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Synlett 2013; 24(15): 1921-1926
DOI: 10.1055/s-0033-1339489
DOI: 10.1055/s-0033-1339489
letter
Diversity-Oriented Approach to Novel Spirocyclics via Enyne Metathesis, Diels–Alder Reaction, and a [2+2+2] Cycloaddition as Key Steps
Authors
Further Information
Publication History
Received: 20 March 2013
Accepted after revision: 09 July 2013
Publication Date:
14 August 2013 (online)
This paper is dedicated to the memory of Professor A. Srikrishna, Department of Organic Chemistry, Indian Institute of Science, Bangalore, India.
Abstract
A simple protocol for the synthesis of indane-based spirocyclics has been developed via enyne metathesis, Diels–Alder reaction, and a [2+2+2] cycloaddition as key steps starting from indane-1,3-dione. The key diene building block was assembled by enyne metathesis. In this sequence, rongalite is used as a green reagent to prepare the sultine intermediate, which is a useful precursor to generate the transient diene.
Keywords
spirocyclic compounds - [2+2+2]-cycloaddition reaction - rongalite - enyne metathesis - Diels–Alder reactionSupporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
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- 20 Preparation of 9 The enyne 12 (140 mg, 0.63 mmol) in dry CH2Cl2 (20 mL) was degassed with nitrogen for 10 min, G-II catalyst (39 mg, 7.5 mol%) and Ti(Oi-Pr)4 (23 mg, 20 mol%) were added, and the reaction vessel was kept under ethylene pressure (balloon pressure). The reaction mixture was stirred at r.t. for 16 h. After completion of the reaction (TLC monitoring), the solvent was concentrated, and the crude product was purified by silica gel column chromatography using EtOAc–PE (3:93) to give the white solid compound 9 (67 mg, 48%); mp 123–124 °C; Rf = 0.41 (silica gel, 20% EtOAc–PE). 1H NMR (400 MHz, CDCl3): δ = 2.85–2.87 (m, 4 H), 5.03 (d, J = 17.52 Hz, 1 H), 5.12 (d, J = 10.72 Hz, 1 H), 5.72–5.73 (br, 1 H), 6.54–6.62 (m, 1 H), 7.86–7.88 (m, 2 H), 8.01–8.03 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 39.70, 41.56, 57.77, 115.51, 123.78, 127.58, 132.34, 135.96, 140.68, 141.76, 203.50. IR (KBr): 1597, 1742, 2854, 2923, 3011 cm–1. HRMS (ESI, Q-ToF): m/z calcd for C15H13O2 [M + H]+: 225.0916; found: 225.0912. General Procedure for the Diels–Alder Reaction of 9 and Subsequent Aromatization To a solution of diene building block 9 in toluene (20 mL) was added dienophile (1.5 equiv), and the reaction mixture was heated at 110–120 °C for 24–36 h. Then, the solvent was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography by using EtOAc–PE (40:60) to afford the Diels–Alder adduct. Later, aromatization of the Diels–Alder adduct was carried out with 10 equiv activated MnO2 in 1,4-dioxane (25 mL) at reflux temperature for 20–24 h. The solvent was then removed at reduced pressure, and the crude product was purified by column chromatography using EtOAc–PE (40:60) to afford aromatized products. Compound 13 Yellow solid; mp 171–173 °C; Rf = 0.50 (silica gel, 40% EtOAc–PE). 1H NMR (400 MHz, CDCl3): δ = 3.47 (s, 2 H), 3.97 (s, 2 H), 7.64–7.68 (m, 3 H), 7.90–7.94 (m, 2 H), 8.05–8.09 (m, 4 H), 8.36 (d, J = 7.88 Hz, 1 H), 8.82 (s, 1 H), 8.72 (s, 1 H). 13C NMR (100 MHz, CDCl3): δ = 39.37, 43.47, 59.29, 124.02, 128.35, 129.47, 129.53, 129.68, 129.80, 130.27, 130.33, 130.62, 134.58, 135.27, 135.34, 136.31, 141.72, 143.20, 149.91, 183.06, 184.37, 202.68. IR (KBr): 1706, 1739, 2846, 2920, 3055 cm–1. HRMS (ESI, Q-ToF): m/z calcd for C29H17O4 [M + H]+: 429.1127; found: 429.1138. General Procedure for [2+2+2] Cycloaddition A solution of compound 6 (500 mg, 2.25 mmol) and 15 (968 mg, 11.25 mmol) in dry EtOH (50 mL) was degassed with nitrogen for 15 min, afterwards Wilkinson’s catalyst (62 mg, 3.0 mol%) and Ti(Oi-Pr)4 (103 mg, 25 mol%) were added, and the reaction mixture was heated at 75–80 °C for 24 h. After completion of the reaction (TLC monitoring), the solvent was concentrated at reduced pressure, and the crude product was purified by silica gel column chromatography using EtOAc–PE (20:80) to give the white solid compound 25 (70 mg, 7%) and continued elution with EtOAc–PE (60:40) gave a white solid 14 (320 mg, 46%) Compound 14 Mp 112–114 °C; Rf = 0.32 (silica gel, 40% EtOAc–PE). 1H NMR (400 MHz, CDCl3): δ = 3.29 (s, 4 H), 4.69 (s, 4 H), 7.27 (s, 2 H), 7.95–8.03 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ = 41.30, 60.34, 63.15, 124.62, 125.20, 137.42, 139.65, 141.52, 142.88, 204.50. IR (KBr): 1598, 1744, 2987, 3054, 3304 3692 cm–1. HRMS (ESI, Q-ToF): m/z calcd for C19H16O4Na [M + Na]+: 331.0946; found: 331.0933. Compound 25 Mp 187–190 °C; Rf = 0.60 (silica gel, 40% EtOAc–PE). 1H NMR (400 MHz, CDCl3): δ = 1.74–1.75 (br, 1 H), 2.73–2.74 (br, 2 H), 3.07 (s, 2 H), 3.08 (s, 4 H), 6.78–6.80 (m, 3 H), 7.73–7.75 (m, 2 H), 7.80–7.84 (m, 4 H), 7.92–7.94 (m, 2 H). 13C NMR (100 MHz, CDCl3) δ = 24.00, 40.30, 40.52, 58.85, 58.93, 71.65, 78.48, 123.06, 123.77, 123.99, 125.73, 129.00, 134.00, 135.96, 136.03, 139.26, 140.77, 141.52 142.77, 202.36, 202.92. IR (KBr): 1708, 1738, 2160, 2929, 3054 cm–1. HRMS (ESI, Q-ToF): m/z calcd for C30H21O4 [M + H]+: 445.1440; found: 445.1425.
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