Synthesis of Pyrrolizinone and Pyrrolizino[1,2-a]pyrrolizin-5-one Skeletons Starting From Pyrrole through a Single-Step and Catalyst-Free Approach

Karina Amudi; Burak Kuzu; Seda Kolak; Hasan Genç; Nurettin Menges

doi:10.1055/a-2006-4390

Synlett, Table of Contents

Synlett 2023; 34(11): 1265-1269
DOI: 10.1055/a-2006-4390

letter

Synthesis of Pyrrolizinone and Pyrrolizino[1,2-a]pyrrolizin-5-one Skeletons Starting From Pyrrole through a Single-Step and Catalyst-Free Approach

Authors

Karina Amudi

^aPharmaceutical Chemistry Section, Van Yüzüncü Yil University, 65080, Van, Turkey
Burak Kuzu

^aPharmaceutical Chemistry Section, Van Yüzüncü Yil University, 65080, Van, Turkey
Seda Kolak

^bFaculty of Education, Van Yüzüncü Yil University, 65080, Van, Turkey
Hasan Genç

^bFaculty of Education, Van Yüzüncü Yil University, 65080, Van, Turkey
Nurettin Menges ∗

^aPharmaceutical Chemistry Section, Van Yüzüncü Yil University, 65080, Van, Turkey

^cNecmettin Erbakan University, Faculty of Engineering, Department of Biomedical Engineering, 42100, Konya, Turkey

^dNecmettin Erbakan University, Science and Technology Research and Application Center (BITAM), 42100, Konya, Turkey

Abstract

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Abstract

1H-Pyrrole reacted with lactone-type 2,3-furandione derivatives in anhydrous diethyl ether at room temperature to give a series of derivatives of pyrrolizinone (which is among the most important alkaloid skeletons) in a single step without a catalyst. Pyrrolizinone derivatives with a variety of substituents, such as phenyl, substituted phenyl, thienyl, trifluoromethyl, naphthyl, biphenylyl, ester, or oxalate, were obtained. The reaction of an equimolar amount of pyrrole gave pyrrolizinones, whereas an excess of pyrrole gave pyrrolizino[1,2-a]pyrrolizin-5-ones containing a skeleton that had not previously been reported. The purified molecules were obtained in yields of up to 91%. One cyclization process was carried out on a gram scale, yielding 0.952 g (71%) of the corresponding product.

Keywords

furandiones - alkaloids - Michael addition - decarboxylation - pyrrolizinones - pyrrolizinopyrrolizinones

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References

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11 Pyrrolizinones 6a–j; General Method Pyrrole (5, 1 mmol) was added to a solution of the appropriate furandione 4a–j (1 mmol) in dry Et₂O (10 ml) in a round-bottomed flask, and the resulting solution was stirred at rt for 18 h until the reaction should be completed (TLC). The organic layer was extracted with EtOAc (3 × 50 mL), dried (MgSO₄), and concentrated in a low vacuum. The crude product was purified by column chromatography [silica gel, hexane–EtOAc (20:1)]. 2-Benzoyl-1-phenyl-3H-pyrrolizin-3-one (6a) Red viscous liquid; yield: 81%; R_f = 0.80. FTIR (ATR): 3045, 2911, 1725, 1640, 1345, 1215, 685 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.86–7.82 (m, 2 H, Ar-H), 7.53–7.46 (m, 3 H, Ar-H), 7.41–7.35 (m, 2 H, Ar-H), 7.34–7.29 (m, 3 H, Ar-H), 7.13 (dd, J = 0.8, 3.1 Hz, 1 H, Ar-H), 6.41 (dd, J = 0.8, 3.1 Hz, 1 H-Ar-H), 6.21 (t, J = 3.1 Hz, 1 H, Ar-H). ¹³C NMR (100 MHz, CDCl₃): δ = 190.1, 159.2, 153.2, 136.8, 135.2, 133.5, 131.4, 130.3, 129.6, 128.8, 128.7, 128.3, 120.1, 118.7, 116.3, 115.5. HRMS: m/z [M + H]⁺ calcd for C₂₀H₁₄NO₂: 300.1025; found: 300.1018.

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