Categories: Synthesis of N-Heterocycles >
Synthesis of pyrroles
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Recent Literature
An operationally simple, practical, and economical Paal-Knorr pyrrole
condensation of 2,5-dimethoxytetrahydrofuran with various amines and
sulfonamines in water in the presence of a catalytic amount of iron(III)
chloride allows the synthesis of N-substituted pyrroles under very mild
reaction conditions in good to excellent yields.
N. Azizi, A. Khajeh-Amiri, H. Ghafuri, M. Bolourtchian, M. R. Saidi, Synlett, 2009,
2245-2248.
A highly efficient Cu-catalyzed tandem C-N bond-forming reaction of
1,4-dihalo-1,3-dienes allows the synthesis of pyrroles and heteroarylpyrroles
with a wide variety of functional groups and substitution patterns from readily
available precursors.
R. Martín, C. H. Larsen, A. Cuenca, S. L. Buchwald, Org. Lett., 2007,
9, 3379-3382.
An efficient copper-catalyzed double alkenylation of amides with (1Z,3Z)-1,4-diiodo-1,3-dienes
affords di- or trisubstituted N-acylpyrroles in good yields using CuI as
the catalyst, Cs2CO3 as the base, and rac-trans-N,N'-dimethylcyclohexane-1,2-diamine
as the ligand.
X. Yuan, X. Xu, X. Zhou, J. Yuan, L. Mai, Y. Li, J. Org. Chem., 2007,
72, 1510-1513.
A tandem reaction involving cross metathesis followed by concomitant cyclisation
enables the synthesis of substituted pyrroles. Various protected
electron-deficient N-allylamines reacted with α,β-unsaturated carbonyl
compounds in the presence of Lewis acids under the cross metathesis conditions
using a 2nd generation Hoveyda catalyst in order to form pyrroles.
S. Shafi, M. Kędziorek, K. Grela, Synlett, 2011,
124-128.
Titanium-catalyzed intermolecular hydroaminations enabled efficient,
user-friendly one-pot reactions for the preparations of 2-substituted and fully
substituted pyrroles from (E/Z)-chloroenynes and easily accessible
α-haloalkynols, respectively.
L. Ackermann, R. Sandmann, L. T. Kaspar, Org. Lett., 2009,
11, 2031-2034.
Intramolecular cyclizations of 3-alkyne-1,2-diols and 1-amino-3-alkyn-2-ols with
very low catalyst loading of (Ph3P)AuCl-AgNTf2 or (Ph3P)AuCl-AgOTf
proceeded at room temperature to provide various substituted furans and pyrroles
in excellent yields. This method was also fully applicable to the conversion of
26 g of a substrate using only 0.05 mol % each of the Au and Ag catalysts.
M. Egi, K. Azechi, S. Akai, Org. Lett., 2009,
11, 5002-5005.
Manganese(III)-catalyzed formal [3+2] annnulation of vinyl azides and β-keto
acids enables the synthesis of substituted NH pyrroles with a wide range of
substituents.
E. P. J. Ng, Y.-F. Wang, S. Chiba, Synlett, 2011,
783-786.
Furans, pyrroles, and thiophenes are efficiently and conveniently prepared by
gold-catalyzed dehydrative cyclizations of readily available,
heteroatom-substituted propargylic alcohols. The reactions provide essentially
pure aromatic heterocycles in high yields in minutes under open-flask conditions
with low catalyst loadings.
A. Aponick, C.-Y. Li, J. Malinge, E. F. Marques, Org. Lett., 2009,
11, 4624-4627.
A convenient and general one-pot synthesis of substituted pyrroles from
propargylic acetates, silyl enol ethers, and primary amines was catalyzed by
indium trichloride. High yields of various pyrrole derivatives were obtained.
M. Lin, L. Hao, R.-d. Ma, Z.-p. Zhan, Synlett, 2010,
2345-2351.
Highly substituted furans were conveniently synthesized by the
platinum-catalyzed reaction of propargylic oxiranes. Propargylic aziridines were
also reacted with the platinum catalyst to produce the corresponding substituted
pyrroles in good yields.
M. Yoshida, M. Al-Amin, K. Shishido, Synthesis, 2009,
2454-2466.
Aryl-substituted N-tosyl alkynyl aziridines undergo a gold-catalyzed ring
expansion to afford 2,5-substituted pyrrole products. Depending on the the
counterion to the gold catalyst and the solvent, a ring-expansion and
rearrangement leads to 2,4-substituted pyrroles.
P. W. Davies, N. Martin, Org. Lett., 2009,
11, 2293-2296.
L. Ackermann, R. Sandmann, L. T. Kaspar, Org. Lett., 2009,
11, 2031-2034.
(Hetero)aryl-, alkenyl-, and selected alkyl-substituted acid chlorides can be
efficiently coupled with N-Boc-protected propargylamine to produce ynones
which are converted to 2-substituted N-Boc-4-iodopyrroles in a one-pot
reaction. Upon addition of a further alkyne, another Sonogashira coupling can be
carried out in a one-pot fashion.
E. Merkul, C. Boersch, W. Frank, T. J. J. Müller, Org. Lett., 2009,
11, 2269-2272.
A range of 2,5-disubstituted and 2,4,5-trisubstituted pyrroles can be
synthesized from dienyl azides at room temperature using ZnI2 or Rh2(O2CC3F7)4
as catalysts.
H. Dong, M. Shen, J. E. Redford, B. J. Stokes, A. L. Pumphrey, T. G. Driver, Org. Lett., 2007,
9, 5191-5194.
An efficient, solvent-free, microwave-assisted coupling of
chloroenones and amines on the surface of silica gel gave 1,2-disubstituted
homochiral pyrroles in good yields.
F. Aydogan, A. S. Demir, Tetrahedron, 2005,
61, 3019-3023.
The CuI/N,N-dimethylglycine-catalyzed reaction of amines with
γ-bromo-substituted γ,δ-unsaturated ketones in the presence of K3PO4
and NH4OAc gave the corresponding polysubstituted pyrroles in very
good yields.
Y. Pan, H. Lu, Y. Fang, X. Fang, L. Chen, J. Qian, J. Wang, C. Li, Synthesis, 2007,
1242-1246.
A mild, gold(I)-catalyzed acetylenic Schmidt
reaction of homopropargyl azides gave regiospecific substituted pyrroles. A mechanism in which azides serve as nucleophiles toward gold(I)-activated alkynes
with subsequent gold(I)-aided expulsion of dinitrogen is proposed.
D. J. Gorin, N. R. Davis, F. D. Toste, J. Am. Chem. Soc.,
2005, 127, 11260-11261.
A mild, gold(I)-catalyzed cycloisomerization of β-allenylhydrazones provides an
efficient access to multisubstituted N-aminopyrroles in good to excellent
yields with short reaction times through a selective intramolecular 1,2-alkyl or
-aryl migration. This intramolecular cyclization can be applied either to alkyl-
or aryl-substituted allenes.
E. Benedetti, G. Lemière, L.-L. Chapellet, A. Penoni, G. Palmisano, M. Malacria,
J.-P. Goddard, L. Fensterband, Org. Lett., 2010,
12, 4396-4399.
A one-step reaction to assemble pyrroles from α,β-unsaturated imines and acid
chlorides is mediated by triphenylphosphine, which eliminates phosphine oxide to
allow cyclization. This reaction has been employed to access broad range of
pyrroles via modulation of the two building blocks and applied as well to the
synthesis of lukianol A.
Y. Lu, B. A. Arndtsen, Org. Lett., 2009,
11, 1369-1372.
An iron(III)-catalyed four-component coupling reactions of 1,3-dicarbonyl
compounds, amines, aromatic aldehydes, and nitroalkanes without an inert
atmosphere provides highly substituted pyrroles in good yields. Notably, this
method is very cheap, straightforward, and environmentally friendly compared to
existing methods.
S. Maiti, S. Biswas, U. Jana, J. Org. Chem., 2010,
75, 1674-1683.
A fast, mild, and environmentally benign domino reaction enables an efficient
reaction of (E)-β-bromonitrostyrenes with enaminones in water to afford
pyrroles in excellent yields.
M. Rueping, A. Parra, Org. Lett., 2010,
12, 5281-5283.
A cationic N-heterocyclic carbene-gold(I) complex catalyzes the
formation of tri- and tetrasubstituted pyrroles from N-propargyl
β-enaminone derivatives via an amino-Claisen rearrangement to yield α-allenyl
β-enaminones and subsequent cyclization of these intermediates.
A. Saito, O. Konishi, Y. Hanzawa, Org. Lett., 2010,
12, 372-374.
N-Propargylic β-enaminones are common intermediates for the
synthesis of polysubstituted pyrroles and pyridines. In the presence of Cs2CO3
N-propargylic
β-enaminones are cyclized to pyrroles in good to high yields, whereas CuBr leads to pyridines.
S. Cacchi, G. Fabrizi, E. Filisti, Org. Lett., 2008,
10, 2629-2632.
Various 2-alkyl-5-aryl-(1H)-pyrrole-4-ol derivatives were synthesized via
a multicomponent reaction of β-dicarbonyl compounds with arylglyoxals in the
presence of ammonium acetate in water at room temperature.
B. Khalili, P. Jajarmi, B. Eftekhari-Sis, M. M. Hashemi, J. Org. Chem., 2008,
73, 2090-2095.
An efficient and regioselective palladium-catalyzed cyclization of internal
alkynes and 2-amino-3-iodoacrylates gave good yields of highly
functionalized pyrroles.
M. L. Crawley, I. Goljer, D. J. Jenkins, J. F. Mehlmann, L. Nogle, R.
Dooley, P. E. Mahaney, Org. Lett., 2006, 8, 5837-5840.
In(OTf)3 or In(NTf2)3 effectively catalyze the
cycloisomerization reaction of α-propargyl-β-keto esters and their imine
analogues to afford trisubstituted furans and pyrroles, respectively. Both
terminal and internal alkynes take part in the reaction with good
functional-group compatibility in the presence of only a small catalyst loading.
H. Tsuhi, K.-i. Yamagata, Y. Ueda, E. Nakamura, Synlett, 2011,
1015-1017.
A Mn(III)-catalyzed reaction of vinyl azides with 1,3-dicarbonyl compounds gave
a broad range of polysubstituted N-H pyrroles in good yields.
Y.-F. Wang, K. K. Toh, S. Chiba, K. Narasaka, Org. Lett.,
2008,
10, 5019-5022.
Two methods for the regioselective synthesis of tetra- and trisubstituted N-H
pyrroles from starting vinyl azides have been developed: A thermal pyrrole
formation via the 1,2-addition of 1,3-dicarbonyl compounds to 2H-azirine
intermediates generated in situ from vinyl azides and a Cu(II)-catalyzed
synthesis with ethyl acetoacetate through a 1,4-addition.
S. Chiba, Y.-F. Wang, G. Lapointe, K. Narasaka, Org. Lett., 2008,
10, 313-316.
S. Chiba, Y.-F. Wang, G. Lapointe, K. Narasaka, Org. Lett., 2008,
10, 313-316.
A three-component reactions of arylacyl bromides, amines, and dialkyl
acetylenedicarboxylate in the presence of iron(III) chloride as a catalyst at
room temperature afforded polysubstituted pyrroles in high yields.
B. Das, G. C. Reddy, P. Balasubramanyam, B. Veeranjaneyulu, Synthesis, 2010,
1625-1628.
A new and efficient three-component reaction between dialkyl
acetylenedicarboxylates, aromatic amines, triphenylphosphine, and arylglyoxals
afforded polysubstituted pyrrole derivatives in high yields. The reactions were
performed in dichloromethane at room temperature and under neutral conditions.
M. Anary-Abbasinejad, K. Charkhati, H. Anaraki-Ardakani, Synlett, 2009,
1115-1117.
A reaction between dialkyl acetylenedicarboxylates and β-aminoketones promoted
by triphenylphosphine allows an efficient one-pot synthesis of polysubstituted
2,5-dihydropyrrole derivatives. The prepared 2,5-dihydropyrroles can be easily
oxidized to the corresponding pyrrole derivatives with chromium trioxide.
M. Anary-Abbasinejad, E. Poorhassan, A. Hassanabadi, Synlett, 2009,
1929-1932.
A basic functionalized ionic liquid, 1-butyl-3-methylimidazolium hydroxide ([bmim]OH),
catalyzed the three-component condensation reaction of acid chlorides, amino
acids, and dialkyl acetylenedicarboxylates in water to afford functionalized
pyrroles in high yields.
I. Yavari, E. Kowsari, Synlett, 2008,
897-899.
The reaction of an enaminone, which can be derived from two primary amines and
diketene, in the presence of nitrostyrene gives functionalized pyrrole
derivatives in very good yields.
A. Alizadeh, A. Rezvanian, H. R. Bijanzadeh, Synthesis, 2008,
725-728.
A silver(I)-promoted oxidative
cyclization of homopropargylamines at room temperature provides pyrroles.
Homopropargylamines are readily available by the addition of a propargyl
Grignard reagent to Schiff bases.
S. Aggarwal, H.-J. Knölker, Org. Biomol. Chem., 2004, 2,
3060-3062.
A general, highly flexible Cu-catalyzed domino C-N coupling/hydroamination
reaction constitutes a straightforward alternative to existing methodology
for the preparation of pyrroles and pyrazoles.
R. Martin, M. R. Rivero, S. L. Buchwald, Angew. Chem. Int. Ed., 2006, 45, 7079-7082.
An efficient and highly versatile microwave-assisted Paal-Knorr condensation
of various 1,4-diketones gave furans, pyrroles and thiophenes in good yields.
In addition, transformations of the methoxycarbonyl moiety, such as Curtius
rearrangement, hydrolysis to carboxylic acid, or the conversion into amine
by reaction with a primary amine in the presence of Me3Al, are
described.
G. Minetto, L. F. Raveglia, A. Sega, M. Taddei, Eur. J. Org. Chem., 2005,
5277-5288.
A direct synthesis of pyrroles from imines, acid chlorides, and alkynes
mediated by isocyanides proceeds with a range of substrates, providing a method
to generate various pyrroles in high yield. Mechanistic studies suggest a
generation of imino analogues of münchnones, which can undergo in situ coupling
with alkynes to liberate isocyanate and form the pyrrole product.
D. J. St. Cyr, N. Martin, B. A. Arndtsen, Org. Lett., 2007,
9, 449-452.
The nucleophilic addition of sodium azide to 1,2-allenyl esters regio- and
stereoselectively generates
vinyl azides in excellent yields.
A sequential reaction for the synthesis of pyrroles using 1-allyllic 1,2-allenyl
esters as substrates is developed
on the basis of a domino process involving nucleophilic addition,
cycloaddition, denitrogenation, and aromatization.
X. Huang, R. Shen, T. Zhang, J. Org. Chem., 2007,
72, 1534-1537.
The synthesis of N-acylpyrroles from primary aromatic amides and
excess 2,5-dimethoxytetrahydrofuran in presence of one equivalent of thionyl
chloride offers short reaction times, mild reaction conditions, and easy
workup.
A. R. Ekkati, D. K. Bates, Synthesis, 2003, 1959-1961.
Propargyl vinyl ethers and aromatic amines are effectively converted into tetra- and pentasubstituted
5-methylpyrroles through a
silver(I)-catalyzed propargyl-Claisen rearrangement, an amine condensation, and
a gold(I)-catalyzed 5-exo-dig heterocyclization in a convenient one-pot process.
J. T. Binder, S. F. Kirsch, Org. Lett.,
2006, 8, 2151-2153.
Various 2,3,4-trisubstituted pyrroles are easily accessible in one step from
readily available acetylenes and acceptor-substituted methyl isocyanides by base-mediated
or copper-catalyzed cycloadditions. Scope and limitations of both pyrrole
syntheses are discussed.
O. V. Larionov, A. de Meijere, Angew. Chem. Int. Ed., 2005,
44, 5664-5667.
A New Use of Wittig-Type Reagents as 1,3-Dipolar Cycloaddition Precursors
and in Pyrrole Synthesis
D. J. St. Cyr, B. A. Arndtsen, J. Am. Chem. Soc.,
2007,
129, 12366-12367.
A
novel and efficient multicomponent reaction of N-tosylimines, DMAD,
and isocyanides for the synthesis of 2-aminopyrrole systems was uncovered.
V. Nair, A. U. Vinod, C. Rajesh, J. Org. Chem., 2001, 66,
4427-4429.
A Au(I)-catalyzed hydroamination or hydration of 1,3-diynes allows access to
2,5-diamidopyrroles and 2,5-diamidofurans. This method can also be expanded to
2,5-disubstituted furans and 1,2,5-trisubstituted pyrroles.
S. Kramer, J. L. H. Madsen, M. Rottländer, T. Skrydstrup, Org. Lett., 2010,
12, 2758-2761.
A robust and operational simple route to 2,4-disubstituted pyrrole
heterocycles relying upon a cascade reaction is air and moisture tolerant and is
performed at ambient temperature. Control over the reaction conditions provides
ready access to isopyrroles, 2,3,4-trisubstituted pyrroles and 3-substituted
pyrollidin-2-ones.
B. M. Trost, J.-P. Lumb, J. M. Azzarelli, J. Am. Chem. Soc., 2011,
133, 740-743.
A new microwave-assisted rearrangement of 1,3-oxazolidines scaffolds is the
basis for a new, metal-free, direct, and modular construction of
tetrasubstituted pyrroles from terminal-conjugated alkynes, aldehydes, and
primary amines under very simple and environmental-friendly experimental
conditions.
D. Tejedor, D. González-Cruz, F. García-Tellado, J. J. Marrero-Tellado, M.
L. Rodríguez, J. Am. Chem. Soc.,
2004, 126, 8390-8391.
Coupling of acetylene, nitrile, and a titanium reagent generated new
azatitanacyclopentadienes in a highly regioselective manner. The subsequent
reaction with sulfonylacetylene and electrophiles gave substituted pyridines
virtually as a single isomer. Alternatively, the reaction of
azatitanacyclopentadienes with an aldehyde or another nitrile gave furans or
pyrroles having four different substituents again in a regioselective manner.
D. Suzuki, Y. Nobe, R. Tanaka, Y. Takayama, F. Sato, H. Urabe, J. Am. Chem. Soc.,
2005, 127, 7474-7479.
An efficient synthesis of 2,3,4-trisubstituted pyrroles via intermolecular
cyclization of alkylidenecyclopropyl ketones with amines was observed. A
mechanism involving a distal cleavage of the C-C bond of the cyclopropane ring
is discussed.
L. Lu, G. Chen, S. Ma, Org. Lett.,
2006, 8, 835-838.
Several aryl-substituted pyrrole derivates were prepared conveniently in a
microwave-assisted one pot-reaction from but-2-ene-1,4-diones and
but-2-yne-1,4-diones via Pd/C-catalyzed hydrogenation of the carbon-carbon
double bond/triple bond followed by amination-cyclization.
H. S. P. Rao, S. Jothilingam, H. W. Scheeren, Tetrahedron, 2004, 60, 1625-1630.
1,3,4-triaryl-2,5-dihydropyrroles were synthesized using the McMurry coupling
reaction as key step. A facile and reliable non-catalytic photoconversion of
1,3,4-triaryl-2,5-dihydropyrroles furnished 1,3,4-triarylpyrroles in good yields.
D. X. Zeng, Y. Chen, Synlett,
2006, 490-492.
1-Vinylpyrroles are formylated by the N,N-dimethylformamide/oxalyl
chloride reagent system to give the corresponding 1-vinylpyrrole-2-carbaldehydes
in good yields in short reaction times.
A. I. Mikhaleva, A. V. Ivanoc, E. V. Skital'tseva, I. A. Ushakov, A. M.
Vasil'tsov, B. A. Trofimov, Synthesis, 2009,
587-590.
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