Tetrabutylammonium Bromide Catalyzed Tandem Addition/Cyclization of o-Aralkynylaryl Aldehydes with Trimethyl(trifluoromethyl)silane: Synthesis of Trifluoromethyl Group Containing Phthalans

Abstract

A tetrabutylammonium bromide catalyzed trifluoromethylation/cyclization reaction of o-aralkynylaryl aldehydes with trimethyl(trifluoromethyl)silane and cesium fluoride has been developed. A variety of 1-alkylidene-3-(trifluoromethyl)phthalans were prepared in moderate to excellent yields by tandem nucleophilic addition and cyclization.

Key words

heterocycles - polycycles - cyclizations - alkylations - ­aldehydes - alkynes

• References

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• 12 1-Alkylidine-3-(trifluoromethyl)-1,3-dihydro-2-benzofurans 2; General Procedure A flame-dried Schlenk tube equipped with a magnetic stirring bar was charged with o-aralkynylaryl aldehyde 1 (0.3 mmol), TMSCF₃ (0.9 mmol), CsF (0.6 mmol), TBAB (0.06 mmol), and anhyd toluene (2 mL), and the mixture was stirred at 0 °C for 1 h. H₂O (2 equiv) was added and the mixture was stirred at 80 °C for 6 h. The mixture was then poured into EtOAc and extracted with EtOAc (3 × 10 mL). The organic layers were combined, dried (Na₂SO₄), and concentrated under vacuum. The residue was purified by flash column chromatography (hexane–EtOAc). (1Z)-1-Benzylidene-3-(trifluoromethyl)-1,3-dihydro-2-benzofuran (2a) White solid; yield: 73.1 mg (88%); mp 47.5–48.5 °C. IR (KBr): 2991, 1742, 1242, 1047, 848, 797 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.73 (d, J = 7.9 Hz, 2 H), 7.58 (d, J = 8.1 Hz, 1 H), 7.48 – 7.45 (m, 2 H), 7.41 – 7.34 (m, 3 H), 7.22 – 7.18 (m, 1 H), 6.03 (s, 1 H), 5.83 (q, J = 6.0 Hz, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 153.8, 135.6, 135.0, 132.8, 130.1, 129.2, 128.5, 128.4, 126.3, 123.0 (q, J _C–F = 279.6 Hz), 122.8, 120.1, 99.0, 81.5 (q, J _C–F = 34.3 Hz). ¹⁹F NMR (470 MHz, CDCl₃): δ = –77.95. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₁₂F₃O⁺: 277.0835; found: 277.0819.
• 13 Crystallographic data for compound 2f have been deposited with the accession number CCDC 968707 and can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: [phone]; E-mail: [e-mail]; Web site: www.ccdc.cam.ac.uk/conts/retrieving.html.