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

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.

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

References and Notes

For a review of the alkylation of acetal, see:

<A NAME="RS06406ST-1A">1a</A> Mukaiyama T. Murakami M. Synthesis  1987,  1043 

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<A NAME="RS06406ST-1D">1d</A> Lindell SD. Elliott JD. Johnson WS. Tetrahedron Lett.  1984,  25:  3947 

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<A NAME="RS06406ST-2B">2b</A> Fujioka H. Okitsu T. Sawama Y. Murata N. Li R. Kita Y. J. Am. Chem. Soc.  2006,  128:  5930 

<A NAME="RS06406ST-2C">2c</A>

After our previous work (ref. 2a), we found that the use of 2,4,6-collidine in place of 2,6-lutidine gave better results in deprotection of acetals (ref. 2b). Then 2,4,6-collidine was used as a base in this work.

<A NAME="RS06406ST-3">3</A> Gilman H. Jones RG. Woods LA. J. Org. Chem.  1952,  17:  1630 

For the representative reactions of organocopper reagents with achiral and/or chiral acetals and ketals, see ref. 1b. See also:

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<A NAME="RS06406ST-5">5</A>

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.

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<A NAME="RS06406ST-7">7</A> Johnson CR. Dutra GA. J. Am. Chem. Soc.  1973,  95:  7783 

<A NAME="RS06406ST-8">8</A> Johnson CR. Dutra GA. J. Am. Chem. Soc.  1973,  95:  7777