A new palladium catalyst system for the cyanation of aryl chlorides with K4[Fe(CN)6]

Reaction Scheme

Abstract

Potassium 1-(alkoxy/acyloxy)alkyltrifluoroborates have been synthesized through a copper-catalyzed?diboration of aldehydes and subsequent conversion of the?resulting potassium 1-(hydroxy)alkyltrifluoroborates. The?palladium-catalyzed Suzuki?Miyaura reaction employing the?potassium 1-(benzyloxy)alkyltrifluoroborates with aryl and?heteroaryl chlorides provides access to protected secondary alcohols in high yields. The ?-hydride elimination pathway is avoided through use of the benzyl protecting group, which is proposed to stabilize the diorganopalladium intermediate by coordination of the arene to the metal center. This cross-coupling is stereospecific with complete retention of stereochemistry.

Substrates

Procedure

In a Biotage microwave vial equipped with a stir bar was successively introduced cataCXium A-Pd-G2 9 (2.5 �mol, 0.075 equiv), potassium 1-(benzyloxy)-3-phenyl-propyltrifluoroborate (0.3 mmol, 1 equiv), and CsOH-H2O (1.5 mmol, 5 equiv). The vial was sealed with a cap lined with a disposable Teflon septum, and evacuated under vacuum and purged with Ar three times. The electrophile was then added using a microsyringe (0.3 mmol, 1 equiv) followed by 0.3 mL of degassed CPME and 0.3 mL of degassed H2O. The resulting mixture was placed in an oil bath preheated to 105 �C and stirred for 24 h. After cooling to rt, the vial was uncapped, and the reaction mixture was diluted with EtOAc (3 mL) and H2O (3 mL). The reaction mixture was extracted with EtOAc (3 x 3 mL) and dried (MgSO4). The solvent was removed in vacuo, and the product was purified by flash column chromatography on silica gel or Florisil using a mixture of EtOAc/hexanes as the eluent.

Products

Materials

     
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