Towards a Scalable Synthesis of 2-Oxabicyclo[2.2.0]hex-5-en-3-one Using Flow Photochemistry

Abstract

Cyclobutene lactones hold great potential as synthetic building blocks, yet their preparation by photochemical rearrangement in batch can often be a bottleneck in synthetic studies. We report the use of flow photochemistry as a tool to enable a higher-throughput approach to the synthesis of 2-oxabicyclo[2.2.0]hex-5-en-3-one, which reduces reaction times from 24 h to 10 min. Accordingly, a significantly improved throughput of 144 mg/h (vs 14–21 mg/h in batch) was achieved. Scale-out experiments showed problematic reactor fouling and steps were taken to explore and minimize this effect.