Suzuki-Miyaura Cross-Coupling of Potassium Dioxolanylethyltrifluoroborate and Aryl/Heteroaryl Chlorides

Reaction Scheme

Abstract

A robust and general catalyst system�facilitates the alkoxylation of activated heteroaryl halides with primary, secondary, and select tertiary alcohols without the need for an excess of either coupling partner (see scheme). This catalyst system displays broad functional-group tolerance and excellent regioselectivity, and is insensitive to the order of reagent addition.

Substrates

Procedure

A 10-mL pressure vessel was charged with 2-hydroxyethyl- pyridine (1 equiv), anhydrous toluene (2.5 mL, 0.2 M), and a stirbar. Next, aryl halide (1 equiv), Pd2(dba)3 (5 mol%), Josiphos (10 mol%), and Cs2CO3 (2 equiv) were added as solids. With stirring, the reaction mixture was degassed under a stream of N2 for 2 min. The reaction vessel was sealed, and the reaction mixture heated to the indicated temperature; reaction progress was monitored by LCMS. After the indicated period of time, the reaction mixture was cooled to room temperature and diluted with 10 mL EtOAc. The organic phase was washed sequentially with 10 mL saturated aq. NaHCO3 and 10 mL brine. The organics were dried over MgSO4, filtered, and concentrated in vacuo. Purification by either reverse phase preparative HPLC or by normal phase elution on SiO2 (as indicated) provided the title compounds.

Products

Materials

     
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