Organic Letters
Letter
Scheme 4, a number of 2H-pyrroles 4 with diverse aryl
substituents were obtained in 53−71% yield. The reaction
Scheme 3. Cycloaddition of 1,3-Diphenyl-2-azaallyl Anions
to 1,4-Diphenylbutadiyne6
a
Scheme 4. Synthesis of 2H-Pyrroles
It is relevant to emphasize that polyarylated 2H-pyrroles are
of special interest because of their unique structural
architecture and applications as precursors in heterocyclic
synthesis.7 Despite the many efforts invested to the develop-
ment of methodology for the preparation of polyarylated 2H-
pyrroles, creation of compound libraries of this class remains a
challenge.7,8 In view of steady interest in 2H-pyrroles,
especially polyarylated ones,8 we have attempted to optimize
the reaction found first in relation to the synthesis of 2H-
pyrroles. The optimization was implemented using the same
substrates pair (1a + 2a). Several selected representative results
of these experiments are collected in Table 1.
Table 1. Optimization of 2H-Pyrrole 4aa Synthesis from
a
Ketimine 1a and Acetylene 2a (Scheme 2)
1a/KOBut molar
yield of 3aa
yield of 4aa
b
b
entry
ratio
oxidant
(%)
(%)
1
2
3
4
5
6
7
8
1:1
1:0.2
1:1
1:1
1:0.2
1:1
no
71
70
36
22
68
47
traces
traces
traces
traces
14
20
traces
6
c
air
air
air
c
d
c
c
oxygen
oxygen
chloranil
e
1:0.2
1:0.2
65
66
e
DDQ
a
Conditions: 1a (1 mmol), 2a (1 mmol), KOtBu, DMSO (3 mL),
b
60°C, 15 min. Isolated yield after column chromatography (SiO2, n-
c
hexane/ethyl acetate, 20:1). Bubbling of air (oxygen) for 1 h.
d
e
Bubbling of air for 2 h. 1 mmol, 1 h.
a
Conditions: 1 (1 mmol), 2 (1 mmol), KOBut (0.2 mmol), DMSO
(3 mL), chloranil (1 mmol). Isolated yields after column
chromatography (SiO2, n-hexane/ethyl acetate, 10:1) are given.
The reaction was carried out as follows: the reactants (1a +
2a) were stirred in KOBut/DMSO solution at 60°C for 15
min. The reaction mixture turned reddish-purple right after the
reactants contacted, indicating the generation of azaallyl
anions.1b The color was gradually fading to brown during
the reaction. Next, oxidation on air (oxygen, chloranil, DDQ)
was employed, and the reaction mixture was stirred at the same
temperature for 1−2 h more. The oxidation with air allowed
2H-pyrrole 4aa to be synthesized in a yield of not higher than
20% (1 equiv of KOBut, 2 h, entry 4). With pure oxygen
passing through the reaction mixture with 0.2 equiv of the
base, the yield of pyrroline 3aa was 68%, and 2H-pyrrole was
formed in traces (entry 5), while with 1 equiv of KOBut, the
yield of 3aa dropped to 47%, and the yield of 4aa was found to
be 6% (entry 6). The application of chloranil or DDQ (entries
7, 8) as oxidants resulted in almost quantitative oxidation of
pyrroline 3aa to 2H-pyrrole 4aa for 1 h (65 and 66% yield,
respectively), which is in agreement with the literature data
concerning oxidation of pyrrolines9 and pyrrolidines10 to 2H-
pyrroles. Under the conditions studied, the possible oxidation
of dimsyl anion was not observed.
tolerates a considerable structural diversity of N-benzyl
ketimines covering substituted aromatic, heteroaromatic, and
condensed aromatic moieties. Among functionalities in the
benzene ring are Ph, CF3, F, Cl, Br, and OMe substituents.
Ketimine 1c, a derivative of benzophenone, when reacted with
phenylacetylene 2a, gave 2,2,3,5-tetraphenyl-2H-pyrrole 4ca,
thereby evidencing suitability of the reaction also for the
synthesis of tetraaryl-substituted 2H-pyrroles. 1,4-Bispyrrolyl
benzene 4ra was synthesized in 53% yield from diketimine 1r
(adduct of 1,4-diacetyl benzene and benzylamine). The
reaction proceeded well with several aryl- and hetarylacetylenes
with the donor and acceptor substituents in the benzene ring,
the yields of the corresponding 2H-pyrroles 4ac−aj being 57−
71%.
As it is clear, the synthesized 2H-pyrroles 4 are formed by
oxidation of the intermediate pyrrolines, the products of
superbase-catalyzed [3 + 2] cycloaddition of benzyl ketimines
to arylacetylenes. These intermediates, apart from their
mechanistic importance, arouse self-standing interest as a
valuable class of pyrrole compounds, promising targets for
synthetic and biochemistry. Indeed, the 1-pyrroline core is
widespread in natural products11 and living organisms,12
Next, to assess the scope of the reaction, we have transferred
the best conditions found for the synthesis of 2H-pyrrole 4aa
to other pairs of benzyl ketimines and arylacetylenes with
different combinations of the substituents. As follows from
4122
Org. Lett. 2021, 23, 4121−4126