First Example of a Continuous-Flow Carbonylation Reaction Using Aryl Formates as CO Precursors

• Nerea Alonso^1,3
• Juan de Muñoz¹
• Brecht Egle²
• Johannes L. Vrijdag²
• Wim M. De Borggraeve²
• Antonio de la Hoz³
• Angel Díaz-Ortiz³
• Jesús Alcázar¹

• ¹Janssen Research and Development, Janssen-Cilag Department of Medicinal Chemistry S.A., Toledo, Spain
• ²Molecular Design and Synthesis University of Leuven, Department of Chemistry, Heverlee Belgium
• ³Universidad de Castilla-La Mancha Facultad de Ciencias y Tecnologías Químicas Real, Spain

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.

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