Synlett 2013; 24(19): 2575-2580
DOI: 10.1055/s-0033-1339881
letter
© Georg Thieme Verlag Stuttgart · New York

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

Yuuki Fujimoto
a  School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo, 192-0392, Japan   Fax: +81(42)6763257   eMail: tmatsumo@toyaku.ac.jp
,
Ryohei Itakura
b  Department of Chemistry, Tokyo Institute of Technology, 2-12-1, Ookayama, Meguro-ku, Tokyo, 152-8551, Japan   Fax: +81(3)57342788   eMail: ksuzuki@chem.titech.ac.jp
,
Hiroki Hoshi
a  School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo, 192-0392, Japan   Fax: +81(42)6763257   eMail: tmatsumo@toyaku.ac.jp
,
Hikaru Yanai
a  School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo, 192-0392, Japan   Fax: +81(42)6763257   eMail: tmatsumo@toyaku.ac.jp
,
Yoshio Ando
b  Department of Chemistry, Tokyo Institute of Technology, 2-12-1, Ookayama, Meguro-ku, Tokyo, 152-8551, Japan   Fax: +81(3)57342788   eMail: ksuzuki@chem.titech.ac.jp
,
Keisuke Suzuki
b  Department of Chemistry, Tokyo Institute of Technology, 2-12-1, Ookayama, Meguro-ku, Tokyo, 152-8551, Japan   Fax: +81(3)57342788   eMail: ksuzuki@chem.titech.ac.jp
,
Takashi Matsumoto*
a  School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo, 192-0392, Japan   Fax: +81(42)6763257   eMail: tmatsumo@toyaku.ac.jp
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Publikationsverlauf

Received: 19. Juli 2013

Accepted after revision: 02. September 2013

Publikationsdatum:
30. September 2013 (online)


Abstract

A novel and efficient synthesis of xanthones is described. 2-(Trimethylsilyl)phenyl 2-fluorobenzoate derivatives undergo Fries-type rearrangement and intramolecular SNAr 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.

Supporting Information

 
  • 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 SNAr 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.