First Halogen Dance Reaction on Oxazoles. Synthesis of 4,5-Disubstituted 2-Phenyloxazoles

Abstract

The halogen dance reaction was investigated on the ­oxazole system for the first time. Various 5-substituted 4-bromo-2-phenyloxazole derivatives are accessible via this convenient methodology.

halogen dance - metalation - lithiation - oxazole

References

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General Procedure for the Halogen Dance Reaction: A freshly prepared solution of LDA (1.5 equiv) in anhyd THF (10 mL) was added to a solution of 5-bromo-2-phenyloxazole (1; 1 equiv) in anhyd THF at -80 °C under nitrogen. The reaction was monitored by TLC, once the reaction had reached completion (after 15-30 min,) the corresponding electrophile (1.5 equiv in 5 mL anhyd THF) was added and the reaction was allowed to warm to 0 °C over 1 h. Water was added to this solution and 2/3 of the THF was removed under reduced pressure. The mixture was extracted with CH₂Cl₂ and washed with sat. NaHCO₃ and brine. The organic layer was dried over Na₂SO₄, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography.

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(4-Bromo-2-phenyloxazol-5-yl)phenylmethanol ( 6b): Beige crystals (78%); mp 116-119 °C; ¹H NMR (CDCl₃): δ = 3.15 (br s, 1 H, OH), 6.00 (s, 1 H, CH), 7.20-7.56 (m, 8 H, H3′, H4′, H5′, 5H′′), 7.84-7.99 (m, 2 H, H2′, H6′); ¹³C NMR (CDCl₃): δ = 67.0 (d, CHOH), 114.7 (s, C4), 126.2 (d, CH), 126.3 (s, C1′), 126.5 (d, CH), 128.4 (d, C4′), 128.5 (d, CH), 128.5 (d, CH), 131.1 (d, C4′′), 139.4 (s, C1′′), 148.3 (s, C5), 161.4 (s, C2).