Ru-Catalyzed Carbonylative Murai Reaction: Directed C3-Acylation of Biomass-Derived 2-Formyl Heteroaromatics

Article abstract of DOI:10.1002/adsc.202000249

The Murai reaction is a ruthenium-catalyzed transformation leading to alkylated arenes through the C?C bond formation between an alkene and an arene bearing a directing group. Discovered in the nineties, this useful C?H activation based coupling has been the object of intense study since its discovery. After having studied the Murai reaction on 2-formylfurans of biomass derivation, we describe here the carbonylative version applied to 2-formylfurans, 2-formylpyrrols and 2-formylthiophenes. This acylation reaction takes place regioselectively at C3 position of the heterocyclopentadienes thanks to the installation of removable imine directing groups. The transformation can be achieved by treating the two reaction partners with a catalytic amount of Ru₃(CO)₁₂, in toluene at 120–150 °C, after CO bubbling, at atmospheric pressure. DFT computations of the full catalytic cycle help in deciphering the mechanism of this transformation, and to rationalize the different behaviors depending on the nature of imine directing groups. (Figure presented.).

Full text of DOI:10.1002/adsc.202000249

Title: Ru-Catalyzed Carbonylative Murai Reaction: Directed C3-
Acylation of Biomass-Derived 2-Formyl Heteroaromatics
Authors: Giovanni Poli, Julie Oble, Roberto Sala, Fares Roudesly, and
Luis Veiros
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Advanced Synthesis & Catalysis
10.1002/adsc.202000249
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Ru-Catalyzed Carbonylative Murai Reaction: Directed C3-
Acylation of Biomass-Derived 2-Formyl Heteroaromatics
a,b
a
c
b
a,
Roberto Sala, Fares Roudesly, Luis F. Veiros, Gianluigi Broggini, Julie Oble, *
a,
and Giovanni Poli *
a
Sorbonne Université, Faculté des Sciences et Ingénierie, CNRS, Institut Parisien de Chimie Moléculaire, IPCM, 4
place Jussieu, 75005 Paris, France
E-mail: julie.oble@sorbonne-universite.fr, giovanni.poli@sorbonne-universite.fr
Dipartimento di Scienza e Alta Tecnologia (DISAT), Università degli Studi dell’Insubria, Via Valleggio 9, Como
b
(
CO), Italy
c
Centro de Química Estrutural and Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de
Lisboa, Av Rovisco Pais, 1049-001 Lisboa, Portugal
Received: ((will be filled in by the editorial staff))
Dedicated to the memory of Professor Kilian Muñiz
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. The Murai reaction is a ruthenium-catalyzed
transformation leading to alkylated arenes through the C–C
bond formation between an alkene and an arene bearing a
directing group. Discovered in the nineties, this useful C–H
activation based coupling has been the object of intense
study since its discovery. After having studied the Murai
reaction on 2-formylfurans of biomass derivation, we
describe here the carbonylative version applied to 2-
formylfurans, 2-formylpyrrols and 2-formylthiophenes. This
acylation reaction takes place regioselectively at C3 position
of the heterocyclopentadienes thanks to the installation of
removable imine directing groups.
The transformation can be achieved by treating the two
reaction partners with a catalytic amount of Ru (CO)12, in
toluene at 120-150 °C, after CO bubbling, at atmospheric
pressure. DFT computations of the full catalytic cycle help
in deciphering the mechanism of this transformation, and to
rationalize the different behaviors depending on the nature of
imine directing groups.
3
Keywords: carbonylation; C-H activation; homogeneous
catalysis; Murai reaction; ruthenium;
C–H activation process,[15–17] without prior
modification of the redox state of the aldehyde
function, is an extremely attractive eco-compatible
strategy that remains scarcely explored on furfurals. In
particular, most of the reported examples address
Introduction
Furfural
1
and the related compound 5-
(
hydroxymethyl)furfural (HMF) 2 are important
[1,2]
[18–21]
[22]
building blocks
derived from cyclodehydration of
arylation,
alkenylation,
alkylation and the
lignocellulosic biomass.[
3,4]
Since their large-scale
alkynylation at C5 of the furan ring, which is the
most electron-rich site. In contrast, C3–H
functionalization at the formyl-furan unit via directing
[23]
production from agricultural residues is developed
worldwide, these synthons constitute highly sought-
after raw materials for the sustainable production of
groups that overwhelm the natural C5 preference has
[5]
[24–26]
value-added compounds for industrial purposes.
been scarcely studied
and remains a challenge.
Consequently, their valorization has become a
privileged approach for the replacement of depleting
fossil resources. Accordingly, simple transformations
Within a broad project directed toward the
sustainable functionalizations of furfural derivatives
[27–
focused on TM-catalyzed C–H activation process,
of 1[ and 2
6–9]
[10–13]
into more elaborated intermediates,
29]
we have recently established that the TM-catalyzed
C3–H activation of furfurals can be successfully
achieved by using nucleophilic TM catalysts that
undergo an initial oxidative addition step of the
biofuels, as well as some applications in the fields of
polymers,[ have been already reported. Currently,
the development of new selective functionalizations of
furfurals is becoming a competitive area of research to
access more complex furan-containing heterocycles.
In this perspective, the selective formation of new
bonds through direct transition metal (TM) catalyzed
14]
[16]
targeted C–H bond. On the contrary, electrophilic
TM-complexes that elicit an electrophilic concerted
metalation-deprotonation mechanism appear to be
proscribed. Accordingly, we reported a Ru(0)-
1
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Advanced Synthesis & Catalysis
10.1002/adsc.202000249
catalyzed hydrofurylation of olefins (Murai
1e).
Although
some
TM-catalyzed
direct
reaction)[
30,31]
that involved the directed C3–H
functionalizations of pyrrole or thiophene 2-
carboxaldehydes have been reported, these studies
activation of the furan ring through the transient
[39–42]
involvement of an amino-imine directing group
have mainly addressed C5-arylation
and C5-
Figure 1a).[ A thorough experimentation supported
27]
alkylation, while the C3-functionalization has been
[23]
(
[24,43]
by DFT calculations revealed that only a bidentate
N,N’-imino-amino directing group was able to
efficiently promote the desired alkene hydroarylation.
This result led us to envisage an extension of this C3-
functionalization strategy toward a carbonylative
only very marginally explored.
Herein, we disclose the first C3-carbonylative
versions of the Murai reaction on furfural derivatives,
pyrrole 2-carboxaldehydes and their benzo-fused
analogs – indoles – as well as on thiophene 2-
carboxaldehydes, through their corresponding
aldimines, which act as removable directing groups.
Optimal imines to be used for each type of substrate
were established through an in-depth experimental
screening, while DFT computations provided
[
32]
version of the Murai reaction
using carbon
monoxide (CO) as a natural[33] and cheap C1 source
(
Figure 1c). To the best of our knowledge, there is only
one example reporting the C3-propionylation of
furfural t-butylimine, which takes place under high
pressure of CO and ethylene (Figure 1b).[
34,35]
From a
mechanistic insights.
[44]
synthetic viewpoint, the direct C3-acylation of
furfurals is a particularly attractive transformation, as Results and Discussion
it is complementary to the Friedel-Crafts acylation,
which generally occurs at the C4 position of the 2-
Development of a Ru-catalyzed C3-acylation of
formylfuran unit.[
36]
furfurylimines. From the outset of this study, the use
of an atmospheric pressure of CO has been chosen as
opposed to the use of high pressure, which requires a
special equipment. Accordingly, the reaction media
were saturated by bubbling CO during 5 min before
turning off the cylinder and heating the reaction
mixture. We started our investigation by testing a
[45]
series of furfurylimines (F3(a-j)) – readily prepared
in one step from furfural 1 – in the presence of
triethoxyvinylsilane (4 equiv.) as the alkene partner
and Ru (CO)12 (5 mol%) as the pre-catalyst, in toluene
3
at 120-135 °C (see Supporting Information, Tables 1
and 2). After some preliminary experiments, optimal
results could be obtained using the aromatic electron-
rich p-methoxyphenylimine (PMP-imine) F3c, which
led to the desired C3-acylated imine F4ca in 66% yield
(
85% NMR yield) at 120 °C (Scheme 1). Noteworthy,
in the absence of CO atmosphere, this PMP-imine
[27]
displayed a very low “classic Murai” reactivity.
Furthermore, t-butylimine F3a as well as the N,N’-
bidentate imine F3b, which previously gave
satisfactory results in the C3-propionylation under
[34]
pressure of CO and ethylene (Figure 1b) as well as
[27]
in the C3-alkylation (classic Murai) (Figure 1a),
respectively, failed to afford the corresponding
alkylated or acylated products (Scheme 1).
Figure 1. Ru-catalyzed direct C3-functionalization of
furfural,
2-formylpyrrole
and
2-formylthiophene
derivatives.
Pyrrole 2-carboxaldehyde was another substrate
considered for our carbonylative study (Figure 1d).
Given its accessibility from furfural in one step,
through a Paal-Knorr synthesis,[37] or in three steps
through a carbonyl reduction / Achmatowicz
Scheme 1. Ru-catalyzed direct C3-acylation of
furfurylimines: screening of the imine directing groups.
[45]
The scope of this C3-carbonylative Murai reaction was
subsequently studied with the PMP-imine F3c in the
presence of a variety of trialkoxy-, trialkyl- and triaryl-
[38]
rearrangement / Maillard condensation sequence,
this substrate can be regarded as a biomass-derived
building block, too. Extension to thiophene 2-
carboxaldehyde was also envisaged, to verify the
generality of the heterocyclopentadiene family (Figure
vinylsilanes (4 equiv.) and Ru
3
(CO)12 (5 mol%), in toluene
(
0.5 M) at 120-135 °C during 16-24 h.
2
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Advanced Synthesis & Catalysis
10.1002/adsc.202000249
Scheme 2. Scope of Ru-catalyzed direct C3-acylation of PMP-furfurylimines (top) and acid hydrolysis of the C3-acylated-
imines leading to C3-acylated furfurals (PMP = p-methoxyphenyl, TBS = tert-butyldimethylsilyl) (bottom).
A rapid chromatographic purification on deactivated
silica gel allowed to obtain moderate to good yields of
the corresponding C3-acylated imines F4c(a-e) (53-
(Supporting Information, Table 3). We investigated
next the carbonylative version by prior CO bubbling
during 5 min, as from our previous protocol with the
oxygen-based substrates. To our delight, the two
pyrrole substrates P3Bn(a-b), bearing a bidendate
aminoimine group, as well as of the two substrates
P3Bn(c-d) bearing an electron-rich aromatic imino
group, in the presence of triethoxyvinylsilane (4
equiv.), allowed us to isolate exclusively the acylated
products P4Bn(a-d)a in excellent NMR yields (Scheme
3, bottom). The results, accompanied by additional
optimization parameters such as the nature of the N-
66% isolated yields) (Scheme 2, top). However, in the
case of trialkyl- and triaryl-vinylsilanes, good yields
were only obtained when the mixtures were heated at
1
35 °C. The reaction was also studied with styrenes,
which unfortunately failed to react. The scope was
next extended to C5-substituted furfurals such as 5-
methylfurfural-PMP-imine F5c and the TBS-O-
protected HMF PMP-imine F7c. In the event, the
corresponding C3-acyclated imines F6c(a-d) and
F8c(a-d) could be isolated in reasonable to good yields. protecting group of the pyrrole ring and the number of
The 5-phenyl derivative was also effective, but only
through its p-dimethylaminophenyl-imine F9d,
whereas the PMP-imine led to complex results.
Besides, a double coupling was successfully achieved
with the HMF-dimer diimine F11c using eight
equivalents of triethoxyvinylsilane, which gave the
diacylated HMF imine dimer F11ca. Finally, the
subsequent acid hydrolysis of the alkyl and aryl silyl
derivatives F(4-8)cy enabled access to the C3-
acylated-furfurals F(13-15)y in quantitative yields
silane equivalents are summarized in the Supporting
Information, Tables 4 and 5.
(
Scheme 2, bottom).
Ru-catalyzed C3-acylation of pyrrole and indole 2-
carboxaldimines. We continued our investigations on
pyrrole 2-carboxaldimines, easily prepared from
pyrrole 2-carboxaldehyde P1. The classic Murai
reaction conditions[ were first tested on various N-
benzylpyrrole imines P3Bn(a-c) in the presence of
Scheme 3. Ru-catalyzed Murai reaction and carbonylative
variant of pyrrole 2-carboxaldimines.
27]
triethoxyvinylsilane (3 equiv.) and Ru (CO)12 (5
3
The scope of the C3-carbonylative Murai reaction on
mol%), in toluene (0.5 M) at 135 °C during 16 h. In
the event, N,N’-bidentate imines P3Bn(a-b) and p-
methoxyphenylimine P3Bnc led to traces of the
corresponding C3-alkylated products P4’Bn(a-c)a
together with the C3-acylated ones P4Bn(a-c)a
pyrrole derivatives was carried out on the N,N’-
bidentate imine P3Bna, in the presence of Ru (CO)12 (5
3
mol%), and triethoxy-, triaryl-, trialkyl-vinylsilanes or
styrene derivatives (4 equiv.), in toluene (0.5 M) at
1
35 °C under CO atmosphere during 16 h (Scheme 4,
(
Scheme 3, top). Further optimization tests did not
top).
allow to selectively obtain the C3-alkylated products
3
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Advanced Synthesis & Catalysis
10.1002/adsc.202000249
Scheme 4. Ru-catalyzed directed C3-acylation of pyrrole and indole 2-carboxaldimines.
The use of the alkylimine allowed the direct isolation
of the alkylated aldehydes P13Bny through silica gel
purification. The reaction was additionally explored
on PMP-imines, which are robust aromatic imines
Although the thienyl substrates proved to be less
reactive than the corresponding furyl and pyrrolyl
derivatives, a reactivity trend analogous to the one of
the O-based heterocyclopentadienes was manifest.
Indeed, the bidentate imine T5b reacted as expected
allowing the use of
a
larger variety of
trialkoxyvinylsilanes. In the event, these derivatives
gave us access to different C3-acylated imines from
with triethoxyvinylsilane
triethylvinylsilane and styrene – in presence of
Ru (CO)12 (5 mol%), in toluene (0.5 M) at 135 °C,
–
but not with
[38]
pyrrole P3Bnc, the C5-substituted pyrrole P5Bn
c
and
3
indole I3Bnc (Scheme 4, bottom). With trialkyl- and
triaryl-vinylsilanes, acid hydrolysis of the C3-acylated
imines P4Bnc(d,f), P6Bncd and I4Bnc(d,f) led to the
corresponding aldehydes P13Bn(d,f), P15Bnd and
I13Bn(d,f) in good yields over two steps. In the case of
styrene derivatives, best yields were obtained using
leading to the corresponding C3-alkylated aldehyde
T14a in a moderate yield (Scheme 5, top), and the
corresponding acylated products were never detected,
even when working in the presence of CO atmosphere.
dimethylaminophenyl-imine P3Bn
d
for pyrrole,
whereas PMP-imines P5Bnc and I3Bnc led to desired
product with satisfactory results.
In summary, the reactivity of pyrrole 2-
carboxaldimines and of the benzo-fused analogues
does not parallel that observed with the corresponding
furfurylimines. Indeed, while in the case of the O-
based heterocyclic substrates, bidentate imines allow
C3-alkylation and electron-rich aromatic imines allow
C3-acylation,
with
the
N-based
heterocyclopentadienes both imine types – bidendated
as well as monodentated – allow the C3-acylation and
forbid the “classical Murai”.
Scheme 5. Ru-catalyzed Murai reaction and carbonylative
variant of thiophene 2-carboxaldimines.
Ru-catalyzed C3-alkylation and acylation of
thiophene 2-carboxaldimines. To expand the scope
of this new method, the Murai reactions were also
performed on thiophene 2-carboxaldimines, whether
as bidentate or monodentate imines (PMP-imine).
4
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Advanced Synthesis & Catalysis
10.1002/adsc.202000249
Conversely, treatment of PMP-imine T5c with
triethoxy- (T6ca) or triethyl-vinylsilanes (T6cc) at
1
35 °C gave traces of the corresponding alkylated and
acylated products in the absence of CO, and moderate
yields of the corresponding C3-acylated products
under CO atmosphere (Scheme 5, bottom).
Noteworthy, these reactions required an increase of the
CO bubbling time from 5 to 8 min to totally suppress
the competing alkylated product. The reaction was
also possible with a styrene derivative (8 equiv.) by
increasing the temperature (150 °C) and the reaction
time (48 h). As previously observed, the subsequent
acid hydrolysis of C3-acylated imines T6(c,d)y
enabled access to the C3-acylated-aldehydes T14y in
quantitative yields.
Synthetic applications. The post-functionalization of
some C3-acylated five-membered heterocycles were
next evaluated. First, Tamao-Fleming oxidations were
performed on the C3-acylated furfurylimines F(4,6)ca
as well as on pyrrole P4Bnca and indole 2-
carboxaldimines I4Bncb. Thus, treatment of the above
Scheme 7. Simplified catalytic cycle. Free energy values
relative to the initial reactant, A.
compounds with KF, KHCO
3
and H
2
O
2
led to
corresponding alcohols in good yields, without further
optimizations (Scheme 6, top). Furthermore, treatment
of aldehydes (P,I)13Bnf with KHMDS (1.2 equiv.)
gave the corresponding aldols (P-I)18Bnf in moderate
yields (dr 1:1), without traces of the dehydrated
products (Scheme 6, bottom).
The initial species in the proposed mechanism has the
imine substrate coordinated to the Ru(CO) fragment
3
(A in the calculations). From A, there is an oxidative
addition of the C3–H bond in the pyrrole ring to the
metal center with formation of an hydride
intermediate, complex B, in the opening step of the
mechanism. Thus, the metal is formally oxidized from
0
II
Ru , in A, to Ru , in B. That is a fairly easy step with
a barrier of 14 kcal/mol and a free energy balance of
ΔG = 3 kcal/mol. The reaction proceeds with olefin
coordination followed by insertion into the Ru–H
bond. Alkene coordination occurs with simultaneous
break of imine coordination (intermediate C, see
Supporting Information) and the insertion process
results in a high energy intermediate where
coordination of the newly formed alkyl ligand is
stabilized by a C–H agostic interaction (intermediate
D). Recoordination by the Nimine lone pair breaks the
agostic interaction and results in the alkyl intermediate
E.
Scheme 6. Synthetic applications.
That process overcomes a barrier of 23 kcal/mol
associated with the transition state for olefin insertion
Mechanistic investigations. The mechanism of C3-
(TS ). This is the highest energy transition state along
CD
[
46]
acylation was studied via DFT calculations
for
the path and corresponds to the determining transition
state of the process (TDTS). Overall, alkene insertion
into the hydride complex – from B to E – is a favorable
process with ΔG = –11 kcal/mol. The mechanism
proceeds with CO insertion into the alkyl ligand in E,
resulting in the acyl complex F. The CO insertion step
is clearly endergonic with ΔG = 14 kcal/mol and the
pyrrole P3Bnc with trimethoxyvinylsilane used as
alkene model. The generally accepted mechanism for
the Murai reaction and its carbonylative variant
involves a mononuclear Ru(0) complex as the first
active species.[
47,48]
We thus anticipated the conversion
of the Ru (CO)12 pre-catalyst into a mononuclear
3
ruthenium carbonyl by Ru-Ru breaking and CO
releasing,[ similarly to what previously assumed in
the mechanistic study of the Murai reaction with furan
substrates. Nevertheless, it should be noticed that the
simplicity of the model employed may limit the scope
of the calculations. The simplified calculated catalytic
cycle is represented in Scheme 7, while the complete
reaction free energy profile is presented as Supporting
Information.
corresponding transition state (TS ) has an energy of
EF
49]
13 kcal/mol relative to A, corresponding, thus, to a 21
kcal/mol barrier, measured from E. In the following
step, a new CO molecule coordinates the metal, from
F to H, in a very facile process with a transition state
only 3 kcal/mol less stable than F. The resulting acyl
complex, H, is the most stable species along the entire
mechanism, being 22 kcal/mol more stable than the
5
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Advanced Synthesis & Catalysis
10.1002/adsc.202000249
initial reactant and corresponds to the determining
intermediate in the process (TDI). In the final step, the
acyl ligand inserts into the Ru–Cring bond in a reductive
elimination process that brings the metal back to its
decoordination of the imine nitrogen atom to allow
alkene insertion.
Competition between CO insertion into the alkyl chain
and into the coordinated pyrrole ring was also
addressed by the calculations. The results indicate that
the second process is clearly unfavorable, the energy
difference between the respective transition states
being of 10 kcal/mol (compare Figure S3 with S5 in
SI).
0
initial oxidation state, Ru . This last step is endergonic
(
ΔG = 6 kcal/mol) and overcomes a barrier of 21
kcal/mol, measured from the acyl intermediate, H, to
the following transition TSHI that is 1 kcal/mol more
stable than A. The entire cycle is exergonic, the final
species (I) being 16 kcal/mol more stable than the
initial reagent (A) and has an overall barrier of 27
kcal/mol, measured from H to the transition state for
olefin insertion of the following cycle, TSCD. Closing
of the cycle, with liberation of the acylated product and
coordination of a new imine substrate, from I back to
A, has a favorable free energy balance of ΔG = –2
kcal/mol.
Comparison between the reductive elimination and the
CO insertion steps starting from the common
tricarbonyl intermediates deriving from furan imine
F3b and pyrrole imine P3Bnb after olefin insertion,
shows that the barrier associated with the reductive
elimination is higher than the one associated with the
CO insertion, by 34 kcal/mol in the case of the furan
imine and by 6 kcal/mol in the case of the pyrrole
imine (Figure 2). This confirms that in the presence of
CO atmosphere the reductive elimination step is
always intrinsically disfavored with respect to CO
insertion. This result is in line with the fact that furan
imines of type Fc and Fd as well as pyrrole imines of
type PBnb and PBnc showed successful acylative
reactivity under the reaction conditions, but is not in
accord with the behavior of the furan derivative of type
Fb, which carries the aliphatic imine with amine tail.
We speculate that the failure to observe acylative
reactivity in this latter case has to be due to an
energetically prohibitive step upstream in the cycle,
probably at the alkene insertion stage. Conversely,
successful alkylative reductive elimination – i.e.
classic Murai reactivity – obtained carrying out the
reaction in the absence of CO bubbling, could be
obtained only in the case of the furan derivatives such
as F3b, bearing an imine derived from an aliphatic
amine in turn carrying a pending aliphatic amine tail,
while it failed with the furan derivatives carrying the
aromatic PMP imine as well as with all the pyrrole
derivatives tested. These conclusions are also in line
with the results obtained with 2-formyl-thiophene
derivatives which have shown a similar reactivity
trend to furfuryl derivatives depending on the imine
used. It thus appears that, at least within the
heterocyclopentadiene substrates investigated in our
studies, the classic Murai reactivity can be achieved
only when the following two features are met at the
same time: furan (or thienyl) nucleus, and aliphatic
imine with an amine tail. We speculate that a necessary
Figure 2. Free energy profile (kcal/mol) for the comparison
between CO insertion into the alkyl ligand (left side) and
insertion of the alkyl into the heterocyclic ring (right side),
[50]
2 2 2 3
R = (CH ) N(CH ) .
Conclusion
In summary, this work showed that the carbonylative
Murai reaction (i.e. the Ru(0)-catalyzed acylation in
the presence of an alkene and excess carbon monoxide
at atmospheric pressure) can be successfully
accomplished at the C3 position of 2-formyl
heterocyclopentadienes thanks to the easy installation
of removable imine directing groups on the formyl
function. The carbonylative C–H activation couplings
developed in this study, greatly expand the scope of the
Murai reaction on the heterocyclopentadienes,
allowing to almost complete the puzzle comprising the
possible alkylative and acylative combinations
(
Scheme 8).
–
though not sufficient – condition to achieve the
Scheme 8. State of the art of the Murai reaction on 2-formyl
classic Murai reaction is the presence of an
alkylamine-derived imine directing group, whose
nitrogen atom stays coordinated to the Ru atom
throughout the catalytic cycle, while the carbonylative
heterocyclopentadiene after this work.
These results are of especial value, if we consider that
the furan substrates are of direct biomass derivation
Murai
reaction
necessarily
involves
the
6
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Advanced Synthesis & Catalysis
10.1002/adsc.202000249
(
furfural and hydroxymethylfurfural), and that
[8] K. Yan, G. Wu, T. Lafleur, C. Jarvis, Renew. Sustain.
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pyrroles can be in turn obtained from furans. This
work, summed with our previous study on the Murai
reaction[ indicate that the outcome of these coupling
reactions highly depend on the subtle interplay
between the nature of the heteroatom of the
heterocycle and on the nature of the directing imine
function. DFT computations shed light on the complex
mechanistic puzzle associated to these coupling
reactions, although a definitive solution has to wait for
further work. Future studies will be directed, inter alia,
to achieve the fourth and last combination left
unsolved: the classical Murai reaction from 2-
formylpyrrole derivatives.
[
9] A. Bohre, S. Dutta, B. Saha, M. M. Abu-Omar, ACS
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The authors would like to acknowledge Horizon 2020 ERANet-
LAC project CelluloseSynThech for financial support as well as
CNRS, Sorbonne Université and Labex Michem (Investissements
d'Avenir program under reference ANR-11-IDEX-0004-02).
Support through CMST COST Action, CA15106 (CHAOS) is also
gratefully acknowledged. L.F.V. acknowledges Fundação para a
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8
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10.1002/adsc.202000249
FULL PAPER
Ru-Catalyzed Carbonylative Murai Reaction:
Directed C3-Acylation of Biomass-Derived 2-
Formyl Heteroaromatics
Adv. Synth. Catal. Year, Volume, Page – Page
Roberto Sala, Fares Roudesly, Luis F. Veiros,
Gianluigi Broggini, Julie Oble,* and Giovanni
Poli*
9
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