A Mn(OAc)₃-Triggered Formation of Cyclopropanes from Ugi Adducts

Abstract

Ugi adducts involving malonic acid monoesters and dialkoxy-substituted aromatic aldehydes can undergo an oxidative dearomatization when treated with Mn(OAc)₃ leading to the formation of fused cyclopropanes as observed in the Buchner reaction of diazo compounds.

Key words

manganese acetate - Ugi reaction - radical cyclization - cyclopropanation

Publikationsverlauf

Eingereicht: 08. November 2022

Angenommen nach Revision: 02. Januar 2023

Accepted Manuscript online:
02. Januar 2023

Artikel online veröffentlicht:
15. März 2023

• References and Notes

• 1 New address: Direction ISAE, ISAE-SUPAERO - 10 Avenue Edouard Belin - BP 54032 - 31055 Toulouse Cedex 4, France.
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First intramolecular Buchner reaction:
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• 6 CCDC 2205405 contains the supplementary crystallographic data for compounds 2b. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
• 7 Typical Procedure for the Synthesis of Ugi Adducts To a solution of 2,3-dimethoxy-benzaldehyde (499 mg, 3.0 mmol, 1.0 equiv) in MeOH (3 mL) were added successively 2-methoxyethylamine (0.263 mL, 3.0 mmol, 1.0 equiv), malonic acid monoethyl ester (0.369 mL, 3.0 mmol, 1.0 equiv), and t-butyl isocyanide (0.341 mL, 3.0 mmol, 1.0 equiv). The resulting mixture was stirred at rt for 16 h. The solvent was removed under reduced pressure, and the crude product was purified by flash chromatography using (Et₂O:PE, 70:30 to 100:0) to afford the desired product 1a in 64% isolated yield (834 mg, 1.9 mmol) as white solid; mp 122–124 °C. R_f = 0.4 (Et₂O). ¹H NMR (400 MHz, CDCl₃, * = minor rotamer): δ = 7.16* (s, 1 H), 7.01–6.95 (m, 1 H, 2 H*), 6.90–6.86 (m, 1 H, 1 H*), 6.78 (dd, J _H–H = 7.7 Hz, J _H–H = 0.7 Hz, 1 H), 6.27 (s, 1 H), 6.13 (s, 1 H), 5.52* (s, 1 H), 4.19–4.11 (m, 2 H, 2 H*), 3.82–3.79 (m, 1 H), 3.82 (s, 3 H), 3.81* (s, 3 H), 3.80* (s, 3 H), 3.79 (s, 3 H), 3.68–3.62* (m, 1 H), 3.53–3.46 (m, 2 H, 2 H*), 3.41 (dd, J _H–H = 7.1 Hz, J _H–H = 4.9 Hz, 1 H), 3.38–3.34* (m, 1 H), 3.29–3.22* (m, 2 H), 3.25* (s, 3 H), 3.11 (s, 3 H), 3.07 (dd, J _H–H = 10.1 Hz, J _H–H = 4.9 Hz, 1 H), 2.81 (ddd, J _H–H = 10.1 Hz, J _H–H = 7.1 Hz, J _H–H = 4.9 Hz, 1 H), 1.37* (s, 9 H), 1.32 (s, 9 H), 1.23 (t, J _H–H = 7.1 Hz, 3 H, 3 H*). ¹³C NMR (100 MHz, CDCl₃, * = minor rotamer): δ = 168.7, 168.6, 168.5*, 168.4*, 167.7*, 167.6, 152.7, 152.4*, 148.2, 147.7*, 129.5, 128.6*, 124.0, 123.9*, 122.6, 120.9*, 113.3*, 112.9, 70.9, 69.5*, 62.4*, 61.4 (1 C, 1 C*), 60.5 (1 C, 1 C*), 58.9, 58.5*, 58.2, 55.8 (1 C, 1 C*), 51.6*, 51.4, 46.4, 45.2*, 41.9*, 41.5, 28.7 (3 C), 28.6* (3 C), 14.1 (1 C, 1 C*). HRMS: m/z calcd for C₂₂H₃₅N₂O₇ ⁺: 439.2439; found: 439.2424. IR (thin film): ν = 3335, 2952, 1746, 1656, 1477, 1307, 1273, 1231, 1045, 886, 752 cm^–1. General Procedure for the Conversion of 1a into 2a To a solution of Ugi adduct 1a (88 mg, 0.2 mmol, 1.0 equiv) in acetic acid (0.03 M) was added Mn(OAc)₃·2H₂O (276 mg, 1.0 mmol, 5.0 equiv) under argon, and the resulting solution was stirred at 90 °C for 5 h until the dark brown color of Mn(III) acetate had disappeared. The solvent was removed under reduced pressure, and the crude mixture was filtered on a small amount of silica gel to remove residues of Mn, then purified by flash chromatography (Et₂O:PE, 90:10 to 100:0) to afford the desired product 2a in 55% isolated yield (53 mg, 0.11 mmol) as yellow oil. R_f = 0.25 (Et₂O). ¹H NMR (400 MHz, CDCl₃): δ = 5.95 (dd, J _H–H = 6.1 Hz, J _H–H = 0.8 Hz, 1 H), 5.87 (s, 1 H), 5.55 (dd, J _H–H = 6.1 Hz, J _H–H = 1.7 Hz, 1 H), 5.07 (s, 1 H), 4.20–4.09 (m, 2 H), 3.81–3.75 (m, 1 H), 3.60–3.55 (m, 1 H), 3.59 (s, 3 H), 3.52–3.47 (m, 1 H), 3.33 (s, 3 H), 3.21 (ddd, J _H–H = 14.7 Hz, J _H–H = 8.8 Hz, J _H–H = 3.5 Hz, 1 H), 2.66 (t, J _H–H = 1.2 Hz, 1 H), 1.97 (s, 3 H), 1.32 (s, 9 H), 1.21 (t, J _H–H = 7.1 Hz, 3 H). ¹³C NMR (100.6 MHz, CDCl₃): δ = 185.7, 169.9, 166.8, 166.0, 162.4, 153.3, 106.8, 70.7, 63.4, 62.7, 58.8, 58.5, 55.7, 51.8, 47.2, 41.9, 41.0, 30.6, 28.7 (3 C), 20.9, 14.0. HRMS: m/z calcd for C₂₃H₃₂N₂O₉ ⁺: 481.2181; found: 481.2178. IR (thin film): ν = 3349, 2971, 1738, 1693, 1221, 1092 cm^–1.
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• 12 Cyclic voltammetry experiments did not allow detecting the enol form of 1a, even at 90 °C.