1,6-Conjugated Addition of Nitromethane to (E)-2-Styrylchromones: A New Synthesis of Novel 2-Substituted 4-Arylpyrrole Derivatives

Abstract

The 1,6-conjugate addition of nitromethane to (E)-2-styrylchromones were achieved, in moderate to good yields, by using DBU as organocatalyst. Reduction studies on the 2-(2-aryl-3-nitropropyl)chromone adducts formed surprisingly led to novel 2-substituted 4-arylpyrrole derivatives. These new derivatives are formed from nitro-group reduction, followed by a 1,4-Michael-type addition of the primary amine intermediate to the α,β-unsaturated carbonyl system of the chromone moiety and concomitant heterocyclic ring opening.

Key words

(E)-2-styrylchromones - nitromethane - 1,6-conjugated addition - 1,4-Michael addition - 2-substituted 4-arylpyrroles - DBU

References and Notes

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15

Typical Procedure for the Preparation of 2-(2-Aryl-3-nitromethyl)chromones 2a-d
A flask containing the appropriate (E)-2-styrylchromone 1a-d (0.104 mmol), nitromethane (0.33 mL), and DBU
(3 µL, 0.021 mmol) was flushed with nitrogen and stirred vigorously at r.t. After the appropriate time (Table  [²] ), the solvent was evaporated under reduced pressure. The residue was taken in EtOAc and purified by preparative TLC on silica. Elution with hexane-EtOAc (7:3 or 1:1) gave the desired products 2a-d (for yields see Table  [²] ).

16

Physical Data of 2-(3-Nitro-2-phenylpropyl)-4 H -chromen-4-one (2a)
Colourless oil. ^¹H NMR (300 MHz, CDCl₃): δ = 8.12 (1 H, dd, J = 1.6, 8.1 Hz, H-5), 7.65 (1 H, ddd, J = 1.6, 7.0, 8.5 Hz, H-7), 7.41-7.18 (7 H, m, H-Ph, H-6, and H-8), 6.03 (1 H, s, H-3), 4.72 (2 H, d, J = 7.6 Hz, β-CH₂NO₂), 4.11-4.01 (1 H, m, H-β), 3.09 (1 H, dd, J = 6.5, 14.5 Hz, H-α), 3.00 (1 H, dd, J = 8.8, 14.5 Hz, H-α). ^¹³C NMR (75 MHz, CDCl₃): δ = 177.7 (C-4), 164.8 (C-2), 156.2 (C-9), 137.2 (C-1′), 133.7 (C-7), 129.2 (C-3′,5′), 128.3 (C-4′), 127.2 (C-2′,6′), 125.7 (C-5), 125.2 (C-6), 123.5 (C-10), 117.7 (C-8), 111.8 (C-3), 79.4 (β-CH₂NO₂), 41.9 (C-β), 38.1 (C-α). HRMS (ESI⁺):
m/z calcd for C₁₈H₁₆NO₄ [M + H]⁺: 310.1074; found: 310.1074.

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( Z )-(2-Hydroxyphenyl) (4-Phenylpyrrolidin-2-ylidene)methyl Ketone (3a)
Yellow solid; mp 113-115 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 13.80 (1 H, s, OH), 9.95 (1 H, s, NH), 7.65 (1 H, dd, J = 1.4, 8.0 Hz, H-6′′′), 7.37-7.24 (6 H, m, H-Ph and H-4′′′), 6.93 (1 H, dd, J = 1.0, 8.3 Hz, H-3′′′), 6.82-6.79 (1 H, m, H-5′′′), 5.87 (1 H, s, H-2), 4.08 (1 H, ddd, J = 1.0, 7.7, 10.6 Hz, H-5′), 3.71 (1 H, dd, J = 7.7, 10.6 Hz, H-5′), 3.64 (1 H, quin, J = 7.7 Hz, H-4′), 3.19 (1 H, dd, J = 7.7, 16.9 Hz, H-3′), 2.93 (1 H, dd, J = 7.6, 16.9 Hz, H-3′). ^¹³C NMR (75 MHz, CDCl₃): δ = 191.3 (C-1), 168.6 (C-2′), 162.3 (C-2′′′), 141.8 (C-1′′), 133.5 (C-4′′′), 128.9 (C-3′′,5′′), 127.7 (C-6′′′), 127.2 (C-4′′), 126.8 (C-2′′,6′′), 120.3 (C-1′′′), 118.2 (C-3′′′), 118.1 (C-5′′′), 85.4 (C-2), 55.2 (C-5′), 41.2 (C-3′), 40.7 (C-4′). HRMS (ESI⁺): m/z calcd for C₁₈H₁₈NO₂ [M + H]⁺: 280.1332; found: 280.1332.

19

Typical Procedure for the Preparation of the 2-Substituted 4-Arylpyrrole Derivatives 3a-d Using Method A Ammonium formate (0.864 mmol) and Pd/C (10%; 7.0 mg) were added to a solution of the appropriate 2-(2-aryl-3-nitropropyl)-4H-chromen-4-one 2a-d (0.082 mmol) in acetone (1 mL), and the reaction mixture was refluxed for 1 h. After cooling to r.t., the reaction mixture was filtered through Celite, and the organic layer was evaporated to dryness. The residue was purified by preparative TLC on silica and eluted with a mixture of hexane-EtOAc (7:3) to give 3a-d (for yields see Table  [³] ).

21

Typical Procedure for the Preparation of the 2-Substituted 4-Arylpyrrole Derivatives 3a-d Using Method B To a solution of the appropriate 2-(2-aryl-3-nitropropyl)-4H-chromen-4-one 2a-d (0.082 mmol) in CHCl₃ (10 mL), tin (powder, 0.81 g) and concd HCl (2.7 mL) were added, and the reaction mixture was stirred for 2 h at r.t. After this period, the reaction mixture was neutralized with NaHCO₃, filtered through Celite, and the solid residue washed with H₂O and CHCl₃. The filtrate was extracted with CHCl₃ (3 × 15 mL), the organic layer dried over Na₂SO₄, and concentrated in vacuo. The residue was purified by preparative TLC on silica eluting with a mixture of hexane-EtOAc (7:3) to afford 3a-d (for yields see Table  [³] ).