One-Pot Assembly of Highly Functionalized Cyclopenta[b]pyrroles via a Calcium(II)- and Copper(II)-Catalyzed Reaction Sequence

Article abstract of DOI:10.1002/adsc.201601301

A user-friendly, calcium(II)- and copper(II)-catalyzed one-pot reaction sequence to furnish cyclopenta[b]pyrroles with a high level of complexity is depicted. The reaction involves the following sequential transformations: (i) an aza-Piancatelli cyclizati

Full text of DOI:10.1002/adsc.201601301

COMMUNICATIONS
DOI: 10.1002/adsc.201601301
One-Pot Assembly of Highly Functionalized Cyclopenta[b]pyr-
roles via a Calcium(II)- and Copper(II)-Catalyzed Reaction
Sequence
Lucile Marin,a Vincent Gandon,a,* Emmanuelle Schulz,a,* and David Lebœufa,*
a
Institut de Chimie Molꢀculaire et des Matꢀriaux dꢁOrsay, CNRS UMR 8182, Universitꢀ Paris-Sud, Universitꢀ
Paris-Saclay, Bꢂtiment 420, 91405 Orsay cedex, France
E-mail: vincent.gandon@u-psud.fr or emmanuelle.schulz@u-psud.fr or david.leboeuf@u-psud.fr
Received: November 25, 2016; Revised: January 17, 2017; Published online: && &&, 0000
Supporting information for this article can be found under: http://dx.doi.org/10.1002/adsc.201601301.
Abstract: A user-friendly, calcium(II)- and cop-
ACHTUNGTRENNUNGper(II)-catalyzed one-pot reaction sequence to fur-
We thought about a different approach (Scheme 2),
building first the cyclopentane moiety through
a simple calcium(II)-catalyzed aza-Piancatelli reaction
(A),[11] which we have recently described,[12,13] before
implementing a copper(II)-catalyzed hydroamination
process (B) to rapidly access the cyclopenta[b]pyrrole
core after a subsequent isomerization. At this stage,
we could envisage to take advantage of the nucleophi-
licity of the pyrrole ring to further functionalize it
through a Friedel–Crafts-type reaction (C) using acti-
vated alcohols prone to deliver stabilized carboca-
tions. The whole process would occur in a one-pot
fashion, being both atom- and time-efficient and re-
quiring only a single purification. Although conceptu-
ally simple, this expedient reaction sequence would
enable access to a novel library of cyclopenta[b]pyr-
roles with a high degree of complexity. Herein, we
disclose our investigations on this one-pot transforma-
nish cyclopenta[b]pyrroles with a high level of com-
plexity is depicted. The reaction involves the fol-
lowing sequential transformations: (i) an aza-Pian-
catelli cyclization, (ii) a hydroamination/isomeriza-
tion process and (iii) a subsequent Friedel–Crafts-
type reaction to afford the desired compounds from
readily available 2-furylcarbinols, anilines and sec-
ondary alcohols with a minimum of precautions.
Keywords: calcium; cyclopenta[b]pyrroles; electro-
cyclization; Friedel–Crafts reaction; hydroamina-
tion
Pyrroles and their derivatives are fundamental tion.
heterocyclic compounds, whose core is present in
ACHTUNGTRENNUNG
many natural products possessing biological activity.[1]
Amongst them, we can cite the cyclopenta[b]pyrroles,
one of the most prominent members being roseophi-
lin (Scheme 1), an alkaloid isolated in 1992 that ex-
hibits antitumor activity.[2,3] To highlight but a few ex-
amples, this skeleton can also be found in inhibitors
of d-amino acid oxidase,[4] cyclooxygenase 2[5] and
MEK,[6] as well as in compounds having anti-inflam-
matory[7] and histamine H4 receptor-regulating activi-
ties.[8] However, despite their significant bioactivity,
general methods to access this motif are rather
scarce.[9] Currently, one of the main strategies is the
direct functionalization of the pyrrole moiety, which
can be reached through a Nazarov cyclization.[10] All
these reactions are reliable processes, but they may
involve tedious steps to prepare the substrate and,
thus, provide the corresponding products with a limit-
ed substitution pattern.
Scheme 1. Selected examples of bioactive cyclopenta[b]pyr-
roles.
Adv. Synth. Catal. 0000, 000, 0 – 0
1
ꢃ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
pared from commercially available 4-bromo-2-fural-
dehyde in a two-step sequence that involved a Sonoga-
shira cross-coupling followed by addition of
a Grignard reagent (see the Supporting Information
for details). Using our standard reaction conditions
[Ca(NTf2)2/(n-Bu)4NPF6 (5 mol%) in nitromethane at
1008C],[12a] the cyclopenta[b]pyrrole 4a was isolated
as sole product in 40% yield (entry 1), deriving likely
from the aza-Piancatelli product 3a. Encouraged by
this result, we screened various solvents, but we only
observed, in each case, the formation of the 4-amino-
cyclopentenone 3a (entries 2–4). Moreover, the use of
the corresponding Brønsted acid, HNTf2, proved to
be unsuitable for the catalytic sequence (entry 5).
From there, we came up with the idea of introducing
a second catalyst that would promote the hydroami-
nation step while being compatible with the calci-
Scheme 2. Straightforward strategy for accessing cyclopen-
ta[b]pyrroles.
AHCTUNGTRENNUNG
As part of our interest in the development of the Cu(OTf)2, which was previously employed with suc-
aza-Piancatelli cyclization, we explored the reactivity cess in various hydroamination reactions.[14,15] This did
of 2-furylcarbinol 1a bearing an alkyne moiety not yield a major improvement in MeNO2 (entry 6),
(Table 1). This type of compound can be easily pre- but, gratifyingly, this bicatalytic approach provided
Table 1. Reaction optimization for the formation of cyclopenta[b]pyrrole 4a.[a]
Entry
Catalyst 1
Catalyst 2
Solvent
T [8 C]
t [h]
Yield of 3a [%]
Yield of 4a [%]
1
2
3
4
5
6
7
8
Ca(NTf2)2/(n-Bu)4NPF6
Ca(NTf2)2/(n-Bu)4NPF6
Ca(NTf2)2/(n-Bu)4NPF6
Ca(NTf2)2/(n-Bu)4NPF6
HNTf2
Ca(NTf2)2/(n-Bu)4NPF6
Ca(NTf2)2/(n-Bu)4NPF6
Ca(NTf2)2/(n-Bu)4NPF6
Ca(NTf2)2/(n-Bu)4NPF6
Ca(NTf2)2/(n-Bu)4NPF6
Ca(NTf2)2/(n-Bu)4NPF6
Ca(NTf2)2/(n-Bu)4NPF6
Ca(NTf2)2/(n-Bu)4NPF6
Ca(NTf2)2/(n-Bu)4NPF6
Ca(NTf2)2
–
–
–
–
MeNO2
HFIP
100
20
100
80
80
80
20
80
80
80
80
80
80
80
80
80
80
0.3
4
0.5
0.3
1
0.25
3
1
0.3
1
2
2
0.6
4
0.3
0.6
0.2
0.5/0.15
1/0.15
0.75/2
–
40[c]
–
–
76[c]
66[c]
70[c]
–
toluene
1,2-DCE
MeNO2
MeNO2
HFIP
toluene
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
HFIP
–
–
10[d]
45[d]
30[d]
25[d]
65[c]
52[d]
22[d]
24[d]
40[d]
47[d]
55[d]
48[d]
–
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OAc)2
CuBr2
CuOTf
CuCl
Cu(OTf)2
Cu(OTf)2
HOTf
–
–
–
–
–
–
–
–
9
10[b]
11
12
13
14
15
16
17
18
19
20
–
–
–
–
Ca(NTf2)2/(n-Bu)4NPF6
Ca(NTf2)2/(n-Bu)4NPF6
Ca(NTf2)2/(n-Bu)4NPF6
Ca(NTf2)2/(n-Bu)4NPF6
89[c]
–
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
80/40
40/20
80/20
74[c]
69[c]
57[c]
–
–
MeNO2
[a]
Reactions conditions: 2-furylcarbinol 1a (1 equiv.) and aniline 2a (1.3 equiv.) in the indicated solvent (0.3M) in the pres-
ence of catalyst 1 (5 mol%) with/or without additive (5 mol%) and catalyst 2 (10 mol%).
[b]
[c]
[d]
Catalyst 2 (5 mol%).
Isolated yields.
1
Yields determined by H NMR spectroscopy using p-anisaldehyde as external standard.
Adv. Synth. Catal. 0000, 000, 0 – 0
2
ꢃ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
the desired cyclopenta[b]pyrrole in a good yield
(65%) in 1,2-dichloroethane (1,2-DCE) (entry 9). On
the other hand, performing the reaction in hexafluor-
oisopropyl alcohol (HFIP) and toluene led to poor
yields (entries 7 and 8). We tried to decrease the cata-
lyst loading of Cu(OTf)2 from 10 to 5 mol%, howev-
er, the reaction proceeded at a slower rate furnishing
4a in only 52% yield (entry 10). The reaction was also
tested with various copper salts but they gave the
product in lower yields (entries 11–14). Then, we per-
formed several control experiments, which highlighted
the importance of each component of our protocol.
For instance, the absence of the calcium and/or the
ammonium salt led to a diminished yield (entries 15
and 16). The presence of copper is also necessary
given that triflic acid, alone, is not able to promote
the hydroamination reaction (entry 17). Interestingly,
completing the aza-Piancatelli step (at 808C) before
subjecting the 4-aminocyclopentenone 3a to the cop-
ACHTUNGTRENNUNGper(II)-catalyzed hydroamination (at 408C) in a one-
pot process increased the yield to 74% (entry 18). It
is worth mentioning that using this sequential proce-
dure with HFIP as solvent (at 408C then 208C) has
a significant impact on the formation of the desired
compound (entry 7 versus entry 19). The main benefit
of this sequential approach is to prevent side reac-
tions such as a potential Friedel–Crafts reaction be-
tween the pyrrole formed and 2-furylcarbinol 1a,
which can arise from having calcium(II) and cop-
Scheme 3. Scope of 2-furylcarbinol partners 1b–1h. Reaction
conditions: (1) 2-furylcarbinols 1b–1h (1 equiv.) and aniline
2a (1.3 equiv.) in 1,2-DCE or HFIP (0.3M) in the presence
of Ca(NTf2)2 (5 mol%) and (n-Bu)4NPF6 (5 mol%) at 808C
(A) or 408C (B) for 0.3–1.3 h. (2) Cu(OTf)2 (10 mol%) at
408C (A) or 208C (B) for 0.15–1 h.
ACHTUNGTRENNUNGper(II) salts mixed together. It might also explain why
the yields did not exceed 48% when calcium(II) or
copper(II) were used as sole catalyst (entries 1 and
16). A large range of Lewis and Brønsted acids was be rather unstable and was isolated in a moderate
also surveyed (see the Supporting Information for de- yield (36%).
tails) but did not produce any improvement compared
to the utilization of Ca(NTf2)2/(n-Bu)4NPF6 and a position of the 2-furylcarbinols (Scheme 4). Again,
Cu(OTf)2 in 1,2-DCE and HFIP. the presence of electron- donating and electron-with-
We then set out to focus on the substitution at the
With these optimized conditions in hand, we exam- drawing groups (1i–1k) on the phenyl was well toler-
ined the scope of the transformation. First, we looked ated, furnishing the desired cyclopenta[b]pyrroles in
at the influence of the substitution at the alkyne good yields (4i–4k). A compound bearing a thienyl
moiety (1b–1h) (Scheme 3). Substrates with both elec- group (1l) also underwent the reaction to give the ex-
tron-donating and electron-withdrawing groups on pected product 4l in 68% yield. However, it should be
the aryl substituent delivered good yields (4b and 4c). noted that the isomerization step into 4l required 16 h
In the case of an electron-donating group, using 1,2- to fully occur. Additionally, we found that more hin-
DCE as a solvent produced the best results. On the dered tertiary 2-furylcarbinols such as 1m could also
other hand, with an electron-withdrawing group, use be employed for this sequence provided that HFIP
of HFIP was far more efficient (57% versus 37% in was used as a solvent. The reaction was not limited to
1,2-DCE). Indeed, the Lewis acids might be partly aryl substituents, and could also be achieved in the
trapped by the ester group, thereby disturbing the re- presence of alkyl groups (3n–3r). In agreement with
activity, but could be released due to the strong hy- our previous findings,[12b] the reaction of 1n had to be
drogen-donor ability of HFIP.[16] Employing an o-sub- conducted in HFIP to avoid the formation of the de-
stituted aryl bromide (4d) also required HFIP to oxyaminated product. Using conditions A and B with
afford the desired product. We noticed that the reac- substrates less prone to generate stable carbocations
tion was not only compatible with a phenyl, but also (1o–1r) led to modest yields (20–30%). On the other
with naphthyl (4e), heteroaryl (4f), and alkyl groups hand, when the reaction was carried out in nitrome-
(4g). A 2-furylcarbinol bearing a terminal alkyne re- thane at 908C at a lower concentration (0.06M in-
acted as well; however, the compound (4h) proved to stead of 0.3M) in the simultaneous presence of
Adv. Synth. Catal. 0000, 000, 0 – 0
3
ꢃ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
Scheme 5. Scope of aniline partners 2b–2j. Reaction condi-
tions: (1) 2-furylcarbinols 1a or 1m (1 equiv.) and aniline
2b–2j (1.3 equiv.) in 1,2-DCE or HFIP (0.3M) in the pres-
ence of Ca(NTf2)2 (5 mol%) and (n-Bu)4NPF6 (5 mol%) at
808C (A) or 608C (B) for 0.15–2 h. (2) Cu(OTf)2 (10 mol%)
at 408C (A) or 208C (B) for 0.15–1.5 h.
Scheme 4. Scope of 2-furylcarbinol partners 1i–1r. Reaction
conditions: (1) 2-furylcarbinols 1i–1n (1 equiv.) and aniline
2a (1.3 equiv.) in 1,2-DCE or HFIP (0.3M) in the presence
of Ca(NTf2)2 (5 mol%) and (n-Bu)4NPF6 (5 mol%) at 808C
(A) or 208C (B) for 0.15–1 h. (2) Cu(OTf)2 (10 mol%) at
408C (A) or 208C (B) for 0.15–0.75 h.
crease of the reaction rate.[18] Yet, we have recently
demonstrated that this issue could be tackled by
simply using HFIP as a solvent.[12b] Compound 4ab
was therefore generated in 47% yield. We were also
pleased to observe that the use of a sterically hin-
dered aniline did not pose any problem for the hydro-
Ca(NTf2)2/(n-Bu)4NPF6 and Cu(OTf)2 (10 mol% amination reaction and provided 4ah in 78% yield in
each), compounds 4o–r were obtained in improved HFIP. On the other hand, as we mentioned it in
43–65% yields.[17]
a precedent study,[12b] and in agreement with the pre-
The scope of anilines was also evaluated with 2-fur- viously reported aza-Piancatelli reaction as a general
ylcarbinols 1a and 1m (Scheme 5). A wide range of rule,[18a] more basic alkylamines do not deliver the
ortho-, meta-, para-substituted anilines, bearing elec- corresponding products, which appear to result from
tron-donating and electron-withdrawing groups, led to the sequestering of the Lewis acids by these com-
the formation of the corresponding products in good pounds.
to high yields (up to 98%). While reactions involving
To further illustrate the potential of this methodol-
tertiary 2-furylcarbinol 1m had to be conducted in ogy, we thought about increasing the functionalization
HFIP at 608C, those with 1a gave the best results, of the pyrrole ring through a Friedel–Crafts-type reac-
with the exception of p-anisidine 2b, which was un- tion using activated alcohols (Scheme 6). Thus,
reactive in 1,2-DCE. Indeed, in precedent studies by a series of tetrasubstituted pyrroles was prepared
Hein et al., it was pointed out that anilines bearing starting from 2-furylcarbinol 1m and p-iodoaniline 2a.
electron-donating groups might form an “off-cycle After formation of the cyclopenta[b]pyrrole inter-
species” with the Lewis acid used, resulting in a de- mediate, various secondary alcohols were introduced
Adv. Synth. Catal. 0000, 000, 0 – 0
4
ꢃ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
tion of 4m in HFIP and, then, Friedel–Crafts reaction
in 1,2-DCE after a simple aqueous treatment), the
product could be obtained in 85% yield over 3 steps
[Eq. (1)].[20]
Lastly, it is important to emphasize that this type of
sequence not only works with tertiary 2-furylcarbinol,
but can also be achieved with a secondary 2-furylcar-
binol such as 1a to provide 7 in 75% yield [Eq. (2)].
It is noteworthy that both Ca(II) and Cu(II) are capa-
ble of catalyzing the Friedel–Crafts reaction.[21]
In summary, we have developed a versatile method
for the preparation of highly functionalized cyclopen-
ta[b]pyrroles based on a one-pot sequence involving
an aza-Piancatelli cyclization/hydroamination/isomeri-
zation/Friedel–Crafts reaction. An important feature
of this novel method is the simplicity of its set-up.
Hence, a combination of common calcium(II) and
copper(II) salts can be used to promote this reaction
Scheme 6. Scope of secondary alcohol partners 5a–5k. Reac-
tion conditions: (1) 2-furylcarbinol 1m (1.2 equiv.) and ani-
line 2a (1.6 equiv.) in HFIP (0.3M) in the presence of
Ca(NTf2)2 (6 mol%) and nBu4NPF6 (6 mol%) at 208C for
1 h. (2) Cu(OTf)2 (12 mol%) at 208C for 0.15 h. (3) alcohol
5a–5k (1 equiv.) at 208C. PMP=p-methoxyphenyl.
in the reaction medium. In general, the corresponding sequence in good yields without requiring special pre-
products were obtained in good to excellent yields cautions. This sequence was found to be compatible
(up to 95%). The reaction is quite flexible, tolerating with a wide range of substrates, delivering complex
a great diversity of benzyl, vinyl and propargyl alco- molecules bearing a tri- and tetrasubstituted pyrrole
hols. Based on our recent studies,[12b] we hypothesized moiety. We are currently working on the extension of
that Friedel–Crafts reactions were mediated by this reaction to even more complex structures.
HFIP,[19] whose Lewis acidity was enhanced by either
calcium(II) or copper(II) salts. In this sequence, the
alcohol had to be used as limiting reactant to prevent
Experimental Section
the contamination of the desired pyrrole by the ether
product, resulting from the alcohol reacting with
itself.
General Procedure for the Cyclization Reaction
During the course of our investigation, the only ex-
ception was 2-cyclohexen-1-ol, which decomposed in
To a solution of 2-furylcarbinol 1 (1 equiv.) and aniline 2
(1.3 equiv.) in 1,2-DCE or HFIP (0.3M) were added
HFIP. However, by using a two-step sequence (forma- Ca(NTf2)2 (5 mol%) and (n-Bu)4NPF6 (5 mol%). The reac-
Adv. Synth. Catal. 0000, 000, 0 – 0
5
ꢃ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
tion mixture was stirred at the indicated temperature until
TLC showed full conversion (t1). After t1, Cu(OTf)2
(10 mol%) was added and the reaction mixture was stirred
at the indicated temperature until TLC showed full conver-
sion (t2). Then, the crude product was purified by flash
column chromatography using gradients of pentane/EtOAc
to give the desired products.
[9] For recent examples, see: a) L. Zhang, X. Xu, W. Xia,
Q. Liu, Adv. Synth. Catal. 2011, 353, 2619–2623; b) M.
Yoshida, Y. Maeyama, M. Al-Amin, K. Shishido, J.
Org. Chem. 2011, 76, 5813–5820; c) J. Du, B. Zhou, Y.
Yang, Y. Li, Chem. Asian J. 2013, 8, 1386–1390; d) C.
Wang, C. Dong, L. Kong, Y. Li, Y. Li, Chem. Commun.
2014, 50, 2164–2166; e) K. Wu, P. Wu, J. Chen, C. Sun,
Z. Yu, Adv. Synth. Catal. 2015, 357, 3353–3358; f) X.
Yang, P. Wu, J. Chen, C. Sun, Z. Yu, Chem. Eur. J.
2015, 21, 9323–9327; g) X.-Q. Mou, Z.-L. Xu, S.-H.
Wang, D.-Y. Zhu, J. Wang, W. Bao, S.-J. Zou, C. Yang,
D. Zhang, Chem. Commun. 2015, 51, 12064–12067.
[10] a) C. Song, D. W. Knight, M. A. Whatton, Org. Lett.
2006, 8, 163–166; b) J. A. Malona, J. M. Colbourne,
A. J. Frontier, Org. Lett. 2006, 8, 5661–5664; c) A. Y.
Bitar, A. J. Frontier, Org. Lett. 2009, 11, 49–52; d) M.
Fujiwara, M. Kawatsura, S. Hayase, M. Nanjo, T. Itoh,
Adv. Synth. Catal. 2009, 351, 123–128; e) C. Huang, R.
Ding, C. Song, J. Lu, L. Liu, X. Han, J. Wu, H. Hou, Y.
Fan, Chem. Eur. J. 2014, 20, 16156–16163; f) E. Li, C.
Li, J. Wang, J. Wang, L. Dong, X. Guo, C. Song, J.
Chang, Tetrahedron 2014, 70, 874–879; g) T. Vaidya, R.
Cheng, P. N. Carlsen, A. J. Frontier, R. Eisenberg, Org.
Lett. 2014, 16, 800–803.
General Procedure for the Cyclization Reaction
Involving a Friedel–Crafts-Type Reaction
To a solution of 2-furylcarbinol 1m (1.2 equiv.) and aniline
2a (1.6 equiv.) in HFIP (0.3M) were added Ca(NTf2)2
(6 mol%) and (n-Bu)4NPF6 (6 mol%). The reaction mixture
was stirred at 408C for 0.67 h (t1). After t1, Cu(OTf)2
(12 mol%) was added and the reaction mixture was stirred
at room temperature for 0.15 h (t2). After t2, the alcohol
(1 equiv.) was added and the reaction mixture was stirred at
room temperature until TLC showed full conversion (t3).
Then, the crude product was purified by flash column chro-
matography using gradients of pentane/EtOAc to give the
desired products.
[11] For reviews on Ca(II) catalysis, see: a) J.-M. Begouin,
M. Niggemann, Chem. Eur. J. 2013, 19, 8030; b) Topics
in Organometallic Chemistry, Vol. 45, (Ed.: S. Harder),
Springer, Berlin, 2013.
[12] a) D. Lebœuf, E. Schulz, V. Gandon, Org. Lett. 2014,
16, 6464–6467; b) D. Lebœuf, L. Marin, B. Michelet, A.
Perez-Luna, R. Guillot, E. Schulz, V. Gandon, Chem.
Eur. J. 2016, 22, 16165–16171.
[13] For recent reviews, see: a) C. Piutti, F. Quartieri, Mole-
cules 2013, 18, 12290–12312; b) L. I. Palmer, J. Read
de Alaniz, Synlett 2014 25, 8–11.
[14] For selected examples, see: a) M. Yang, J. Tang, R. Fan,
Chem. Commun. 2012, 48, 11775–11777; b) T. Ishikawa,
T. Soneharan, M. Minakawa, M. Kawatsura, Org. Lett.
2016, 18, 1422–1425; c) R. Blieck, J. Bahri, M. Taillefer,
F. Monnier, Org. Lett. 2016, 18, 1482–1485.
[15] For a recent review on late transition metal-catalyzed
hydroamination reactions, see: L. Huang, M. Arndt, K.
Gooßen, H. Heydt, L. J. Gooßen, Chem. Rev. 2015,
115, 2596–2697, and references cited therein.
[16] For reviews, see: a) J.-P. Bꢀguꢀ, D. Bonnet-Delpon, B.
Crousse, Synlett 2004, 18–29; b) I. A. Shuklov, N. V.
Dubrovina, N. V. Bçrner, Synthesis 2007, 2925–2943;
c) T. Sugiishi, M. Matsugi, H. Hamamoto, H. Amii,
RSC Adv. 2015, 5, 17269–17282; d) J. Wencel-Delord, F.
Colobert, Org. Chem. Front. 2016, 3, 394–400.
Acknowledgements
We thank CNRS, Ministꢀre de l’Enseignement Supꢁrieur et de
la Recherche, Universitꢁ Paris-Sud and Institut Universitaire
de France (IUF) for the support of this work.
References
[1] For a recent review, see: V. Estꢀvez, M. Villacampa,
J. C. Menꢀndez, Chem. Soc. Rev. 2014, 43, 4633–4657,
and references cited therein.
[2] For reviews, see: a) A. Fꢄrstner, Angew. Chem. 2003,
115, 3706–3728; Angew. Chem. Int. Ed. 2003, 42, 3582–
3603; b) D. X. Hu, D. M. Withall, G. L. Challis, R. J.
Thomson, Chem. Rev. 2016, 116, 7818–7853.
[3] For total syntheses, see: a) A. Fꢄrstner, H. Weintritt, J.
Am. Chem. Soc. 1998, 120, 2817–2825; b) P. E. Harring-
ton, M. A. Tius, J. Am. Chem. Soc. 2001, 123, 8509–
8514; c) D. L. Boger, J. Hong, J. Am. Chem. Soc. 2001,
123, 8515–8519; d) J. H. Frederich, P. G. Harran, J. Am.
Chem. Soc. 2013, 135, 3788–3791.
[4] M. L. R. Heffernan, Q. K. Fang, R. J. Foglesong, S. C.
Hopkins, C. O. Ogbu, M. Soukri, K. L. Spear, PCT Int.
Appl. WO2011011330 A2, 2011.
[5] B. Zhong, M. Li, P. R. China Patent CN 1955163 A,
[17] These reaction conditions were also tested with sub-
strate 1a, but they did not give better yields (61%).
[18] a) D. Yu, V. T. Tahai, L. I. Palmer, G. K. Veits, J. E.
Cook, J. Read de Alaniz, J. E. Hein, J. Org. Chem.
2013, 78, 12784–12789; b) R. Chung, D. Yu, V. T. Thai,
A. F. Jones, G. K. Veits, J. Read de Alaniz, J. E. Hein,
ACS Catal. 2015, 5, 4579–4585.
[19] For the addition of arenes to indolyl alcohols mediated
by fluorinated solvents, see: H. Wen, L. Wang, L. Xu,
Z. Hao, C.-L. Shao, C.-Y. Wang, J. Xiao, Adv. Synth.
Catal. 2015, 357, 4023–4030.
2007.
[6] M. E. Adams, M. B. Wallace, T. Kanouni, N. Scorah,
S. M. OꢁConnell, H. Miyake, L. Shi, P. Halkowycz, L.
Zhang, Q. Dong, Bioorg. Med. Chem. Lett. 2012, 22,
2411–2414.
[7] X.-T. Xu, X.-Q. Mou, Q.-M. Xi, W.-T. Liu, W.-F. Liu,
Z.-J. Sheng, X. Zheng, K. Zhang, Z.-Y. Du, S.-Q. Zhao,
S.-H. Wang, Bioorg. Med. Chem. Lett. 2016, 26, 5334–
5339.
[8] Y. Tachibana, M. Miyagawa, T. Masuda, T. Hasegawa,
PCT Int. Appl. WO2011013752 A1, 2011.
Adv. Synth. Catal. 0000, 000, 0 – 0
6
ꢃ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
[20] For calcium(II)-catalyzed Friedel–Crafts reactions, see:
M. Niggemann, M. J. Meel, Angew. Chem. 2010, 122,
3767–3771; Angew. Chem. Int. Ed. 2010, 49, 3684–3687.
[21] When the cyclopenta[b]pyrrole 4a was subjected to
either Ca(II) or Cu(II) reaction conditions in the pres-
ence of 5a, compound 7 was obtained in 75% and 65%
yields, respectively.
Adv. Synth. Catal. 0000, 000, 0 – 0
7
ꢃ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
8 One-Pot Assembly of Highly Functionalized
Cyclopenta[b]pyrroles via a Calcium(II)- and Copper(II)-
Catalyzed Reaction Sequence
Adv. Synth. Catal. 2017, 359, 1 – 8
Lucile Marin, Vincent Gandon,* Emmanuelle Schulz,*
David Lebœuf*
Adv. Synth. Catal. 0000, 000, 0 – 0
8
ꢃ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!