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\DOI{10.5802/crchim.420}
\datereceived{2025-09-02}
\daterevised{2025-09-05}
\dateaccepted{2025-09-08}
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\begin{document}

\begin{noXML}

\CDRsetmeta{articletype}{review}

\title{Cobalt-catalyzed cross-electrophile couplings: from
electrosynthesis to conventional chemistry}

\alttitle{Couplages \'{e}lectrophiles crois\'{e}s catalys\'{e}s au
cobalt : de l'\'{e}lectrosynth\`{e}se \`{a} la chimie conventionnelle}

\author{\firstname{Corinne} \lastname{Gosmini}\CDRorcid{0000-0002-1355-2301}}
\address{Institut de Chimie Mol\'{e}culaire et des Mat\'{e}riaux d'Orsay (ICMMO), 
CNRS UMR 8182, Universit\'{e} Paris-Saclay, B\^{a}timent Henri Moissan, 
17 avenue des Sciences, 91400 Orsay, France}
\email{corinne.gosmini@cnrs.fr}

\keywords{\kwd{Cobalt catalysis}
\kwd{Reductive and electroreductive cross-coupling}
\kwd{C--C bond formation}}

\altkeywords{\kwd{Catalyse au cobalt}
\kwd{Couplage crois\'{e} r\'{e}ducteur et \'{e}lectror\'{e}ducteur}
\kwd{Formation de liaison C--C}}

\begin{abstract}
Cobalt-catalyzed reductive cross-couplings, also known as
cross-electrophile couplings (XECs), have emerged as a valuable and
sustainable alternative to classical cross-coupling strategies. Unlike
traditional methods relying on preformed organometallic reagents,
cobalt catalysis enables the direct coupling of two electrophiles,
offering broad functional group tolerance, access to diverse
C(sp\textsuperscript{2})--C(sp\textsuperscript{2}), C(sp\textsuperscript{2})--C(sp\textsuperscript{3}), and
C(sp\textsuperscript{3})--C(sp\textsuperscript{3}) bonds, and compatibility with mild conditions.
Building on early electrochemical studies, significant progress has
been made in both electrosynthesis (eXEC) and conventional approaches
(XEC), highlighting cobalt's cost-effectiveness, ecological advantages,
and complementary reactivity compared to nickel. This account
summarizes the development of cobalt-catalyzed reductive
cross-couplings, from pioneering contributions to recent advances, with
emphasis on mechanistic aspects and substrate scope.
\vspace*{-2pt}
\end{abstract}

\begin{altabstract}
Les couplages crois\'{e}s r\'{e}ducteur catalys\'{e}s par le cobalt,
\'{e}galement connu sous le nom de couplages crois\'{e}s
d'\'{e}lectrophiles (XEC), constituent une alternative durable et
efficace aux m\'{e}thodes classiques de couplage. Contrairement aux
approches traditionnelles reposant sur l'utilisation de r\'{e}actifs
organom\'{e}talliques pr\'{e}form\'{e}s, la catalyse au cobalt permet
l'assemblage direct de deux \'{e}lectrophiles. Elle pr\'{e}sente une
large tol\'{e}rance vis-\`{a}-vis des groupes fonctionnels et permet la
formation de liaisons C(sp\textsuperscript{2})--C(sp\textsuperscript{2}),
C(sp\textsuperscript{2})--C(sp\textsuperscript{3}) et C(sp\textsuperscript{3})--C(sp\textsuperscript{3}) dans des
conditions douces. \`{A} partir des premiers travaux r\'{e}alis\'{e}s
par \'{e}lectrosynth\`{e}se, d'importants progr\`{e}s ont \'{e}t\'{e}
r\'{e}alis\'{e}s tant en synth\`{e}se \'{e}lectrochimique qu'en chimie
conventionnelle, mettant en avant le faible co\^{u}t, l'empreinte
\'{e}cologique favorable et la r\'{e}activit\'{e} compl\'{e}mentaire du
cobalt par rapport au nickel. Cette revue r\'{e}sume le
d\'{e}veloppement de ces m\'{e}thodes, des contributions pionni\`{e}res
aux avanc\'{e}es r\'{e}centes, en insistant sur les aspects
m\'{e}canistiques et la diversit\'{e} des substrats.
\end{altabstract}

\editornote{Article submitted by invitation}
\alteditornote{Article soumis sur invitation}

\maketitle

\twocolumngrid

\end{noXML}

\xsection{}
Nowadays, the formation of carbon--carbon (C--C) bonds via
cross-electrophile coupling (XEC) or electrochemical cross-electrophile
coupling (eXEC), catalyzed by transition metals, has emerged as a
powerful and attractive strategy in synthetic 
chemistry~\cite{1a,1b,1c}. The construction of C--C bonds is
fundamental to the synthesis of a wide range of key molecules,
including pharmaceuticals, agrochemicals, and basic organic materials.
Compared to classic cross-coupling reactions involving the reaction of
an organometallic (nucleophile) with an electrophile in the
presence of a transition metal catalyst (notably palladium, as
recognized by the 2010 Nobel Prize in  Chemistry)~\cite{2}, XEC or eXEC
reactions offer several key advantages (Scheme~\ref{sch1}). Notably,
they eliminate the need for the preparation and handling of sensitive
organometallic compounds in stoichiometric amount, simplify
operations through one-step procedures, and exhibit broad functional
group 
\mbox{tolerance.}

\begin{scheme*}
\includegraphics{sc01}
\vspace*{4pt}
\caption{\label{sch1}Conventional cross-coupling vs  cross-electrophile
coupling.}
\vspace*{-10pt}
\end{scheme*}

Although cobalt-catalyzed cross-couplings with organometallic reagents
(e.g., Grignard {reagents} or zinc species) have been described, XECs
(previously called reductive or direct couplings) have emerged as a
robust and versatile  alternative~\cite{3a,3b,3c,3d}.  These reactions
enable the formation of diverse carbon--carbon and carbon--heteroatom 
bonds---including Csp$^{2}$--Csp$^{2}$, Csp$^{2}$--Csp$^{3}$,
Csp$^{3}$--Csp$^{3}$, and Csp--Csp$^{3}$ linkages---under mild
conditions, using two electrophilic partners such as stable halides or
pseudo-halogenated substrates. 

Prior to the emergence of modern XEC, eXEC of two 
electrophiles~\cite{4a,4b,4c} had already been explored, particularly
by P\'{e}richon and coworkers, predominantly using nickel 
catalysts~\cite{5}. These early contributions laid the foundation for
the development of a wide range of nickel-catalyzed eXEC methods.

In an effort to replace nickel with a more cost-effective and
environmentally benign alternative, we pioneered the use of cobalt in
electroreductive C--C bond formation via sacrificial anode 
processes~\cite{6}. Cobalt is particularly attractive due to its low
cost, broad functional tolerance, and improved ecological footprint
compared to nickel. Despite the increased accessibility of
electrosynthesis in recent years---thanks in part to the advent of
user-friendly equipment such as the IKA ElectraSyn---this technique was
historically regarded as more complex and less practical than
conventional synthetic methods, which significantly limited its
adoption within the organic chemistry community.

It is worth noting that the concept of XEC dates back to the 19th
century, with Wurtz's pioneering work using stoichiometric sodium metal
at elevated  temperatures~\cite{7}. However, such harsh conditions were
incompatible with many functional groups, which curtailed its utility.
To overcome the challenges associated with electrosynthesis or the use
of palladium at high  temperature~\cite{8a,8b}, we reported in 2003 the
first XEC of two distinct electrophiles under non-electrochemical
conditions, employing a first-row transition metal catalyst, Co, in
combination with metal reducers (Zn or  Mn)~\cite{9}. This approach
offered excellent functional group tolerance and operational
simplicity.

Since 2010, the field of XEC has witnessed substantial growth, with
many research groups initiating work in this area, primarily
concentrating on nickel-catalyzed  transformations~\cite{10a,10b,10c}.
These transformations typically use Ni(II) precursors along with either
metallic reductants (Zn, Mn) or homogeneous reductants such as
tetrakis(dimethylamino)ethylene  (TDAE)~\cite{11} or
bis(pinacolato)diboron (B$_{2}$pin$_{2}$)~\cite{12}. In contrast,
examples involving other metals---such as  Cu~\cite{13}, Fe~\cite{14},
or Cr~\cite{15}---remain comparatively rare. Photoredox catalysis has
also emerged as a complementary strategy to minimize the use of
stoichiometric metal reductants in  XECs~\cite{16a,16b}.

Despite being less extensively developed than nickel-catalyzed systems,
cobalt-catalyzed XECs have shown interesting complementary reactivity
and offer unique advantages in certain  transformations~\cite{17}.
Recognizing these advantages, we have pursued our studies on cobalt
catalysis, particularly for the formation of Csp$^{2}$--Csp$^{2}$,
Csp$^{2}$--Csp$^{3}$, and Csp$^{3}$--Csp$^{3}$ bonds.

This account highlights the contributions of our laboratory to the
development of cobalt-catalyzed reductive cross-coupling reactions for
the construction of C--C bonds from C--X (X ${=}$ Cl, Br, I), C--O, C--N,
and C--S bonds, using both electrochemical (eXEC) and conventional
(XEC) approaches.

These methods are operationally simple and robust. In the case of eXEC,
reactions are typically conducted in undivided cells equipped with an
iron anode and a nickel foam cathode, with the choice of anode proving
critical to the success of the reaction. Both electrochemical and
classical approaches are carried out in solvents such as acetonitrile
(CH$_{3}$CN) or dimethylformamide (DMF), with or without pyridine,
under inert atmosphere (argon) at room temperature or {moderate}
temperatures (up to 50~\textdegree C). The cobalt catalyst generally
consists of commercially available CoBr$_{2}$ or CoCl$_{2}$, with
negligible differences observed between these two salts.
Additionally, the use of ancillary ligands (e.g., bipyridine or
phosphines) is not always required, further simplifying the protocol.

\begin{scheme*}
\includegraphics{sc02}
\vspace*{6pt}
\caption{\label{sch2}Electroreductive cobalt-catalyzed cross-coupling
of functionalized phenyl halides with 4-chloroquinoline derivatives.}
\end{scheme*}

\begin{scheme*}
\includegraphics{sc03}
\vspace*{6pt}
\caption{\label{sch3}Synthesis of unsymmetrical biaryls by
electroreductive cobalt-catalyzed cross-coupling of aryl halides.}
\vspace*{-10pt}
\end{scheme*}

\section{Formation of C(sp$^{\xmathbf{2}}$)--C(sp$^{\xmathbf{2}}$) bonds}

\subsection{Biaryl formation}
Unsymmetrical biaryls are key structural motifs found in a broad range
of biologically active compounds, including natural products,
pharmaceuticals, functional materials, and 
agrochemicals~\cite{18a,18b,18c}.  Traditionally, their synthesis
involves the transition-metal-catalyzed cross-coupling of an aryl
halide with an organometallic reagent---such as arylboronic acids,
arylzinc, stannane, or Grignard derivatives---typically mediated by
palladium or nickel catalysts.

Pioneering work by Kharasch and coworkers has demonstrated that aryl
Grignard reagents can undergo efficient homocoupling in the presence of
catalytic amounts of first-row transition metal salts such as
cobalt(II) chloride  (CoCl$_{2}$)~\cite{19}. Beyond homocoupling,
cobalt has also proven to be an effective catalyst for cross-coupling
reactions between two different aryl partners. Notably,  Nakamura
et~al.~\cite{20}  and von Wangelin  et~al.~\cite{21}  have
independently showed that cobalt salts catalyze the cross-coupling
between aryl Grignard reagents and aryl or heteroaryl halides, enabling
the formation of unsymmetrical biaryls. This strategy has since been
extended to include aryl tosylates as electrophilic partners by using a
cobalt diisopropyl disubstituted bis(phosphino)pyridine pincer
($\mbox{}^{\mathrm{iPr}}$PNP)-based  
\mbox{catalyst~\cite{22}.}

In a complementary approach using commercially available precursors,
cobalt precatalysts bearing N-heterocyclic carbene (NHC) ligands, have
also been employed in Suzuki--Miyaura cross-coupling reactions of aryl
chlorides and bromides with 
\mbox{arylboronic} pinacol esters, activated in
situ with alkyllithium  reagents~\cite{23}.

To circumvent the need for stoichiometric organometallic reagents, the
first cobalt-catalyzed eXEC was developed for biaryl synthesis.
Initially, the method used aryl halides and 4-chloroquinolines as
electrophilic partners  (Scheme~\ref{sch2})~\cite{24}. This was later
expanded to include couplings between two distinct aryl halides 
(Scheme~\ref{sch3})~\cite{25}. In both cases, the reactions were
conducted in an undivided electrochemical cell equipped with an iron
anode and required pyridine as a ligand to activate the cobalt
catalyst.

\begin{scheme*}
\includegraphics{sc04}
\vspace*{4pt}
\caption{\label{sch4}Cobalt-catalyzed formation of unsymmetrical biaryl
compounds and proposed mechanism.}
\vspace*{-10pt}
\end{scheme*}

The aromatic moiety involved in these transformations can accommodate a
broad range of electron-donating and electron-withdrawing substituents.
In 2008, the cobalt-catalyzed synthesis of biaryls via eXEC was
successfully adapted to conventional chemical methods by changing some
parameters  (Scheme~\ref{sch4}). These included reactions between two
aryl halides or between an aryl halide and a heteroaryl halide with
comparable  reactivities~\cite{26}.  In this protocol, manganese powder
was employed as the reductant in a DMF/pyridine solvent system. The
cobalt(II) bromide (CoBr$_{2}$) catalyst, ligated with
triphenylphosphine (PPh$_{3}$), enabled the efficient formation of
unsymmetrical biaryls in good yields. With these adapted reaction
conditions, the proposed mechanism proceeds via a non-radical pathway.

We applied this strategy to the synthesis of 2-(4-tolyl)benzonitrile, a
key intermediate in the preparation of sartans---widely used
antihypertensive agents. More recently, we demonstrated that cobalt
catalysis could be extended to inert C--CN bond activation, thereby
enabling the challenging formation of biaryls from aryl halides and
benzonitriles---an approach that poses a greater synthetic challenge 
(Scheme~\ref{sch5})~\cite{27}.  In this system, the addition of
AlMe$_{3}$ to the reaction medium enhanced the reactivity of the
aryl--CN bond.

\begin{scheme}
\includegraphics{sc05}
\vspace*{4pt}
\caption{\label{sch5}Cobalt-catalyzed biaryl formation mediated by
C(sp$^{2}$)--CN bond activation.}
\vspace*{-10pt}
\end{scheme}

Combined DFT calculations and experimental studies revealed that the
reaction proceeds through the in situ generation of two low-valent
cobalt species: a Co(I) species that activates the aryl halide, and a
Co(0) species that facilitates the cleavage of the aryl--CN bond.
Consistent with earlier findings by Chatani  et~al.~in rhodium 
catalysis~\cite{28}, an intramolecular version of this transformation
was also shown to be feasible, albeit requiring prolonged reaction
times.

\subsection{Formation of vinyl arenes}
Although Heck et~al.~initially reported the formation of styrene in low
yield from vinyl acetate, via palladium catalysis, the first efficient
XEC between an aryl and a vinyl compound was achieved through
electrosynthesis using a sacrificial anode and cobalt catalysis. This
approach enabled, for the first time, the use of vinyl acetates as
reagents, compounds that are readily accessible from abundant carbonyl
precursors, inexpensive, stable, and environmentally benign.

Although being considered highly attractive alkenyl reagents, vinyl
acetates are rarely employed due to their low intrinsic reactivity.
Daves {and Arai} described the first direct Pd-catalyzed vinylation
starting from vinyl acetate and iodo compounds. However, poor yields
were  obtained~\cite{29a,29b}.  Our group was the first to report a
cobalt-catalyzed electrochemical vinylation of aryl halides using vinyl
acetates  (Scheme~\ref{sch6}). This reaction was performed in an
undivided cell equipped with an iron anode and a mixture of 
acetonitrile/pyridine~\cite{30}.  This method afforded good to
excellent yields, although it required a stoichiometric amount of
bipyridine, which remains a notable limitation.

\begin{scheme*}
\includegraphics{sc06}
\vspace*{6pt}
\caption{\label{sch6}Cobalt-catalyzed electrochemical vinylation of
aryl halides using vinylic acetates.}
\end{scheme*}

\begin{scheme*}
\includegraphics{sc07}
\vspace*{6pt}
\caption{\label{sch7}Cobalt-catalyzed vinylation of functionalized aryl
halides with vinyl acetates and proposed mechanism.}
\vspace*{-4pt}
\end{scheme*}

In 2005, we adapted this transformation to a conventional chemical
method using manganese as the reductant, this time employing only a
catalytic amount of bipyridine (Scheme~\ref{sch7})~\cite{31}.  The
proposed mechanism involves a six-membered transition state in which
the aryl group adds to the more substituted carbon of the double bond.

Later, Shu et~al.~described several nickel-catalyzed XECs for C--C bond
formation using alkenyl acetates as starting  materials~\cite{32}.

A similar strategy was applied to the synthesis of stilbenes from
$\rmbeta$-bromostyrenes and aryl halides 
(Scheme~\ref{sch8})~\cite{33}.  These compounds are of significant
interest due to their presence in the manufacture of industrial dyes,
dye lasers, optical brighteners, scintillator, other materials, and a
wide range of biologically active molecules, including resveratrol and
combretastatin. Stilbenes can be obtained via XEC between aryl halides
and bromostyrenes using cobalt catalysis. However, halostyrenes (X ${=}$
Cl or Br) are more reactive than vinyl acetates and must be added
dropwise to prevent dimerization.

\begin{scheme*}
\includegraphics{sc08}
\vspace*{4pt}
\caption{\label{sch8}Cobalt-catalyzed vinylation of aromatic halides 
using $\rmbeta$-halostyrenes.}
%\vspace*{-10pt}
\end{scheme*}

\begin{scheme*}
\includegraphics{sc09}
\vspace*{4pt}
\caption{\label{sch9}Access to functionalized benzotropones, azepanes,
and piperidines by reductive cross-coupling of  $\rmalpha$-bromo enones
with $\rmalpha$-bromo enamides.}
\vspace*{-10pt}
\end{scheme*}

Aryl bromides bearing electron-donating or electron-withdrawing groups
in the \textit{ortho}, \textit{meta}, or \textit{para} positions
afforded good yields. Moreover, this method proceeds with complete
retention of the double bond configuration, in contrast to reactions
catalyzed by nickel.

\subsection{Formation of 1,3-dienes}
1,3-Dienes are a prominent class of functional molecules with diverse
applications in materials science, natural product synthesis, and
pharmaceuticals. Recent years have seen significant progress in both
their synthesis and utilization. Beyond classic methods such as the
Wittig and Julia reactions, 1,3-dienes can be accessed through elegant
transition-metal-catalyzed coupling strategies. This includes
palladium-catalyzed Suzuki, Stille, and Heck reactions involving vinyl
halides, as well as transformations using alkynes, allenes, and
carbenes. Moreover, ruthenium-, iridium-, and palladium-catalyzed
processes offer straightforward access to 1,3-dienes as well.

Nickel-catalyzed XECs developed by Gong and Shu et~al.~allow the
formation of vinyl--vinyl frameworks from vinyl halides and vinyl
triflates, or between two vinyl  halides~\cite{34a,34b}. While
cobalt-catalyzed couplings using vinyl Grignard or vinyl zinc reagents
with vinyl halides, triflates, or acetates have been reported, the only
cobalt-catalyzed XEC between two vinyl compounds was described by Beng
et~al., involving $\rmalpha$-bromo enones and $\rmalpha$-bromo enamides
for the synthesis of azepanes, piperidines, and benzotropones
(Scheme~\ref{sch9})~\cite{35}.

\section{Formation of C(sp$^{\xmathbf{2}}$)--C(sp$^{\xmathbf{3}}$) bonds}
The earliest cobalt-catalyzed XEC leading to a Csp$^{2}$--Csp$^{3}$
bond formation was achieved via electrosynthesis, similar to
nickel-based systems. 

\subsection{Coupling of aryl  halides with allylic\newline compounds}
This initial transformation involving aryl halides and allyl acetates
was reported by electrosynthesis. 
\mbox{Unlike} nickel catalysis, which
required dropwise addition of reactive allyl chlorides or 
acetate~\cite{36},  the cobalt system allowed the addition of allyl
acetates at the beginning of the reaction, simplifying the procedure.
The reaction was conducted in an undivided cell with an iron anode,
using cobalt bromide as the catalyst in acetonitrile/pyridine 
(Scheme~\ref{sch10})~\cite{37}.

\begin{scheme*}
\includegraphics{sc10}
\vspace*{4pt}
\caption{\label{sch10}Cobalt-catalyzed electrochemical coupling between
aromatic halides and allylic acetates.}
\end{scheme*}

Aryl bromides bearing electron-donating or 
\mbox{-withdrawing} groups in
\textit{ortho}, \textit{meta}, or \textit{para} positions were well
tolerated. In contrast, aryl chlorides required electron-withdrawing
substituents. Heteroaryl substrates such as bromothiophenes or
chloroquinaldines were also compatible. Remarkably, unlike many other
methods, the major product was the linear isomer. This electrochemical
synthesis was patented in  2001~\cite{38}.  Due to the perceived
complexity of electrochemical methods at the time, we later developed a
conventional chemical variant. Although this reaction was the first XEC
involving a non-noble metal, yields were lower with substituted allyl
acetates compared to the electrochemical  approach~\cite{39}. Depending
on the nature of the halide on aryl moiety, conditions are different 
(Scheme~\ref{sch11}).

\begin{scheme*}
\includegraphics{sc11}
\vspace*{4pt}
\caption{\label{sch11}Cross-coupling between aryl halides and allylic
acetates using a cobalt catalyst.}
\vspace*{-7pt}
\end{scheme*}

\subsection{Coupling of aryl halides with benzylic\newline compounds}
Cobalt catalysis also enables coupling of aryl halides with benzylic
compounds. Prior to exploring XECs, Gosmini and Knochel jointly
demonstrated that  arylzinc~\cite{40}  or benzylzinc~\cite{41} 
reagents could react with benzyl chlorides or aryl halides,
respectively, under cobalt catalysis. However, these methods required
the use of preformed organozinc species.

To overcome this limitation, a direct cobalt-catalyzed reductive
arylation of benzyl chlorides with aryl halides was developed to
synthesize diarylmethanes---key motifs in pharmaceuticals,
agrochemicals, and supramolecular  chemistry~\cite{42}. This protocol,
which tolerates a wide range of functional groups, proceeds under mild
conditions (rt to 35~\textdegree C) in acetonitrile without the need
for ligands and uses pyridine as a cosolvent  (Scheme~\ref{sch12}).
Heteroaryl bromides were also successfully employed.

\begin{scheme*}
\includegraphics{sc12}
\vspace*{5pt}
\caption{\label{sch12}Cross-electrophilic coupling benzyl chlorides and
(Het)aryl bromides.}
\vspace*{-1pt}
\end{scheme*}

Due to environmental concerns associated with halides, alternative
electrophiles are being explored. Weix et~al.~reported a dual
Ni/Co-catalyzed coupling of benzyl mesylates with aryl halides
employing cobalt phthalocyanine as a radical  precursor~\cite{43}.
Inspired by this, our team demonstrated that benzyl
mesylates---generated in situ from benzylic alcohols---could replace
benzyl chlorides 
\mbox{using} simple cobalt bromide catalysis without ligands 
(Scheme~\ref{sch13})~\cite{44}. This method tolerates various
functional groups on both benzyl and aryl moieties.

\begin{scheme*}
\includegraphics{sc13}
\vspace*{5pt}
\caption{\label{sch13}Ni/Co or Co-catalyzed formation of functionalized
diarylmethanes from  benzyl alcohols and aryl halides.}
\vspace*{-2pt}
\end{scheme*}

More recently, this strategy was extended to bench-stable benzyl
sulfonium salts  (Scheme~\ref{sch14})~\cite{45}. Under conditions
similar to those optimized for mesylates, initial cross-coupling
reaction yields were low but improved significantly upon addition of
bipyridine. Mechanistic studies suggest that low-valent cobalt
activates both aryl halides and C--S bonds via single-electron
transfer, generating benzyl radicals.

\begin{scheme*}
\includegraphics{sc14}
\vspace*{5pt}
\caption{\label{sch14}Synthesis of diarylmethanes by cobalt-catalyzed
reductive cross-coupling via Csp$^{3}$--S bond activation.}
\vspace*{-7pt}
\end{scheme*}

\subsection{Coupling of aryl halides with non-activated alkyl
halides}
Earlier studies primarily utilized activated alkyl electrophiles such
as benzyl or allyl derivatives. Jacobi von  Wangelin  et~al.~used iron
or cobalt catalysis in combination with magnesium as a reductant to
expand the scope to non-activated alkyl halides. However, the
underlying mechanism involves the in situ formation of Grignard
reagents, which 
\mbox{inherently} limits the functional group tolerance of the
\mbox{reaction~\cite{46}.}

Later, a more versatile system based on 
CoBr$_{2}$/{\ubreak}iPr$_{2}$PhP/Mn in
DMF/pyridine at 30~\textdegree C was developed  (Scheme~\ref{sch15}).
This protocol tolerated functional groups and gave improved yields when
using monodentate phosphine ligands, in contrast to bidentate nitrogen
ligands. A slight excess of alkyl bromide was required, unlike the
stoichiometric amounts typically sufficient for more reactive alkyl
partners.

\begin{scheme*}
\includegraphics{sc15}
\vspace*{4pt}
\caption{\label{sch15}Cobalt-catalyzed alkylation of aryl halides.}
%\vspace*{-10pt}
\end{scheme*}

The mechanistic hypothesis is similar to other cobalt-catalyzed
diarylmethane formation  (Scheme~\ref{sch16}). The initiating step is
the reduction of the Co(II) precatalyst into the active low-valent
Co(I) species by manganese. Subsequent oxidative addition to the aryl
bromide forms an aryl Co(III) intermediate, which is reduced to
arylcobalt(II). At the same time, the reduction of alkyl compound leads
to the alkyl radical intermediate. Finally, the alkyl arylcobalt
complex, generated from the combination of the alkyl radical and the
arylcobalt complex, provides the cross-coupling product by reductive
elimination together with the regeneration of the active species Co(I),
closing the catalytic cycle.

\begin{scheme*} 
\includegraphics{sc16}
\vspace*{4pt}
\caption{\label{sch16}Proposed mechanism.}
\vspace*{-10pt}
\end{scheme*}

\subsection{Coupling of vinyl compounds with benzyl chloride}
Beyond aryl partners, vinyl halides can also be coupled with benzyl
chlorides. A cobalt/manganese system using CoBr$_{2}$(PPh$_{3}$)$_{2}$
was reported in acetonitrile with NaI as additive 
(Scheme~\ref{sch17}). Electron-withdrawing groups required elevated
temperatures (50~\textdegree C), while electron-donating groups allowed
reactions at 0~\textdegree C to room temperature. Lipshutz 
et~al.~\cite{47}  previously described a similar transformation using
palladium without organic solvents. More recently, Reisman  and
Cherney~\cite{48}  developed an enantioselective nickel-catalyzed 
cross-coupling of secondary benzyl chlorides with styrenyl bromides.
However, their method was not stereospecific: $Z$-alkenyl bromides
yielded exclusively $E$-products. In contrast, the cobalt/manganese
system preserved the stereochemistry of the starting\break material.

\begin{scheme*} 
\includegraphics{sc17}
\vspace*{4pt}
\caption{\label{sch17}Cobalt-catalyzed reductive cross-coupling between
styryl and benzyl halides.}
\vspace*{-3pt}
\end{scheme*}

\begin{scheme*} 
\includegraphics{sc18}
\vspace*{4pt}
\caption{\label{sch18}Co-catalyzed reductive allylation of alkyl
halides with allylic acetates  and carbonates.}
\vspace*{-9pt}
\end{scheme*}

\section{Formation of C(sp$^{\xmathbf{3}}$)--C(sp$^{\xmathbf{3}}$) bonds}
Reductive cross-coupling between two alkyl electrophiles has emerged as
a powerful strategy for constructing C(sp$^{3}$)--C(sp$^{3}$) bonds---a
long-standing challenge in organic synthesis due to issues such as
$\rmbeta$-hydride elimination and the control of the selectivity.
While nickel catalysis has traditionally dominated this field, cobalt
has recently gained attention as a sustainable and versatile
alternative, offering distinct reactivity profiles.

Historically, the Wurtz reaction was one of the earliest alkyl--alkyl
coupling methods. However, it was limited to the synthesis of
symmetrical alkanes due to uncontrolled radical formation. More modern
approaches involve the cross-coupling of alkylmetals with alkyl
halides, typically catalyzed by palladium or nickel. Yet, when using
non-activated alkyl halides, undesired $\rmbeta$-hydride elimination
often occurs due to slow reductive elimination, especially in the
absence of bulky electron-rich phosphine or N-heterocyclic carbenes
(NHC) ligands.

Nickel-catalyzed XECs have shown promise in suppressing
$\rmbeta$-hydride elimination by leveraging low-valent metal centers
under reducing  conditions~\cite{49}.   However, cobalt catalysis
offers complementary advantages, including broader functional group
tolerance and enhanced radical reactivity.

Cobalt complexes stabilized by ligands such as bipyridines,
phenanthrolines, or salen-type frameworks can mediate the coupling of
two unactivated alkyl halides in the presence of external reductants
like zinc or manganese. Alternatively, electrochemical reduction can
generate low-valent cobalt species in situ, eliminating the need for
sacrificial metals.

A key advantage of cobalt catalysis is its ability to suppress
homocoupling and promote cross-coupling selectivity, particularly when
using sterically or electronically differentiated electrophiles. Unlike
palladium, cobalt catalysts are more effective in radical-mediated
pathways and exhibit higher tolerance to functional groups.

\begin{scheme*}
\includegraphics{sc19}
\vspace*{5pt}
\caption{\label{sch19}Co-catalyzed cross-electrophile couplings of
benzyl sulfonium salts with allyl esters or ethers.}
\vspace*{-4pt}
\end{scheme*}

\begin{scheme*} 
\includegraphics{sc20}
\vspace*{5pt}
\caption{\label{sch20}Cobalt-catalyzed cross-electrophile couplings of
benzyl Katritzky salts with allyl esters or ethers.}
\vspace*{-8pt}
\end{scheme*}

\subsection{Coupling of alkyl halides with allyl acetates}
While cobalt-catalyzed homocoupling of non-activated alkyl halides has
been  reported~\cite{50},  
\mbox{heterocoupling} has also been
achieved---either between an activated and a non-activated alkyl
electrophile, or between two activated alkyl species such as benzyl or
allyl compounds.

In 2011, we reported the first reductive cobalt-catalyzed
Csp$^{3}$--Csp$^{3}$ formation by describing the allylation of alkyl
halides using either allyl acetates or allyl carbonates, depending on
the nature of the alkyl halide (Scheme~\ref{sch18})~\cite{51}.  The
reaction was effective with primary, secondary, and tertiary alkyl
substrates and was conducted in a mixture of acetonitrile and pyridine.

For reactive alkyl halides such as benzyl chlorides, alkyl iodides, or
alkyl bromides bearing  $\rmbeta$-electron-withdrawing groups, more
reactive allyl carbonates were preferred over acetates, and the
reaction temperature was lowered to 50~\textdegree C (versus
80~\textdegree C). With substituted allyl compounds, the linear product
was consistently favored. Experimental evidence supported the
involvement of alkyl radical intermediates.

\subsection{Coupling of activated alkyl compounds with allylic
compounds}
More recently, the cobalt-catalyzed reductive alkylation was extended
to other activated alkyl 
\mbox{electrophiles,} including benzyl sulfonium
salts and Katritzky pyridinium salts, and XEC of benzyl sulfonium salts
with $O$-allyl electrophiles, using simple CoBr$_{2}$ and Mn as
reductant in acetonitrile without ligands, was demonstrated 
(Scheme~\ref{sch19})~\cite{52}. This system activated both C--S bonds
(from sulfonium salts) and C--O bonds (from allyl esters or ethers),
enabling the synthesis of functionalized alkyl--olefinic compounds in
moderate to good yields. Notably, these reactions involved two
non-halogenated electrophiles---a first in cobalt-catalyzed C--C bond
formation. 

While nickel-catalyzed  cross-coupling reactions with Katritzky salts
had been described by Watson  et~al., Ni  et~al., and Rueping 
et~al.~\cite{53a,53b,53c}, they typically involved alkyl metals or aryl
halides. The only cobalt-catalyzed variant was reported by Kojima and
Matsunaga et~al.~via cobalt/organophotoredox dual catalysis, but it was
limited to secondary alkyl pyridinium  salts~\cite{54}.  A similar
transformation using benzylic Katritzky salts was also 
reported~\cite{55}.  This method offers a simple and efficient
alternative for synthesizing allyl--benzyl derivatives, using
CoBr$_{2}$, under mild conditions  (Scheme~\ref{sch20}). The reaction
was also applicable to allyl alkyl ethers, as 
\mbox{previously} shown with
benzyl sulfonium salts. Mechanistic studies suggest the formation of
benzyl radicals from pyridinium or sulfonium salts, and
$\rmpi$-allylcobalt intermediates from allyl compounds.

Benzyl sulfonium salts were also shown to couple with benzyl chlorides
or alkyl iodides, yielding functionalized alkyl  derivatives~\cite{56} 
(Scheme~\ref{sch21}). Preliminary mechanistic investigations suggest
the involvement of two radical species---one from the sulfonium salt
and the other from the alkyl halide.

\begin{scheme*} 
\includegraphics{sc21}
\vspace*{6pt}
\caption{\label{sch21}Cobalt-catalyzed cross-electrophile couplings of
benzyl sulfonium salts with alkyl iodides or benzyl chlorides.}
\vspace*{-8pt}
\end{scheme*}

\section{Conclusion}
Cobalt-catalyzed reductive cross-coupling, also known as
cross-electrophile coupling (XEC), represents a powerful and
sustainable approach for constructing C(sp$^{2}$)--C(sp$^{2}$),
C(sp$^{2}$)--C(sp$^{3}$), and C(sp$^{3}$)--C(sp$^{3}$) bonds from
readily available precursors. This {method} stands out for its ability
to activate non-halogenated electrophiles (e.g., C--O, C--S, or C--N
bonds), its broad functional group tolerance, and its compatibility
with mild conditions. Importantly, it circumvents the need for
stoichiometric organometallic reagents that are typically required in
traditional approaches. Although cobalt was the first catalyst used to
achieve efficient chemical XECs, its applications remain less explored
than those of nickel. Continued advances in catalyst design,
mechanistic insight, reaction scope, and integration with
electrochemical and/or photochemical methods are expected to unlock the
full potential of cobalt catalysis in modern synthetic chemistry.

\section*{Declaration of interests}
The author does not work for, advise, own shares in, or receive funds
from any organization that could benefit from this article, and has
declared no affiliations other than their research organization.

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