Novel One-Pot Synthesis of Xanthones via Sequential Fluoride Ion-Promoted Fries-Type Rearrangement and Nucleophilic Aromatic Substitution

Abstract

A novel and efficient synthesis of xanthones is described. 2-(Trimethylsilyl)phenyl 2-fluorobenzoate derivatives undergo Fries-type rearrangement and intramolecular S_NAr reaction in a one-pot sequential manner under fluoride ion-promoted mild conditions. The method provides efficient access to xanthones that have significant steric congestion around the C9 carbonyl, which are not readily available by conventional methods.

Key words

xanthone - Fries-type rearrangement - nucleophilic aromatic substitution - fluoride ion

• References and Notes


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Recently, Larock and co-workers reported a xanthone synthesis involving a similar reaction pathway in which the aryl anion, formed by nucleophilic attack of a carboxylate anion of o-haloarenecarboxylic acid to aryne, undergoes Fries-type rearrangement and subsequent intramolecular S_NAr reaction. See:
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• 22 One-Pot Synthesis of Xanthones; Typical Procedure (Table 2, Entry 4): Powdered 4 Å molecular sieves (3.0 g) were placed in a two-necked, round-bottom flask, and dried by heating with a heat gun under vacuum. The flask was cooled to r.t. and filled with argon, then THF (9 mL) and TBAF (1.0 M in THF, 0.60 mL, 0.60 mmol) were added. After stirring for 1.5 h at 25 °C, a solution of ester 5d (202 mg, 599 μmol) in THF (10 mL) was added and stirring was continued for 15 min. The reaction was quenched by the addition of pH 7 phosphate buffer (0.1 M) at 0 °C, and molecular sieves were removed by filtration through a pad of Celite. The filtrate was washed with brine, dried over Na₂SO₄, and concentrated. The residue was purified by column chromatography on silica gel (hexane–EtOAc, 2:1) to give xanthone 6d (141 mg, 97%) as a white solid. Recrystallization from hexane–EtOAc gave 6d as colorless needles.