A regioselective one-pot method for the synthesis of 1-ethyl 2,4-dihydrochromene3,4-cpyrroles in 63–94% yields from available 2-phenyl-, 2-trifluoro(trichloro)methyl- or ...2-phenyl-2-(trifluoromethyl)-3-nitro-2H-chromenes and ethyl isocyanoacetate through the Barton–Zard reaction in ethanol at reflux for 0.5 h, using K2CO3 as a base, has been developed.
The AgOAc-catalysed reaction of 3-nitro-2-phenyl-2H-chromenes with stabilized azomethine ylides generated from the imines based on methyl glycinate and arylaldehydes leads to a mixture of endo and ...endo’ isomers of the corresponding chromeno3,4-cpyrrolidines in a ratio of 2.0–2.3:1 in 85–93% total yields as a result of a Michael addition/Mannich reaction sequence. In a similar reaction involving 2-trifluoromethyl-3-nitro-2H-chromenes, only endo chromeno3,4-cpyrrolidines are formed in 85–94% yields. 3-Nitro-2-(trichloromethyl)-2H-chromenes under the same conditions react with these azomethine ylides to give the corresponding Michael adducts as individual anti-isomers with the cis,trans-configuration of the chromane ring in 40–67% yields. Some 4-CF3-substituted chromano3,4-cpyrrolidines exhibited high cytotoxic activity against HeLa human cervical carcinoma cells.
Reductive cyclization of trans,trans- and trans,cis-isomers of the 2-CF3-substituted 3-nitro-4-phenacylchromanes with Zn-based reductive systems, depending on the conditions, affords ...4-CF3-substituted 1,3a,4,9b-tetrahydrochromeno3,4-bpyrrole 3-oxides, 1,3a,4,9b-tetrahydrochromeno3,4-bpyrroles, or 1,2,3,3a,4,9b-hexahydrochromeno3,4-bpyrroles in good yields without changing the relative configuration of the pyran ring. A similar process involving the 2-CCl3-substituted 3-nitro-4-phenacylchromanes is accompanied by reductive dehalogenation to form the corresponding 4-dichloromethyl-substituted fused chromanes along with the 3-(2-hydroxyaryl)-2-(2,2-dichlorovinyl)-5-phenyl-2H-pyrroline 1-oxides as pyran ring opening products. The structure and relative configuration of the obtained products was reliably confirmed by X-ray diffraction analysis and 2D NMR spectroscopy.
A regio- and stereoselective method for the synthesis of
N
-unsubstituted 3-aryl-4-(trifluoromethyl)-4
H
-spirochromeno3,4-
c
-pyrrolidine-1,3'-oxindoles in 24–79% yields, based on the ...three-component reaction of 3-nitro-2-(trifluoromethyl)-2
H
-chromenes with azomethine ylides generated
in situ
from benzylamines and isatins by refluxing in CH
2
Cl
2
for 24 h has been developed. 3-Phenyl-4-(trifluoromethyl)-4
H
-spirochromeno3,4-
c
pyrrolidine-1,3'-oxindoles were obtained in 36–71% yields
via
the three-component reaction of 3-nitro-2-(trifluoromethyl)-2
H
-chromene, isatins, and L-phenylglycine proceeding in EtOH at 60°C for 5 h. The resulting compounds exhibited cytotoxic activity against human cervical cancer HeLa cells in the micromolar concentration range.
A diastereoselective method was developed for the synthesis of 4-trifluoromethyl- and 4-phenyl-substituted 3a-nitro-2,3,3a,9b-tetrahydro-4
H
-thieno3,2-
c
chromen-3-ols having
cis
configuration of ...substituents at the C-3, C-3a, C-4 atoms and the 9b-CH hydrogen atom from the available starting materials – 3-nitro-2
H
-chromenes and 2,5-dihydroxy-1,4-dithiane in 80–92% yields. This approach relied on a tandem of Michael and Henry reactions between 3-nitro-2
H
-chromenes and
in situ
generated mercaptoacetaldehyde in Et
2
O at room temperature over 4–6 h, using Et
3
N as catalyst.
A regioselective method for the synthesis of ethyl 3,4-dihydrochromeno3,4-
c
pyrazole-1-carboxylates from 2-substituted 3-nitro-2
H
chromenes and ethyl diazoacetate in 68–87% yields was developed. ...This approach involves an AgOAc-catalyzed 1,3-dipolar cycloaddition of ethyl diazoacetate to nitrochromenes followed by elimination of HNO
2
by the action of DBU.
1,3-Dipolar cycloaddition of stabilized azomethine ylides generated
in situ
from isatins and proline to 3-nitro-2-phenyl-2-trifluoromethyl-2
H
-chromenes in
i
-PrOH proceeds stereoselectively at room ...temperature and leads to the formation of hexahydro-6
H
-spirochromeno3,4-
a
-pyrrolizine-11,3'-indolin-2'-ones with the
cis
arrangement of the trifluoromethyl group and the nitro group. A similar reaction with the participation of thiaproline-based ylides at 50°С leads to mixtures of diastereomeric tetrahydro-6
H
,9
H
-spirochromeno3',4':3,4pyrrolo1,2-
c
thiazole-11,3'-indolin-2'-ones with a predominance of the
cis
- or
trans
-isomer. The stereochemistry of the obtained products was confirmed by the NOESY experiment and X-ray structural analysis.
A regioselective one-pot method for the synthesis of 1-ethyl 2,4-dihydrochromene3,4-cpyrroles in 63-94% yields from available 2-phenyl-, 2-trifluoro(trichloro)methyl- or ...2-phenyl-2-(trifluoromethyl)-3-nitro-2H-chromenes and ethyl isocyanoacetate through the Barton-Zard reaction in ethanol at reflux for 0.5 h, using Ksub.2COsub.3 as a base, has been developed.
A method for a regio- and stereoselective synthesis of
N
-unsubstituted 3-aryl-4-(trifluoromethyl)-4
H
-spirochromeno3,4-
c
pyrrolidine-1,11'-indeno1,2-
b
quinoxalines in 52–85% yields based on the ...three-component reaction of 3-nitro-2-trifluoromethyl-2
H
-chromenes with azomethine ylides generated
in situ
from benzylamines and indeno1,2-
b
quinoxalin-11-one by heating under reflux in CH
2
Cl
2
for 2 h in the presence of 0.1 equiv of pyrrolidine was developed. The resulting compounds exhibited moderate cytotoxic activity against HeLa human cervical carcinoma cells in the concentration range of 10
–5
–10
–4
M.
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