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Synlett 2006(18): 3077-3080  
DOI: 10.1055/s-2006-951509
LETTER
© Georg Thieme Verlag Stuttgart · New York

Highly Chemoselective Alkylation of Acetals Using TESOTf-2,4,6-Collidine-Gilman Reagent Combination

Hiromichi Fujioka*, Takashi Okitsu, Yoshinari Sawama, Takuya Ohnaka, Yasuyuki Kita*
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka, 565-0871, Japan
Fax: +81(6)68798229; e-Mail: fujioka@phs.osaka-u.ac.jp; e-Mail: kita@phs.osaka-u.ac.jp;
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Publication History

Received 10 April 2006
Publication Date:
25 October 2006 (online)

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Abstract

A new alkylation method of acetals has been developed by the reaction of the cationic intermediates, obtained by TESOTf-2,4,6-collidine treatment of acetals, followed by a Gilman reagent. The feature of the method is high chemoselectivity, which could not be attained by previously reported methods. Reaction proceeds under weakly basic conditions that acid-labile functional groups can tolerate.

Key words

alkylation - acetals - TESOTf-2,4,6-collidine - Gilman reagent - chemoselectivity - basic conditions

    References and Notes

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5

Typical Reaction Procedure: Reaction of Acetal 1a and Ph 2 CuLi (Table 1, Entry 5).
To a solution of an acetal 1a (36.2 mg, 0.179 mmol) in CH2Cl2 (1.79 mL) were added 2,4,6-collidine (71 µL, 0.537 mmol) and TESOTf (81 µL, 0.358 mmol) at 0 °C under N2 atmosphere and the reaction mixture was stirred at the same temperature. After checking for the disappearance of 1a by TLC (0.5 h), Ph2CuLi (prepared according to Johnson’s method [8] ) was added to the reaction mixture and stirred for 0.5 h. Disappearance of the polar component was ascertained by TLC analysis. The reaction mixture was quenched with sat. aq NH4Cl and stirred for more than 10 min at r.t. The mixture was extracted with CH2Cl2, the organic layer was washed with brine, dried over Na2SO4, filtered, and evaporated in vacuo. The residue was purified by flash SiO2 column chromatography using hexane-Et2O (100:1) to give 2a (41.5 mg, 93%) as a colorless oil.
(1-Methoxydecyl)benzene (2a): colorless oil. IR (KBr): 1493, 1454, 1101 cm-1. 1H NMR (300 MHz, CDCl3): δ = 0.87 (3 H, t, J = 6.0 Hz), 1.12-1.45 (14 H, m), 1.54-1.68 (1 H, m), 1.72-1.87 (1 H, m), 3.20 (3 H, s), 4.07 (1 H, t, J = 6.8 Hz), 7.23-7.37 (5 H, m). 13C NMR (75 MHz, CDCl3): δ = 14.1, 22.7, 25.8, 29.3, 29.5 (2 C), 29.6, 31.9, 38.2, 56.6, 84.2, 126.7, 127.4, 128.3, 142.6. Anal. Calcd for C17H28O: C, 82.20; H, 11.36. Found: C, 82.23; H, 11.42.