First Cyclocondensations of 1,3-Bis(trimethylsilyloxy)buta-1,3-dienes with 1,1-Dimethoxy-4,4,4-trifluorobut-1-en-3-one

Abstract

The formal [3+3] cyclocondensation of 1,3-bis(trimethylsilyloxy)buta-1,3-dienes with 1,1-bis(methoxy)trifluoromethyl-1-en-3-ones afforded functionalized 3-methoxy-5-(trifluoromethyl)phenols with very good regioselectivity.

Key words

arenes - cyclizations - regioselectivity - silyl enol ethers

References and Notes

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General Procedure for the Synthesis of 3a-t
To a CH₂Cl₂ solution (2 mL/1 mmol of 1) of 1 (1.0 mmol) was added 2 (2.0 mmol) and, subsequently, TiCl₄ (0.1 mL, 1.0 mmol) at -78 ˚C. The temperature of the solution was allowed to warm to 20 ˚C during 12-14 h with stirring. To the solution was added HCl (10%, 10 mL) and the organic and the aqueous layer were separated. The latter was extracted with CH₂Cl₂ (2 × 10 mL). The combined organic layers were dried (Na₂SO₄), filtered, and the filtrate was concentrated in vacuo. The residue was purified by chromatography.
Methyl 2-Hydroxy-3,4-dimethoxy-6-(trifluoro-methyl)benzoate (3r) Starting with 1 (0.184 g, 1.0 mmol), 2r (0.581 g, 2.0 mmol) and TiCl₄ (0.1 mL, 1.0 mmol) in CH₂Cl₂ (2 mL), 3r was isolated as a slightly yellow solid (0.140 g, 50%); mp 60-62 ˚C; R _f  = 0.67 (n-heptane-EtOAc, 3:2). ^¹H NMR (300 MHz, CDCl₃): δ = 3.93, 3.95, 3.96 (s, 3 H, OCH₃), 6.90 (s, 1 H, H-5), 10.27 (s, 1 H, OH). ^¹³C NMR (75 MHz, CDCl₃): δ = 52.7, 56.1, 60.7 (OCH₃), 103.6 (q, J _C-F = 6.7 Hz, C-5), 106.9 (C-1), 123.1 (q, J _C-F = 271.1 Hz, CF₃), 125.3 (q,
J _C-F = 32.2 Hz, C-6), 138.8, 154.8, 155.0 (C), 168.8 (CO). ^¹9F NMR (282 MHz, CDCl₃): δ = -58.2 (CF₃). IR (ATR):
ν = 2961 (w), 2855 (w), 1683 (m), 1602 (m), 1413 (m), 1256 (s), 1109 (s), 1023 (s), 963 (s), 922 (s), 840 (s), 709 (s) cm^-¹. GC-MS (EI, 70 eV): m/z (%): 280 (54) [M⁺], 249 (39), 248 (83), 247 (14), 220 (100), 219 (44), 205 (35), 189 (15), 188 (34), 93 (15). HRMS (EI, 70 eV): m/z calcd for C₁₁H₁₁F₃O₅ [M⁺]: 280.05557; found: 280.05531. Anal. Calcd for C₁₁H₁₁F₃O₅ (280.20): C, 47.15; H, 3.96. Found: C, 47.11; H, 3.89.

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CCDC-686385 contains all crystallographic details for compound 3l and is available free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or can be ordered from the following address: Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: [phone] or [e-mail].