Synlett 2008(4): 597-599  
DOI: 10.1055/s-2008-1032095
LETTER
© Georg Thieme Verlag Stuttgart · New York

Heck Reactions of Crotonaldehyde

Michael Stadler, Benjamin List*
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany
Fax: +49(208)3062999; e-Mail: list@mpi-muelheim.mpg.de;
Further Information

Publication History

Received 19 December 2007
Publication Date:
12 February 2008 (online)

Abstract

A direct method for the synthesis of β,β-disubstituted-α,β-unsaturated aldehydes via Heck reaction of aryl halides with crotonaldehyde and related substrates has been developed. The reaction provides rapid access to products usually prepared via multistep sequences. The power of the method in combination with an organocatalytic transfer hydrogenation is illustrated with a short asymmetric synthesis of (S)-Florhydral®.

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Representative Experimental Procedure for the Heck Reaction of Crotonaldehyde (Table 1, Entry 2)
4-Bromotoluene (256.4 mg, 1.5 mmol), TBACl (438 mg, 1.57 mmol), and NaOAc (148 mg, 1.80 mmol) were suspended in NMP (8 mL). Palladium acetate (6.8 mg, 0.03 mmol) in NMP (4 mL) was added, followed by croton-aldehyde (250 µL, 3 mmol). Oxygen was removed by two cycles of freeze-pump-thaw. The mixture was then heated at an oil-bath temperature of 90 °C for 75 min. After being cooled, the reaction mixture was poured into a half-concentrated aqueous solution of NaHCO3 (80 mL) and extracted three times with CH2Cl2 (120 mL in total). The combined organic fractions were washed with brine once, dried over MgSO4, and concentrated under reduced pressure. The resulting solution in NMP was directly loaded onto a column packed with silica gel and eluted with Et2O-pentane (15:85, v/v) to yield the product in fractions of pure E- and Z-isomers (70% combined yield).