Sequential Organozinc Formation and Negishi Cross-Coupling of Amides Catalysed by Cobalt Salt

Article abstract of DOI:10.1002/adsc.201801577

Herein, a cobalt-catalysed Negishi-type cross-coupling of amide derivatives is described. Apart from being the first example of cobalt-catalysed Negishi-type coupling of amides, the process described employs a unique, simple, and cheap catalytic system to perform both the organozinc formation and the Negishi-type coupling. Indeed, the same cobalt(II) bromide salt used to form the arylzinc species from aryl bromides is then re-used to perform the cross coupling of this resulting arylzinc with N-benzoyl glutarimides at room temperature. The main advantages of the reaction presented are its robustness and ease of use. Indeed, the reactions of organozinc formation and Negishi-type coupling are performed without precautions toward water or oxygen. (Figure presented.).

Full text of DOI:10.1002/adsc.201801577

Title: Sequential Organozinc Formation and Negishi Cross-Coupling of
Amides Catalysed by Cobalt Salt.
Authors: Céline Dorval, Elodie Dubois, Yann Bourne-Branchu, Corinne
Gosmini, and Grégory Danoun
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801577
Link to VoR: http://dx.doi.org/10.1002/adsc.201801577

10.1002/adsc.201801577
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Sequential Organozinc Formation and Negishi Cross-Coupling
of Amides Catalysed by Cobalt Salt
Céline Dorval, Elodie Dubois, Yann Bourne-Branchu, Corinne Gosmini* and Grégory
Danoun*
a
LCM, CNRS, Ecole Polytechnique, Université Paris-Saclay, 91128 Palaiseau Cedex (France)
E-mail: corinne.gosmini@polytechnique.edu; gregory.danoun@polytechnique.edu
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
aryl zinc reagents.[9] This reaction is attractive since it
Abstract. Herein, a cobalt-catalysed Negishi-type cross-
is performed very fast at room temperature (within 10
min for some substrates) with the bench-stable
NiCl2(PPh3)2 catalyst. Then, by tuning the catalytic
system, this type of coupling has been broadened to
N,N-di-Boc[10] and N-acyl succinimide.[11] Meanwhile,
Garg published the first Negishi-type cross-coupling
reaction allowing the alkylation of the less distorted
N-alkyl, Ts or N-alkyl, Boc amide derivatives[12]
catalysed by Ni(cod)2/SIPr (Scheme 1, B).[13]
coupling of amide derivatives is described. Apart from
being the first example of cobalt-catalysed Negishi-type
coupling of amides, the process described employs a
unique, simple, and cheap catalytic system to perform both
the organozinc formation and the Negishi-type coupling.
Indeed, the same cobalt(II) bromide salt used to form the
arylzinc species from aryl bromides is then re-used to
perform the cross coupling of this resulting arylzinc with
N-benzoyl glutarimides at room temperature. The main
advantages of the reaction presented are its robustness and
ease of use. Indeed, the reactions of organozinc formation
and Negishi-type coupling are performed without
precautions toward water or oxygen.
Although organozinc compounds present high
nucleophilicity and offer an excellent functional
group tolerance, their preparation can be delicate to
handle. Indeed, they are mostly prepared either in one
step by insertion of activated zinc powder in the
presence of LiCl[14] or in two steps by transmetalation
between a beforehand prepared organolithium or
organomagnesium reagent and zinc salt. In both cases,
their formation requires highly anhydrous and
anaerobic conditions. In 2003, we revealed an easy to
handle cobalt-catalysed formation of aryl zinc
Keywords: Amides; Cobalt; Negishi-type cross-coupling;
Organozinc reagent; One-pot reaction.
Amides are one of the major building blocks of life
probably thanks to the high stability of the amide
function.[1] This robustness of the amidic bond, in
particular toward nucleophilic attack, comes from the
delocalization of the electrons of the nitrogen lone
pair and those of the carbonyl moiety (Scheme 1,
A).[2] Nonetheless, the disruption of the amidic
resonance through steric and/or electronic effects on
the nitrogen substituents induces a distortion of the
N–C amidic bond, and therefore enables its
activation.[3] Even though those so-called “twisted
amides” are known from the 1940’s,[4] it is only in
2015 that they emerged as useful electrophilic
partners in transition-metal catalysed coupling
reactions.[5] Since then, both decarbonylative[6] and
non-decarbonylative cross-coupling reactions have
been developed resulting in the formation of carbon–
heteroatom as well as carbon–carbon bonds.[7]
compounds,
necessitating
no
particular
precautions,[15] and their reactivity in Negishi-type
reactions[16-17] with acid chloride or anhydride
derivatives,[18] among others.[19] This method is quite
efficient requiring no additional ligand for the
reaction to perform at room temperature. Moreover,
the process is easy to use and robust since the
reaction can be run in solvents neither particularly
dried nor degassed and under air, without decreasing
the yield of the transformation. Recently, we first
revealed the ability of cobalt salt to activate the
amidic bond of twisted amides in order to achieve the
non-thermodynamically favored amide to ester
transformation.[20] Taking all this into account, we
therefore have been curious to develop the first
cobalt-catalysed Negishi-type cross-coupling reaction
involving amides as coupling partners and offering a
simple process and neither anhydrous nor anaerobic
conditions. Furthermore, it could be of great interest
to achieve a sequential method in which the unique
cobalt salt is used as catalyst, not only for the
preparation of the zinc species, but also to perform
Whereas
Suzuki-Miyaura-type
cross-coupling
reactions have been quite broadly studied, only few
examples of Negishi-type coupling reactions have
been released. In 2016, Szostak disclosed the first
nickel-catalysed Negishi-type cross-coupling reaction
between highly distorted N-acyl glutarimides[8] and
1
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10.1002/adsc.201801577
Advanced Synthesis & Catalysis
the Negishi-type cross-coupling reaction, without any
additional catalyst (Scheme 1, C).
simplifies the treatment of the reaction. Indeed, in
this case, no workup is needed and the whole reaction
mixture can be subjected to column chromatography
to give the product in quantitative yield.
According to previous literature by Szostak and
Garg,[9-13] imides, including N-benzoyl glutarimides,
do not react with organozinc reagents. However,
these reactions were carried out in THF, toluene, or
ether. We therefore decided to verify whether this is
valid for acetonitrile, the solvent used to perform our
coupling reaction. To this end, we first prepared the
p-tolylzinc derivative by transmetalation of zinc
chloride salt with both the corresponding Grignard
and lithium reagents. Then, for both organozinc
species, 2 equivalents of the arylzinc solution were
added into a vial containing a solution of the N-
benzoyl glutarimide (2) in acetonitrile (1 M) on one
hand, and a vial containing a solution of the N-
benzoyl glutarimide (2) and CoBr2 (10 mol%) in
acetonitrile (1 M) on the other hand. Regardless of
which organozinc species was used, the reactions
performed without cobalt salt showed no diaryl
ketone product (1) whereas the ones carried out with
10 mol% of CoBr2 led to more than 90% yield of the
desired product (1), hence validating the necessity of
the cobalt salt to achieve this Negishi-type coupling.
We then tried to lower the amount of the arylzinc
coupling partner up to the stoichiometry (1.5
equivalents of aryl bromide corresponding to 1.05
equivalents of zinc compound). To our best delight,
no significant decrease of the yield was observed
(Scheme 2) confirming the high efficiency of the
coupling even in stoichiometric amount of the
organozinc reagent. However, based on our precedent
publications on arylzinc formation,[15] all zinc
compounds are not prepared with equal efficiency.
For simplicity and considering the low cost of the
cobalt catalyst used, we decided to investigate the
scope of the reaction by using 2 equivalents of aryl
bromides compared to the amide to ensure optimal
conditions in all cases.
Scheme 1. A. Amide resonance; B. Previous Negishi-type
cross-coupling of amides; C. This work.
We investigated this sequential strategy involving
Negishi-type coupling on N-benzoyl glutarimide (2).
This distorted amide has already shown high
reactivity in cross-coupling reaction and especially in
Negishi-type reaction.[8,9] We decided to form the
organometallic
coupling
partner,
p-tolylzinc
derivative according to our procedure, using simple
cobalt (II) bromide salt as catalyst in presence of an
excess of metallic zinc powder activated by 40 mol%
of allyl chloride and traces of TFA in acetonitrile
(1 M).[15] The formation of the p-tolylzinc species
was monitored by GC, using tetradecane as internal
standard, following the amount of aromatic iodide
formed after iodination of a sample of the mixture.
After approximately 1 h of reaction, the p-
bromotoluene was fully converted into, for the most
part, zinc compound (on average 70-80% of p-
iodotoluene), the rest being a mix of dimers and
toluene. Subsequently, 1 mL of this mixture (2
equivalents of aryl bromide corresponding to 1.4
equivalents of zinc compound) was added into a vial
containing N-benzoyl glutarimide (2; 0.5 mmol) and
the resulting mixture was stirred overnight at room
temperature. We were pleased to observe a near total
conversion of the amide starting material (2) into the
corresponding diaryl ketone (1) in 94% yield
(Scheme 2). We also tried to filter the aforementioned
organozinc compound solution in order to get rid of
the zinc powder in excess before performing the
coupling reaction. The resulting orange solution
containing arylzinc species and homogenous cobalt
catalyst was then added again onto the N-benzoyl
glutarimide (2). This also led to the corresponding
diaryl ketone (1) in near-quantitative yield (Scheme
2). It is important to note that with both procedures,
the coupling reaction is really straightforward,
leading only to the desired diaryl ketone product 1.
However, the second process, involving the simple
filtration step of the organozinc species, mostly
Scheme 2. Study of the sequential organozinc formation
and Negishi cross-coupling of amides. The yields were
determined by GC analysis using dodecane as internal
[a]
standard. The solution of organozinc was filtered prior
to use.
2
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10.1002/adsc.201801577
Advanced Synthesis & Catalysis
Finally, we evaluated the range of distorted amides
In order to provide a really useful and efficient
process, a one-pot procedure performing both
reactions was attempted. This one-pot procedure
allowed to decrease the amount of bromoarene used
to 1.25 equivalents as well as the catalyst loading to
12.5 mol%. After simple filtration of the reaction
mixture through a pad of celite and purification on
column chromatography, the corresponding diaryl
ketone was obtained in pure form with an excellent
yield of 92% (Scheme 4). The development of this
procedure offers a cheap and easy to handle
alternative to the reductive cross-coupling previously
described using nickel catalyst.[21]
which can be activated by this process. Only highly
distorted N-acyl glutarimide (2) and succinimide (3)
can actually be converted using this catalytic process.
Less-distorted amides (4-7) such as N-Boc (5) or N-
Ts (6) are completely recovered and therefore
unreactive in the reaction conditions. This selectivity
is synthetically interesting since it thus allows the
coupling of N-acyl glutarimide without modification
of the other aforementioned twisted amides (Scheme
2).
With these conditions in hand, we then
investigated the scope of the reaction (Scheme 3).
First, different arylzinc were formed and engaged in
the Negishi-type cross-coupling with N-benzoyl
glutarimide (2). Arylzinc carrying an electron-
donating group such as methyl, methoxy or even a
catalyst poisoning thiomethyl group show good
reactivity and lead to the corresponding diaryl ketone
(1 and 8-10) in good to excellent yields. For the
organozinc bearing an electron-withdrawing group as
well as heteroarylzinc species, the diaryl ketones (11-
14) were obtained in moderate yields. In terms of
amide diversity, the same trend was observed. Indeed,
N-benzoyl glutarimide with an electron-withdrawing
group (20-21) lead to moderate yields while those
with an electron-donating group (15-19) lead to
excellent yields. Finally, steric hindrance seems to
have an influence on the arylzinc (10 vs 8) but not on
the amide moiety (18 vs 19).
Scheme 4. One-pot procedure involving organozinc
formation and Negishi cross-coupling
In conclusion, we have developed the first cobalt-
catalysed Negishi-type cross-coupling reaction
involving amides as coupling partners. The process
uses a simple and cheap catalytic system. First, the
cobalt (II) bromide salt catalyses both the preparation
of the zinc species as well as the Negishi-type cross-
coupling reaction. Second, the reaction is quite
efficient since no additional ligand for the cobalt
catalyst is needed to carry out the sequential
organozinc formation and the coupling reaction at
room temperature. In addition, the set-up of the
reaction is robust and easy to handle since it
necessitates neither distilled solvent nor aqueous
work-up, leading to the pure cross-coupled product
after simple column chromatography. Finally, this
method shows its great usefulness by reaching the
pure product in one-pot procedure with lowered
amounts of zinc species and catalyst.
Experimental Section
General procedure for the organozinc formation and
Negishi-type cross-coupling of amides
A 20 mL vial was charged with CoBr2 (109 mg, 0.5 mmol,
0.1 equiv.) and zinc powder (981 mg, 20 mmol, 4 equiv.)
and sealed. MeCN (5 mL) was then added, followed by
allyl chloride (163 µL, 2 mmol, 0.4 equiv.) and TFA (50
µL). After 15 min at room temperature, the bromoarene (5
mmol) was added in one portion and the reaction was
stirred at room temperature until complete conversion of
the bromoarene (typically 1 hour). 1 mL of the resulting
slurry was taken via a syringe equipped with a filter. The
clear orange solution was then added into a 20 mL vial
containing the amide derivative (0.5 mmol) and the
resulting solution was stirred overnight at room
temperature. A precipitate appeared during the reaction.
The resulting mixture was taken and injected directly on a
silica gel column chromatography for purification (eluent:
petroleum ether / ethyl acetate).
Scheme 3. Scope of the reaction. Isolated yields were
noted. [a] 20 mol% of CoBr2 and 80 mol% of allyl chloride
were used.
3
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10.1002/adsc.201801577
Advanced Synthesis & Catalysis
Acknowledgements
[10] S. Shi, M. Szostak, Org. Lett. 2016, 18, 5872-5875.
[11] S. Shi, M. Szostak, Synthesis 2017, 49, 3602-3608.
We thank the Ministère de l’Enseignement Supérieur et de la
Recherche (PhD grant to Y.B. and C.D.). This work was
supported by CNRS and the Ecole Polytechnique. We
acknowledge the members of Laboratoire de Synthèse Organique
for donating chemicals.
[12] Y. Bourne-Branchu, C. Gosmini, G. Danoun, Chem.
Eur. J., in press, DOI: 10.1002/chem.201802635.
[13] B. J. Simmons, N. A. Weires, J. E. Dander, N. K.
Garg, ACS Catal. 2016, 6, 3176-3179.
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4
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10.1002/adsc.201801577
Advanced Synthesis & Catalysis
COMMUNICATION
Sequential Organozinc Formation and Negishi
Cross-Coupling of Amides Catalysed by Cobalt
Salt.
Adv. Synth. Catal. Year, Volume, Page – Page
Céline Dorval, Elodie Dubois, Yann Bourne-
Branchu, Corinne Gosmini* and Grégory Danoun*
5
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