Continuous Flow Synthesis of Ketones from Carbon Dioxide and Organolithium or Grignard Reagents

Angewandte Chemie 53(32), 8416-8420, DOI: 10.1002/anie.201405014

We describe an efficient continuous flow synthesis of ketones from CO2 and organolithium or Grignard reagents that exhibits significant advantages over conventional batch conditions in suppressing undesired symmetric ketone and tertiary alcohol byproducts. We observed an unprecedented solvent-dependence of the organolithium reactivity, the key factor in governing selectivity during the flow process. A facile, telescoped three-step–one-flow process for the preparation of ketones in a modular fashion through the in-line generation of organometallic reagents is also established.