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Synlett 2005(12): 1917-1921  
DOI: 10.1055/s-2005-871938
LETTER
© Georg Thieme Verlag Stuttgart · New York

Metal Chloride-Promoted Aldol Reaction of α-Dimethylsilylesters with Aldehydes, Ketones, and α-Enones

Katsukiyo Miura*a,b, Takahiro Nakagawaa,b, Akira Hosomi*a,b
a Department of Chemistry, 21st Century COE, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8571, Japan
b CREST, Japan Science and Technology Corporation (JST), Tsukuba, Ibaraki 305-8571, Japan
Fax: +81(29)8536503; e-Mail: miura@chem.tsukuba.ac.jp; e-Mail: hosomi@chem.tsukuba.ac.jp;
Further Information

Publication History

Received 13 May 2005
Publication Date:
07 July 2005 (online)

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Abstract

In the presence of a catalytic amount of LiCl, α-dimethylsilylesters (α-DMS-esters) 1 smoothly reacted with various aldehydes at 30 °C to give aldols in good to high yields. On the other hand, the aldol reaction with ketones was effectively promoted by MgCl2 rather than by LiCl. α-Enones also underwent the metal chloride-promoted addition of 1 at the carbonyl carbon or β-carbon.

Key words

aldehydes - aldol reactions - ketones - Michael additions - α-silylesters

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12

General Procedure for the Aldol Reaction of 1 with Aldehydes 2
Under the atmosphere, dry LiCl (5.5 mg, 0.13 mmol) was added to a two-necked, round-bottomed flask (10 mL), which was connected with a nitrogen balloon. After introduction of nitrogen, DMF (1.0 mL) was added to the flask. The mixture was warmed to 30 °C under stirring. After 10 min, 2 (0.50 mmol) and 1 (0.60 mmol) were added to the mixture. After being stirred for 5 h, the reaction mixture was treated with 2 M aq HCl (1 mL) for 5 min and neutralized with sat. aq NaHCO3. The aqueous mixture was extracted with EtOAc (3 × 10 mL). The extract was dried over Na2SO4 and evaporated. The crude product was purified by silica gel column chromatography.

19

As shown in Table [3] , the reaction of 1a with 8a proceeded efficiently irrespective of the metal chloride used. This observation may be due to higher coordinating ability (Lewis basicity) of α-enones, which allows carbonyl activation even with less Lewis acidic metal ions. For the coordinating ability of α-enones, see ref. 17a.