Rhodium-Catalyzed Reaction of 2H-Azirines with Carbonyl-ene-yne Compounds Giving 1-Furyl-2-aza-1,3-dienes

Abstract

A rhodium(II)-catalyzed reaction of carbonyl-ene-yne compounds, which are used as furylcarbene precursors, with 2H-azirines gave 1-furyl-2-aza-1,3-dienes as products. We propose that the title compounds are formed by the addition of furylcarbene–rhodium(II) complexes to 2H-azirines followed by opening of 2H-azirine rings.

Key words

alkynes - rhodium - carbenes - azirines - ring-opening reaction

• References and Notes


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A few stoichiometric or catalytic reactions of 2H-azirines with carbene complexes were reported. See:
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• 12 General procedure for the catalytic reactions: A solution of [Rh₂(OAc)₄] (1.1 mg, 2.5 μmol), carbonyl-ene-yne 1 (21.0 mg, 0.10 mmol), and azirine 2 (0.50 mmol) in CH₂Cl₂ (1.0 mL) was stirred at r.t. for 2 h. The reaction mixture was filtered through a pad of Florisil with EtOAc, and the solvent was removed under reduced pressure. The yield of azadiene 3 was estimated by ¹H NMR analysis of the crude product with nitromethane (0.10 mmol, 5.4 μL) as internal standard. The remaining azirine 2 was distilled off by Kugelrohr distillation. The residue was passed through a pad of Florisil to give azadiene 3. Azadiene 3an: Yield: 28.3 mg (0.080 mmol, 80%); pale-orange oil. ¹H NMR (CDCl₃): δ = 1.67 (s, 3 H), 1.71–1.82 (m, 4 H), 2.25 (s, 3 H), 2.74–2.90 (m, 4 H), 7.11 (d, J = 6.8 Hz, 2 H), 7.22 (t, J = 7.3 Hz, 1 H), 7.34 (t, J = 6.8 Hz, 1 H), 7.36 (t, J = 7.3 Hz, 2 H), 7.42 (t, J = 7.3 Hz, 2 H), 7.55 (s, 1 H), 7.65 (d, J = 7.3 Hz, 2 H). ¹³C NMR (CDCl₃): δ = 19.4, 21.8, 22.4, 22.5, 22.9, 23.1, 121.3, 124.7, 126.8, 127.1, 128.1, 128.4, 128.5, 130.2, 131.1, 132.8, 137.0, 144.3, 144.8, 146.5, 148.3. HRMS (FAB): m/z [M + H]⁺ calcd for C₂₅H₂₆NO: 356.2014; found: 356.2014. Azadiene 3bn: Yield: 24.9 mg (0.065 mmol, 65%); pale-yellow oil. ¹H NMR (CDCl₃): δ = 1.66 (s, 3 H), 1.68–1.85 (m, 4 H), 2.25 (s, 3 H), 2.65–2.89 (m, 4 H), 3.82 (s, 3 H), 6.90 (d, J = 8.8 Hz, 2 H), 7.11 (d, J = 7.3 Hz, 2 H), 7.34 (t, J = 7.8 Hz, 1 H), 7.42 (t, J = 7.3 Hz, 2 H), 7.53 (s, 1 H), 7.59 (d, J = 8.8 Hz, 2 H). ¹³C NMR (CDCl₃): δ = 21.8, 22.5, 22.5, 22.8, 23.2, 55.3, 114.0, 119.7, 124.4, 126.3, 127.1, 128.4, 130.3, 132.3, 137.2, 144.2, 144.8, 145.9, 148.6, 158.7. HRMS (FAB): m/z [M + H]⁺ calcd for C₂₆H₂₈NO₂: 386.2120; found: 386.2115.Azadiene 3cn: Yield: 31.3 mg (0.080 mmol, 80%); pale-yellow oil. ¹H NMR (CDCl₃): δ = 1.67 (s, 3 H), 1.70–1.85 (m, 4 H), 2.25 (s, 3 H), 2.70–2.90 (m, 4 H), 7.11 (d, J = 7.3 Hz, 2 H), 7.33 (t, J = 7.3 Hz, 2 H), 7.36 (t, J = 7.3 Hz, 1 H), 7.42 (t, J = 7.3 Hz, 2 H), 7.53 (s, 1 H), 7.57 (d, J = 8.8 Hz, 2 H). ¹³C NMR (CDCl₃): δ = 19.4, 21.9, 22.4, 22.5, 22.9, 23.1, 121.8, 125.9, 127.2, 128.1, 128.6, 128.7, 129.8, 130.3, 132.5, 133.3, 137.0, 144.1, 144.8, 146.7, 147.3. HRMS (FAB): m/z [M + H]⁺ calcd for C₂₅H₂₅ClNO: 390.1625; found: 390.1637. Azadiene 3dn: Yield: 21.0 mg (0.057 mmol, 57%); pale-orange oil. ¹H NMR (CDCl₃): δ = 1.66 (s, 3 H), 1.67–1.82 (m, 4 H), 2.23 (s, 3 H), 2.36 (s, 3 H), 2.54 (t, J = 5.9 Hz, 2 H), 2.88 (t, J = 6.3 Hz, 2 H), 7.09 (d, J = 7.8 Hz, 2 H), 7.15–7.22 (m, 3 H), 7.27–7.33 (m, 2 H), 7.39 (t, J = 7.3 Hz, 2 H), 7.53 (s, 1 H). ¹³C NMR (CDCl₃): δ = 19.4, 20.8, 21.8, 22.2, 22.4, 22.8, 23.2, 122.0, 125.3, 127.0, 127.1, 128.0, 128.5, 129.0, 130.27, 130.31, 130.9, 132.6, 137.0, 137.1, 144.4, 144.8, 146.9, 149.9. HRMS (FAB): m/z [M + H]⁺ calcd for C₂₆H₂₈NO: 370.2171; found: 370.2183. Azadiene 3en: Yield: 14.8 mg (0.049 mmol, 49%); pale-orange oil. ¹H NMR (CDCl₃): δ = 1.68 (s, 3 H), 2.31 (s, 3 H), 6.72 (d, J = 3.4 Hz, 1 H), 6.79 (d, J = 3.4 Hz, 1 H), 7.12 (d, J = 6.8 Hz, 2 H), 7.28 (t, J = 7.8 Hz, 1 H), 7.33–7.38 (m, 1 H), 7.39 (d, J = 6.3 Hz, 2 H), 7.42 (d, J = 7.3 Hz, 2 H), 7.45 (s, 1 H), 7.73 (d, J = 6.8 Hz, 2 H). ¹³C NMR (CDCl₃): δ = 19.3, 22.0, 107.4, 115.4, 124.3, 127.3, 128.0, 128.6, 128.7, 130.1, 130.3, 134.4, 137.0, 143.2, 144.2, 152.9, 155.7. HRMS (FAB): m/z [M + H]⁺ calcd for C₂₁H₂₀NO: 302.1545; found: 302.1536.
• 13 Geometry of azadiene 3ar was determined by ¹H NMR NOE experiments, see Figure 1.
• 14 Fragmentation from metal-free azirinium ylide or a metallacycle generated by the insertion of B into the C–N single bond of 2n could be an alternative route to the 2-azadiene.
• 15 The reason for stereoselective formation of 3ao–3ar may be that the transition state from C settles into the conformation with the least steric hindrance.
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• 17 Reduction of azadiene 3an: To a solution of azadiene 3an (35.5 mg, 0.10 mmol) in THF (1.0 mL) was added LiAlH₄ (19.0 mg, 0.50 mmol) in one portion, and the reaction mixture was stirred at 40 °C for 2 h. The reaction was quenched with 1.0 M aq NaOH, and extracted with EtOAc. The organic layer was dried over Na₂SO₄, filtered, and concentrated under vacuum to give a crude product imine 4. The residue was used in the next reduction without further purification. The second reduction of imine 4 was performed under the same conditions as the first reduction of azadiene 3an. The crude mixture was subjected to column chromatography on silica gel (hexane–EtOAc, 10:1) to give amine 5. Imine 4: ¹H NMR (CDCl₃): δ = 1.11 (s, 3 H), 1.14 (s, 3 H), 1.60–1.80 (m, 4 H), 2.43 (t, J = 5.5 Hz, 2 H), 2.75 (t, J = 5.9 Hz, 2 H), 2.85 (septet, J = 7.0 Hz, 1 H), 4.31 (s, 2 H), 7.12–7.40 (m, 6 H), 7.42 (t, J = 7.0 Hz, 2 H), 7.58 (d, J = 7.0 Hz, 2 H). Amine 5: Yield: 25.0 mg (0.070 mmol, 70%); pale-yellow oil. ¹H NMR (CDCl₃): δ = 0.73 (d, J = 6.4 Hz, 3 H), 0.96 (d, J = 6.8 Hz, 3 H), 1.60–1.79 (m, 4 H), 1.83 (br s, 1 H), 1.85 (octet, J = 6.8 Hz, 1 H), 2.17–2.35 (m, 2 H), 2.75 (t, J = 6.4 Hz, 2 H), 3.33 (d, J = 7.3 Hz, 1 H), 3.45 (d, J = 14.6 Hz, 1 H), 3.63 (d, J = 14.2 Hz, 1 H), 7.19 (t, J = 7.3 Hz, 1 H), 7.23–7.35 (m, 5 H), 7.37 (t, J = 7.8 Hz, 2 H), 7.60 (d, J = 7.3 Hz, 2 H). ¹³C NMR (CDCl₃): δ = 19.4, 19.6, 20.4, 22.8, 23.0, 23.4, 34.4, 42.4, 68.3, 118.9, 120.3, 124.1, 125.9, 126.8, 127.9, 128.3, 128.5, 132.2, 142.4, 145.4, 146.8. HRMS (FAB): m/z [M + H]⁺ calcd for C₂₅H₃₀NO: 360.2327; found: 360.2324.