LE
NG
ING
BO
UN
DA
RIE
S
22
F. M
ET
Z C
hem
Sp
ec
2006
Th
is w
ork
is t
he r
esu
lt o
f a c
on
sta
nt
co
mm
itm
en
t o
f m
an
y t
eam
s :
•Synth
esis
chem
istr
y,
•An
aly
sis
,
•Pro
ce
ss d
eve
lop
me
nt,
•Manufa
ctu
ring,
•Ma
rke
tin
g &
Sa
les,
•Health &
Safe
ty,
•Re
gu
lato
ry
•…
TH
AN
KS
TO
EV
ER
YB
OD
Y !
!!
