Microwave-Assisted Suzuki Couplings with Pd EnCat^TM

Significance

A Suzuki cross-coupling protocol promoted by a polyurea-microencapsulated palladium catalyst (Pd EnCat^TM) under microwave irradiation in batch and continuous-flow mode was developed. The microwave-assisted reactions of 31 aryl halides and 11 boronic acids were performed with Pd EnCat^TM and Bu₄NOAc at 120-140 °C for 6-15 min in batch mode, generating a potential array of 341 compounds (>98% purity: 131 examples, >80% purity: 40 examples, <80% purity: 55 examples, incomplete reaction: 69 examples, no reaction: 46 examples). The product purity was improved dramatically when the reactions were heated at 50 W and the temperature did not exceed 76 °C with the help of compressed-air cooling (4 bar, 22 °C temperature) [normal irradiation: <10% to 98% purity; cooled irradiation: 74% to >98% purity (18 examples)]. This microwave irradiation reaction system with external cooling was applied to continuous-flow mode.