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Synlett 2010(19): 2947-2949  
DOI: 10.1055/s-0030-1259031
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Regioselective Alkylation of Catechols via Mitsunobu Reactions

Xiaolong Wang*a, Tingting Jua, Xiaodong Lia, Xiaoping Caob
a School of Chemical and Biological Engineering, Lanzhou Jiaotong University, Lanzhou 730070, P. R. of China
Fax: +86(931)4956512; e-Mail: wangxl@mail.lzjtu.cn;
b Department of Chemistry, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China
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Publication History

Received 1 September 2010
Publication Date:
10 November 2010 (online)

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Abstract

A mild and efficient Mitsunobu protocol for the regioselective alkylation of catechols such as 3,4-dihydroxybenzaldehyde and methyl 3,4-dihydroxybenzoate is described. The para-alkylation products could be easily prepared via the Mitsunobu reaction with high selectivity in moderate to good yields.

Key words

regioselective alkylation - Mitsunobu reaction - catechol - 3,4-dihydroxybenzaldehyde - different acidity

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General Procedure for the Regioselective Alkylation under Mitsunobu Conditions: DIAD (4.5 mmol) and Ph3P (4.5 mmol) were dissolved in anhyd THF (20 mL), and the solution was cooled in an ice bath. Alcohol (3 mmol) was added. After the mixture was stirred for 10 min, a solution of catechol (3 mmol) in anhyd THF (5 mL) was added immediately. After stirring for 30 min, the reaction mixture was warmed to r.t. and stirred. When the reaction was judged to be complete (TLC), the mixture was evaporated under vacuum and the residue was purified by column chroma-tography on silica gel eluting with a mixture of PE and EtOAc.
Spectral Data for Methyl 4-Butyloxy-3-hydroxybenzoate (Table 1, Entry 10): colorless crystals; mp 114-115 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 0.99 (t, J = 7.2 Hz, 3 H), 1.50 (m, 2 H), 1.82 (m, 2 H), 3.87 (s, 3 H), 4.10 (t, J = 6.4 Hz, 2 H), 5.71 (s, 1 H), 6.85 (d, J = 9.2 Hz, 1 H), 7.59 (m, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 13.7, 19.1, 31.0, 51.9, 68.8, 110.6, 115.5, 122.7, 123.1, 145.3, 149.8, 166.8.