Regio- and Diastereoselective Synthesis of Novel Polycyclic Pyrrolo[2,1-a]isoquinolines Bearing Indeno[1,2-b]quinoxaline Moieties by a Three-Component [3+2]-Cycloaddition Reaction

Firouz Matloubi Moghaddam; Atiyeh Moafi; Behzad Jafari; Alexander Vilinger; Peter Langer

doi:10.1055/s-0039-1690768

Synlett, Table of Contents

Synlett 2020; 31(03): 267-271
DOI: 10.1055/s-0039-1690768

letter

Regio- and Diastereoselective Synthesis of Novel Polycyclic Pyrrolo[2,1-a]isoquinolines Bearing Indeno[1,2-b]quinoxaline Moieties by a Three-Component [3+2]-Cycloaddition Reaction

Firouz Matloubi Moghaddam ∗

^aLaboratory of Organic Synthesis and Natural Products, Department of Chemistry, Sharif University of Technology, Azadi Street, PO Box 11155-9516, Tehran, Iran Email: matloubi@sharif.edu

,

Atiyeh Moafi

^aLaboratory of Organic Synthesis and Natural Products, Department of Chemistry, Sharif University of Technology, Azadi Street, PO Box 11155-9516, Tehran, Iran Email: matloubi@sharif.edu

,

Behzad Jafari

^bInstitut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany

,

Alexander Vilinger

^bInstitut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany

,

Peter Langer

^bInstitut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany

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Abstract

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Abstract

A regio- and diastereoselective synthesis of 2,3-dihydro-10b′H-spiro[indeno[1,2-b]quinoxaline-11,1′-pyrrolo[2,1-a]isoquinoline]-2′,3′-diylbis(phenylmethanone) derivatives containing four contiguous chiral stereocenters was achieved through 1,3-dipolar cycloaddition of isoquinolinium N-ylides in a one-pot three-component reaction. The desired products were obtained in short reaction times and in moderate to high yields (up to 92%) under relatively mild reaction conditions. The structure and relative stereochemistry of the desired product was confirmed by X-ray diffraction analysis.

Key words

pyrroloisoquinolines - indenoquinoxalines - spiro compounds - diastereoselectivity - 1,3-dipolar cycloaddition - multicomponent reaction

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References

References and Notes

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31 1-Aryl-2-(11H-indeno[1,2-b]quinoxalin-11-ylidene)ethanones 3; General Procedure NaOAc (1.5 mmol) was added to a solution of ninhydrin (1 mmol) and the appropriate phenylenediamine 1 (1 mmol) in EtOH (4 mL), and the solution was stirred for 1 h at r.t. Then, the appropriate 1-aryl-2-(triphenylphosphoranylidene)ethanone 4 (1.5 mmol) was added and the mixture was stirred at the reflux until the reaction was complete (TLC; 2 h). The mixture was then filtered and the product was recrystallized from EtOH.
32 Products 6a–o : General Procedure A mixture of isoquinoline (1 mmol) and the appropriate phenacyl bromide 5 (1 mmol) in CH₃CN (3 mL) was stirred at r.t. for 15 min. Et₃N (1 mmol) and the appropriate ketone 3 (1 mmol) were added, and the mixture was stirred under reflux until the reaction was complete (TLC; hexane–EtOAc, 1:2). The pure products was then simply collected by filtration and dried in air. (2′-Benzoyl-2′,3′-dihydro-10b′H-spiro[indeno[1,2-b]quinoxaline-11,1′-pyrrolo[2,1-a]isoquinolin]-3′-yl)(4-tolyl)methanone (6b) Orange solid; yield: 411 mg (69%); mp 207–209 °C. IR (KBr) = 1679, 1615, 14.99, 1460, 1328, 1238, 1130 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ_H = 2.41 (s, 3 H, CH₃), 5.23 (d, ³ J _HH = 7.5 Hz, 1 H, CH pyrrolidine), 5.31 (d, ³ J _HH = 5.4 Hz, 1 H, olefinic CH), 5.36 (d, ³ J _HH = 7.7 Hz, 1 H, N–CH pyrrolidine), 6.25–6.28 (t, ³ J _HH = 7.5 Hz, 1 H, H–Ar), 6.38 (s, 1 H, benzylic CH), 6.43 (d, ³ J _HH = 5.4 Hz, 1 H, olefinic CH–N), 6.53 (d, ³ J _HH = 7.5 Hz, 1 H, H–Ar), 6.56–6.60 (t, ³ J _HH = 7.5 Hz, 2 H, H–Ar), 6.65 (d, ³ J _HH = 7.5 Hz, 1 H, H–Ar), 6.70–6.75 (m, 3 H, H–Ar), 6.99–7.02 (t, ³ J _HH = 7.5 Hz, 1 H, H–Ar), 7.20–7.23 (t, ³ J _HH = 7.5 Hz, 1 H, H–Ar), 7.32 (d, ³ J _HH = 7.5 Hz, 3 H, H–Ar), 7.62 (d, ³ J _HH = 7.5 Hz, 1 H, H–Ar), 7.78–7.81 (m, 3 H, H–Ar), 8.07 (d, ³ J _HH = 9.5 Hz, 1 H, H–Ar), 8.10 (d, ³ J _HH = 8.0 Hz, 2 H, H–Ar), 8.32 (d, ³ J _HH = 9.4 Hz, 1 H, H–Ar). ¹³C NMR (125 MHz, CDCl₃): δ_C = 21.7, 57.3, 65.3, 65.9, 69.8, 98.3, 121.2, 124.0, 124.1, 124.6, 126.1, 127.1, 127.2, 127.4, 127.6, 128.5, 128.9, 129.0, 129.1, 129.6, 129.7, 129.8, 130.9, 132.5, 132.8, 132.9, 134.0, 136.6, 137.3, 141.5, 142.2, 144.3, 144.7, 154.5, 160.4, 197.0, 197.4. Anal. calcd for C₄₁H₂₉N₃O₂ (595.70): C, 82.67; H, 4.91; N, 7.05. Found: C, 82.64; H, 4.96; N, 6.97. Crystal Data for 6b: C₄₁H₂₉N₃O₂: M_W = 595.67, monoclinic, P21/c, a = 10.0450(8) Å, b = 17.0959(14) Å, c = 18.8967(15) Å, β = 104.646(2)°, V = 3139.7(4) Å³, Z = 4, D _c = 1.293 mg/m³, F(000) = 1281; crystal dimensions: 0.26 × 0.15 × 0.12 mm, radiation, Mo Kα (λ = 0.71073 Å), 3.424 ≤ 2θ ≤ 26.999, intensity data were collected at 123(2) K with a Bruker APEX area-detector diffractometer, employing the ω/2θ scanning technique, in the range –12 ≤ h ≤ 12, –21 ≤ k ≤ 21, –24 ≤ l ≤ 24. The structure was solved by a direct method; all nonhydrogen atoms were positioned and anisotropic thermal parameters were refined from 6837 observed reflections with R _(into) = 0.0404 by a full-matrix least-squares technique converging to R1 = 0.0520, and wR2 = 0.1166 [I > 2σ(I)].
33 CCDC 1949927 contains the supplementary crystallographic data for compound 6b. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.

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