Aerobic waste-minimized Pd-catalysed C–H alkenylation in GVL using a tube-in-tube heterogeneous flow reactor

Abstract

Herein we report the design and application of a tube-in-tube packed-bed flow reactor for the first time for the development of a heterogeneous palladium catalysed oxidative C–C bond formation process. In particular, we have defined an innovative tube-in-tube protocol for the Fujiwara–Moritani C–H alkenylation reaction in biomass-derived γ-valerolactone. Thanks to this novel flow system, the oxidative C–H activation process has been conducted using a sub-stoichiometric amount of an external organic oxidant (benzoquinone) in the presence of molecular oxygen as a benign sacrificial oxidant. The protocol features very limited metal leaching and high stability of the catalyst over time. In this study, the applicability of the protocol to a range of substituted acetanilides and N-methoxybenzamides and various electron-poor alkenes has been demonstrated. The practical utility of the tube-in-tube reactor has also been proved by performing the flow methodology on a multi-gram scale.