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Negishi Reaction in Water at Room Temperature using TPGS-750-M

Description

TPGS-750-M, DL-α-Tocopherol methoxypolyethylene glycol succinate, is a designer surfactant composed of a lipophilic α-tocopherol moiety and a hydrophilic PEG-750-M chain, joined by an inexpensive succinic acid linker. TPGS-750-M spontaneously forms micelles upon dissolution in water. The balance and composition of lipophilic and hydrophilic components have been tailored to promote a broad array of chemistry in water. Furthermore, this new, more practical surfactant can be readily be substituted for older amphiphiles, usually with equal or greater efficiency in terms of both yield and reaction times.

Conducting transition metal-catalyzed cross-coupling chemistry in water instead of organic solvent has a number of potential benefits in terms of cost, environmental impact, safety, and impurity profiles. Increasing focus on “Green” chemical processes has further promoted recent developments in this field. The actual means of implementing reactions in water, however, especially at room temperature and for water insoluble, organic substrates, has not always been clear.

One solution applied to a broad range of transition-metal-catalyzed processes is the use of small amounts of a nanomicelle-forming amphiphile in water, which provides a lipophilic medium where cross-coupling reactions can take place. Initially, the viability of surfactant promoted, transition metal-catalyzed chemistry in water at room temperature was investigated with a variety of surfactants with PTS, an α-tocopherol based diester of sebacic acid, the most effective. A number of palladium and ruthenium-catalyzed processes were found to be amenable to mild, room temperature reactions in water. Products can be recovered from the aqueous phase using standard extraction procedures and in high isolated yields.1 TPGS-750-M is a second generation surfactant designed with physical properties to promote a broader array of chemistry in water more efficiently than seen with PTS.2

Precautions

Please consult the Safety Data Sheet for information regarding hazards and safe handling practices.

Procedures

Negishi Reaction – Transition-Metal-Catalyzed Cross-Coupling Reaction in Water at Room Temperature using TPGS-750-M

In a reaction flask under argon containing zinc dust/powder (195 mg, 3 mmol) and PdCl2(Amphos)2 (3.5 mg, 0.005 mmol, Catalog Number 678740) is added a solution of 2 wt % of TPGS-750-M in water (3.0 mL, Catalog Number 733857). N,N,N',N'-tetramethylethylenediamine (116 mg, 1 mmol, Catalog Number 411019) is added at room temperature followed by the addition of alkyl halide (2.0–3.0 mmol) and aryl or alkenyl bromide (1 mmol). The flask is stirred vigorously at room temperature for 12–48 h. The reaction mixture is then filtered through a bed of silica gel and the bed is further washed (3 x 5 mL) with Et2O to collect all of the coupled material. The volatiles are removed in vacuo to afford the crude product that is subsequently purified by flash chromatography on silica gel.

Materials

     

 References

  1. Lipshutz, B.H. et al., Olefin Cross-Metathesis Reactions at Room Temperature Using the Nonionic Amphiphile “PTS”: Just Add Water. Organic Letters, 10, 1325-1328 (2008).
  2. Lipshutz, B.H. et al., TPGS-750-M: A Second-Gereation Amphiphile for Metal-Catalyzed Cross-Couplings in Water at Room Temperature. J. Org. Chem., 76, 4379-4391 (2011).

 

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