Mendeleev
Communications
Mendeleev Commun., 2020, 30, 185–187
Regioselectivity of the Chan–Lam coupling of ambident
nitropyrazoles with trans-styrylboronic acid
Dmitry V. Davydov, Petr K. Sazonov* and Yurii F. Oprunenko
Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russian
Federation. Fax: +7 495 939 1854; e-mail: pksspk00@gmail.com
DOI: 10.1016/j.mencom.2020.03.018
Regioselectivity of the Chan–Lam coupling of ambident
nitropyrazoles with trans-styrylboronic acid depends on the
base and catalyst nature and can vary the N(1)/N(2)-isomer
ratio from ~2:1 to ~1:2. 2-Methyl-4-nitro- and 2,4-dinitro-
imidazoles are unreactive in this reaction. The structure of
N(1)/N(2) isomers was elucidated by NOE measurements
and by the comparison of experimental and DFT calculated
NO2
N
NO2
N
NO2
N
R2
R2
R2
B(OH)2 catalyst
base
R1
Ph
R1
R1
+
+
N
N
N
Ph
H
R , R2 = H, Me, NO2
1
20–51%
25–70% Ph
1
3
C NMR chemical shifts.
Keywords: pyrazoles, nitropyrazoles, vinylpyrazoles, vinylboronic acids, Chan–Lam reaction, copper catalysis, 13C NMR, DFT.
N-Modified nitroazoles are valuable compounds due to their high
biological and pharmacological activity and synthetic
R3
R2
X
catalyst
base
1
applications. In particular, some nitro-N-vinylazoles possess
N
+
Ph
2
good antimicrobial and antyinflammatory activity and are
R1
N
2a–c
a X = Br
H
applied for synthesis of other classes of heterocyclic compounds
R1
R2
R3
3
4
1a–d
such as nucleosides and nucleotides and N-fused heterocycles.
Classical methods for the synthesis of nitro-N-vinylazoles are
+
–
b X = I Ph(TsO )
c X = B(OH)2
1
1
1
1
a, 3a, 4a
H
H
H
NO2
NO2
b, 3b, 4b Me
3(b),4(a)
typically based on multistage chemical processes.
From
c, 3c
d, 3d
H
Me
NO2 NO2
NO
R3
the practical point of view, only the direct regioselective
N-modification of ambident anions of nitroazoles with available
R3
2 Me
R2
R2
5
N
agents can be optimal. At the same time, we could not find any
+
N
N
modern procedure for the N-vinylation of nitroazoles employing
transition metal catalysis.
In principle, catalytic N-vinylation of non-symmetrical
nitropyrazoles with various vinyl-containing reagents can give
two isomers (Scheme 1).
R1
R1
N
Ph
Ph
3a–d
4a,b
Scheme 1 For details and yields, see Tables 1 and 2.
Initially, we tried to perform direct coupling of available
3
-nitropyrazole 1a with trans-styryl bromide 2a in the presence
yield of products 3a, 4a was observed both in MeCN and DMF
(Table 1, entry 1).
6
of CuI under conditions described by Taillefer. Very low total
Table 1 Optimization of N-vinylation of 3-nitropyrazole 1a with trans-styryl-containing reactants 2a–c.
N(1)/N(2)
(3a:4a)
ratioc
Vinylation
reactant
Atmo-
sphere
Yield
Yield
Entry
Catalysta
Solvent
T/°C
t/h
Base, additive
of 3a (%)b of 4a (%)b
1
2
3
4
5
6
7
8
9
2a
2b
2b
2b
2c
2c
2c
2c
2c
2c
2c
CuI
Pdd
MeCN, DMF 80
6
6
6
Cs CO3
Ar
Ar
very low
traces
very low
traces
traces
traces
traces
–
–
–
–
–
2
MeCN
CH Cl
20
20
Al O basic
2
3
CuI
[Cu (TMEDA) (OH) ]Cl Ar
traces
2
2
2
2
2
2
CuI
MeCN
80 (MW) 0.25 DBU
Ar
air
air
O2
O2
O2
O2
O2
traces
tracesa
very lowe very low
CuCl
CuCl
CuSO4
Cu(OAc)2
MeOH
CH Cl
65
20
20
20
20
20
20
6
6
NaOH
Py or Et N
2
2
3
CH Cl
24
24
24
24
24
Py
42
40f
45
31
25
20
20
22
30
51
~2.1
~2.0
~2.1
~0.9
~0.5
2
2
2
2
2
2
CH Cl
Py
2
Cu(OTf) ·PhH
CH Cl
Py
2
2
1
1
0
1
[Cu (TMEDA) (OH) ]Cl CH Cl
Py, MS 4 Å
2
2
2
2
2
[Cu (TMEDA) (OH) ]Cl CH Cl
K CO3
2
2
2
2
2
2
a
b
c
1
d
1
0 mol% of [Cu] catalyst. Isolated yield after TLC. Calculated from H NMR data of the reaction mixtures purified by flash chromatography. Pd/Al O
2
3
e
f
basic. Up to 20% of 1,4-diphenylbutadiene formed. trans-Styryl acetate (~3%) was found in the reaction mixture.
©
2020 Mendeleev Communications. Published by ELSEVIER B.V.
–
185 –
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
Davydov, Dmitry V.
