Synlett 2004(8): 1363-1366  
DOI: 10.1055/s-2004-825621
LETTER
© Georg Thieme Verlag Stuttgart · New York

Bifunctional Molecular Linchpins: A Three-Component Coupling Protocol Employing 2-Bromoallyltrimethylsilane

Amos B. Smith III*, Matthew O. Duffey
Department of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of ­Pennsylvania, Philadelphia, PA 19104, USA
Fax: +1(215)8985129; e-Mail: smithab@sas.upenn.edu;
Further Information

Publication History

Received 19 March 2004
Publication Date:
04 June 2004 (online)

Abstract

A new three-component coupling protocol, exploiting 2-bromoallyltrimethylsilane as a bifunctional linchpin, has been developed. The reaction sequence entails the following steps: lithiation of the vinyl bromide, addition of an aromatic or aliphatic aldehyde, execution of a solvent controlled 1,4-Brook rearrangement induced by HMPA to generate an allyl anion, and addition of a reactive second electrophile. Yields are moderate to good.

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Enolization of propionaldehyde led to homoaldol coupled products. α-Branched aldehydes such as isobutyraldehyde and cyclohexane carboxaldehyde afforded similar results, although minor amounts of the tricomponent coupled products were observed.

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A representative procedure for the three-component coupling is as follows. To a solution of 2-bromo-allyltrimethylsilane (1.12 g, 5.8 mmol) in 18 mL dry THF under argon was added 6.8 mL t-BuLi (1.7 M solution in hexanes) at -78 °C. The resulting yellow solution was stirred at -78 °C for 1 h. Benzaldehyde (590 µL, 5.8 mmol) was added and the reaction mixture was stirred an additional 3 h at -78 °C. A solution of HMPA (4 mL, 23 mmol) and allyl bromide (1.5 mL, 17 mmol) in 4 mL THF was added. The reaction mixture was then warmed to 0 °C in an ice bath and allowed to warm slowly to r.t. and stir overnight. The reaction was then quenched with 5 mL HCl (1 M). An additional 15 mL H2O were added and the aqueous layer was extracted with Et2O (3 × 60 mL). The combined organic layers were then dried over MgSO4, filtered and concentrated under reduced pressure. Purification by silica gel flash column chromatography (eluent 7:1 hexanes-ethyl acetate) afforded 700 mg of 16 (69%) as a colorless oil.