Synthesis of Functionalized Diaryl Ethers by [3+3] Cyclization of 1,3-Bis(Silyl Enol Ethers) with 2-Aryloxy-3-(silyloxy)alk-2-en-1-ones

Abstract

Functionalized and sterically encumbered diaryl ethers were prepared by [3+3] cyclization of 1,3-bis(silyl enol ethers) with 2-aryloxy-3-(silyloxy)alk-2-en-1-ones.

Key words

arenes - cyclizations - diaryl ethers - silyl enol ethers

References and Notes

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9

General Procedure for the Synthesis of Diaryl Ethers 6a-n.
To a CH₂Cl₂ solution (2 mL/mmol) of 4 (1.0 mmol) and 5 (1.0 mmol) was added TiCl₄ (1.0 mmol) at -78 °C. The solution was allowed to warm to ambient temperature within 20 h. To the solution was added a sat. solution of NaHCO₃ (10 mL). The organic and the aqueous layer were separated and the latter was extracted with Et₂O (3 × 30 mL). The filtrate was concentrated in vacuo and the residue was puri-fied by chromatography (silica gel, EtOAc-n-heptane, 1:4).
Synthesis of Methyl 4,6-Dimethyl-5-(4-chloro-phenoxy)salicylate ( 6h).
Starting with 1,3-bis(silyl enol ether) 5d (500 mg, 1.9 mmol), 3-(siloxy)alk-2-en-1-one 4d (574 mg, 1.9 mmol) and TiCl₄ (0.21 mL, 1.9 mmol), 6h was isolated as a colorless solid (315 mg, 54%); mp 83 °C. ¹H NMR (300 MHz, CDCl₃): δ = 2.09 (s, 3 H, CH₃), 2.30 (s, 3 H, CH₃), 3.95 (s, 3 H, OCH₃), 6.67 (d, 2 H, J = 9.0 Hz, ArH), 6.76 (s, 1 H, ArH), 7.20 (d, 2 H, J = 9.0 Hz, ArH), 11.10 (s, 1 H, OH). ¹³C NMR (75 MHz, CDCl₃): δ = 15.2, 17.1, 52.2 (CH₃), 111.1 (C), 115.7 (2 C), 117.6 (CH), 126.3 (C), 129.6 (2 C, CH), 133.5, 139.7, 143.6, 156.5, 159.7, 171.7 (C). IR (KBr): 3431 (m), 2959 (w), 1661 (s), 1486 (s), 1442 (m), 1361 (m), 1326 (s), 1318 (s), 1074 (m), 825 (m), 803 (m) cm^-1. GC-MS (EI, 70 eV): m/z (%) = 306 (33) [M⁺], 274 (100), 246 (10), 163.1 (8). Anal. Calcd (%) for C₁₆H₁₅ClO₄ (306.74): C, 62.65; H, 4.93. Found: C, 62.42; H, 4.68.