Activation of Enediynes via Intramolecular Iodoetherification

Abstract

Intramolecular iodoetherification can be a powerful method for activation of acyclic enediyne. However, the activation depends upon the chain length and the electronic nature of the enediyne (whether aliphatic or benzo-fused).

Key words

enediyne - iodoetherification - Bergman cyclization

References and Notes

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12

To a solution of compound 3 (150 mg, 1.03 mmol) in anhyd MeCN (10 mL), NIS (278 mg, 1.23 mmol) was added and stirred for 3 d under inert atmosphere. The reaction mixture was extracted with Et₂O, washed with brine, dried over Na₂SO₄, and concentrated in vacuo. The crude was purified via chromatography (SiO₂, hexane-EtOAc = 30:1) to yield the desired compound 5 (34%).
Selected Spectral Data
Compound 5: ¹H NMR (200 MHz, CDCl₃): δ = 3.35 (2 H, t, J = 4.0 Hz, CH ₂CH₂O), 4.26 (2 H, t, J = 4.1 Hz, CH₂CH ₂O), 5.64 (1 H, d, J = 8.4 Hz, ArCHCHOCH₂), 6.54 (1 H, d, J = 8.4 Hz, ArCHCHOCH₂), 7.28 (1 H, d, J = 8.3 Hz, ArH), 7.38 (1 H, d, J = 8.3 Hz, ArH). ¹³C NMR (50 MHz, CDCl₃): δ = 43.02, 71.28, 100.68, 100.76, 108.71, 136.99, 138.08, 139.11, 142.38, 146.99. MS (EI): m/z = 398.87 [MH⁺].
Compound 6: ¹H NMR (200 MHz, CDCl₃): δ = 2.84, 4.42 (2 H, ABX, J _AX = 4.2 Hz, J _BX = 0.0 Hz, J _AB = 14.6 Hz, ArCH ₂CHOH), 5.09 (1 H, dd, J = 1.8, 4.7 Hz, ArCHOHCH₂), 7.25 (1 H, d, J = 8.2 Hz, ArH), 7.34 (1 H, d, J = 8.3 Hz, ArH). ¹³C NMR (50 MHz, CDCl₃): δ = 42.84, 68.66, 87.07, 89.96, 137.35, 138.69, 149.76, 153.60. MS (EI): m/z = 395.88 [MNa⁺], 354.85 [M - H₂O].

13

To a solution of alcohol 6 (10 mg, 0.037 mmol) in CH₂Cl₂ (5 mL), Ac₂O (4 µL, 0.044 mmol), Et₃N (6 µL, 0.044 mmol), and DMAP (5 mol%) were added at 0 °C. The reaction mixture was stirred for 10 min after which it was poured into H₂O and CH₂Cl₂. The organic layer was washed with H₂O, dried, and then evaporated. The compound 6a was then isolated by column chromatography (SiO₂, hexane-EtOAc = 30:1) as a white solid (98%).
Selected Spectral Data
Compound 6a: ¹H NMR (400 MHz, CDCl₃): δ = 2.14 (3 H, s, CH ₃COOCH), 2.94, 3.50 (2 H, ABX, J _AX = 4.4 Hz, J _BX = 0.0 Hz, J _AB = 14.8 Hz, ArCH ₂CHOH), 5.87 (1 H, d, J = 4.0 Hz, ArCHOHCH₂), 7.28 (1 H, d, J = 8.4 Hz, ArH), 7.36 (1 H, d, J = 8.0 Hz, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 20.87, 40.93, 69.12, 87.09, 88.71, 138.09, 139.96, 148.64, 150.16, 170.50. MS (EI): m/z = 413.35 [M⁺].