Subscribe to RSS
DOI: 10.1055/s-2004-825621
Bifunctional Molecular Linchpins: A Three-Component Coupling Protocol Employing 2-Bromoallyltrimethylsilane
Publication History
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.
Key words
Brook rearrangement - multicomponent coupling - bifunctional linchpins - organolithium reagents
-
1a
Smith AB.Boldi AM. J. Am. Chem. Soc. 1997, 119: 6925 -
1b
Smith AB.Pitram SM.Boldi AM.Gaunt MJ.Sfouggatakis C.Moser WH. J. Am. Chem. Soc. 2003, 125: 14435 -
2a
Brook AG. Acc. Chem. Res. 1974, 7: 77 -
2b
Brook AG.Bassindale AR. In Rearrangements of Ground Excited States Vol. 2:de Mayo P. Academic Press; New York: 1980. p.149 -
2c
Moser WH. Tetrahedron 2001, 57: 2065 ; and references cited therein -
3a
Smith AB.Zhuang L.Brook CS.Boldi AM.McBriar MD.Moser WH.Murase N.Nakayama K.Verhoest PR.Lin Q. Tetrahedron Lett. 1997, 38: 8667 -
3b
Smith AB.Zhuang L.Brook CS.Lin Q.Moser WH.Trout REL.Boldi AM. Tetrahedron Lett. 1997, 38: 8671 -
3c
Smith AB.Lin Q.Nakayama K.Boldi AM.Brook CS.McBriar MD.Moser WH.Sobukawa M.Zhuang L. Tetrahedron Lett. 1997, 38: 8675 -
3d
Smith AB.Pitram SM. Org. Lett. 1999, 1: 2001 -
3e
Smith AB.Doughty VA.Sfouggatakis C.Bennett CS.Koyanagi J.Takeuchi M. Org. Lett. 2002, 4: 783 -
3f
Smith AB.Pitram SM.Fuertes MJ. Org. Lett. 2003, 5: 2751 - 4
Marumoto S.Kuwajima I. J. Am. Chem. Soc. 1993, 115: 9021 - 5
Takaku K.Shinokubo H.Oshima K. Tetrahedron Lett. 1998, 39: 2575
References
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.
7A 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.