A Novel Synthesis of Trifluoromethylated Multi-Substituted Alkenes via Regio- and Stereoselective Heck Reaction of (E)-4,4,4-Trifluoro-1-phenyl-2-buten-1-one

Abstract

Treatment of (E)-4,4,4-trifluoro-1-phenyl-2-buten-1-one with various aryldiazonium salts in the presence of a palladium catalyst led to a smooth Heck reaction, furnishing α-arylated adducts in good yields.

Heck reaction - aryldiazonium salts - fluoroorganic compounds

References and Notes

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The Heck reaction of β-fluoro-alkylated α,β-unsaturated carbonyl compounds with aryl halide in the presence of a palladium catalyst has been reported, however, neither high regioselectivity nor high yields have been achieved (yield: <48%, regioselectivity <29:71), see:

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<A NAME="RS11106ST-9">9</A>

The stereochemistry was determined on the basis of the chemical shifts in the ¹H NMR spectra according to the literature; see ref. 8.

<A NAME="RS11106ST-10">10</A>

Method A; Typical Procedure: To a solution of Pd₂(dba)₃·CHCl₃ (10 mol%) and P(o-Tol)₃ (40 mol%) in EtOH was added (E)-4,4,4-trifluoro-1-phenyl-2-buten-1-one (50 mg, 0.25 mmol) and p-fluorophenyldiazonium tetrafluoro-borate (115 mg, 0.55 mmol) at r.t., and the resulting mixture was stirred at 40 °C for 2 h. After cooling to r.t., the mixture was poured into a sat. aq solution of NH₄Cl, and the resulting mixture was extracted three times with Et₂O. The combined organic layers were washed with a sat. solution of NaCl, dried over anhyd Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography to give the corresponding Heck adduct (43 mg, 0.45 mmol; Z/E, 89:11; 58% yield). Z-Isomer: ¹H NMR (CDCl₃) δ = 6.15 (q, J = 7.1 Hz, 1 H), 7.02-7.07 (m, 2 H), 7.38-7.47 (m, 4 H), 7.50-7.60 (m, 1 H), 7.86-7.92 (m, 2 H). ¹⁹F NMR (CDCl₃): δ = -59.1 (d, J = 7.1 Hz, 3 F), -110.2 to -110.3 (m, 1 F). E-Isomer: ¹H NMR (CDCl₃): δ = 6.09 (q, J = 7.1 Hz, 1 H). ¹⁹F NMR (CDCl₃): δ = -57.3 (d, J = 7.1 Hz, 3 F), -111.78 to -111.84 (m, 1 F).
Method B: The reaction was carried out in the presence of Pd₂(dba)₃·CHCl₃ in THF at reflux. The workup was the same as Method A.