Further Insight into the Photochemical Behavior of Aromatic γ,δ-Epoxy Ketones: A New Approach for Synthesis of 4-Methyleneisochromanols

Abstract

The photochemical behavior of methyl-substituted aromatic γ,δ-epoxy ketones was investigated by irradiation with a 500 W high-pressure mercury lamp in benzene which led to the formation of 4-methyleneisochromanols through δ-hydrogen abstraction–epoxy rearrangement–1,5-biradical cyclization reactions.

Key words

γ,δ-epoxy ketones - photochemical behavior - 4-methyleneisochromanol - epoxy rearrangement - 1,5-biradical cyclization

• References and Notes


For reviews, see:
• 1a Griesbeck AG, Hoffmann N, Warzecha K. Acc. Chem. Res. 2007; 40: 128
• 1b Winkler JD, Bowen CM, Liotta F. Chem. Rev. 1995; 95: 2003
• 1c Hoffmann N. Pure Appl. Chem. 2007; 79: 1949
• 1d CRC Handbook of Organic Photochemistry and Photobiology . Griesbeck A, Oelgemöller M, Ghetti F. CRC Press; Boca Raton: 2011. 3rd ed.; and references cited therein
• 2 Hoffmann N. Chem. Rev. 2008; 108: 1052

For a general review of the Norrish type II reaction, see:
• 3a Wagner P, Park BS In Organic Photochemistry . Vol. 11. Padwa A. Chap. 4 Marcel Dekker; New York: 1991
• 3b Wagner JP. CRC Handbook of Organic Photochemistry and Photobiology . Horspool W, Lenci F. CRC Press; Boca Raton, FL: 2004. 2nd ed. Chap. 58
• 4 Shao Y, Yang C, Gui W, Liu Y, Xia W. Chem. Commun. 2012; 48: 3560
• 5a Dijoux-Franca M.-G, Tchamo D, Cherel B, Cussac M, Tsamo E, Mariotte A.-M. J. Nat. Prod. 2001; 64: 832
• 5b Fusetani N, Sugawara T, Matsunaga S, Hirota H. J. Org. Chem. 1991; 59: 4971
• 6a Matsuya YJ, Ohsawa N, Nemoto H. J. Am. Chem. Soc. 2006; 128: 13072
• 6b Frimer AA, Weiss J. J. Org. Chem. 1993; 58: 3660
• 6c Morris JC, Bungard CJ. J. Org. Chem. 2002; 67: 2361
• 6d Anderson EA, Alexanian EJ, Sorensen EJ. Angew. Chem. Int. Ed. 2004; 43: 1998
• 6e Shi L, Meyer K, Greaney MF. Angew. Chem. Int. Ed. 2010; 49: 9250
• 7 Typical Experimental Procedure for the γ,δ-Epoxy Ketone 3 and Isochromanol 4 To round-bottomed flask was added olefin 7 (0.2 mmol), acetone (2 mL), H₂O (1 mL), MeCN (1 mL), NaHCO₃ (2 mmol), 18-crown-6 (0.002 mmol), the mixture was cooled to 0 °C, and Oxone (0.6 mmol) was dissolved in H₂O and added slowly. After addition, the reaction was stirred at the same temperature until no starting material could be detected by TLC. The mixture was extracted with CH₂Cl₂, the combined organic phase was washed with sat. NaHCO₃, brine, and dried over Na₂SO₄, then quickly purified through a neutral Al₂O₃ gel column (PE–EtOAc) to give 3, which is unstable, refrigerated storage. The γ,δ-epoxy ketone 3 (0.1 mmol) in anhydrous benzene (10 mL) was treated with N₂ for 10 min in darkness, and then irradiated by a 500 W high-pressure mercury lamp with condensate until no starting material could be detected by TLC. The solvent was removed in vacuo, and the residue was purified by silica gel column chromatography (PE–EtOAc) to give the desired product 4. 1-(4-tert-Butylphenyl)-4-methyleneisochroman-3-ol (4k) Colorless oil. Yield 45%. ¹H NMR (400 MHz, CDCl₃): δ = 7.72 (d, 1 H, J = 7.8 Hz), 7.42 (d, 2 H, J = 7.3 Hz), 7.29 (d, 3 H, J = 7.1 Hz), 7.19 (t, 1 H, J = 7.4 Hz,), 6.79 (d, 1 H, J = 7.7 Hz), 6.07 (s, 0.77 H), 5.91 (s, 0.24 H), 5.85 (s, 0.78 H), 5.82 (s, 0.74 H), 5.79 (s, 0.22 H), 5.67 (d, 0.22 H, J = 7.8 Hz), 5.53 (s, 0.22 H), 5.35 (s, 0.77 H), 3.21 (d, 0.20 H, J = 7.7 Hz), 3.08 (s, 0.74 H), 1.35 (s, 9 H).¹³C NMR (100 MHz, CDCl₃): δ = 151.4, 151.3, 141.6, 139.6, 138.1, 137.8, 137.0, 136.7, 131.5, 129.8, 128.5, 128.0, 127.4, 127.3, 126.6, 126.5, 125.5, 124.2, 123.9, 110.8, 107.7, 94.1, 93.9, 79.1, 73.2, 34.6, 31.4. ESI-HRMS: m/z calcd for C₂₀H₂₃O₂ ⁺: 295.1698 [M + H]⁺; found: 295.1696.