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\DOI{10.5802/crchim.370}
\datereceived{2024-09-19}
\daterevised{2024-10-24}
\dateaccepted{2024-12-05}
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\dateposted{2025-02-21}
\begin{document}

\begin{noXML}

\CDRsetmeta{articletype}{clarification}

\title{Toolbox for emerging fluorinated groups}

\alttitle{Bo\^{i}te \`{a} outils pour les groupements fluor\'{e}s
\'{e}mergents}

\author{\firstname{Javid} \lastname{Rzayev}\CDRorcid{0009-0000-6615-6647}\IsEqualContrib}
\address{INSA Rouen Normandie, Univ Rouen Normandie, CNRS, Normandie
Univ, Institut CARMeN UMR 6064, INC3M FR 3038, F-76000 Rouen, France}

\author{\firstname{Zhenbang} \lastname{Chang}\CDRorcid{0009-0006-9758-463X}\IsEqualContrib}
\addressSameAs{1}{INSA Rouen Normandie, Univ Rouen Normandie, CNRS,
Normandie Univ, Institut CARMeN UMR 6064, INC3M FR 3038, F-76000 Rouen, France}

\author{\firstname{Tatiana} \lastname{Besset}\IsCorresp}
\addressSameAs{1}{INSA Rouen Normandie, Univ Rouen Normandie, CNRS,
Normandie Univ, Institut CARMeN UMR 6064, INC3M FR 3038, F-76000 Rouen, France}
\email[T. Besset]{tatiana.besset@insa-rouen.fr}

\shortrunauthors

\keywords{\kwd{Organofluorine chemistry}\kwd{Synthetic methodologies}\kwd{Eco-friendly transformations (C--H activation)}\kwd{Emergent functionalized fluorinated groups}}

\altkeywords{\kwd{Chimie du fluor}\kwd{M\'{e}thodes synth\'{e}tiques}\kwd{Transformations \'{e}co-compatibles (activation C--H)}\kwd{Groupements fluor\'{e}s fonctionnalis\'{e}s \'{e}mergents}}

\thanks{University of Rouen Normandy, INSA Rouen Normandy, Centre
National de la Recherche Scientifique (CNRS), European Regional
Development Fund (ERDF), Labex SynOrg (ANR-11-LABX-0029), Carnot
Institute I2C, Graduate School of Research XL-Chem (ANR-18-EURE-0020 XL
CHEM), Region Normandie, European Research Council (ERC) (grant
agreement no. 758710), French National Research Agency
(ANR-21-CE07-0035, ANR-21-CE07-0035-02, ANR-22-CE92-0083).}

\begin{abstract}
Organofluorine chemistry is a research field of rapid expansion. Due to
the unique properties of the fluorine atom and the fluorinated
residues, innovation is required to push forward the boundaries of this
very active research field by expanding the toolbox for emerging
fluorinated groups. In this account, an overview of our recent journey
in organofluorine chemistry is provided from the design of
CF\textsubscript{2}FG- and SCF\textsubscript{2}FG-containing reagents to their applications
in unprecedented \mbox{transformations}. 
\end{abstract}

\begin{altabstract}
La chimie des organofluor\'{e}s est un domaine de recherche en pleine
expansion. En raison des propri\'{e}t\'{e}s uniques de l'atome de fluor
et des r\'{e}sidus fluor\'{e}s, des solutions innovantes sont
n\'{e}cessaires pour repousser les limites de ce domaine de recherche
tr\`{e}s actif en \'{e}largissant la bo\^{i}te \`{a} outils pour les
groupes fluor\'{e}s \'{e}mergents. Cet article r\'{e}sume nos
r\'{e}centes contributions dans la chimie des organofluor\'{e}s, depuis
la conception de r\'{e}actifs contenant du CF\textsubscript{2}FG et du SCF\textsubscript{2}FG jusqu'\`{a} leurs applications dans des transformations in\'{e}dites.
\end{altabstract}

\maketitle
{\vspace*{.6pc}}

\twocolumngrid

\end{noXML}

\section{Introduction} \label{sec1}

The field of organofluorine chemistry is a vibrant research area in
which the quest for innovation towards molecular diversity is steadily
increasing{\break} \cite{1a,1b,1c,1d,1e,1f,1g,1h,1i,1j,1k,1l}; for
examples, see~\cite{1m,1n}. Indeed, the unique properties of the most
electronegative element of the periodic table to modify the physical
and chemical properties of the molecule~\cite{2a,2b}, in which it is
incorporated, render fluorinated molecules essential in various fields
including materials, agrochemical, and pharmaceutical
industries~\cite{3a,3b,3c,3d}. Incorporating fluorine-containing motifs
in the search for new drugs remains a powerful approach to developing
new products for enhanced societal benefits. To push beyond the
frontiers of knowledge, one paradigm was to design and study original
functionalized fluorinated moieties as a potent alternative to the
classical fluorine atom and the CF$_{3}$ group \mbox{generally} found
in molecules. Although the synthesis route to these newly designed 
fluorinated-group-containing molecules remains quite restricted
compared to the large number of existing fluorinated and
trifluoromethylated molecules, major advances have been made over the
years. Recently, attention has been focused on the CF$_{2}$H residue
and related groups (e.g., SCF$_{2}$H and OCF$_{2}$H groups)~\cite{4}.
In the quest to find original fluorinated moieties with unique
properties, the design of straightforward tools for the synthesis of
CF$_{2}$FG- and SCF$_{2}$FG-containing molecules has garnered
significant interest~\cite{5a,5b,5c,5d}. These fluorinated moieties are
appealing thanks to their unique properties, reactivity, degradation
pathways, and a high modularity potential (towards other fluorinated
moieties), and provide medicinal chemists a powerful toolbox for new
drug discovery. Hence, the research field has been rapidly growing over
the past years.\ Retrosynthetic disconnections to produce these
compounds might rely on different pathways, namely (1)~building the
fluorinated moieties and (2)~its direct incorporation into the target
molecules; we focused on the last approach with the synthesis of
suitable reagents. The account provides an overview of our main
contributions to the field with the design of original reagents and
their applications. Therefore, the review is organized according to the
nature of the fluorinated moieties and their applications. 

\vspace*{2pt}

\section{Design of CF$_{2}$SO$_{2}$Ph- and{\hfill\break}
CHFMe-containing reagents} \label{sec2}

\vspace*{2pt}

\subsection{Design of a bench-stable{\hfill\break}
PhSO$_2$CF$_2$-containing reagent{\hfill\break} for C--H
electrophilic{\hfill\break}
(phenylsulfonyl)difluoromethylation~\cite{6}} \label{sec2.1}

\vspace*{2pt}

In our quest towards emergent fluorinated groups, we focused on the
PhSO$_{2}$CF$_{2}$ residue. The latter is an important precursor of
fluorinated units of interest including difluoromethyl
(HCF$_{2}$), difluoromethylene (--CF$_{2}$--), and 
difluoromethylidene (${=}$CF$_{2}$) groups. Different approaches have
been developed to build up a PhSO$_{2}$CF$_{2}$--C bond. While most of
them relied on the use of nucleophilic sources of the
(phenylsulfonyl)difluoromethyl residue or via radical
processes, the number of electrophilic sources is in sharp contrast
rather limited. Pioneering works have been conducted by the groups of
Hu~\cite{7a,7b,7c} and Shibata~\cite{8}. With an electrophilic source derived
from hypervalent iodine, Hu and co-workers developed an efficient
reagent for the functionalization of thiols as well as in
copper-catalyzed vinyl and allyl (phenylsulfonyl)difluoromethylation
reactions. In the case of Shibata, the functionalization of C(sp$^{3}$)
centers of ${\upbeta}$-ketoesters, ${\upbeta}$-diketones, and
dicyanoalkylidenes was achieved thanks to a sulfonium salt. 
Inspired by these major advances, we synthesized a
{\fontsize{9.7}{11.7}\selectfont\textit{S}-([phenylsulfonyl]difluoromethyl)dibenzothiophenium}
salt (Scheme~\ref{sch1}). Key features related to this electrophilic
reagent are large-scale synthesis (an approximately 40 g scale without
the need for ozone depleting reagents)~\cite{9a,9b} and 
three-step/one-purification synthesis from suitable biaryl disulfide
and (difluoromethyl)sulfonylbenzene in 51\% overall yield with an
estimated global cost of about 10.6~{\texteuro}/g. Thanks to a
transition metal free process, the
(phenylsulfonyl)difluoromethylation of various
classes of compounds was successfully achieved. A~panel of
aniline derivatives and electron-rich (hetero)arenes as well as phenol
and anisole derivatives underwent this transformation. 
Moreover, the potential of reagent~\textbf{I} was further demonstrated
by the functionalization of C(sp$^{3}$)-centered nucleophiles and for
S--CF$_{2}$SO$_{2}$Ph bond formation. The synthetic utility of this
functionalized fluorinated moiety was illustrated by its conversion
into the high-value-added HCF$_{2}$ group, the late functionalization
of bioactive molecules, and the synthesis of lidocaine analogues
bearing either a CF$_{2}$H or a CF$_{2}$SO$_{2}$Ph motif.\ To ensure a
safe process, the stability of this reagent and key intermediates of
its synthesis was studied by differential scanning calorimetry
measurements \cite{9a,9b}.

\begin{scheme*}
{\vspace*{-.2pc}}
\includegraphics{sc01}
{\vspace*{.5pc}}
\caption{\label{sch1}Design of a bench-stable
PhSO$_{2}$CF$_{2}$-containing reagent~\textbf{I} for C--H electrophilic
(phenylsulfonyl)difluoromethylation. (a)~Reaction conditions: aniline
(3~equiv.), \textbf{I} (0.3~mmol, 1~equiv.), CH$_{2}$Cl$_{2}$,
21~{\textdegree}C, 24~h, Ar. (b)~Reaction conditions: phenol
derivatives or (hetero)arenes (1.5~equiv.), \textbf{I} (1.0~equiv.),
DMF, 50~{\textdegree}C, 3~h, Ar.}
{\vspace*{-.8pc}}
\end{scheme*}

\looseness=-1
We then explored other applications of this reagent to delineate its
potential~\cite{10}. As part of our ongoing research about 
transition-metal-catalyzed C--H bond functionalization, 
\textit{S}-([phenylsulfonyl]{\ubreak}difluoromethyl)dibenzothiophenium
salt \textbf{I} was applied as an electrophilic source for the first
copper-catalyzed (phenylsulfonyl)difluoromethylation of the
vinylic-C(sp$^{2}$)--H bond of acrylamides under robust reaction
conditions (80~{\textdegree}C, air; Scheme~\ref{sch2}). Using a native
functional group, the transformation turned out to be completely
\textit{Z}-selective. To further showcase the interest in this method
from an industrial perspective, a copper-mediated alternative was also
smoothly developed. Mechanistic studies supported by DFT calculations
enabled identifying the true nature of the active catalyst and shed
light on the critical roles of TFA and NMF used as additives in the
reaction. 

\begin{scheme*}
{\vspace*{-.2pc}}
\includegraphics{sc02}
{\vspace*{.3pc}}
\caption{\label{sch2}Copper-catalyzed and mediated C--H
(phenylsulfonyl)difluoromethylation of acrylamides.}
{\vspace*{-1.3pc}}
\end{scheme*}

\subsection{Original synthetic pathway for the synthesis of
OCHFMe~\cite{11}} \label{sec2.2}

Due to the recent demand for the OCF$_{3}$ group, there is strong
interest in providing synthetic tools for the efficient synthesis of
OCHFMe-containing molecules (Scheme~\ref{sch3}). With this in mind, we
developed the synthesis of novel reagent~\textbf{II}, an electrophilic
source of CHFMe. The bench-stable, air- and moisture-tolerant
sulfonium salt~\textbf{II} was prepared as a 3:1 mixture of
diastereoisomers from thiophenol in five steps. The functionalization
of a variety of phenols and alcohols was smoothly
achieved with a good functional group tolerance (CN, ketone, ester, and
nitro groups). The functionalization of heterocyclic derivatives is of
high importance in pharmaceutical and agrochemical research as
illustrated with 3-hydroxyquinoline. Under the same reaction
conditions, homobenzylic alcohol was converted into the OCHFMe
derivative in 59\% yield. Interestingly, the approach was further
applied to construct the SCHFMe motif. It is worth mentioning that
these thiophenols can be further converted into the corresponding
sulfones.

\begin{scheme*}
\includegraphics{sc03}
\caption{\label{sch3}Synthesis of an electrophilic source \textbf{II}
of CHFMe and applications. (a)~Reaction conditions: reagent~\textbf{II}
(1.0~equiv.), ROH (1.2~equiv.), Cs$_{2}$CO$_{3}$ (1.2~equiv.), MeCN,
rt, 16~h. (b)~Reaction conditions: reagent~\textbf{II}
(1.0~equiv.), RSH (1.2~equiv.), Cs$_{2}$CO$_{3}$ (1.2~equiv.), MeCN,
rt, 16~h. (i)~\textit{m}CPBA, CH$_{2}$Cl$_{2}$, rt, 2~h.}
{\vspace*{-1.5pc}}
\end{scheme*}

\section{Original reagents as sulfur-containing{\hfill\break}
fluorinated group sources} \label{sec3}

The design for unprecedented reagents as sources of sulfur-containing
fluorinated groups has garnered interest, and key players in the field
have been particularly active in providing new synthetic
tools{\break} \cite{5a,5b,5c,5d}.

In the past years, we have pursued our longstanding aim of developing
synthetic routes to difluoromethylthiolated
scaffolds.\ Hence, we have
\mbox{designed} and synthesized a library of reagents, capable of
acting as both electrophilic and radical sources of SCF$_{2}$FG
residues (FG ${=}$ PO(OEt)$_{2}$, CO$_{2}$Et). These reagents have opened
up new vistas in reactivity and possible transformations beyond what
could historically be achieved using nucleophilic sources, widening
further the chemical space of functionalized fluorinated molecules.
Proving an array of original CF$_{2}$FG and SCF$_{2}$FG sources would
be useful for the organic and medicinal chemist, providing 
tools for exploring new chemical spaces as well as offering new
perspectives in drug discovery programs. We believe that innovation and
future developments related to the residues of the non-persistent
fluorinated moieties CF$_{2}$R and SCF$_{2}$R will constitute an
interesting and promising lead to follow for developing new products
for enhanced societal benefits.

\subsection{New tools for forging C--SCF$_{2}$PO(OEt)$_{2}${\hfill\break}
bonds~\cite{12a,12b}} \label{sec3.1}

In recent years, there has been considerable interest in the synthesis
of molecules substituted with SCF$_{2}$H and SCF$_{2}$FG (FG ${=}$
functional group). Conventional methods involve introducing the
CF$_{2}$H motif onto sulfur derivatives. However, since 2015, new tools
have enabled the direct introduction of SCF$_{2}$H and SCF$_{2}$FG
moieties, which is a considerable advance. In this context, we chose to focus on
the SCF$_{2}$PO(OEt)$_{2}$ moiety, a novel fluorinated moiety
(Hansch--Leo parameter ($\uppi$) of~0.76). Indeed, benefiting from an
efficient route to prepare anilines \textit{N}-substituted with an SCN
group~\cite{13}, we synthesized a new electrophilic reagent \textbf{III} enabling
the introduction of the SCF$_{2}$PO(OEt)$_{2}$ group starting from 
\textit{N}-SCN-mesityl aniline via the in situ
generation of a CuCF$_{2}$PO(OEt)$_{2}$ species
(Scheme~\ref{sch4})~\cite{12a}.

\begin{scheme*}
\includegraphics{sc04}
{\vspace*{.9pc}}
\caption{\label{sch4}Synthesis of an electrophilic
SCF$_{2}$PO(OEt)$_{2}$-containing reagent and the study of its
applications. Reaction conditions: (i)~CH$_{3}$COCl (3.0~equiv.),
reagent~\textbf{III} (1.8~equiv.), NMP, 25~{\textdegree}C, 18~h, air.
(ii)~TsOH (2.5~equiv.), reagent~\textbf{III} (1.2~equiv.),
CH$_{2}$Cl$_{2}$, 25~{\textdegree}C, 2~h, air. (iii)~MsOH (1.2~equiv.),
reagent~\textbf{III} (1.0~equiv.), CH$_{2}$Cl$_{2}$, 25~{\textdegree}C,
14~h, air. (iv)~TFA (1.2~equiv.), reagent~\textbf{III} (1.2~equiv.),
CH$_{2}$Cl$_{2}$, 40~{\textdegree}C, 24~h, air. (a)~BiCl$_{3}$
(2~equiv.), reagent~\textbf{III} (1.2~equiv.), H$_{2}$O (2~equiv.),
DCE, 45~{\textdegree}C, 40~h, Ar. (b)~BiCl$_{3}$ (1.8~equiv.),
reagent~\textbf{III} (1.2~equiv.), H$_{2}$O (1.8~equiv.), DCE,
60~{\textdegree}C, 6~h, Ar.}
{\vspace*{-.25pc}}
\end{scheme*}

This reagent was shown to introduce the SCF$_{2}$PO(OEt)$_{2}$ group
onto a number of nucleophiles. First, the electrophilic character of
this reagent was evaluated in Friedel--Crafts reactions. In this way,
several electron-rich indole or aromatic derivatives could be
functionalized. This reaction was extended to the functionalization of
acetophenone derivatives or a $\upbeta$-ketoester. Remarkably, the
transfer of this motif from the reagent to other primary and secondary
anilines, was also achieved. Finally, the synthesis
of non-symmetrical disulfides was carried out and aromatic,
heteroaromatic, and benzylic derivatives were obtained. Furthermore, to
demonstrate the synthetic utility of our approach, we synthesized
diflumidone in three steps from 3-aminobenzophenone in 74\% overall
yield, hitherto synthesized in 28\% yield from the same aniline. With
this new electrophilic source \textbf{III} in hand, we turned our
attention to the functionalization of other classes of compounds, in
particular unsaturated alkene and alkyne derivatives enabling the
formation of C(sp)--, C(sp$^{2}$)--, and
C(sp$^{3}$)--SCF$_{2}$PO(OEt)$_{2}$ bonds. A BiCl$_{3}$-mediated
difunctionalization reaction of alkynes and alkenes enabled the
synthesis of many novel aliphatic and vinyl molecules substituted with
the SCF$_{2}$PO(OEt)$_{2}$ moiety (40~examples, up to 89\% yield). In
addition, an original and selective synthetic route for obtaining
alkynes featuring the SCF$_{2}$PO(OEt)$_{2}$ motif has been
developed~\cite{12b}.

Although reagent \textbf{III} is effective in many reactions, some
synthetic limitations remain.\ As a result, a novel source of
SCF$_{2}$PO(OEt)$_{2}$ enabled to be used in radical
processes~\cite{5c} was developed~\cite{14}.\ Thus \textit{S}-(diethyl
phosphonodifluoromethyl)benzenesulfonothioate, reagent~\textbf{IV}, was
synthesized in one step from reagent~\textbf{III} in the presence of
sodium \textit{para}-toluenesulfinate in acetic acid for 16~h at room
temperature (Scheme~\ref{sch5}). The process is robust as \textbf{IV}
was isolated in 81\% yield on a 1.13~mmol scale and 89\% yield on a
3.25~mmol scale. We studied the stability of reagent~\textbf{IV}.
Although its decomposition was observed in the presence of various
bases in dichloromethane as a solvent, \textbf{IV} was quite stable
under acidic conditions. The functionalization of a wide variety of
aldehydes with NaN$_3$ and PIFA in EtOAc (26~examples, up to 87\%
yield) and the synthesis of unsymmetrical (hetero)aromatic, benzylic,
and aliphatic disulfides (12~examples, up to 91\% yield) were smoothly
achieved  in the presence of LiBr in HFIP.

\begin{scheme*}
{\vspace*{-.6pc}}
\includegraphics{sc05}
\caption{\label{sch5}Synthesis of \textit{S}-(diethyl
phosphonodifluoromethyl)benzenesulfonothioate and its applications.}
{\vspace*{-1.6pc}}
\end{scheme*}

\subsection{Extension to SCF$_{2}$CO$_{2}$Et residues}
\label{sec3.2}

Intrigued about the potential of these ArSO$_{2}$SCF$_{2}$FG reagents,
we investigated the SCF$_{2}$CO$_{2}$Et series (Scheme~\ref{sch6})
\cite{15}.\ A library of
[(ethoxycarbonyl){\ubreak}difluoromethyl]arylsulfonothioate reagents was
synthesized efficiently regardless of substitution patterns and the
nature of substituents (11 examples, up to 98\% yield) using an 
in-house \mbox{synthesized} PhNHCF$_{2}$CO$_{2}$Et reagent~\cite{16}.\ 
To valorize this library of reagents,
(ethoxycarbonyl){\ubreak}difluoromethylthiolation of benzaldehyde was
achieved in the presence of PIFA, sodium azide, and the designed
reagents. It turned out that the nature of substituents on these
reagents strongly impacted the efficiency of the transformation with
aldehydes. Thus, an efficient synthetic route to
(ethoxycarbonyl)difluoromethylthioesters was developed using 
reagent~\textbf{V} (11~examples, up to 93\% yield), broadening the
chemical space of SCF$_{2}$CO$_{2}$Et-containing
molecules.\looseness=-1

\begin{scheme*}
\includegraphics{sc06}
{\vspace*{.75pc}}
\caption{\label{sch6}Synthesis of a library of
[(ethoxycarbonyl)difluoromethyl]arylsulfonothioate reagents and the synthesis route to
(ethoxycarbonyl)difluoromethylthioesters.}
{\vspace*{-1.8pc}}
\end{scheme*}

\begin{scheme*}
{\vspace*{-.2pc}}
\includegraphics{sc07}
{\vspace*{.2pc}}
\caption{\label{sch7}Construction of a carbon--SCF$_{2}$R bond on
aliphatic alcohols at a distal position via a 1,5-hydrogen atom
transfer.}
{\vspace*{-.5pc}}
\end{scheme*}

\subsection{Application of designed reagents to {\hfill\break} distal
functionalization of unactivated{\hfill\break} C(sp$^{3}$)--H bond}
\label{sec3.3}

{\vspace*{-2pt}}

The newly designed reagents \textbf{IV} and \textbf{V} were also
successfully applied to the challenging distal \mbox{C(sp$^{3}$)--H}
bond functionalization by means of a HAT process (Scheme~\ref{sch7}).
Indeed, primary, secondary, and tertiary alcohols were selectively
functionalized at the $\updelta$-position by various fluorinated groups
(SCF$_{3}$, SCF$_{2}$H, SCF$_{2}$PO(OEt)$_{2}$, and
SCF$_{2}$CO$_{2}$Et)~\cite{17a,17b}. This metal-free process was
possible thanks to the astute use of phenyliodine(III) diacetate (PIDA)
under blue light irradiation~\cite{18}.

{\vspace*{-2pt}}

\section{Conclusion} \label{sec4}

{\vspace*{-2pt}}

Over the years, synthetic developments have been made to push forward
the boundaries of organofluorine chemistry, especially a new trend
based on functionalized fluorinated residues. In this account, an
overview of our recent contributions to expand the toolbox for emerging
fluorinated groups is \mbox{provided.} By breaking away from the traditional
fluorine atom and trifluoromethyl group, these newly designed
fluorinated groups provide new opportunities by bringing about a high
degree of modularity. Although in its infancy, the design of tools and
synthetic transformations to produce functionalized fluorinated
residues will offer interesting perspectives for drug discovery
together with more sustainable fluorinated molecules and key solutions
to face contemporary societal challenges.

{\vspace*{-3pt}}

\section*{Declaration of interests}

{\vspace*{-3pt}}

The authors do not work for, advise, own shares in, or receive funds
from any organization that could benefit from this article, and have
declared no affiliations other than their research organizations.

{\vspace*{-3pt}}

\section*{Acknowledgments}

{\vspace*{-3pt}}

This work has been partially supported by University of Rouen Normandy,
INSA Rouen Normandy, \mbox{Centre} National de la Recherche
Scientifique (CNRS), \mbox{European} Regional Development Fund (ERDF), Labex
SynOrg (ANR-11-LABX-0029), Carnot Institute I2C, Graduate School of
Research XL-Chem (ANR-18-EURE-0020 XL CHEM), and Region Normandie. TB
thanks the European Research Council (ERC) under the European Union's
Horizon 2020 research and innovation program (grant agreement no.
758710). JR thanks the French National Research Agency
(ANR-21-CE07-0035) for a doctoral fellowship. ZC thanks the CSC for a
doctoral fellowship. The French National Research Agency
(ANR-21-CE07-0035-02 and ANR-22-CE92-0083) is gratefully acknowledged
for generous financial support.

\CDRGrant[ANR]{ANR-11-LABX-0029}
\CDRGrant[ANR]{ANR-18-EURE-0020 XL CHEM}
\CDRGrant[ERC]{758710}
\CDRGrant[ANR]{ANR-21-CE07-0035}
\CDRGrant[ANR]{ANR-21-CE07-0035-02}
\CDRGrant[ANR]{ANR-22-CE92-0083}

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