This paper describes the selective and reproducible debenzylation of benzyloxypyrazinones using flow chemistry to yield N-hydroxypyrazinones. Flow methodology enabled us to avoid overreduction of the compounds to pyrazin-2(1H)-ones.
Authors:Brecht Egle, Juan Muñoz, Nerea Alonso, Wim De Borggraeve, Antonio de la Hoz, Angel Díaz-Ortiz and Jesús Alcázar
The first example of an alkyl–aryl Negishi coupling in a practical, sustainable, and high-yielding process using a silica-supported catalyst in flow is described. Excellent conversions and good functional group compatibility were obtained under very mild conditions. Functionalized alkyl groups were also introduced to provide access to synthetically useful molecules and to demonstrate the versatility of the method. The scalability was assessed, and a throughput of 7.5 mmol/h of processed substrate was achieved. All crude products were free from phosphine derivatives and ready for use in subsequent reaction steps.
Authors:Nerea Alonso, M. Muñoz Juan de, Brecht Egle, Johannes L. Vrijdag, Wim M. De Borggraeve, Antonio de la Hoz, Angel Díaz-Ortiz and Jesús Alcázar
The first continuous flow carbonylation reaction using aryl formates as CO precursor is reported. The reaction is practical, scalable and high yielding. The use of a flow protocol safely allows expanding the scope to activated chlorides, nitrogen heterocycles and to the selective introduction of an ester group in dihalo-derivatives. Further selective reduction of the ester formed to an aldehyde in flow is also described.