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DOI: 10.1055/s-2006-939729
Microwave-Assisted Silyloxy-Cope Rearrangement of syn-Aldol Products in DMF: Enhancement of Rate and Diastereoselectivity
Publication History
Publication Date:
22 May 2006 (online)
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Abstract
Microwave-assisted Cope rearrangements of 1,5-dienes embedded in a syn-aldol structure proceed in substantially reduced reaction times and markedly increased diastereoselectivity when conducted in DMF as solvent.
Key words
aldol products - Cope rearrangement - diastereoselectivity - microwave irradiation
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References and Notes
Typical Experimental Procedure.
A microwave reactor ‘microPREP A’ (MLS GmbH, Germany) with a single magnetron (max. 1200 W, pulsed irradiation, 2.45 GHz) terminal 320 controller, and easy CONTROL 06 software was used for the microwave experiments. A power of max. 500 W was used in all experiments and the temperature inside the reaction mixture was controlled with a ATC-FO 300 fiberoptic sensor inserted into the reaction vessel and automatically adjusted to the set temperature. The amount of 300 mg (0.70 mmol) of 1,5-diene 1a was dissolved in 25 mL dry DMF and placed in a microwave vessel, which was sealed. The sample was irradiated for 15 min at 180 °C whereupon the solvent was evaporated in vacuo. The crude product was analyzed by NMR to determine the diastereoselectivity (25:1) and subsequently purified by flash chromatography over silica gel with Et2O and pentane (1:6) to furnish 275 mg of the Cope product 2a (91%) as a colorless solid. Mp 60-61 °C; [α]D
20 13.0 (c 1.2, CHCl3). IR (film): ν = 3027, 2956, 2858, 1782, 1681 cm-1. 1H NMR (300 MHz, CDCl3): δ = 0.13 (s, 6 H, TBS), 0.92 (s, 9 H, TBS), 1.02 (d, J = 7.0 Hz, 3 H, Me), 2.28-2.32 (m, 2 H), 2.79 (dd, J = 13.0, 9.8 Hz, 1 H, benzyl-H), 2.90 (m, 1 H), 3.34 (dd, J = 13.0, 3.0 Hz, 1 H, benzyl-H), 4.14-4.23 (m, 2 H), 4.31 (dd, J = 10.0, 8.7 Hz, 1 H, 6′-H), 4.72 (m, 1 H), 6.16 (dd, J = 6.0, 1.0 Hz, 1 H, 7′-H), 7.21-7.36 (m, 7 H, 2′-H, 3′H, phenyl-H). 13C NMR (75 MHz, CDCl3): δ = -5.30, -5.22, 18.35, 20.94, 25.76, 28.46, 38.06, 40.63, 55.45, 66.18, 115.10, 121.20, 127.40, 129.10, 129.60, 135.60, 138.30, 151.10, 153.50, 165.10. MS (EI, 70eV): m/z = 429 (1), 414 (10), 372 (20), 185 (100), 91 (45), 73 (99). Anal. Calcd: C, 67.10; H, 8.21; N, 3.26. Found: C, 67.14; H, 8.39; N, 3.13.