Boxed reaction (Catalog No. 747920): Baran Trifluoromethylation Reaction (HetAr-CF3)

Reagents

Compound Catalog No. Equivalents MW Density Amount mmol
Kit Components            
Zinc trifluoromethane-sulfinate (TFMS) 771406 3.0 367.56   1.1 g 3.0
Luperox® TBH70X (TBHP, 70% aqueous t-BuOOH) 458139 5.0 90.12 0.93 0.69 mL 5.0
             
User Supplied            
Substrate   1       1.0
Solvent         5.0 mL  

Precautions

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

Procedure1

Baran Trifluoromethylation Reaction (HetAr-CF3)

Solvent Systems:

  1. CHCl3:H2O (2.5:1 ratio) – For innate and/or electron rich heterocycles
  2. DMSO – For electron deficient heterocycles

A solution of heterocycle and TFMS in an organic solvent was cooled in an ice-water bath, and this was followed by the slow addition (see notes) of TBHP (70% solution in water) using an Eppendorf® pipette with vigorous stirring. The reaction mixture was warmed to room temperature or 50 °C and monitored by thin-layer chromatography until reaction completion. For substrates that do not achieve reaction completion in 12–24 hours, a second addition of Zn salt (2.0–3.0 equiv.) and TBHP (3.0–5.0 equiv.) may be added to drive the reaction further. On consumption of the starting material, the reaction was partitioned between EtOAc (5.0 mL) and saturated NaHCO3 (5.0 mL), or CH2Cl2 (5.0 mL) and saturated NaHCO3 (5.0 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc or CH2Cl2 (3 x 5.0 mL). The organic layers were dried with Na2SO4, concentrated, and purified by column chromatography on silica gel.

Notes: If the TBHP is added too rapidly, the resulting exotherm can result in reduced yield and selectivity. This is especially important on larger scales, where a syringe pump may be used to add the TBHP.

Metal needles should not be used for adding TBHP as they decompose the reagent.

Materials

     

 Reference

  1. Nature, 492, 95-99 (2012).

 

Luperox is a registered trademark of Arkema Inc.
Eppendorf is a registered trademark of Eppendorf AG.

02/14-1

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