Continuous-Flow N-Heterocyclic Carbene Generation and Organocatalysis

Lorenzo Di Marco; Morgan Hans; Lionel Delaude; Jean-Christophe M Monbaliu

doi:10.1002/chem.201505135

Continuous-Flow N-Heterocyclic Carbene Generation and Organocatalysis

Chemistry. 2016 Mar 18;22(13):4508-14. doi: 10.1002/chem.201505135. Epub 2016 Feb 16.

Authors

Lorenzo Di Marco¹, Morgan Hans¹, Lionel Delaude², Jean-Christophe M Monbaliu³

Affiliations

¹ Center for Integrated Technology and Organic Synthesis, Department of Chemistry, University of Liège, 4000, Liège, Belgium.
² Laboratory of Organometallic Chemistry and Homogeneous Catalysis, Department of Chemistry, University of Liège, 4000, Liège, Belgium.
³ Center for Integrated Technology and Organic Synthesis, Department of Chemistry, University of Liège, 4000, Liège, Belgium. jc.monbaliu@ulg.ac.be.

PMID: 26880372
DOI: 10.1002/chem.201505135

Abstract

Two methods were assessed for the generation of common N-heterocyclic carbenes (NHCs) from stable imidazol(in)ium precursors using convenient and straightforward continuous-flow setups with either a heterogeneous inorganic base (Cs2CO3 or K3PO4) or a homogeneous organic base (KN(SiMe3)2). In-line quenching with carbon disulfide revealed that the homogeneous strategy was most efficient for the preparation of a small library of NHCs. The generation of free nucleophilic carbenes was next telescoped with two benchmark NHC-catalyzed reactions; namely, the transesterification of vinyl acetate with benzyl alcohol and the amidation of N-Boc-glycine methyl ester with ethanolamine. Both organocatalytic transformations proceeded with total conversion and excellent yields were achieved after extraction, showcasing the first examples of continuous-flow organocatalysis with NHCs.

Keywords: carbenes; continuous-flow; microreactors; organocatalysis; transesterification.

Publication types

Research Support, Non-U.S. Gov't