Copper-Catalyzed Selective Pyrrole Functionalization by Carbene Transfer Reaction

Article abstract of DOI:10.1002/adsc.201901629

1H-Pyrroles can be directly functionalized by means of the incorporation of carbene groups from diazo compounds, in a process catalyzed by Tp^xCu complexes (Tp^x=hydrotrispyrazolylborate ligand). The reactions take place with a complete selectivity toward the formal insertion of the carbene into the C_α?H bond, leading to alkylated pyrroles, with no modification of the C_β?H, N?H or C=C bonds of the pyrrole unit. Alkyl substituents at C-ring as well as alkyl, aryl, allyl or alkyne substitution at N atom are tolerated, the strategy affording 20 new pyrrole derivatives. The observance of partial deuteration at the methylene group when the reaction is carried out with added D₂O serves to discard the direct insertion of the carbene group into the C_sp2?H bond, the alternative electrophilic attack to the pyrrole ring being feasible. (Figure presented.).

Full text of DOI:10.1002/adsc.201901629

Title: Copper-catalyzed selective pyrrole functionalization by carbene
transfer reaction
Authors: Anabel Moreno, Francisco Molina, M. Mar Díaz-Requejo, and
Pedro J. Perez
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201901629
Link to VoR: http://dx.doi.org/10.1002/adsc.201901629

10.1002/adsc.201901629
Advanced Synthesis & Catalysis
VERY IMPORTANT PUBLICATION
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Copper-Catalyzed Selective Pyrrole Functionalization by
Carbene Transfer Reaction
Anabel M. Rodríguez,a Francisco Molina,a M. Mar Díaz-Requejo*,a and Pedro J.
Pérez*,a
aLaboratorio de Catálisis Homogénea, Unidad Asociada al CSIC, CIQSO-Centro de Investigación en Química Sostenible
and Departamento de Química, Universidad de Huelva, Campus de El Carmen s/n, 21007-Huelva, Spain
e-mail: perez@dqcm.uhu.es, mmdiaz@dqcm.uhu.es
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. 1H-Pyrroles can be directly functionalized by atom are tolerated, the strategy affording 20 new pyrrole
means of the incorporation of carbene groups from diazo derivatives. The observance of partial deuteration at the
compounds, in a process catalyzed by TpxCu complexes (Tpx methylene group when the reaction is carried out with
= hydrotrispyrazolylborate ligand). The reactions take place added D2O serves to discard the direct insertion of the
with a complete selectivity toward the formal insertion of the carbene group into the Csp2-H bond, the alternative
carbene into the C-H bond, leading to alkylated pyrroles, electrophilic attack to the pyrrole ring being feasible.
with no modification of the C-H, N-H or C=C bonds of the
pyrrole unit. Alkyl substituents at C-ring as well as alkyl,
aryl, allyl or alkyne substitution at N
Keywords: Pyrrole functionalization, copper catalysis,
carbene transfer, diazo compounds, C-H functionalization,
selectivity;
Introduction
The metal-catalyzed carbene transfer reactions
from diazo compounds constitutes a useful tool in
organic synthesis,[1] incorporating such moiety to the
structure of many compounds either by addition to
unsaturated C-X (X = C, N) bonds or by insertion
into saturated C-Y bonds (Y = H, halide). Thus, many
substrates have been modified following this strategy,
including alkanes, alkenes, alkynes, arenes, alcohols
or amines, among others.[1] Heterocycles such as
furans,[2] indoles[2] or pyrroles[3] have also been
employed as substrates, where the carbene group can
be incorporated to several saturated or unsaturated
moieties, catalyst design becoming crucial toward the
control of the selectivity.
Following our previous work[4] on the use of group
11 metal-based catalysts for carbene transfer
reactions from diazo compounds, we have now
focused in pyrroles as substrates. Albeit a number of
transformations have been described involving the
incorporation of a carbene group to pyrrole skeleton,
in an area mainly dominated by rhodium-based
catalysts,[5] we noticed that there is not any example
of 1H-pyrroles being modified by this metal-induced
methodology, only N-protected pyrroles being
employed as substrates. Also, the chemoselectivity of
this transformation is highly dependent on the N-
Scheme 1. Early examples of pyrrole functionalization
by carbene incorporation and the selective
functionalization of CH bonds work described herein.
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901629
Advanced Synthesis & Catalysis
substituent: electron withdrawing groups favor C=C
of diethyl fumarate and maleate. Other TpxCu-based
catalysts were also tested for this transformation,
such as [TpMe2Cu(NCMe)] or TpMsCu(THF), their
activities being moderate compared with that of the
TpBr3-containing catalyst. The [Tp*,BrAg]2 complex[9]
was also tested, yielding a successful 75% yield into
1, in the first example of a silver-based catalyst for
pyrrole functionalization by this methodology. We
also evaluated a series of IPrMCl catalysts (M = Cu,
cyclopropanation
whereas
N-alkyl-substituted
pyrroles often result in C-H insertion products.
Fowler first described[6] the cyclopropanation of a
pyrrole (Scheme 1), using CuBr as the catalyst, and
ethyl diazoacetate as the carbene source. Maryanoff
later reported the insertion into C-H bonds with
[7]
Cu(acac)2. Reiser introduced the chiral version
using Cu-bis(oxazoline), thus inducing enantiomeric
excesses in the mono- and bis-cyclopropane
products.[5d,8]
To the best our knowledge, there are no examples
of the selective functionalization of the C-H bonds of
N-H unprotected pyrroles by carbene incorporation
from a diazo compound. This is a quite challenging
transformation, in view of the potential reaction sites
at a given pyrrole (Scheme 1), where the carbene
group can be transfer to N-H, Csp2-H, Csp3-H or C=C
bonds. Herein we report the excellent activity of
several TpxCu complexes as catalysts for the selective
functionalization of pyrroles, with a noticeable degree
of tolerance to other functional groups. For the Csp2-H
functionalization cases the products correspond to the
formal insertion of the carbene group in such bonds,
albeit this is not the actual case from a mechanistic
point of view.
Ag, Au; IPr = 1,3-bis(2,6-diisopropylphenyl)imidazo-
2-ylidene) in view of the previously reported activity
for carbene transfer reactions.[10] The yields into 1
were lower (Cu, 53%; Ag, 15%; Au, 42%) than those
obtained with the TpBr3M-based catalysts (M = Cu,
Ag).
Ethyl 2-phenyldiazopropionate (PheDA) was
chosen as the model for a disubstituted carbene group.
The reaction barely proceeded at room temperature,
but heating at 60 ºC in DCE induced the complete
consumption of the diazo compound. Compound 2
was formed in 80% yield, derived from the
functionalization of the Cα-H bond (eq 1).
The syntheses of compounds 1 and 2 constitute the
first examples of the direct functionalization of 1H-
pyrrole by carbene insertion, with such high
conversions and selectivity. At variance with the
examples described by Maryanoff,[7] where C-H
Results and Discussion
Pyrrole and unprotected N-H pyrroles as
substrates.
We first targeted the challenging pyrrole as the
substrate, using TpBr3Cu(NCMe) as the catalyst in
view of its outstanding performance in carbene
transfer reactions to saturated and unsaturated
substrates.[4b] With ethyl diazoacetate (EDA) as the
Scheme 3. Alkyl-substituted pyrroles as substrates.
bonds were also altered, in our case only the insertion
into the C-H bonds is observed. In an effort to push
the reaction toward the former, we employed 2-ethyl-
1H-pyrrole as the substrate, under the standard
catalytic conditions (see Scheme 2 and eq 1), with
TpBr3Cu(NCMe) as the catalyst. The products 3 and 4
were obtained in high yields, as inferred from NMR
studies with the reaction crudes (>95%), showing the
exclusive functionalization of the C-H bond
(Scheme 3). Only when 2,5-dimethyl-1-H-pyrrole
was employed, the reaction proceeded at the C-H
bond, leading to the formation of compounds 5 and 6
(Scheme 3, see SI for full description of novel
compounds 3-6).
Scheme 2. TpxCu-catalyzed functionalization of
pyrrole.
carbene source, the reaction proceeded at room
temperature in 1.5 h using 0.01 mmol of catalyst, 20
equiv of EDA and 100 equiv of pyrrole (Scheme 2),
resulting in the selective formation of compound 1,
where the carbene group has formally inserted into
the Cα-H bond in 85% yield (EDA-based).
Compound 1 was fully characterized by NMR
spectroscopy (see SI): it is worth mentioning the
observation of a broad singlet at 8.74 ppm
corresponding to the N-H group.
The remaining
15% of the initial EDA was converted into a mixture
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901629
Advanced Synthesis & Catalysis
The use of 2,4-dimethyl-1H-pyrrole brought some
additional information to this catalytic system
(Scheme 4). With EDA as the carbene source and
TpBr3Cu(NCMe) as the catalyst, a mixture of two
Scheme 4. Functionalization of Cβ-H bond using 2,4-
dimethyl-1H-pyrrole as substrate.
Scheme 5. Intramolecular competition for carbene
incorporation in 2-vinyl-1H-pyrrole as the substrate.
different electronic and steric characteristics,
obtaining a nearly equimolar mixture of both
products 12 and 13.
compounds was obtained, derived from carbene
incorporation into both C-H bonds (7, 8), in a ca. 3:1
ratio, favoring that of the insertion into the C-H
bond. Interestingly, the use of other TpxCu catalysts
showed the effect of the catalyst structure in the
reaction outcome. Thus, those bearing TpMe2 or
Tp(CF3)2,Br ligands (with similar steric hindrance but
different electronic density at metal)[11,12] provide a
similar ratio, whereas the bulkier TpMs-containing
catalyst exclusively provided compound 6. Moving to
PheDA as the diazo compound showed the exclusive
formation of 9 with both TpBr3- or TpMs-based
catalysts. These data demonstrate that the carbene
transfer is mainly influenced by the steric pressure of
the Tpx ligand, the  position being more hindered
than the  counterpart in this substrate.
N-Substituted pyrroles as substrates: tolerance to
diverse functional groups.
Once investigated the catalytic behavior of N-H
unprotected pyrroles, we moved onto N-methyl-
pyrrole as the substrate. With TpBr3Cu(NCMe) as the
catalyst and EDA as the carbene source, the room
temperature transformation led to the formation of the
product 14 in 70 % yield (by NMR quantification of
the reaction crude, diethyl fumarate and maleate
accounting for 100% of the initial EDA) formed upon
incorporation of the carbene unit into the Cα-H bond
The collected results demonstrate the
preferential incorporation of the carbene group into
the Csp2-H bonds of pyrrole ring, with no
modification of the N-H or the C=C bonds neither the
alkyl substituents. To evaluate an intramolecular
competition for the carbene group, we synthesize 2-
vinyl-1H-pyrrole. Scheme 5 shows the results
obtained using different TpxCu-based catalysts and
two diazo compounds. In the case of the EDA,
products derived from the insertion into the Cα-H
bond (10) as well as from the addition to the vinyl
C=C bond (11) are observed. Electron-poor metal
catalysts (containing TpBr3 or Tp(CF3)2,Br ligands)
provide distribution of products 10:11 close to
equimolar (42:58, 46:54) whereas the sterically
similar, more electron rich TpMe2Cu clearly favors the
formation of 11 (16:84). Steric factors appear
prominent when the very bulky TpMsCu catalyst is
employed, leading to a 12:88 ratio for 10:11. Unlike
with EDA, no significant changes in the
regioselectivity can be observed in the case of PheDA
as the diazo reagent for the selected catalysts with
Scheme 6. Reaction of 1-methyl-1H-pyrrole with ethyl
diazoacetate using TpBr3Cu(NCMe) as the catalyst.
(Scheme 6). During the purification of the reaction
mixture by column chromatography, compound 15
(Scheme 6) was also obtained, in addition to 14,
albeit it was not detected at the end of the reaction,
thus forming due to partial decomposition during
purification. The use of TpMe2Cu(NCMe) and
TpMsCu(THF) did not improve the results with the
perbromo catalyst, the amount of 15 remaining as
minor in all cases after column chromatography.
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901629
Advanced Synthesis & Catalysis
When PheDA was used as the carbene source,
Table 1. N-Substituted pyrroles as substrates for
carbene incorporation.
heating at 60 ºC was required to accomplish the
consumption of the diazo compound, employing
TpBr3Cu(NCMe) as catalyst, and using
a
[Cu]:[PhEDA]:[N-Methyl-pyrrole] ratio of 1:20:100.
After 4h of reaction time, compound 16 (Scheme 7).
The use of two equiv of PheDA led to the
Scheme 7. Mono- and disubstituted functionalization of
N-methylpyrrole with ethyl 2-phenyldiazopropionate.
quantitative formation of compound 17, as the result
of the double functionalization of the pyrrole at both
C-H bonds (see SI for detailed description of the
products, including X-ray characterization for 17). As
expected, the double activation is favored when using
a two-fold excess of PheDA with respect to the
pyrrole
Next we studied the scope of this transformation
regarding the substitution at nitrogen, with a series of
2,5-dimethyl-N-substituted pyrroles. Table 1 shows
the results obtained, for both EDA and PheDA as
carbene sources. In all cases the insertion of the
carbene unit into the C-H bond was observed, in
spite of the presence of alkene or alkyne
functionalities attached to the N atom. Alkyl and
cycloalkyl Csp3-H bonds were also tolerated, in spite
of the capabilities of the TpBr3Cu(NCMe) catalyst to
transfer the carbene group to those bonds. N-Boc and
N-Ph 1H pyrroles constitute the limit of the system,
seems they do not provide the expected products,
whereas 1,5-dimethyl-1H-pyrrole-2-carbonitrile only
gives minor yields (10-15%) of the insertion product.
The methodology presented herein provides a
series of 26 functionalized pyrroles, from which only
three have been previously reported using carbene
transfer reactions from diazo compounds (5,[13] 7[14]
and 14[6]), assessing the potential of this catalytic
system as a synthetic tool.
[a] Reactions carried out at room temperature with 0.01 mmol of
catalyst, 20 equiv of EDA and 100 equiv of the corresponding
pyrrole in 6 mL of CH2Cl2. Reaction time: 2 h.
[b] Reactions carried out at 60 ºC with 0.01 mmol of catalyst, 20
equiv of PheDA and 100 equiv of the corresponding pyrrole in 6 mL
of CH2Cl2. Reaction time: 4 h.
[c] Yields determined by NMR using 1,3,5-trimethoxybenzene as
internal standard. Diethyl fumarate and maleate accounted for 100%
of initial diazo compound.
Scheme 5. Scope reaction with N-substituted pyrroles.
the NMR spectra of these experiments, as well as that
in the absence of D2O. Partial deuteration of the
methylene group attached to the pyrrole ring was
observed, as inferred from the appearance of a 1:1:1
triplet due to the -CHD- group (Figure 1).
Noteworthy, the degree of deuteration increased
when augmenting the amount of added D2O. We
interpret this observation as a proof of the absence of
a direct insertion of the carbene into the Csp2-H. A
similar behavior was observed using pyrrole or 2,5-
dimethylpyrrole as the starting materials (see SI).
Mechanistic interpretation.
The reaction outcome of the catalytic system
reported herein corresponds to the formation of
compounds which can be formally considered as the
result of the metal-mediated transfer and insertion of
a carbene group into a Csp2-H bond. To shed light on
this issue, the reaction of 2-ethyl-1H-pyrrole with
EDA was carried out in the presence of added D2O,
with TpBr3Cu(NCMe) as the catalyst. Figure 1 shows
These
observations
demonstrate
that
the
aforementioned direct insertion is not possible, since
otherwise no deuteration would take place.
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901629
Advanced Synthesis & Catalysis
The alternative should be based on an aromatic
electrophilic substitution. This is in agreement with
the lack of reactivity observed with pyrroles bearing
substituents such as Boc or Ph at the N or CN at the
C-ring. It is well established that such substituents
Conclusions
We have found that complexes TpxCu (Tpx =
trispyrazolylborate ligand) catalyze the transfer of
carbene units from diazo compounds to 1H-pyrroles
Scheme 8: Mechanistic proposal for the carbene transfer to pyrroles catalyzed by TpxCu.
reduce the electronic density at the heterocycle.
promoting the selective modification of the C-H
bonds affording the formal insertion products, leaving
the other potential reaction sites such as NH, C=C or
other substituents at C (alkyl) or N (alkene, alkyne,
alkyl) undisturbed. Only in the case of vinylic
substitution at the C induces a certain loss of
selectivity. The reaction takesplace through an
Based on the experimental data available and
literature precedents, Scheme 8 shows a mechanistic
proposal for this transformation. The carbene group is
added to the aromatic ring generating a zwitterionic
species.[15] A similar behavior has been recently
reported for the arene functionalization by carbene
insertion using group 11 metal-based catalysts.[10]
Following the same pathway, a hydrogen atom is
transferred to the ester moiety, leading to an enolate
electrophilic
attack of
the
copper-carbene
intermediate with the formation of ylidic species en
route to the final formal insertion product.
intermediate, which
protonation/deprotonation processes
undergoes
involving
adventitious water or added D2O, thus providing the
final product.
Experimental Section
All air– and moisture–sensitive manipulations were
carried out with standard Schlenck techniques under
nitrogen atmosphere or in
a glovebox (MBRAUN
UNILAB). Solvents were purchased from commercial
sources, dried by distillation under nitrogen atmosphere
using the suitable drying agent and deoxygenated
immediately before their use. Reagents were acquired from
Aldrich and used without any further purification.
Commercially unavailable pyrroles were obtained
following synthetic routes previously described in the
literature, and which are detailed in the supporting
information. The copper catalysts were synthesized by
literature procedures. NMR spectra were recorded on the
Agilent 400MR and Agilent 500DD2 spectrometers. X-ray
studies were performed in a Bruker D8 QUEST ECO.
High resolution mass spectroscopy experiments were
carried out at the Centre of Research Technology and
Innovation of the University of Seville (CITIUS).
Figure 1. Methylene region of the 1H NMR spectra of
the crude of the reactions of 2-ethyl-1H-pyrrole with
EDA in the absence and presence of D2O.
General Catalytic Procedure: Reaction of ethyl acetate
and pyrroles catalyzed by TpBr3Cu(MeCN). In a Schlenk
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901629
Advanced Synthesis & Catalysis
tube, under inert atmosphere, the catalyst (0.01 mmol) was
dissolved in deoxygenated DCM (6 mL) and the pyrrole
was added (1 mmol). EDA (0.2 mmol) was added in three
portions (3x8.33 µL), every 15 min, and the mixture was
stirred at room temperature for 2 hours. The solvent was
removed under reduced pressure and the reaction crude
was investigated by NMR spectroscopy using
trimethoxybenzene as internal standard. Purification can be
done by column chromatography (petroleum ether:EtOAc
1:1).
Olmos, J. Urbano, P. J. Pérez, Dalton Trans. 2015, 44,
20295.
[5] Selected
examples
of
for
pyrroles
metal-catalyzed
by carbene
functionalization
incorporation: a) K. Liu, G. Xu, J. Sun, Chem. Sci.
2018, 9, 634-639; b) A. D. Yamaguchi, K. M.
Chepiga, J. Yamaguchi, K. Itami, H. M. L. Davies, J.
Am. Chem. Soc. 2015, 137, 644-647; c) Y. Lian, H. M.
L. Davies, Org. Lett. 2012, 14, 1934-1937; d) J.-M.
Yang, C.-Z. Zhu, X.-Y. Tang, M. Shi, Angew. Chem.
Int. Ed. 2014, 53, 5142-5146. e) W.-W. Chan, S.-H.
Yeung, A. S. C. Chan, W.-Y. Yu, Org. Lett. 2010, 12,
604-607; f ) Y. Lian, H. M. L. Davies, Org. Lett.
2010, 12, 924-927; g) S. J. Hedley, D. L. Ventura, P.
M. Dominiak, C. L. Nygren, H. M. L. Davies, J. Org.
Chem. 2006, 71, 5349-5356; h) F. Gnad, M.
Poleschak, O. Reiser, Tetrahedron Lett. 2004, 45,
4277-4280.
Reaction of ethyl diazophenylacetate and pyrroles
catalyzed by TpBr3Cu(MeCN). Following the same
previous protocol, the catalyst (0.01 mmol) was dissolved
in DCE (6 mL) and the pyrrole was added (1 mmol).
PhEDA (0.2 mmol) was added in one portion, and the
o
mixture was stirred at 60 C for 4 hours. The solvent was
evaporated by reduced pressure and the residue was
purified through a column of silica gel (eluent: petroleum
ether:EtOAc, 1:1).
[6] S. R. Tanny, J. Grossman, F. W. Fowler, J. Am. Chem.
Soc. 1972, 94, 6495-6501.
[7] a) B. E. Maryanoff, J. Org. Chem. 1979, 44, 4410-
4419; b) B. E. Maryanoff, J. Org. Chem. 1982, 47,
3000-3002.
Experimental procedures, spectroscopic and analytical data
of compounds 1-27, are provided in the Supporting
Information. CCDC-1978196 contains the supplementary
crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge
[8] L. K. A. Pilsl, T. Ertl, O. Reiser, Org. Lett. 2017, 19,
2754-2757.
[9] J. Urbano, T. R. Belderrain, M. C. Nicasio, S.
Trofimenko, M. M. Díaz-Requejo, P. J. Pérez,
Organometallics 2005, 24, 1528-1532.
Crystallographic
Data
Centre
via
[10] M. R. Fructos, M. Besora, A. A. C. Braga, M. M.
www.ccdc.cam.ac.uk/data_request/cif.
Díaz-Requejo,
F.
Maseras,
P.
J.
Pérez,
Organometallics 2017, 36, 1, 172-179.
[11] M. A. Mairena, J. Urbano, J. Carbajo, J. J. Maraver, E.
Álvarez, M. M. Díaz-Requejo, P. J. Pérez, Inorg.
Chem. 2007, 46, 7428.
Acknowledgements
[12] R. Gava, A. Olmos, B. Noverges, T. Verea, E.
Álvarez, T. R. Belderrain, A. Caballero, G. Asensio,
P. J. Pérez ACS Catal., 2015, 5, 6, 3726.
[13] A. K. Clarke, M. J. James, P. O’Brien, R. J. K. Taylor,
W. P. Unsworth Angew. Chem. Int. Ed. 2016, 55,
13798.
Support for this work was provided by the MINECO (CTQ2017-
82893-C2-1-R and PO FEDER 2014-2020, UHU-1254043).
AMR thanks MINECO for a FPU fellowship.
[14] S. J. Chambers, G. Coulthard, W. P. Unsworth, P.
O’Brien, R. J. K. Taylor, Chem. Eur. J. 2016, 22,
6496.
[15] H. M. L. Davies, S. Hedley Chem. Soc. Rev. 2007, 36,
1109-1119.
References
[1] a) Q.-Q. Cheng, M. P. Doyle, Adv. Organomet. Chem.
2016, 66, 1-31; b) N. J. Thumar, Q. H. Wei, W. H.
Hu, Adv. Organomet. Chem. 2016, 66, 33-91; c) M. P.
Doyle, T. Ye, M. A. McKervey Modern Catalytic
Methods for Organic Synthesis with Diazo
Compounds, John Wiley & Sons, New York, 1998;
120, 8292; d) T. Ye, M. A. McKervey, Chem. Rev.
1994, 94, 1091.
[2] a) A. Caballero, M. M. Díaz-Requejo, S. Trofimenko,
T. R. Belderrain, P. J. Pérez, J. Org. Chem. 2005, 70,
6101-6104; b) M. Delgado-Rebollo, A. Prieto, P. J.
Pérez, ChemCatChem 2014, 6, 2047-2052.
[3] a) T. F. Schneider, J. Kaschel, D. B. Werz Angew.
Chem., Int. Ed. 2014, 53, 5504. (b) X. Xu, M. P.
Doyle, Acc. Chem. Res. 2014, 47, 1396; c) H. M. L.
Davies, J. E. Spangler, Adv. Heterocyclic Chem. 2013,
110, 43-72.
[4] a) J. M. Muñoz-Molina, T. R. Belderrain, P. J. Pérez,
Coord. Chem. Rev. 2019, 390, 171–189; b) A.
Caballero, M. M. Díaz-Requejo, M. R. Fructos, A.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901629
Advanced Synthesis & Catalysis
FULL PAPER
Copper-catalyzed selective pyrrole
functionalization by carbene transfer reaction
Adv. Synth. Catal. Year, Volume, Page – Page
Anabel M. Rodríguez,a Francisco Molina,a M. Mar
Díaz-Requejo*,a and Pedro J. Pérez*,a
7
This article is protected by copyright. All rights reserved.