Sustainable Pathways to Pyrroles through Iron-Catalyzed N-Heterocyclization from Unsaturated Diols and Primary Amines

Article abstract of DOI:10.1002/cssc.201600607

Pyrroles are prominent scaffolds in pharmaceutically active compounds and play an important role in medicinal chemistry. Therefore, the development of new, atom-economic, and sustainable catalytic strategies to obtain these moieties is highly desired. Direct catalytic pathways that utilize readily available alcohol substrates have been recently established; however, these approaches rely on the use of noble metals such as ruthenium or iridium. Here, we report on the direct synthesis of pyrroles using a catalyst based on the earth-abundant and inexpensive iron. The method uses 2-butyne-1,4-diol or 2-butene-1,4-diol that can be directly coupled with anilines, benzyl amines, and aliphatic amines to obtain a variety of N-substituted pyrroles in moderate-to-excellent isolated yields.

Full text of DOI:10.1002/cssc.201600607

DOI: 10.1002/cssc.201600607
Communications
Sustainable Pathways to Pyrroles through Iron-Catalyzed
N-Heterocyclization from Unsaturated Diols and Primary
Amines
Tao Yan and Katalin Barta*[a]
Pyrroles are prominent scaffolds in pharmaceutically active
compounds and play an important role in medicinal chemistry.
Therefore, the development of new, atom-economic, and sus-
tainable catalytic strategies to obtain these moieties is highly
desired. Direct catalytic pathways that utilize readily available
alcohol substrates have been recently established; however,
these approaches rely on the use of noble metals such as
ruthenium or iridium. Here, we report on the direct synthesis
of pyrroles using a catalyst based on the earth-abundant and
inexpensive iron. The method uses 2-butyne-1,4-diol or 2-
butene-1,4-diol that can be directly coupled with anilines,
benzyl amines, and aliphatic amines to obtain a variety of N-
substituted pyrroles in moderate-to-excellent isolated yields.
tions[8] have already been established. These stoichiometric
routes however, may suffer from poor substrate accessibility,
harsh reaction conditions, and multi-step syntheses leading to
the formation of waste and low atom economy.[9] Thus, the de-
velopment of new catalytic methods to create the pyrrole scaf-
fold efficiently is subject of intensive research.[10] Several ele-
gant approaches were recently reported that rely on the cata-
lytic dehydrogenation of easily accessible alcohol substrates
(Scheme 1A) that are broadly related to the borrowing hydro-
gen strategy.[11] In 2013, Beller and co-workers reported a ruthe-
nium-catalyzed three-component pyrrole synthesis where sec-
ondary alcohols, diols, and primary alcohols were coupled in
analogy to the classical Hantzsch synthesis.[12] Michlik and
Kempe achieved the direct iridium-catalyzed coupling of alco-
hols and amino alcohols to obtain pyrroles.[13] Milstein and co-
workers described a method to obtain pyrroles from similar
substrates using ruthenium catalysts.[14] In 2011, Schley et al.
described the formation of pyrroles from 1,4-diols and
amines.[15] During the course of these reactions, the alcohol
substrates undergo dehydrogenation to the corresponding car-
bonyl compounds, which further react with the amine to form
the desired pyrrole product; the hydrogen equivalents bor-
rowed from the alcohol substrate are concomitantly liberated
from the catalyst.[12–15]
Pyrroles are important building blocks in medicinal chemistry[1]
and many pharmaceutically active compounds contain these
moieties. For example, aloracetam[2] was previously used in
studies for treating Alzheimer’s disease, isamoltane[3] was
shown to exhibit anxiolytic effects on rodents, and elopipra-
zole[4] is an antipsychotic drug (Figure 1).
Owing to the importance of pyrroles, many classical synthet-
ic pathways such as the Hantzsch,[5] Knorr,[6] and Paal–Knorr[7]
synthesis (Scheme 1A) as well as related multicomponent reac-
In the studies by the groups of Watanabe[16] and Williams[17]
it was shown that pyrroles can also be directly obtained from
amines and unsaturated diols such as 2-butyne-1,4-diol using
an appropriate ruthenium catalyst. In this case it was proposed
that the reaction likely proceeds through an internal hydro-
gen-transfer isomerization to the corresponding dicarbonyl
compounds that subsequently undergo pyrrole formation with
an amine reaction partner.
Our group has previously established the first iron-catalyzed
formation of pyrrolidines[18] from amines and 1,4-butane-diol
using Knçlker’s homogeneous iron catalyst (Scheme 1B).[19,20]
Based on our previous results[18,21] and the reports by the
groups of Watanabe and Williams, we envisioned the possibili-
ty of the iron-catalyzed direct pyrrole formation starting from
primary amines and unsaturated diols. A reactivity similar to
the ruthenium-based systems was expected since the iron
complex is capable of alcohol dehydrogenation as well as
double bond hydrogenation (Scheme 2; see also Schemes S1
and S2 in the Supporting Information).
Figure 1. Bioactive compounds containing pyrrole moieties.
[a] T. Yan, Dr. K. Barta
Stratingh Institute for Chemistry
University of Groningen
Nijenborgh 4, 9747 AG Groningen (Netherlands)
E-mail: k.barta.@rug.nl
We started our investigation using 2-butyne-1,4-diol (2a)
and 4-(N,N-dimethylamino)-aniline (1a) to establish the iron-
catalyzed methodology towards pyrroles (Table 1). Similar to
our previous works,[18,21] Cat 1 was selected as the precatalyst
Supporting Information for this article can be found under http://
dx.doi.org/10.1002/cssc.201600607.
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Scheme 1. (A) Classical synthetic and “modern”, catalytic pathways to access pyrroles. (B) Iron-catalyzed direct synthesis of pyrrolidines and pyrroles from
amines and diols.
Table 1. Establishing ideal reaction conditions to obtain N-(4-dimethyl-
amino-phenyl)-pyrrole (3a) from 4-(N,N-dimethylamino)-aniline (1a) and
1,4-diols (2a, 2b).[a]
Entry
2
Solvent
T
Conv.1a [%][a]
Select. 3a[b]
[8C]
[%]
1
2
3
4
5
6
7
8
9
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
THF
110
110
110
110
110
110
130
120
110
110
120
67
70
68
67
71
65
68
67
66
69
71
98 (83)
95 (76)
44
dioxane
CH3CN
DMF
CMPE
toluene
toluene
toluene
toluene
CPME
73
Scheme 2. Possible pathways for pyrrole formation based on Ref. [16].
TMS=trimethylsilyl.
>99
>99
94
90
>99
10
11
25
63 (59)
toluene
whereas Me3NO was used to generate the catalytically active
iron complex (Scheme 2, see also the Supporting Information,
Schemes S3 and S4).
[a] General reaction conditions: General procedure (see Supporting Infor-
mation, page S2), 0.5 mmol 1a, 1 mmol 2, 0.02 mmol Cat 1, 0.04 mmol
Me3NO, 2 mL solvent, 18 h, 110–1308C. [b] Based on GC-FID (FID=flame
ionization detector), isolated yields shown in parentheses.
A variety of solvents were screened, and the reaction tem-
perature varied between 110–1308C. The first attempts at
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110 8C in the solvents tetrahydrofuran (THF), dioxane, acetoni-
trile (CH3CN), and dimethylformamide (DMF) resulted in very
similar conversion values of up to 70% and moderate product
selectivities (Table 1, entries 1–4). Conversion of 1a and prod-
uct selectivity slightly improved in cyclopentyl methyl ether
(CPME) and toluene at 1108C (Table 1, entries 5 and 6).
Table 2. Direct synthesis of N-substituted pyrroles from anilines and 1,4-
diols.[a]
The results could be further improved to full conversion of
1a and near perfect selectivity to 3a at 1308C in toluene and
a very good 83% isolated yield of 3a was achieved (Table 1,
entry 7).
Entry Amine (1)
Alcohol (2) Product (3) Conv. 1[b] Select. 3[b]
[%]
[%]
Similarly, full conversion but slightly lower 3a yield (76%)
was obtained when the reaction was conducted at 1208C
(Table 1, entry 8).
1
2
3
1b
1c
1d
2a
3b
3c
3d
92
90 (80)
After having established that diol 2a can be successfully
used as the substrate to form 3a, we explored the use of cis-2-
butene-1,4-diol (2b) as the starting material. Catalytic runs
conducted using 2b in toluene and CPME at 1108C resulted in
94% and 90% conversion but only 44 and 25% selectivity to
3a, respectively (Table 1, entries 9 and 10). At 1208C, full con-
version of 1a and a good isolated yield of 3a (59% ) was ob-
tained (Table 1, entry 11) without significant over-reduction to
pyrrolidines.[16] Therefore, 2b can be regarded as alternative re-
action partner to 2a despite the slightly lower product yields
obtained.
2a
2b
42
>99
– (36)
90 (59)
2a
2b
33
91
– (30)
75 (47)
2b
2b[c]
85
98
63 (45)
72 (54)
4
5
6
1e
1 f
1g
3e
3 f
3g
With the optimized reaction conditions in hand, a variety of
anilines were tested (Table 2). Electron-rich 4-methoxy-aniline
(1b) reacted smoothly with 2-butyne-1,4-diol (2a), leading to
80% isolated yield of 3b (Table 2, entry 1). When 4-methyl-ani-
line (1c) was used as substrate, much lower conversion and
36% isolated yield of 3c was obtained. Similar behavior was
observed in the reaction of electron-poor 4-fluoro-aniline (1d)
with 2-butyne-1,4-diol (2a), which yielded 30% of 3d at 33%
substrate conversion. Interestingly, in both of these cases
almost full conversion and much higher product selectivity
were achieved when cis-2-butene-1,4-diol was employed as
coupling partner instead of 1a, providing 59% and 47% isolat-
ed yields of 3c and 3d, respectively (Table 2, entries 2 and 3).
According to these results, 2b was selected for further reac-
tions with 4-chloro-aniline (1e), 4-bromo-aniline (1 f), and 3,4-
(methenedioxy)-aniline (1g). In all these cases excellent sub-
strate conversions and very good product selectivity was ob-
served and the desired products 3e, 3 f, and 3g were obtained
in 45%, 44%, and 37% isolated yields respectively, (Table 2, en-
tries 4–6). It was also shown that product selectivity and isolat-
ed yields could be improved in the coupling of 1e with
4 equivalents of diol 2b. Ortho-substituted anilines (1h–1j)
could also be successfully used whereby electron-donating
substituents gave better product yields (Table 2, entries 7–9).
After aniline derivatives were converted to N-phenyl-pyrroles
successfully, primary aliphatic amines were explored under
standard reaction conditions using 2-butyne-1,4-diol (2a) as re-
action partner. Interestingly, a series of benzyl amines with
varying electronic properties all afforded full substrate conver-
sions, excellent product selectivity, and good isolated yields of
the desired N-benzylpyrroles. The coupling of benzylamine
(5a) with 2a lead to the formation of N-benzylpyrrole (6a)
with 61% isolated yield (Table 3, entry 1). Similarly, good results
2b
2b
94
61 (44)
68 (37)
>99
7
8
9
1h
1i
2b
2b
2b
3h
2i
77
90
56
42 (36)
52 (25)
36 (15)
1j
2j
[a] General reaction conditions: General procedure (see Supporting Infor-
mation, page S2), 0.5 mmol 1a, 1 mmol 2a, 0.02 mmol Cat 1, 0.04 mmol
Me3NO, 2 mL toluene, 18 h, 1308C unless otherwise specified; see also
Table S2. [b] Based on GC-FID, isolated yields shown in parentheses.
[c] The reaction was operated in a sealed 20 mL vial with 4 equiv. 2b in
22 h.
were obtained with a variety of halogenated benzyl amines
such as 4-chloro-benzylamine (5b), 4-fluoro-benyzlamine (5c),
3-trifluoromethyl-benzylamine (5d), and 3-fluoro-4-chloro-ben-
zylamine (5e), which afforded the corresponding N-(4-chloro-
benzyl)-pyrrole (6b), N-(4-fluorobenzyl)-pyrrole (6c), N-(3-tri-
fluoromethylbenzyl)-pyrrole (6d), and N-(3-fluoro-4-chloroben-
zyl)-pyrrole (6e) products in 57%, 52%, 55% and 65% isolated
yields, respectively (Table 3, entries 2–5). With electron-rich
benzylamines 5 f and 5g, the desired N-(4-methylbenzyl)-pyr-
role (5 f) and N-piperonyl-pyrrole (5g) were obtained in good
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ments. Indeed, gel permeation chromatography (GPC) meas-
urements of the crude product mixture confirmed the pres-
ence of oligomeric side products for a typical run with 2-
butyne-1,4-diol and benzylamine (Supporting Information,
Scheme S5) in the broad molecular weight (Mw) range of 300–
5000 gmolÀ1. In addition, when 2a alone was subjected to
standard catalytic conditions, full substrate conversion was ob-
served alongside the formation of a black precipitate and no
volatiles were detected by GC measurement (Supporting Infor-
mation, Table S3, entry 3). Furthermore, GPC measurement
confirmed the formation of oligomeric side products (Support-
ing Information, Scheme S6). Thus, the most likely source of
such competing side reactions is the isomerization of substra-
te 2a to the corresponding a,b-unsaturated aldehyde as
shown in Scheme 2 and Schemes S1 and S2 in the Supporting
Information.
Table 3. Direct synthesis of N-substituted pyrroles from anilines and 1,4-
diols.[a]
Entry
Amine (5)
Product (6)
Select. 3[b]
[%]
1
2
3
5a
5b
5c
6a
6b
6c
90 (61)
85 (57)
73 (52)
4
5d
6d
88 (55)
Other reaction pathways such as the formation of secondary
or tertiary amines that may be a result of over-alkylation and
imine reduction were not observed, indicating the preference
for intramolecular pyrrole formation. Also, the corresponding
pyrrolidine analogues were only sparingly observed when 2b
was used as substrate. More mechanistic and spectroscopic in-
sights are required to understand the sequence of reaction
steps occurring. This will lead to improvement of product
yields. Future research should also address a broader substrate
scope, especially different substitution patterns on the pyrrole
ring.
5
6
7
5e
5 f
5g
6e
6 f
6g
87 (65)
87 (65)
83 (55)
8
9
5h
5i
6h
6i
92 (76)
71 (43)
In conclusion, herein we describe the first iron-catalyzed
direct method for the catalytic formation of pyrroles by cou-
pling of unsaturated diols with primary amines. The work pre-
sented herein is aimed to be a proof-of-principle rather than
a methodology study. Nonetheless, various derivatives of ani-
lines and benzyl amines as well as other aliphatic primary
amines were successfully used in the construction of pyrrole
moieties, which are important scaffolds in medicinal chemistry.
The desired product yields range from high to moderate and
future studies will address further mechanistic details of this in-
teresting transformation. The presented catalytic strategy is
direct, straightforward, and allows the use of a wide range of
amines. Notably, this new catalytic method relies on the use of
an inexpensive and abundant homogeneous catalyst for the
construction of scaffolds that are highly relevant in the phar-
maceutical industry.
10
11
12
5j
5k
5l
6j
6k
6l
– (41)
86 (42)
85 (33)
[a] General reaction conditions: General procedure (see Supporting Infor-
mation, page S2), 0.5 mmol 5, 1 mmol 2a, 0.02 mmol Cat 1, 0.04 mmol
Me3NO, 2 mL toluene, 18 h, 1308C; see also Table S3; in all cases full con-
version was obtained. [b] Based on GC-FID, isolated yields shown in pa-
rentheses.
isolated yields (65% and 55%; Table 3, entries 6 and 7). Inter-
estingly, even 3-picolylamine (5h) reacted smoothly with 2-
butyne-1,4-diol (2a), forming N-(3-picolyl)pyrrole in 76% isolat-
ed yield, although pyridine is a potential ligand that may coor-
dinate to iron[22] (Table 3, entry 8). Product N-furfuryl-pyrrole
(6i), which was already proposed as food additive,[23] was ob-
tained in 43% yield from furfurylamine (5i) (Table 3, entry 9).
For other aliphatic amines such as 2-phenylethamine (5g) and
dodecylamine (5k), the corresponding pyrrole products were
obtained in 41% and 42% isolated yield (Table 3, entries 10
and 11). Cyclohexylamine (5l) reacted with 2a, providing N-cy-
clohexylpyrrole (6l) in 33% yield (Table 3, entry 12).
To summarize the results in Tables 1, 2, and 3 discussed
above, generally good-to-excellent substrate conversions were
seen. Similarly, product selectivity was good to excellent based
on GC-FID and GC-MS measurements, albeit the isolated prod-
uct yields were lower. This may be an indication of side reac-
tions involving species not detectable by these GC measure-
Experimental Section
Representative procedures—synthesis of 3a from 4-(N,N-dime-
thylamino)-aniline (1a) and 2-butyne-1,4-diol (2a). An oven-dried
20 mL Schlenk tube, equipped with stirring bar, was charged with
4-(N,N-dimethylamino)-aniline (0.5 mmol, 0.068 g), 2-butyne-1,4-
diol (1 mmol, 0.086 g), iron complex Cat 1 (4 mol%, 8 mg), and
Me3NO (8 mol%, 3 mg) under air. Then, the Schlenk tube was sub-
sequently connected to an argon line and a vacuum–argon ex-
change was performed three times. Toluene (solvent, 2 mL) was
charged under an argon stream. The Schlenk tube was capped, the
mixture was rapidly stirred at room temperature for 1 min, and
then placed into a preheated oil bath at 1308C and stirred for
18 h. The reaction mixture was cooled to room temperature and
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Am. Chem. Soc. 2010, 132, 18326–18339; h) E. Lourdusamy, L. Yao, C. M.
Park, Angew. Chem. Int. Ed. 2010, 49, 7963–7967; Angew. Chem. 2010,
122, 8135–8139.
the crude mixture was filtered through Celite, eluted with ethyl
acetate, and concentrated in vacuo. The residue was purified by
flash column chromatography (SiO2, Pentane/EtOAc 95:5 to 80:20)
to provide the pure amine product 3a (0.077 g, 83% isolated
yield). For characterization see the Supporting Information, Pages
S9 and S16.
[11] a) A. J. A. Watson, J. M. J. Williams, Science 2010, 329, 635–636; b) G.
Guillena, D. J. Ramon, M. Yus, Chem. Rev. 2010, 110, 1611–1641; c) S.
Bꢂhn, S. Imm, L. Neubert, M. Zhang, H. Neumann, M. Beller, ChemCat-
Chem 2011, 3, 1853–1864; d) G. E. Dobereiner, R. H. Crabtree, Chem.
Rev. 2010, 110, 681–703; e) C. Gunanathan, D. Milstein, Science 2013,
341, 1229712; f) Q. Yang, Q. Wang, Z. Yu, Chem. Soc. Rev. 2015, 44,
2305–2329; g) A. Quintard, J. Rodriguez, ChemSusChem 2016, 9, 28–30.
[12] a) M. Zhang, H. Neumann, M. Beller, Angew. Chem. Int. Ed. 2013, 52,
597–601; Angew. Chem. 2013, 125, 625–629; b) M. Zhang, X. Fang, H.
Neumann, M. Beller, J. Am. Chem. Soc. 2013, 135, 11384–11388.
[13] S. Michlik, R. Kempe, Nat. Chem. 2013, 5, 140–144.
Acknowledgements
The authors thank Prof. Dr. Ben L. Feringa (University of Groni-
gen) for fruitful discussions. K.B. is thankful for the generous sup-
port from the EU Horizon 2020, ERC-Starting Grant 2015, Grant
number: CatASus 638076.
[14] D. Srimani, Y. Ben-David, D. Milstein, Angew. Chem. Int. Ed. 2013, 52,
4012–4015; Angew. Chem. 2013, 125, 4104–4107.
[15] N. D. Schley, G. E. Dobereiner, R. H. Crabtree, Organometallics 2011, 30,
4174–4179.
Keywords: amines · dehydrogenation · diols · iron catalysis ·
pyrrole synthesis
[16] Y. Tsuji, Y. Yokoyama, K.-T. Huh, Y. Watanabe, Bull. Chem. Soc. Jpn. 1987,
60, 3456–3458.
[17] a) S. J. Pridmore, P. A. Slatford, A. Daniel, M. K. Whittlesey, J. M. J. Wil-
liams, Tetrahedron Lett. 2007, 48, 5115–5120; b) S. J. Pridmore, P. A. Slat-
ford, J. E. Taylor, M. K. Whittlesey, J. M. J. Williams, Tetrahedron 2009, 65,
8981–8986.
[1] V. Bhardwaj, D. Gumber, V. Abbot, S. Dhimana, P. Sharmaa, RSC Adv.
2015, 5, 15233–15266.
[2] F. Fischer, M. Matthisson, P. Herrling, Neurodegener. Dis. 2004, 1, 50–70.
[3] P. C. Waldmeier, M. Williams, P. A. Baumann, S. Bischoff, M. A. Sills, R. F.
Neale, Naunyn-Schmiedeberg’s Arch. Pharmacol. 1988, 337, 609–620.
[4] I. Van Wijngaarden, C. G. Kruse, R. Van Hes, J. A. M. Van der Heyden,
M. T. M. Tulp, J. Med. Chem. 1987, 30, 2099–2104.
[5] A. Hantzsch, Ber. Dtsch. Chem. Ges. 1890, 23, 1474–1476.
[6] L. Knorr, Ber. Dtsch. Chem. Ges. 1884, 17, 1635–1642.
[7] C. Paal, Ber. Dtsch. Chem. Ges. 1885, 18, 367–371.
[8] V. Estꢁvez, M. Villacampa, J. C. Menendez, Chem. Soc. Rev. 2014, 43,
4633–4657.
[9] a) B. M. Trost, Science 1991, 254, 1471; b) P. T. Anastas, J. C. Warner,
Green Chemistry: Theory and Practice; Oxford University Press, Oxford,
England, 1998.
[10] a) I. Nakamura, Y. Yamamoto, Chem. Rev. 2004, 104, 2127–2198; b) N. T.
Patil, Y. Yamamoto, ARKIVOC 2007, 121–141; c) X. Xin, D. Wang, X. Li, B.
Wang, Angew. Chem. Int. Ed. 2012, 51, 1693–1697; Angew. Chem. 2012,
124, 1725–1729; d) Y. Jiang, W. C. Chan, C. M. Park, J. Am. Chem. Soc.
2012, 134, 4104–4107; e) M. P. Huestis, L. Chan, D. R. Stuart, K. Fagnou,
Angew. Chem. Int. Ed. 2011, 50, 1338–1341; Angew. Chem. 2011, 123,
1374–1377; f) S. Rakshit, F. W. Patureau, F. Glorius, J. Am. Chem. Soc.
2010, 132, 9585–9587; g) D. R. Stuart, P. Alsaben, M. Kuhn, K. Fagnou, J.
[18] T. Yan, B. L. Feringa, K. Barta, Nat. Commun. 2014, 5, 5602.
[19] H.-J. Knçlker, E. Baum, H. Goesmann, R. Klauss, Angew. Chem. Int. Ed.
1999, 38, 2064–2066; Angew. Chem. 1999, 111, 2196–2199.
[20] a) A. Quintard, T. Constantieux, J. Rodriguez, Angew. Chem. Int. Ed. 2013,
52, 12883–12887; Angew. Chem. 2013, 125, 13121–13125; b) A. Quin-
tard, J. Rodriguez, Angew. Chem. Int. Ed. 2014, 53, 4044–4055; Angew.
Chem. 2014, 126, 4124–4136; c) A. J. Rawlings, L. J. Diorazio, M. Wills,
Org. Lett. 2015, 17, 1086–1089; d) H.-J. Pan, T. W. Ng, Y. Zhao, Chem.
Commun. 2015, 51, 11907–11910; e) S. Elangovan, J.-B. Sortais, M.
Beller, C. Darcel, Angew. Chem. Int. Ed. 2015, 54, 14483–14486; Angew.
Chem. 2015, 127, 14691–14694.
[21] T. Yan, B. L. Feringa, K. Barta, ACS Catal. 2016, 6, 381–388.
[22] C. P. Casey, H. Guan, J. Am. Chem. Soc. 2009, 131, 2499–2507.
[23] P. Y. Nikolov, V. A. Yaylayan, J. Agric. Food Chem. 2012, 60, 10155–10161.
Received: May 6, 2016
Revised: June 29, 2016
Published online on && &&, 0000
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T. Yan, K. Barta*
Iron for production: Pyrroles are promi-
nent scaffolds in medicinal chemistry
and several pharmaceutically active
compounds comprise this moiety.
Therefore, the development of catalytic
methods for the direct synthesis using
earth-abundant metals such as iron is
highly desired. Using an iron-based cat-
alyst, we achieve the construction of up
to 22 examples of diverse N-substituted
pyrrole moieties in moderate to very
good isolated yields.
&& – &&
Sustainable Pathways to Pyrroles
through Iron-Catalyzed N-
Heterocyclization from Unsaturated
Diols and Primary Amines
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