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Synlett 2005(3): 501-505  
DOI: 10.1055/s-2005-862356
LETTER
© Georg Thieme Verlag Stuttgart · New York

Tandem Catalysis: A Ring-Closing Metathesis Followed by Dehydrogenative Oxidation to Afford Substituted Indenones

Willem A. L. van Otterlo*, E. Mabel Coyanis, Jenny-Lee Panayides, Charles B. de Koning, Manuel A. Fernandes
Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits, 2050, Johannesburg, South Africa
Fax: +27(11)7176749; e-Mail: willem@aurum.chem.wits.ac.za;
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Publication History

Received 29 October 2004
Publication Date:
04 February 2005 (online)

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Abstract

Grubbs second generation catalyst converts substituted 1-(2-propenylphenyl)prop-2-en-1-ols into substituted indenols or indenones depending on the reaction conditions employed. The formation of indenones represents the first example of a tandem ruthenium-mediated ring-closing metathesis-dehydrogenative oxidation reaction.

Key words

metathesis - ruthenium - dehydrogenations - tandem ­reactions - indenols - indenones

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Work taken from the post-doctoral research project of Dr. E. M. Coyanis and the ongoing MSc project of Ms J.-L. Panayides.

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Typical Experimental Procedure for Forming Indenols:
Grubbs catalyst 1 (5 mol%) was added to a degassed solution (N2) of 5a (262 mg, 0.62 mmol) in CH2Cl2 (25 mL). The solution was then stirred under N2 at r.t. for 3 h. After evaporation of the solvent and column chromatographic purification of the residue (5-10% EtOAc-hexane), 4-isopropoxy-5-methoxy-1H-inden-1-ol (6a) was obtained as a pale yellow oil (191 mg, 87%). 1H NMR (200 MHz, CDCl3, assignments with the same superscript may be interchanged): δ = 7.12 (d, 1 H, J = 7.9 Hz, 7-H), 6.73 (d, 1 H, J = 5.6 Hz, 3-H), 6.66 (d, 1 H, J = 7.9 Hz, 2-H), 6.27 (dd, 1 H, J = 5.6 and 2.0 Hz, 6-H), 5.04 (br s, 1 H, 1-H), 4.33 [br sept, 1 H, J = 6.2 Hz, CH(CH3)2], 3.80 (s, 3 H, OCH3), 2.08 (br s, 1 H, OH), 1.28 [d, 3 H, J = 6.4 Hz, CH(CH 3)CH3], 1.25 [d, 3 H, J = 6.5 Hz, CH(CH3)CH 3]. 13C NMR (50 MHz, CDCl3): δ = 153.3 (C), 140.1 (C), 138.4 (C), 137.8 (CH), 136.7 (C), 129.2 (CH), 118.9 (CH), 109.4 (CH), 77.1 (OCH), 75.6 (C-O), 55.9 (OCH3), 22.5 (CH3), 22.4 (CH3).
IR: 3400(br), 1674, 1617, 1596, 1556 cm-1. HRMS (CI): m/z calcd for C13H16O3: 220.10995; found: 220.10990. MS: m/z (%) = 220 (69) [M + ], 179 (18), 178 (100), 177 (28), 176 (16), 163 (41), 161 (12), 149 (16), 147 (18), 146 (18), 135 (10), 118 (10), 77 (10), 69 (11), 57 (14), 55 (12), 43 (28), 41 (19).

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All new compounds were identified using routine spectroscopy and gave satisfactory data.

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In an attempt to improve the yields of indenols 6d and 6e we protected the alcohol functionalities of 5d and 5e with acetyl groups. However, much to our surprise, the RCM reactions of these substrates, at r.t. or at 110 °C, did not proceed to afford the acetyl-protected cyclic products and only starting material was recovered.

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Typical Experimental Procedure for Forming Indenones:
Grubbs catalyst 1 (8 mol%) was added to a degassed solution (N2) of 5a (141 mg, 0.54 mmol) in toluene (10 mL). The solution was then heated at 80 °C under N2 for 2 h. Evaporation of the solvent and column chromatographic purification of the residue (20% EtOAc-hexane) then afforded 4-isopropoxy-5-methoxyinden-1-one (7a) as a yellow semi-solid (72 mg, 62%). 1H NMR (200 MHz, CDCl3): δ = 7.64 (d, 1 H, J = 5.8 Hz, H-3), 7.38 (d, 1 H, J = 7.8 Hz, H-7), 6.60 (d, 1 H, J = 7.8 Hz, H-6), 5.86 (d, 1 H, J = 5.8 Hz, H-2), 4.40 [sept, 1 H, J = 6.1 Hz, CH(CH3)2], 3.87 (s, 3 H, OCH3), 1.31 [d, 6 H, J = 6.1 Hz, CH(CH 3)2]. 13C NMR (50 MHz, CDCl3): δ = 197.2 (C=O), 158.8 (C), 145.5 (CH), 142.0 (C), 137.5 (C), 127.9 (CH), 123.9 (C), 119.7 (CH), 109.8 (CH), 75.9 (OCH), 56.1 (OCH3), 22.4 (CH3). IR: 1708, 1604 cm-1. HRMS (CI): m/z calcd for C13H14O3: 218.09430; found: 218.09433. MS: m/z (%) = 218 (29) [M + ], 193 (21), 178 (20), 177 (40), 176 (100), 175 (25), 163 (17), 161 (23), 149 (37), 147 (20), 105 (21), 91 (17), 77 (26), 73 (23), 69 (22), 57 (33), 55 (26), 43 (49), 41 (46).

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X-ray crystal structure of 4-isopropoxy-5-methoxy-2-methyl-3-phenylinden-1-one (7f): crystallized from CHCl3, formula: C20H20O3, M = 308.36, color of crystal: yellow, prism, crystal size 0.31 × 0.20 × 0.02 mm, a = 6.3298 (11) Å, b = 18.133 (3) Å, c = 7.7645 (13) Å, β = 110.094 (3)°, V = 836.9 (2) Å3, ρcalc = 1.224 Mg/m3, µ = 0.081 mm-1, F(000) = 328, Z = 2, monoclinic, space group P21, T = 293 K, 5132 reflections collected, 2444 independent reflections, θmax = 26.50°, 212 refined parameters, maximum residual electron density 0.129 and -0.161 e·Å-3. R1 = 0.0421, wR2 = 0.0813. Crystallographic data for the structure have been deposited with the Cambridge Crystallographic Data Centre as deposition No. CCDC-250072.