Cobalt-catalyzed C(sp2)?CN bond activation: Cross-electrophile coupling for biaryl formation and mechanistic insight

Coupling for Biaryl Formation and Mechanistic Insight

Research Article

Cobalt-Catalyzed C(sp )−CN Bond Activation: Cross-Electrophile

Celine Dorval, Maxime Tricoire, Jeanne-Marie Begouin, Vincent Gandon,* and Corinne Gosmini*

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sı Supporting Information

ABSTRACT: Herein, we report a cross-electrophile coupling of

benzonitrile derivatives and aryl halides with a simple cobalt-based

catalytic system under mild conditions to form biaryl compounds.

Even though the cobalt catalyst is able to activate the C(sp )−CN

bond alone, the use of the AlMe Lewis acid enhances the reactivity

of benzonitriles and improves the cross-selectivity with barely any

inﬂuence on the functional group compatibility. X-ray structure

determination of an original low-valent cobalt species combined

with catalytic and stoichiometric reactions reveals a catalytically

active cobalt(I) species toward the aryl halide partner. On the other hand, experimental insights, including cyclic voltammetry

experiments, suggest the involvement of a cobalt complex of a lower oxidation state to activate the benzonitrile derivative. Finally,

density functional theory calculations support the proposed mechanistic cycle involving two low-valent cobalt species of diﬀerent

oxidation states to perform the reaction.

KEYWORDS: cobalt, catalysis, benzonitriles, reductive cross-coupling, biaryl, cross-electrophile coupling

INTRODUCTION

which makes them appealing for late-stage cross-coupling

reactions. Therefore, despite its high bond dissociation energy

■

Beneﬁting from more than 50 years of research, noble metals

have a longstanding record in the ﬁeld of homogeneous

(

PhCN ∼ 132 kcal/mol), chemists have been attracted to

activate this unstrained C(sp )−CN bond with transition

metals.

Stoichiometric activation studies with diﬀerent metals have

revealed two major activation pathways (Scheme 1a). The ﬁrst

pathway involves mainly electron-rich metal(0) complexes,

catalysis. However, the depletion of their resources, implying

high costs and sustainability issues, has stimulated the search

for non-noble metal surrogates. These studies have revealed

unsuspected reactivities and notably led to the development

of ﬁrst-row transition metal-catalyzed cross-electrophile

coupling reactions that have emerged as a powerful tool to

create carbon−carbon (C−C), bonds in particular for biaryl

which insert via oxidative addition into the C(sp )−CN bond

14,15

(

pathway A).

The second activation mode relies on the

assistance of silicon, in which the prior formation of a silylated

complex is followed by the migratory insertion of the nitrile

formation. In contrast with the traditional redox-neutral

couplings, cross-electrophile couplings require no preliminary

preparation of a stoichiometric nucleophilic organometallic

species, which makes them more straightforward and often

allows better functional group tolerance. First, mainly based on

the activation of two halide derivatives, the limited availability

and diﬃcult synthesis of such substrates have led chemists to

4,16

into the M−Si bond (pathway B).

Among metals reported

to activate C(sp )−CN bonds, Ni, Rh, and Pd have been

7,9b,17

mainly applied in catalysis.

Notably, in cross-coupling

reactions, apart from a particular cross-coupling between

benzonitrile and azole derivatives, thus, necessitating to

employ a nickel(0)/alkyl phosphine catalyst to be able to

consider other types of electrophiles to perform such

activate the C(sp )−CN bond via pathway A, biaryl formation

reactions.

from benzonitriles has been reported using a nickel catalyst

In this area, one of the biggest challenges remains the

activation of thermodynamically stable C−C bonds. In

particular, even though great improvements have been made

recently, metal-catalyzed activation of unstrained C−C

with organometallic coupling partners such as aryl Grignard

21,22

reagents,

arylboronic esters, and arylmanganese com-

7,9

Received: September 7, 2020

Revised: October 7, 2020

bonds is still largely underdeveloped. Among them, the

activation of the C(sp )−CN bond is believed to have a great

potential to develop original synthetic methodologies.

Indeed, benzonitriles are relatively abundant and more and

more readily accessible from ubiquitous functional groups.

They are also quite stable under various reaction conditions,

XXXX American Chemical Society

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Scheme 1. (a) Diﬀerent Metal-Catalyzed Activation

Pathways; (b) Redox-Neutral Coupling with Benzonitrile

Derivatives and Nucleophilic Organometallic Reagents; (c)

Intramolecular Cross-Electrophile Coupling from

Benzonitrile Derivatives; and (d) Intermolecular Cross-

Electrophile Coupling from Benzonitrile Derivatives (This

Work)

diﬃcult activation of benzonitriles makes this challenge even

bigger. To the best of our knowledge, this is the ﬁrst example

of catalytic cross-coupling reactions involving C−CN

activation with cobalt.

RESULTS AND DISCUSSION

■

Optimization Study. The optimized conditions of the

reaction are shown in Table 1. Reaction of benzonitrile (1)

Table 1. Optimization of the Reaction Conditions

yield 3 yield 4 yield 5

entry deviation from standard conditions

(%)

None

CoBr (20 mol %), PPh (40 mol %)

CoBr (20 mol %), dtbbipy

(

40 mol %)

DMF/pyridine (10/1) instead of

DMF

80 °C instead of 50 °C

Me SiSiMe (1.0 equiv) as additive

BPh (1.0 equiv) as additive

AlMe₃(1.0 equiv) as additive

CoBr Bipy (10 mol %) and AlMe

(

0.5 equiv) as additive

Deviation from Entry 9 as New Standard Conditions

1.5 equiv of Mn

(

79)

1.5 equiv ArCl

without CoBr Bipy₂

without Mn

Reaction conditions: benzonitrile 1 (1 mmol, 1.0 equiv), methyl 4-

chlorobenzoate 2 (2 mmol, 2.0 equiv), CoBr Bipy (20 mol %), Mn

powder (4.0 equiv), DMF (1 M), 50 °C, and 24 h. See the Supporting

Information for full optimization details. _cYield determined by GC

using pentadecane as an internal standard. Yield calculated toward 2.

pounds (Scheme 1b). The use of such organometallic species

makes easy the reduction of nickel(II)/alkyl phosphine

precatalysts into nickel(0) active species, which can then

Solution of AlMe₃(2 M) in toluene. Bipy: 2,2′-bipyridine and

dtbbipy: 4,4′-di-tert-butyl-2,2′-bipyridine. Isolated yield.

insert into the C(sp )−CN bond according to pathway A.

However, the use of nucleophilic species might sometimes be

incompatible with late-stage derivatization and sensitive

and methyl 4-chlorobenzoate (2 ) in the presence of preformed

CoBr Bipy (20 mol %) (see S4 ) and Mn powder (4.0 equiv)

functional groups. Chatani et al. disclosed a rhodium-

catalyzed silicon-assisted (pathway B) cross-electrophile

coupling from benzonitrile derivatives (Scheme 1c), which

could overcome these drawbacks. Nevertheless, high temper-

ature and restriction to intramolecular arylation reduce its

applicability.

in N,N-dimethylformamide (DMF) at 50 °C for 24 h aﬀorded

the heterocoupling product (3) in 62% yield (entry 1) along

with homocoupling products of both partners (4 and 5) in 7

and 30%, respectively, and about 20% of 1 unreacted. Under

the same conditions, NiBr (dme) associated with the 2,2′-

bipyridine ligand aﬀorded a much lower yield (12%),

highlighting the advantage of developing new cobalt-catalytic

systems for cross-electrophile couplings (see Table S1 entry

20).

Cobalt complexes have already shown to be eﬃcient

catalysts to perform cross-electrophile coupling reac-

b,26,27

tions.

Moreover, we and others have revealed the great

ability of cobalt complexes to perform cross-coupling reactions

A ﬁrst screening of diﬀerent kinds of ligands (see Table S1)

showed the great superiority of N,N-heterocyclic ones to

perform the reaction (entry 2). Changing the simple 2,2′-

bipyridine ligand for bulkier and electron-richer ones resulted

in the lower conversion of 1 (entry 3). Interestingly, contrary

to many cobalt-catalyzed cross-electrophile couplings reported

of partners other than halide derivatives. Therefore, as part of

our continuous eﬀort to develop eﬃcient couplings from more

stable and available halide surrogates, we disclose herein an

attractive cobalt-catalyzed intermolecular cross-electrophile

coupling to form biaryls from benzonitrile derivatives under

mild conditions (Scheme 1d). The major challenge of such

intermolecular coupling is to favor cross-selectivity from two

electrophilic starting materials displaying the same reactivity

28b,30

in DMF,

pyridine as a cosolvent is of no use to improve

the transformation (entry 4), leading to an increased formation

of 5. Although elevated temperature is crucial for some

19,20,23,25

toward transition metals. In the present methodology, the

methodologies reported to activate the C−CN bond,

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Table 2. Scope of the Reaction

Reactions performed on the 1 mmol scaleisolated yields. 10 mmol scale. GC yield using n-pentadecane as an internal standard. NMR yield.

Without AlMe .

in our case, raising the temperature above 50 °C showed a

detrimental eﬀect (entry 5), with higher amounts of remaining

and 5. To diminish the quite signiﬁcant amount of 1

unreacted, we therefore tried to add some additives (see Table

S4 ).

not adequate to perform the reaction as a sole reducing agent

(see Table S5 entry 5).

Scope of the Reaction. With the optimized conditions in

hand, we then investigated the scope of the title transformation

(Table 2). The reaction works in accordance with most cross-

electrophile couplings catalyzed by cobalt previously repor-

Indeed, previous reports have shown that the use of

additives dramatically facilitated the insertion of transition

5b,26,27,30

ted

and is highly sensitive to the electronic properties

metal catalysts into the C(sp )−CN bond of benzonitrile

of the substrates, sometimes necessitating tuning of the

coupling partners to induce cross-selectivity. It should be

pointed out that the superior reactivity of aryl iodides

compared to that of aryl cyanides mainly led to the

homocoupling products of the aryl iodide substrates instead

of cross-coupling products. For benzonitrile (3) or derivatives

bearing moderately electron-donating groups (6, 7, and 8), the

cross-coupling performed smoothly with activated chloroaryl

derivatives bearing electron-withdrawing groups (EWGs) (9,

10, and 11). Unsurprisingly, when reacted with electron-richer

aryl chlorides for which the oxidative addition is less-favorable,

the benzonitrile derivatives preferably dimerized to give lower

yields (12, 13, 14, and 15). Nevertheless, better selectivities

were obtained when using more reactive bromoaryl analogues.

In the same way, highly electron-rich benzonitriles showed

poor or no reactivity, presumably because of a diﬃcult

oxidative addition, even with an increased amount of activating

Lewis acid (see S9.2 ).

derivatives, either by assistance or by acting as a Lewis acid

to weaken the C(sp )−CN bond. The use of hexamethyldi-

silane showed only a slight improvement in the yield (entry 6),

suggesting its prominent role as a Lewis acid than as an

assistant to the insertion, like in the method developed by

0a,25

19,31b,c

Chatani.

Although BPh

(entry 7) was prejudicial

displayed the best eﬃciency to

1c,d

to the reactivity, AlMe₃

overcome the lack of reactivity of 1 (entry 8). The use of

AlMe not only increased the selectivity (see Figures S1 and

S2) toward the formation of 3, signiﬁcantly reducing the

amount of 5 to 18%, but also enabled us to maintain a high

yield with lower catalyst loading (entry 9) and reductant

quantity (entry 10), actually close to the stoichiometry (see

Table S6 entry 6). However, a reduced amount of 2 resulted in

a lower yield (entry 11), yet still satisfactory in case a high-

value halide derivative is used. Finally, no product was detected

when the cobalt catalyst was removed (entry 12), whereas a

small amount of product could be observed without Mn (entry

On the contrary, benzonitriles bearing strongly EWGs (16)

or moderately EWGs at an activated position (17 and 18)

3). Indeed, AlMe might play the role of the reductant but is

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with an integer chemical formula is shown in Figure 1 . The

Research Article

showed great reactivity but preferentially dimerized, leading to

a lower yield when reacted with chloroaryl derivatives under

standard reaction conditions. Although removing AlMe₃

proved not suﬃcient enough (16), choosing the more reactive

bromoaryl counterpart as the coupling partner usually aﬀorded

the cross-coupled product in good yields (16 and 19). As for

benzonitriles bearing moderately EWGs (20 and 21), the

cross-coupling performed easily with an activated arylchloride

partner in good to very good yields.

state after reduction by Mn powder. From the previous dark

blue solution, crystals of a cobalt reduced species were grown

and isolated in 65% yield (see S4.). The resulting Co-Red

species crystalize in the P6 22 space group. A grown structure

Steric hindrance, such as the methyl group in the ortho-

position of any of the coupling partners, was not well tolerated

because of favored dimerization of the other unhindered

partner (see S9.2). Unlike its homologue in the para-position,

-methoxybenzonitrile aﬀorded 2-hydroxybenzonitrile as the

major product, coming from the deprotection of the starting

material mediated by AlMe (22). This deprotection is thus

promoted by the proximity of AlMe to the methoxy group,

clearly indicating its chelation to the nitrile moiety in order to

activate it. However, when no side reactions are competing,

high yields can be reached even though longer reaction times

are needed, like in an intramolecular reaction (23).

Interestingly, despite the presence of AlMe , sensitive func-

Figure 1. ORTEP of the reduced cobalt complex Co-Red [3

2−

−

tional groups such as acetals (24), benzyl- (25) and even silyl-

protected phenols (26), or alcohols (27) usually gave good

yields with only small amounts of the deprotected starting

material even in the ortho-position.

[Co Bipy ] ; [Co Bipy ] ; 2 [MnBr ] ; Br ] at 50% probability

3 3 4

ellipsoids with H atoms and the solvent omitted and 2,2′-bipyridine

ligands in a wireframe for clarity.

electroneutrality principle allowed the attribution of oxidation

Mechanistic Insight. Intrigued by the unusual reactivity of

this simple cobalt-based catalytic system toward stable

benzonitrile derivatives, we then focused on obtaining some

states for each Co atom with a resulting 3/1 ratio of Co Bipy /

Co Bipy . A close look at characteristic bond distances (see

Table S9) and comparison with literature values validated

the 3/1 ratio found and indicated a charge repartition mainly

centered on the metallic atoms in the solid state of Co (Bipy )

see S6 for full details on X-ray structure solving). Moreover,

insight into the mechanism of the reaction. In particular, a

plot of the time dependence for the reaction progress for

products 3 and 5 at the beginning of the reaction (see Figure

S3 ) showed two diﬀerent induction periods for each substrate

to be activated, with 2 being reacted faster than 1. This

peculiar observation encouraged us to investigate mainly which

species could activate both partners.

(

the X-ray structure of Co-Red is consistent with the

observation by Willett and Anson that Co complexes of

less than three 2,2′-bipyridines per cobalt have high propensity

to redistribute their ligands to ﬁll their coordination sites in

order to gain stability. Because the ligand redistribution is

Above all, we started to study the nature of the catalysis. We

envisioned that two types of catalysts could perform such

cross-coupling after reduction of the cobalt precatalyst by Mn

powder. On one hand, homogeneous low-valent cobalt species

could be the active catalyst. On the other hand, heterogeneous

38,39

believed to generate cobalt(0),

this led us to propose the

following equation for the formation of Co-Red (Chart 1).

Chart 1. Equation of Reduction/Ligand Redistribution of

catalysis might be eﬀective with either cobalt nanoparticles or

a blend of activated cobalt/manganese metals involved. To

verify the nature of the catalysis, we subjected a solution of the

precatalyst CoBr Bipy in DMF to reduction with Mn powder

CoBr Bipy by Mn Powder

overnight. The resulting dark blue supernatant of reduced

species was submitted to the mercury drop test with the

coupling partners 1 and 2 separately (see S3.2) If the

heterogeneous cobalt metal catalyst was involved, no reactivity

Besides, this result points out the importance of having

investigated the nature of the catalysis. Finally, this process of

reduction/ligand redistribution would be in accordance with

the induction period previously observed (Figure S3 ).

would be observed with Hg because of metal poisoning, by

amalgamating or adsorbing on the metal surface. However,

signiﬁcant amounts of methyl benzoate (9%) and 5 (13%)

were observed from the reaction of 2 with the supernatant,

We thus performed catalytic experiments in DMF at 50 °C

regardless of the presence of Hg . The reactivity of the

for 12 h in the presence of Mn (2.0 equiv) and employing

remaining activated cobalt/manganese blend was also

evaluated with 2 and this time, no reactivity was observed.

Although these results seem to be consistent with homoge-

neous catalysis, surprisingly, similar experiments with 1 led to

no reactivity in all cases (see S3.2 ), preventing us from drawing

any conclusions.

either Co-Red (Scheme 2i) or CoBipy ·2BF (Scheme 2ii)

3 4

as a precatalyst. Both complexes aﬀorded the same yield of the

cross-coupled product than CoBr Bipy (Scheme 2iii) under

the same conditions, highlighting that complexes of cobalt

surrounded by three 2,2′-bipyridine ligands are suitable

precatalysts for the transformation and the possible involve-

ment of such species as catalytic active species. Interestingly,

removal of Mn with Co-Red as a precatalyst under similar

conditions did not lead to any cross-coupling product,

Although it seems well established that Co precatalysts

5b,36

aﬀord Co species after reduction by Zn powder,

we could

not ﬁnd any report indicating clearly the resulting oxidation

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Scheme 2. Catalytic Reactions in DMF (1.0 M), 50 °C, 12 h

with Mn (2.0 equiv), and (i) Co-Red; (ii) CoBipy ·2BF ;

Mn. Figure 2 shows the obtained cyclic voltammograms of

Co Bipy either alone (A ) or mixed beforehand with 1 in DMF

and (iii) CoBr Bipy as a Precatalyst; (iv) Catalytic

Reactions in DMF (1.0 M), 50 °C, 12 h Using Co-Red as a

Precatalyst without Mn

Yields determined by GC using n-pentadecane as an internal

Figure 2. Cyclic voltammograms of A and B in DMF. A: 1 mM

standard.

[

Co Bipy ] and B: 1 mM [Co Bipy ] mixed beforehand with 1 in

−

DMF; glassy carbon working electrode; and scan rate 1 V s .

Supporting electrolyte: 100 mM tetrabutylammonium tetraﬂuorobo-

rate. See Supporting Information S.7 for full experiment details.

indicating the essential role of Mn within the catalytic cycle

(

Scheme 2iv).

We then focused on stoichiometric reactions of Co-Red

with 1 and 2 separately (Scheme 3). To our delight, 58% of 2

for 12 h at 50 °C (B). The cyclic voltammogram of A revealed

a 2-electron reduction wave at E° = −1.55 V versus SCE,

−I

Scheme 3. Stoichiometric Reactions with Co-Red in DMF

which corresponds to the Co /Co couple. The partially

(0.1 M), 50 °C, 12 h, and (i) 2; (ii) 1

reversible 1-electron wave at E = −0.86 V versus SCE can be

assigned to the oxidation of Co into Co species. By

comparison, the cyclic voltammogram of B disclosed a slower

electron transfer, presenting also a 2-electron reduction wave,

but at E° = −1.58 V versus SCE.

The combination of this result together with the observation

of the free 2,2′-bipyridine ligand and density functional theory

Yields determined by GC using n-pentadecane as an internal

standard.

(DFT) calculations conﬁrmed the formation of a new cobalt

species, which could be consistent with [Co Bipy (PhCN)]

Co1) and could then be possibly reduced by Mn (see Figure

was converted into methyl benzoate (ArH 38%) and dimethyl

biphenyl-4,4′-dicarboxylate 5 (Ar−Ar 10%), conﬁrming Co-

Red to be an active species with halogenoaryl derivatives

S9 ). Indeed, even though we observed no clear sign of

reactivity following the reduction step in the timescale of cyclic

voltammetry (5 V s down to 50 mV/s), adding Mn powder

−1

(

Scheme 3i). The control stoichiometric experiment with

to a stoichiometric mixture of Co-Red and 1 did lead to the

conversion of 41% of 1 and the formation of biphenyl 4 (Ph−

Ph) in 10% yield after stirring in DMF at 50 °C for 12 h

CoBipy ·2BF indeed conﬁrmed that only the Co species of

Co-Red is active toward 2 (see Scheme S11 ).

In accordance with what has previously been suggested

during the mercury drop test (see S3.2 ), Co-Red did not seem

to exhibit any reactivity toward 1 because stoichiometric

reaction did not lead to any conversion (Scheme 3ii).

However, interestingly, precipitation of cobalt complexes of

the mixture with toluene and analysis of the toluene

supernatant in gas chromatography (GC) showed appreciable

amounts of the free 2,2′-bipyridine ligand (see Scheme S12 ).

(

Scheme 4).

Scheme 4. Stoichiometric Reactions with Co-Red, 1, and

Mn in DMF (0.1 M), 50 °C, 12 h

In contrast, the same experiment carried out with CoBipy ·

Yields determined by GC using n-pentadecane as an internal

BF instead (see Scheme S13 ) produced only trace amounts

standard.

of free 2,2′-bipyridine, suggesting that the displacement of the

ligand by 1 preferably occurs with the Co Bipy rather than the

Co Bipy complex composing Co-Red (Figure 1). Besides,

Therefore, all these results led us to consider an initiation

computational data conﬁrmed that the substitution of one 2,2′-

phase composed of (i) formation of [Co Bipy (PhCN)] Co1,

bipyridine ligand by one benzonitrile 1 is indeed energetically

by substitution of one 2,2′-bipyridine of Co Bipy arising from

more favorable with Co Bipy than with Co Bipy (see S.8.1 ).

Co-Red, by one benzonitrile and (ii) reduction of the resulting

Concurrently, we performed cyclic voltammetry experi-

ments. To avoid any complexity of the cyclic voltammograms

complex by Mn, prior to the insertion into the C(sp )−CN

bond (Scheme 5). Besides, the presence of this initiation phase

would be in agreement with the relatively low conversion of 1

with Co-Red in the presence of Mn (Scheme 4) and the longer

induction period needed to activate 1 than that of 2, which has

due to the mixture of Co Bipy /Co Bipy of Co-Red, all the

experiments were performed with the complex Co Bipy

generated in situ by reduction of CoBipy ·2BF in DMF by

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Scheme 5. Computational Data for the Involvement of

when Ar = Ph. After that, two diﬀerent ligand exchanges

might take place between the complexes Co4 and Co5.

Formal Cobalt(0) or Cobalt(−I) Species in the Initiation

Phase for the Insertion into the C(sp )−CN Bond of 1

Indeed, the two aryl ligands could be carried either by a Co

species (Co6) (Scheme 6, I) or a Co species (Co7) (Scheme

III

, II) that then would each ultimately undergo irreversible

reductive elimination to aﬀord the biaryl product. These two

steps, for one and the other possibilities, were evaluated by

DFT calculations with 1 and 2 as model substrates. Ligand

exchange to form Co6 is endergonic by 9.9 kcal/mol. The

following reductive elimination requires 16.4 kcal/mol free

energy of activation and is exergonic by 18.8 kcal/mol (see

Scheme S18 ). On the other hand, the exchange to generate

Co7 is now exergonic by 8.6 kcal/mol, but the consecutive

reductive elimination step necessitates 23.7 kcal/mol free

energy of activation, which is higher than the one computed in

the mechanism I (see Scheme S19 ). Therefore, even though

more experiments would still be needed to fully rule out other

mechanistic cycles, all these considerations led us to favor the

proposed mechanism I. Finally, to close the catalytic cycle I,

Oxidation state is indicative, as it is known that 2,2′-bipyridine is a

redox noninnocent ligand that can bear the charge repartition.

been observed on the plot of the time dependence for the

reaction progress (Figure S3). Of note, because the cyclic

voltammogram of B displayed a 2-electron reduction wave, we

investigated the possible involvement of formal Co (Co2) or

formal Co (Co3) species for the insertion into the C(sp )−

CN bond of benzonitrile 1.

As shown in Scheme 5, primary DFT calculations suggested

that both species could be accounted for the insertion into the

C(sp )−CN bond but with a quite higher free energy of

activation computed for Co3 (22.9 kcal/mol) than for Co2

irreversible reductive elimination occurs from Co species Co6

to aﬀord the biaryl product and regenerate formal Co species

−

able to activate benzonitrile derivatives again (cycle I-B),

whereas reduction of Co8 by Mn and recoordination of the

,2′-bipyridine ligand regenerate Co Bipy (cycle I-A).

CONCLUSIONS

■

(

12.8 kcal/mol) (see Schemes S20 and S21 for further details).

As a consequence, we propose the two following catalytic

In conclusion, we have developed a simple cobalt-catalyzed

cross-electrophile coupling between benzonitrile derivatives

and aryl halides under mild conditions. The use of the AlMe₃

Lewis acid boosts the reactivity of benzonitrile derivatives and

promotes cross-selectivity without overly aﬀecting functional

group tolerance. Furthermore, we believe that this work brings

major insights into the understanding of this type of reactivity

and the mechanism of cobalt-catalyzed cross-electrophile

couplings. On one hand, X-ray structure determination of

unusual Co-Red species has revealed an original reduction/

ligand redistribution from the CoBr Bipy precatalyst by Mn,

cycles depicted in Scheme 6. In both cases, ﬁrst, CoBr Bipy is

reduced by Mn to aﬀord Co Bipy after ligand redistribution

(Chart 1). On one hand, insertion into the C−Cl bond occurs

to give Co4 (cycles I-A and II-A). On the other hand,

substitution of one 2,2′-bipyridine by one benzonitrile leads to

the complex Co1, which can then undergo reduction by one

electron from Mn to aﬀord the complex Co2 (initiation). This

is driven by subsequent insertion into the C(sp )−CN bond,

allowing Co5, with a free energy of activation of 12.8 kcal/mol

⧧

Scheme 6. Simpliﬁed Proposed Catalytic Cycles with ΔG of the Corresponding Insertion/Reductive Elimination Steps

kcal/mol) for Ar = 4-MeCO C H and Ar = Ph and Geometry of the C−CN Bond Activation TS with Selected Distances in

Å (See S8.2 for Full Details on DFT Calculations); (I) Reductive Elimination Occurs on a Cobalt(II) Species in Cycle B; (II)

Reductive Elimination Occurs on a Cobalt(III) Species in Cycle A

Oxidation state is indicative, as it is known that 2,2′-bipyridine is a redox noninnocent ligand that can bear the charge repartition.

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(1) Johansson Seechurn, C. C. C.; Kitching, M. O.; Colacot, T. J.;

Research Article

which associated with catalytic and stoichiometric experiments

the CINES (project A0070810977). We also would like to

thank G. Danoun and C. Tard for insightful discussions on this

indicated a Co Bipy active species toward aryl halides. On the

other hand, stoichiometric studies combined with cyclic

voltammetry experiments suggested the involvement of a

new cobalt complex induced by the replacement of the 2,2′-

bipyridine ligand by the benzonitrile derivative. The latter can

project and A. Per

ot for helpful DFT calculations.

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ASSOCIATED CONTENT

sı Supporting Information

The Supporting Information is available free of charge at

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■

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AUTHOR INFORMATION

Corresponding Authors

■

(6) Selected recent examples: for biaryl formation: (a) Ackerman, L.

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Vincent Gandon − Laboratoire de Chimie Moleculaire, CNRS

UMR 9168, Ecole Polytechnique, Institut Polytechnique de

Paris, 91128 Palaiseau Cedex, France; Institut de Chimie

Molec

182, Universite

Email: vincent.gandon@polytechnique.edu

ulaire et des Mater

iaux d’Orsay (ICMMO), CNRS UMR

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Corinne Gosmini − Laboratoire de Chimie Moleculaire, CNRS

UMR 9168, Ecole Polytechnique, Institut Polytechnique de

Paris, 91128 Palaiseau Cedex, France; orcid.org/0000-

002-1355-2301 ; Email: corinne.gosmini@

polytechnique.edu

Authors

Cel

ine Dorval − Laboratoire de Chimie Moleculaire, CNRS

2019, 58, 12081−12085. (f) Ni, S.; Li, C.-X.; Mao, Y.; Han, J.; Wang,

UMR 9168, Ecole Polytechnique, Institut Polytechnique de

Paris, 91128 Palaiseau Cedex, France

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Maxime Tricoire − Laboratoire de Chimie Moleculaire, CNRS

UMR 9168, Ecole Polytechnique, Institut Polytechnique de

Paris, 91128 Palaiseau Cedex, France

Jeanne-Marie Begouin − Laboratoire de Chimie Moleculaire,

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CNRS UMR 9168, Ecole Polytechnique, Institut Polytechnique

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(

Complete contact information is available at:

https://pubs.acs.org/10.1021/acscatal.0c03903

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Notes

The authors declare no competing ﬁnancial interest.

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Acyclic Systems by C −C Bond Cleavage of Cyclopropanes. Chem.

ACKNOWLEDGMENTS

■

We thank CNRS and Ecole Polytechnique for ﬁnancial

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