Development of copper-catalyzed enantioselective decarboxylative aldolization for the preparation of perfluorinated 1,3,5-triols featuring supramolecular recognition properties

Article abstract of DOI:10.1039/c9sc05196a

Fluorine is able to confer unique properties to organic molecules but the scarcity of natural organofluorine sources renders the development of new synthetic methods highly desirable. Using a chiral BOX/Cu combination, enantioselective decarboxylative aldolization of perfluorinated aldehydes has been developed. Most notably, the reaction occurring under mild conditions and with high enantiocontrol can create ketodiols in one single synthetic operation, which are precursors of crucial perfluorinated 1,3,5-triols. In addition, the reaction performed with chloral, validates the proposed transition state model based on steric interactions and provides the first enantioselective synthesis of hexachlorinated ketodiol of great synthetic utility. The ability of perfluorinated 1,3,5-triols to form a central hydrogen-bonding framework allows strong coordination of anions and the chirality obtained through the catalyst-controlled synthetic sequence demonstrates the selective chiral anion recognition ability of polyols.

Full text of DOI:10.1039/c9sc05196a

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Development of a copper-catalyzed enantioselective
decarboxylative-aldolization for the preparation of perfluorinated
1,3,5-triols featuring supramolecular recognition properties
Received 00th January 20xx,
Céline Sperandio,a Jean Rodriguez,a Adrien Quintard,*a
Fluorine is able to confer unique properties to organic molecules but the scarcity of natural organofluorine sources render
the development of new synthetic methods highly desirable. Using a chiral BOX/Cu combination, an enantioselective
decarboxylative aldolization on perfluorinated aldehydes has been developed. Most notably, the reaction occurring under
mild conditions and with high enantiocontrol can create in one single synthetic operation ketodiols, precursors of crucial
perfluorinated 1,3,5-triols. In addition, the reaction performed with chloral, argues for steric repulsions in the transition
state and provides the first enantioselective synthesis of naturally occurring hexachlorinated ketodiol 8 of great synthetic
utility. The ability of perfluorinated 1,3,5-triols to form a central hydrogen-bonding framework allows strong coordination
of anions and the chirality obtained through the catalyst-controlled synthetic sequence demonstrates the selective chiral
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
anion
recognition
ability
of
polyols.
provided by a single alcohol hydrogen bond. This is why
despite their ubiquity in numerous highly bioactive natural
products and drugs, synthetic flexible acyclic polyols have only
been identified recently for their coordination and catalytic
properties.5 It was shown notably by the group of Kass that
multiplication of alcohol functions5e-g or insertion of adjacent
CF3 groups6 could increase the H-bonding strength of the core
alcohols H-bonding frameworks. This role of the CF3
substituents over alcohol properties is further highlighted by
the unique reactivity promoted by the use of
hexafluoroisopropanol as solvent (HFIP).7 However, the
enantioselective elaboration of perfluorinated alcohols still
constitutes a major synthetic challenge. This considerably
limits the construction of new scaffolds featuring enhanced
supramolecular chiral recognition properties. As a result,
designing new types of chiral perfluorinated alcohols and
discovering new approaches for their enantioselective
preparation is highly desirable.
Introduction
Organic molecules efficient in selective supramolecular
recognition are central to numerous drugs, nano-devices,
catalysts or materials.1 As a result, chemist's ability to design
and prepare host molecules with improved binding affinities
and selectivities is crucial. However, the preparation of original
molecular objects has for long remained limited by the
availability of the starting materials or current existing
synthetic methods. This is especially true regarding fluorine
containing molecules notably the ones possessing strong
electron-withdrawing perfluorinated chains ((CF2)n-CF3), able
to confer unique properties to numerous drugs, materials or
catalysts.2 While fluorine insertion can impressively improve
these supramolecular interactions, the preparation of these
molecules depends exclusively on synthetic chemist's ability to
accommodate this particular atom through a reliable synthetic
route, rendering the discovery of original synthetic methods of
great value.3
In this context, we hypothesized that combining a central chiral
1,3,5-triol motif with adjacent electron-withdrawing
perfluorinated chains would provide innovative molecules for
application in selective supramolecular recognition by anions
binding (Scheme 1.a). These molecules would bridge the gap
between known achiral or racemic flexible acyclic alcohols5,6
and more classical chiral receptors8 with strong implications in
Given the progress made in the last decades towards more
efficient synthesis thanks to catalysis,4 it should now be
possible to conceive on a routine basis the de novo design and
synthesis of improved molecular objects through the parallel
on demand development of original catalytic methods.
Among potential motifs for host molecules design, acyclic
alcohols are particular due to the relatively weak interactions
anion
coordination
or
catalysis.
In addition, in order to readily prepare these chiral complex
molecules, we desired to perform the parallel development of
an original and modular enantioselective catalyst-controlled
method also amenable to target other scaffolds of interest
(Scheme 1.b).
Aix Marseille Univ, CNRS, Centrale Marseille, iSm2, Marseille, France.
E-mail: adrien.quintard@univ-amu.fr
Homepage: http://ism2.univ-amu.fr/fr/annuaire/stereo/quintardadrien
Electronic
Supplementary
Information
(ESI)
available:
See
DOI: 10.1039/x0xx00000x
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Herein, we report our success at fulfilling this double goal of efficiency of such catalysts structures in our process. While it
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constructing rapidly and with excellent stereocontrol the was previously shown that the bi-directiDoOnIa: 1l0a.1l0d3o9l/izCa9tSiCo0n51w96aAs
desired perfluorinated 1,3,5-triols of enhanced supramolecular poorly efficient using organocatalytic activation modes on
properties starting from bio-sourced 1,3-acetonedicarboxylic aliphatic aldehydes,15b the increased electrophilic character of
acid
(2
)
through
a
stereocontrolled bi-directional perfluorinated aldehydes facilitated the formation of the
decarboxylative aldolization. (Scheme 1.b).
ketodiol 4a albeit in poor stereocontrol (entries 1-3). Among
all catalysts tested, 10 mol% of quinine provided at the best
17% ee with a total lack of diastereocontrol (1:1 dr) (entry 2).
This absence of diastereocontrol indicates that the first
generated stereocenter does not control the formation of the
second.
Table 1 Identification of a suitable catalytic system for the bi-
directional aldolization on perfluorinated aldehyde 1a
O
F
F
H2O
H
1a
OH
O
OH
F3C
O
F
F
F
F
cat
F
F
F3C
CF3
O
O
THF, rt, 5 h
4a
F
F
F
F
Scheme
1 Proposed enantioselective approach towards
HO
Ph
OH
2
perfluorinated 1,3,5-triols and their supramolecular
coordination properties
Ph
R
Ph
Ph
Ph
R
L2, R = i-Pr
L3, R = t-Bu
L4, R = Bn
L5, R = Ph
P
N
N
N
N
N
O
O
O
O
O
L6
L1
Results and discussion
Development of a catalytic enantioselective perfluorinated
1,3,5-triols synthesis
Entry
Catalyst
Yielda
drb
eec
1
2
3
(S,S)-TUC (10 mol%)
38%
ndd
ndd
1:1
1:1
1:1
2%
Among the limited number of methods able to create
enantioenriched perfluorinated secondary alcohols,9,10 the
aldol reaction seems the most promising given its ability to
potentially assemble rapidly elaborated fragments while
controlling the hydroxy functionalized stererocenters.11
However, the reported aldolization reactions are unfortunately
limited to the generation of simple trifluoromethylated
ketols.12 In addition, the most efficient ones are incompatible
with perfluorinated aldehyde hydrates thus requiring the
application of more elaborated hemiacetals, while suffering
from excessive reaction times (4 to 7 days). These slow kinetics
constitute a sever limitation for their desired implementation
to the proposed more challenging cascade preparation of
1,3,5-triol cores.12d,12f 13
Quinine (10 mol%)
17%
10%
(DHQD)2PHAL (10 mol%)
Cu(OTf)2 (10 mol%) / L1-4 (13
4
mol%)
34-64%
1:1
0%
74%
(54%)e
4:1
(32:1)
5
Cu(OTf)2 (10 mol%) / L5 (13 mol%)
88 (97%)e
6
7
Cu(OTf)2 (10 mol%) / L6 (13 mol%)
Cu(OTf)2 (10 mol%)
55%
73%
58%
4:1
-62%f
-
1:1
8g
L5 (10 mol%)
1:1
0%
To successfully create rapidly perfluorinated 1,3,5-triols, we
proposed to take advantage of the high reactivity of 1,3-
Cu(OTf)2 (10 mol%) / L5 (13
9
mol%)+ 4 Å MS
33%
59%
56%
4:1
4:1
4:1
86%
88%
82%
acetonedicarboxylic acid (2
) towards multiple additions.14
10
11
Cu(OTf)2 (10 mol%) / L5 (22 mol%)
Previous aldolizations using this precursor are based on
substrate-controlled diastereoselective approaches15 and we
set out to identify a suitable catalytic activation mode for the
more challenging enantioselective addition to perfluorinated
aldehyde hydrate 1a (table 1).16
Cu(OTf)2 (13 mol%) / L5 (10 mol%)
a
b
c
Isolated yield. Determined by 19F NMR and gas chromatography. Determined by
d
chiral gas chromatography. Full conversion, yield not determined. e yield, dr and ee in
f
parenthesis and yield are given after purification by recrystallization. Opposite
g
Given the behavior of a broad range of organocatalysts in enantiomer obtained. Reaction run over 12 hours. The same result is observed using
various decarboxylative processes,14b-d we first checked the
toluene as solvent.
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The apparent lack of selectivity of most organocatalysts lead Lewis acids.15 In addition, in our process, goVoiedw AlertivcleelOsnlionef
DOI: 10.1039/C9SC05196A
us turn our attention to the alternative use of Lewis acids such enantiocontrol are obtained regardless of the Cu/L* ratio
as chiral copper complexes, initially introduced in indicating that the kinetic of aldolization by the generated
decarboxylative aldolizations by the group of Shair.17 chiral copper complex is much faster than the basic BOX ligand
Disappointingly, phosphine containing ligand L1 or different or Cu(OTf)2 alone (entries 10-11).19
bis-oxazolines (BOX) ligands containing isopropyl, tert-butyl or More surprisingly, determination of the absolute configuration
benzyl substituents (L1-4) were totally unable to control the of the ketodiol (vide infra), indicated that the same Cu/L5
stereoselectivity of the aldolization forming 4a as a racemate combination was inducing an opposite sense of
and a 1:1 anti-meso mixture (entry 4). In sharp contrast, enantioinduction compared to previously disclosed results by
phenyl substitution in L5 dramatically changed the transition Shair on the aldolization using aliphatic aldehydes.17c,d Control
state of the aldolization providing 4a in 4:1 dr and 88% ee experiment performing the reaction on aliphatic aldehyde
5,
(entry 5). Of interest, the stereopurity of the ketodiol could be indicated that the aldol product was formed without any
6
easily improved by purification through simple recrystallization stereocontrol using the same conditions as for perfluorinated
(32:1 dr and 97% ee). Finally, increasing the flexibility by aldehyde 1a (Scheme 2, (a)).
removing the gem-dimethyl linker in L6 slightly decreased the
O
selectivity providing 4a in 62% ee of the opposite enantiomer
(entry 6).
5
OH
O
OH
Cu(OTf)2 (10 mol%),
L5 (13 mol%)
H
(a)
O
O
O
This unique enantiocontrol using the simple phenyl substituted
BOX ligand L5 is in contrast to previous studies on
aldolization,17c,d,18 and suggests interactions between the
aromatics and the perfluorinated chains during the
enantiodetermining step.
In order to further understand this mechanism, several control
experiments were also performed. Using Cu(OTf)2 alone, 4a
was formed in a 1:1 dr, indicating that the creation of the
second stereocenter is not arising from substrate control but
from a control by the chiral ligand (entry 7). Using L5 alone as
reported by Ma,12f 4a could be formed after prolonged
reaction time albeit without any diastereo- or enantiocontrol,
confirming the role of the copper complex (entry 8).
6
THF, rt, 5 h
31% yield
0%
ee
dr
HO
OH
1:1
2
O
H2O
H
OH
O
OH
Cu(OTf)2 (10 mol%),
L5 (13 mol%)
Cl3C
O
7
(b)
Cl3C
CCl3
O
O
8
THF, rt, 4 h
68% yield
90% ee
HO
OH
4:1 dr
2
Scheme 2 Bi-directional aldolization with other aldehydes
In order to better understand the interactions ongoing in our
bi-directional aldolization, we subjected chloral hydrate
the same conditions. Through the use of Cu(OTf)2
combination, ketodiol diol
and 90% ee (Scheme 2, (b)). Of importance, this
7
to
/
L5
Adding 4 Å molecular sieves to the reaction did not change the
enantioselectivity (86% ee) while considerably decreasing the
yield (33%, Table 1, entry 9). This suggests that the water
present does not interfere in the transition state but might
8 was formed in 68% yield, 4:1 dr
hexachlorinated ketodiol
8
is the structure of a natural product
considerably
catalyst
possibly through copper
complex protonation.
In sharp contrast to the
aldolization reported by
help
turn-over
a) Catalytic cycle:
O
CO2
H2O
H
*
*
TfOH
+ H2O
L
L
Rf
L
L
Cu
Cu
O
O
O
O
Ligand exchange
CO2H
CO2H
Aldolization (TS)
and decarboxylation
OTf
Rf
*
O
*
C
L
L
B
L
L
Deprotonation
Cu
Cu
O
aldehydes,
excess
Cu*
O
OH
O
O
Shair
on
aliphatic
where
was
CO2H
O
Aldolization
Rf
O
*
(catalyst control)
*
BOX
A
D
OTf
L
L
and decarboxylation
L
L
Cu
responsible for the
deprotonation of the
pro-nucleophile,17c,d use
Cu
OH
O
O
O
OH
O
O
OH
OH
OH
Rf
H2O
H
Rf
Protonation
Rf
Rf
Rf
Rf
CO2
2
Rf
F
E
+ H2O
of
ligand is not necessary
to obtain good
a large excess of
proton source
b) Postulated transition state (TS):
a
(1) favored
(2) unfavored
O
efficiency during this
transformation (entries
10-11). This is in
agreement with the
reported reactivity of
ketodiacid
requiring any base for
its activation by simple
O
N
O
H
N
O
N
H
F
Cu
H
N
F
H
F
F
O
Cu
O
F
O
F
O
O
OH
O
F
OH
F
F
HO2C
F
F
HO2C
F
2
not
F
F
Scheme 3: Proposed catalytic cycle and postulated transition state
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that might explain the observed toxicity of oxitropis common Insertion of linear alkyl chain (10), aromatic (11)Voierw tAertirctle-bOunltinyel
feed plants.20 The corresponding racemic molecule had already groups (12-14) were possible providing tDhOeI:11,03.1-k0e39to/Cls9SiCn0751696toA
been
desymmetrization, highlighting the synthetic potential of this complex, much higher reaction TOF is observed as compared
enantioselective preparation of 8 21 to previous studies.12d,f Indeed, full conversion is obtained
prepared
and
further
derivatized
through 96% ee. It must be pointed out that using the chiral copper
.
Altogether, these results suggest that the present process is after only few hours vs. 4-7 days for the previous works, a
mechanistically distinct from previous Cu/BOX-catalyzed strong improvement leaving room for optimization of the
decarboxylative aldolizations with non-fluorinated aliphatic conditions to adjust better the apparent results to the
aldehydes pointing out
substituent of the ligand.
a
crucial role of the aromatic different keto-acid structures. Finally, single crystal X-ray
diffraction of 14 confirmed the absolute configuration of the
A catalytic cycle for the bi-directional aldolization taking into obtained products.24
account all these observations is depicted in Scheme 3. From
the carboxylic acid coordinated chiral complex
deprotonation provides the reactive enolate
A,
As
B
.
OH
O
OH
O
R
O
O
demonstrated previously, the aldolization event creating the
Rf
Rf
Cu(OTf)2 (10 mol%)
L5 (13 mol%)
17d
new stereocenter precedes the decarboxylation.15c,
With
4a-c
HO
OH
O
2
H2O
H
or
these experimental evidences, a potential preferred transition
state accounting for the unique stereocontrol is presented in
Scheme 3.b.(1). The crucial interaction governing the
enantiodiscrimination might arise from F-π aromatic repulsion
disfavoring transition state (2). This is further confirmed by the
THF, rt, 4 h
or
Rf
O
OH
O
O
1a-c
R
Rf
Rf = (CF2)nCF3
OH
10-14
9a-c
OH
O
OH
F
OH
O
OH
F
F
F
F
F
F
F
F
F
F
CF3
F3C
CF3
excellent result obtained using chloral
7 and eliminates a
F3C
4a
4b
F
F
F
F
F
F
F
discrimination through less conventional F-π aromatic
attractive interactions.22 In addition to additional interactions,
the better results obtained with halogenated aldehydes vs.
aliphatic ones might also originate from their higher
electrophilicity. This might favor a faster nucleophilic addition
prior to competing ligand exchange between the ketodiacid
F
F
54% yield
32:1 dr
97% ee
60% yield
11.5:1 dr
97% ee
OH
O
OH
O
OH
O
OH
F
F
F
F3C
CF3
CF3 Ph
CF3
7
F
4c
10
11
71% yield
11.5:1 dr
96% ee
59% yield
76% ee
33% yield
80% ee
and the chiral ligand.15b From the resulting enolate
exchange followed by the second catalyst controlled
aldolization-decarboxylation provides the new enolate . The
C, ligand
O
OH
F
O
OH
F
F
E
CF3
CF3
12
13
F
control of the second aldolization event by the chiral ligand is
responsible for an overall increase in the enantiomeric excess
on the product at the expense of the diastereoselectivity
through an amplification of chirality.23 At this stage, enolate
protonation potentially assisted by the water coming from the
57% yield
96% ee
54% yield
82% ee
O
OH
F
F
CF3
F
F
F
F
14 (Cu/L5 1/1)
58% yield
80% ee
aldehyde hydrate source provides alcoholate
exchange with a new molecule of keto-diacid
F
2
. Final ligand
liberates the
Scheme 4 Scope of the copper catalyzed enantioselective
enantioenriched product and regenerates the active catalytic
specie
aldolization with perfluorinated aldehydes
A
.
With a convenient method to directly access the desired
enantioenriched ketodiols, simple sodium borohydride
reduction provided the three different perfluorinated 1,3,5-
triols 3a-c with different lateral chains length (Scheme 5). Of
interest, all three triols were crystalline, allowing the
preparation of these crucial compounds in good yield and
nearly perfect stereocontrol (11.5:1 to 30:1 dr and >96% ee) by
a simple recrystallization. Single crystal X-ray diffraction of triol
3c also further confirmed the absolute configuration.24 Of
importance, in the crystal assembly, the molecular packing is
stabilized through several fluorine atom acting as hydrogen
bond acceptors, adding new evidences to the long debate on
the existence of such interactions.25
With the optimized conditions in hand, different ketodiols 4a-c
possessing perfluorinated chains of different length were
prepared through the bi-directional cascade (Scheme 4).
Reaction conditions tolerated the insertion of perfluorinated
chains of C1 (4c), C3 (4a) or C4 (4b) length. In addition, in all
cases the ketodiols were generated in good yields (54-71%
yield) and good to excellent diastereo- and enantiocontrols
(11.5:1 to 32:1 dr and 96-97% ee). Of particular interest, the
developed conditions are amenable to scale up (25 mmol of
starting
1
)
without tedious column chromatography
requirement while tolerating the presence of water arising
from the use of the commercial hydrate forms of the
perfluorinated aldehydes.
In addition to the bi-directional reaction, we also tested the
present conditions in the addition of different 1,3-keto-acids 9.
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(8100 M-1), a crucial parameter for further application of our
triols to other technologies.
OH
O
OH
OH
OH
OH
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DOI: 10.1039/C9SC05196A
NaBH4,
Rf
Rf
Rf
Rf
THF/MeOH,
0 °C, 30 min
3a-c
4a-c
Table 2 Anion binding properties of perfluorinated 1,3,5-triols
OH
OH
OH
OH
OH
OH
F
F
F
F
F
F
F
F
F
F3C
CF3
in CD3CN.a
F3C
CF3
3a
3b
F
F
F
F
F
F
F
F
F
F
F
93% yield
32:1 dr
89% yield
30:1 dr
N(n-Bu)4
X
97% ee
97% ee
CD3CN
H
O
H
OH
OH
OH
H
OH
OH
OH
N(n-Bu)4
O
O
+
X
F
F
F
Rf
Rf
Rf
Rf
3c
F
F
91% yield
11.5:1 dr
96% ee
F
O
O
O
O
O
P
P
Scheme 5 Reduction of the ketodiols and single crystal X-ray
diffraction of 3c
O
O
O
N(n-Bu)4
N(n-Bu)4
( )-15
S
( )-15
R
Perfluorinated 1,3,5-triols, new tools for selective
supramolecular recognition
3a
3b
3c
As mentioned in the introduction host molecules able to
recognize through supramolecular interactions different guests
are crucial for a wide array of applications. Most notably,
anion coordination is central for sensing, extraction, catalysis,
smart materials and for the discovery of innovative
therapies.26 In this context, identifying new non-charged
molecules for anion coordination is of crucial importance. For
this purpose, we initially tested the anion binding properties in
CD3CN of the three triols to the biologically relevant chloride
-
2100 M-1
3750 M-1
8100 M-1
1790 M-1
4.5
4400 M-1
K (Cl ) 25°C
K (S)-15
K (R)-15
nd
nd
nd
nd
nd
nd
K (S)-15/K (R)-15
-
a
The addition of X to the polyols resulted in large downfield shifts of the hydroxyl
1
hydrogens. Association constants from triplicate experiments were obtained by fitting
these spectroscopic data to 1 : 1 binding isotherm models, using the Thordarson
method.
anion through H NMR monitoring using Thodarsson's method
(table 2).27
All three triols provided remarkable chloride binding ability for
such poorly preorganized acyclic non-charged host, with 1:1
host:guest coordination constants ranging from 2100 to 4400
M-1. Most notably, the association constant did not follow a
linear behavior depending on the length of the fluorinated
chain, indicating that the electron-withdrawing character of
the side chain is not the single responsible for the enhanced
binding. Indeed, while the C1 (3c) and C4 (3b) perfluorinated
chains provided the higher constants, the C3 (3a) chain gave
lower binding.
With the excellent behavior of all three triols on the model
chloride anion, we next turned our attention to the more
challenging coordination to chiral anions. Molecule’s ability to
selectively recognize one enantiomer of a chiral guest is
fundamental for many important biological processes, as
different enantiomers often possess totally different biological
profiles but is also of importance for catalysis.28
Conclusions
Identifying new scaffolds and concomitantly discovering new
synthetic strategies to directly access them, represents a step
forward highlighting the maturity of organic chemistry. In this
manuscript, we have demonstrated that chiral perfluorinated
triols could be efficiently prepared diastereo- and enantio-
selectively through
a
copper-catalyzed bi-directional
decarboxylative aldolization followed by reduction. The use of
a phenyl substituted bis-oxazoline ligand provides unique
enantiocontrol through crucial aromatic-fluorine interactions.
The reaction occurs rapidly under mild conditions and
tolerates the presence of water. Furthermore, the reaction
could be extended to the preparation of naturally occuring
hexachlorinated ketodiol of great synthetic utility.
In addition, we have shown that the obtained perfluorinated
1,3,5-triols possess enhanced recognition ability. The strength
of the central triol framework ensures excellent anion binding
properties while the key molecules demonstrate the selective
chiral anion recognition ability of synthetic 1,3-polyols.
The present study opens broad perspectives for the
preparation of chiral fluorinated scaffolds. In addition, it also
broadens the possibilities offered by alcohol coordination with
strong implications ranging from biology to materials or
catalysis.
For this purpose, we choose to study 3b, possessing one of the
best binding constant and the longer perfluorinated chain for
potential interactions, to test fluorinated triols ability in chiral
recognition of model binol-phosphate derived anion 15 29
. Of
utmost importance, this triol was able to selectively recognize
both enantiomers of the phosphate 15, providing a K(S)/K(R) of
4.5, among the highest observed for such anion.5,6 This clearly
demonstrates for the first time the efficiency of acyclic polyols
scaffolds as platform for chiral recognition. In addition, the
anion binding constant with the major enantiomer is high
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P. Nicolet and D. Bonnet-Delpon, J. Org. Chem. 2011, 76, 1126;
d) J. Mendizabal, P. de March, J. Recasens, A. VirgiVliie,wAA.rtAicllveaOrnelinze-
Larena, J. Elguero and I. Alkorta, TetrahedDroOnI:,1200.11023,96/C89,S9C6045519;6eA)
M. Samet, A. Fattahib and S. R. Kass, Org. Biomol. Chem. 2015,
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Naubron, M.Giorgi, M. Yemloul, J-L. Parrain, J. Rodriguez and A.
Quintard, Chem. Eur. J. 2019, DOI: 10.1002/chem.201902983.
7 For a review, see: I. Colomer, A. E. R. Chamberlain, M. B.
Author contributions
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
Conflict of interest
Haughey and T. J. Donohoe. Nature Reviews Chemistry, 2017, 1,
A patent on the preparation and properties of perfluorinated
1,3,5-triols has been submitted by Céline Sperandio, Jean
Rodriguez and Adrien Quintard. Patent declaration. EP19
305862.5. Submitted 27 June 2019.
0088.
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Acknowledgement
The Centre National de la Recherche Scientifique (CNRS) and
the Aix-Marseille Université are warmly acknowledged for
financial support. All technical staff from Aix-Marseille
Spectropole are acknowledged for their support.
A. Narayama, Y. Abe and S. Iwasa, Chem. Commun. 2012, 48
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