Continuous-Flow Pd-Catalyzed Carbonylation of Aryl Chlorides with Carbon Monoxide at Elevated Temperature and Pressure

Alejandro Mata; Christopher A Hone; Bernhard Gutmann; Luc Moens; C Oliver Kappe

doi:10.1002/cctc.201801974

Continuous-Flow Pd-Catalyzed Carbonylation of Aryl Chlorides with Carbon Monoxide at Elevated Temperature and Pressure

ChemCatChem. 2019 Feb 6;11(3):997-1001. doi: 10.1002/cctc.201801974. Epub 2019 Jan 15.

Authors

Alejandro Mata^{1

2}, Christopher A Hone^{1

2}, Bernhard Gutmann^{1

2}, Luc Moens³, C Oliver Kappe^{1

2}

Affiliations

¹ Center for Continuous Flow Synthesis and Processing (CCFLOW) Research Center Pharmaceutical Engineering GmbH (RCPE) Inffeldgasse 13 Graz 8010 Austria.
² Institute of Chemistry University of Graz NAWI Graz Heinrichstrasse 28 Graz A-8010 Austria.
³ Janssen Research and Development Turnhoutseweg 30 Beerse 2340 Belgium.

Abstract

The development of a continuous-flow protocol for a palladium-catalyzed methoxycarbonylation of (hetero)aryl chlorides using carbon monoxide gas and methanol is described. (Hetero)aryl chlorides are the least expensive of the aryl halides, but are underutilized in carbonylation reactions due to their very poor reactivity. The described protocol exploits intensified conditions at elevated temperature and pressure, which are readily accessed within a continuous-flow environment, to provide moderate to excellent product yields (11 examples) in a short 16 min residence time. The continuous-flow protocol enables the safe and potentially scalable carbonylation of aryl chlorides using CO gas.

Keywords: (hetero)aryl chlorides; Pd-catalyzed; carbon monoxide; carbonylation; continuous flow; gas-liquid transformation.