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"This is the peer reviewed version of the following article: ngew. Chem., Int. Ed. 2017, 56 (24), 6708-6710,, which has been published in final
form at http://onlinelibrary.wiley.com/doi/10.1002/anie.201702188/abstract. This article may be used for non-commercial
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Forging C–C Bonds Through Decarbonylation of Aryl Ketones
Rosie J. Somerville[a] and Ruben Martin*[a],[b]
As judged by the wealth of recent literature data, C–C bondformation has evolved into a routine tool for building up
molecular complexity. Indeed, C–C bond-forming techniques
play a prominent role in the preparation of fine chemicals and
pharmaceuticals. However, the success of these methodologies
has contributed to the perception that the field has reached a
certain maturity. This observation is far from the truth, as the
development of new and creative C–C bond-forming reactions
will make more chemical space accessible for organic chemists,
thus improving the flexibility of synthetic design.[1]
classical C–C bond-cleavage methodologies
C

C

H

O

O
R

C

path a

+

C

C

[MLn]
path b

C

C

+

H

R1
R1

O
N

Rh

O
R1 R2
R2
CO
ketone decarbonylation

R

CO

R1

R

O
R

C

O

R1

C–C bond-cleavage via carbonyl decarbonylation
O

H

O

H

[MLn]

+

simple biaryl ketones lacking nearby directing groups has
received much less attention. The first report of simple biaryl
ketone decarbonylation was reported by Brookhart and required
stoichiometric amounts of particularly bulky cyclopentadienyl
Rh(I) complexes.[8] Despite the conceptual interest of these
transformations, the typical use of expensive and noble Rh
complexes may hinder the development of this field of expertise,
thus reinforcing the need for a change in strategy.

R

O
R

R1

R

N
Ar

R

Ar

stoichiometric
[Rh]

Scheme 1. C–C bond-cleavage followed by C–C bond formation.

O

Prompted by the ubiquity of C–C bond-linkages, chemists
have been challenged to design sequential C–C bondcleavage/C–C bond-formations (Scheme 1, path a).[2] While the
release of ring strain makes strained rings susceptible to C–C
bond scission, chemists have also focused their attention on
decarbonylative transformations of unstrained motifs, whereby
C–C cleavage is coupled with extrusion of carbon monoxide
(CO). This allows a common functional group to become a
handle for C–C bond formation (Scheme 1, path b). Although
considerable success has been achieved with aldehydes, aroyl
chlorides, thioesters, esters, and anhydrides, the use of simple
ketones remains difficult due to the strength of the C–C(O) bond
and the affinity of CO for the metal center.[2] Pioneering work by
Teranishi,[3] Murakami and Ito,[4] however, demonstrated the
feasibility of Rh-catalyzed C–C(O) cleavage in strained rings or
diketone precursors (Scheme 2, top). Murai,[5] Shi[6] and Dong[7]
showed that the introduction of directing groups or the use of
diynones could facilitate decarbonylation. However, the use of

[a]

[b]

R. J. Somerville, Prof. R. Martin
Institute of Chemical Research of Catalonia (ICIQ)
The Barcelona Institute of Science and Technology
Av. Països Catalans 16, 43007, Tarragona (Spain)
E-mail: rmartinromo@iciq.es
Prof. R. Martin
ICREA
Passeig Lluïs Companys, 23, 08010 Barcelona Spain

Ar1

Ar2

Ni

CO

Ar1

Ar2

non-noble metals
unstrained ketones
no directing groups

Scheme 2. Rh- and Ni-mediated ketone decarbonylation techniques

In recent years, nickel has received considerable attention in
the cross-coupling arena due to its low price, ability to access
multiple oxidation states and its extensive, yet reactive,
organometallic chemistry.[9] Indeed, nickel catalysts have been
particularly suited to the activation of strong s–bonds.[10]
Prompted by the nickel-mediated decarbonylation study reported
by Ruhland (where proximal chelating groups were
employed),[11] Tobisu and Chatani have recently shown that
nickel complexes can promote activation of the two C–C(O)
bonds of simple diaryl ketones and, after CO extrusion, form the
corresponding biaryl product (Scheme 2, bottom pathway).[12]
Interestingly, although no reactivity was found for electron-rich
phosphines – ligands often used for the Ni-catalyzed activation
of strong s-bonds[10] – the desired decarbonylation was
observed with stronger s-donor N-heterocyclic carbene ligands.

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Me

Ar1
O
Ar2

[Ni(cod)2] (1 equiv)
L1 (1 equiv)
NaOtBu (1 equiv)
PhMe, 160 ºC

Ar1

Ar N

Ar2

“push-pull” effects in C–C bond-cleavage

Me

“push-pull”

R1

N Ar

Cl
L1
Ar = 1,3,5-Me3C6H2

O

Me

NMe2

Me

[Ni(cod)2] (1 equiv)
L1 (1 equiv)

42%

NaOtBu (1 equiv)
PhMe, 100 ºC
R1, R2 = CF3 or Me

R

N
96% (100 mol% Ni)
64% (20 mol% Ni)
CF3

52%
Me

proposed mechanistic rationale
Ar1
O
Ar2

52%

70%

53%

Me

Ph

97%

N
92%

Ni(0)(L1)

L1
Ni
Ar1

facilitated by
e-poor Ar1

O
- C
[Ni]

O
Ar2

Ar1

Ar2

C–C
formation

Ph
64%

Scheme 3. Selected examples of the nickel-mediated ketone decarbonylation.

The generality of the transformation was briefly investigated,
and a variety of diaryl ketones possessing different substitution
patterns participated well in the reaction (Scheme 3).[12] Notably,
the presence of ortho-substituents did not hinder the reaction.
The reaction generally required stoichiometric amounts of both
[Ni(cod)2] and L1, along with high temperatures (160 ºC). Note,
however, that a substrate with a 3-substituted quinolinyl motif
allowed for the use of 20 mol% Ni(cod)2, with a 64% yield of the
biaryl product being obtained. Although full interpretation of
these results awaits further investigations, the turnover observed
with this substrate certainly paves the way for future directions of
this transformation. The chemoselectivity issues of the reaction
could not fully be assessed, probably due to the high
temperatures required for effecting the transformation. Although
beyond the scope of this reaction, a successful extension to aryl
alkyl ketones would provide an intriguing new entry to alkylated
arenes without the need for directing groups.[5]

+

facilitated by
e-rich Ar2

CO
extrusion

Ar1

Me

Me

N

C–C
cleavage

OC L1
Ni

O

R
20% (R = Me)
7% (R = CF3)

R2
59%

CF3

Ar1

Ar2

+
Ni(0)(L1)(CO)

Scheme 4. “Push-pull” effects and mechanistic rationale.

Crossover experiments with substrates bearing electronicallydifferentiated arenes provided compelling evidence for an
intramolecular mechanism.[12] Mechanistic understanding of the
transformation, however, remains elusive at this time. The
authors proposed a scenario involving an initial oxidative
addition into one of the C–C(O) bonds, followed by
decarbonylation and a final reductive elimination (Scheme 4,
bottom). In order to obtain empirical evidence for this pathway,
the authors speculated that whereas oxidative addition should
occur at the most electron-poor C–C(O) bond adjacent to an
electron-poor arene, the subsequent C–C cleavage should be
favored by a more electron-rich arene moiety. This hypothesis
turned out to be correct, with diaryl ketones containing both
electron-withdrawing and electron-donating groups providing
higher conversions than regular arenes possessing either
electron-withdrawing or electron-rich groups (Scheme 4, top).
Although these experiments certainly shed light on the different
behavior exerted by electronically-differentiated arenes, the
inclusion of a computational study and physical organic
investigations would have been necessary to fully explain the
elementary steps of this reaction. Given the ability of low-valent
Ni(0) complexes possessing electron-rich ligands to bind to
carbonyl compounds in a h2-fashion,[13] we speculate that the
formation of such a complex would precede and facilitate the a
priori uphill C–C(O) bond-cleavage.
According to the postulated mechanism, a [Ni(0)(L1)(CO)n]
complex is generated during the reaction. Although the authors
did not report the synthesis of such a complex, indirect evidence
for its formation came from an IR spectrum of the crude reaction
mixture that revealed a distinctive stretching frequency at 1980
cm-1.[12] As the affinity of low-valent metal complexes for CO can
make turnover problematic, we believe that future research
should be focused on overcoming this drawback. Indeed, the
release of CO from a low-valent Ni(0) species is certainly not
impossible, as demonstrated by recent reports of nickelcatalyzed decarbonylative coupling reactions of aryl esters.[14]
Although the reasons behind successful catalyst turnover were

HIGHLIGHT
not investigated in every case, techniques used to prevent
deactivation of the Ni catalyst include carrying out the reaction
under a flow of N2,[14b] and the use of high temperatures.[14c]
Alternatively, one could envision trapping the extruded CO in a
complementary side reaction, a technique that has already been
employed in aldehyde carbonylation.[15] In any case, we are
certainly confident that the recent protocol discovered by Tobisu
and Chatani12] could provide a significant technological push
towards a more prolific use of abundant first-row transition
metals in decarbonylation strategies. We anticipate that a deep
understanding of the mechanism obtained by combining
theoretical and experimental techniques will set the basis for
future advances in this field.
In conclusion, electron-rich Ni(0) complexes have been shown
to be suitable for effecting a rather elusive ketone
decarbonylation, and thus complement existing methodologies
based on noble Rh complexes. This finding establishes an
important proof of concept that showcases the unique ability of
nickel species to trigger interesting bond disconnections, and
further reinforces the potential of using decarbonylation as a tool
for organic synthesis. We certainly expect continued growth in
this rather unexplored field of expertise.

Acknowledgements
We thank ICIQ, MINECO (CTQ2015-65496-R and Severo
Ochoa Excellence Accreditation 2014-2018, SEV-2013-0319) for
support. R. J. Somerville thanks the “La Caixa“ Severo Ochoa
program for a predoctoral fellowship.
Keywords: nickel • C–C cleavage • decarbonylation • crosscoupling • C–C bond formation
[1]

In Metal-Catalyzed Cross-Coupling Reactions, 2nd ed. (Eds. A. De
Meijere, F. Diederich), Wiley-VCH, Weinheim, 2004

[2]

[3]
[4]
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[6]

[7]
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[10]

[11]
[12]
[13]

[14]

[15]

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c) F. Chen, T. Wang, N. Jiao, Chem. Rev. 2014, 114, 8613-8661
K. Kaneda, H. Azuma, M. Wayaku, S. Teranishi, Chem. Lett. 1974, 3,
215-216.
M. Murakami, H. Amii, Y. Ito, Nature 1994, 370, 540-541.
N. Chatani, Y. Ie, F. Kakiuchi, S. Murai, J. Am. Chem. Soc. 1999, 121,
8645-8646.
Z.-Q. Lei, H. Li, Y. Li, X.-S. Zhang, K. Chen, X. Wang, J. Sun, Z.-J. Shi,
Angew. Chem. Int. Ed. 2012, 51, 2690-2694; Angew. Chem. 2012, 124,
2744-2748.
A. Dermenci, R. E. Whittaker, Y. Gao, F. A. Cruz, Z.-X. Yu, G. Dong,
Chem. Sci. 2015, 6, 3201-3210
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HIGHLIGHT
Rosie J. Somerville, Ruben Martin*
Page No. – Page No.
Forging C–C Bonds Through
Decarbonylation of Aryl Ketones
Nickel’s ability to cleave strong s-bonds is again in the spotlight after a recent report
that demonstrates the feasibility of nickel complexes to promote decarbonylation of
diaryl ketones. This transformation involves the cleavage of two strong C-C(O)
bonds and avoids the use of noble metals, hence reinforcing the potential of
decarbonylation as a technique for forging C–C bonds.

ketones to be C—C bonds to be formed from simple substrates and avoids the use
of rare and expensive rhodium.