Cross-Coupling of Mesylated Phenol Derivatives with Potassium Cyclopropyltrifluoroborate

Reaction Scheme

Abstract

A robust and efficient protocol for the introduction of the dioxolanylethyl moiety onto various aryl and heteroaryl halides has been developed, providing cross-coupling yields up to 93%. Copper-catalyzed borylation of 2-(2-bromoethyl)-1,3-dioxolane with bis(pinacolato)diboron followed by treatment with potassium bifluoride provides the key organotrifluoroborate reagent.

Substrates

Procedure

In an oven-dried 8 mL microwave vial was introduced bis(di-tert-butyl(4-dimethylaminophenyl)- phosphine)dichloropalladium(II) (9 mg, 5 mol %), the dioxolanylethyltrifluoroborate 1 (0.275 mmol, 1.1 equiv) and Cs2CO3 (244 mg, 3 equiv). The vial was sealed with a cap lined with a disposable PTFE septum and evacuated under vacuum and purged with N2 (x3). Degassed toluene (1 mL) and H2O (0.25 mL) were added by syringe, followed by the desired electrophile (1 equiv). (When the aryl or heteroaryl halide was a solid, it was added after the base). The reaction mixture was then placed in an oil bath preheated at 100 �C and stirred for 14 h at this temperature. After cooling to rt, the vial was uncapped and diluted with H2O (3 mL) and EtOAc (5 mL x 2). The combined organics were dried (MgSO4) and filtered through Celite and concentrated in vacuo. Purification of the crude was performed by flash chromatography with hexanes/EtOAc: 100/0 to 60/40 with 1% Et3N.

Products

Materials

     
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