Rapid Generation and Safe Use of Carbenes Enabled by a Novel Flow Protocol with In-line IR spectroscopy

A powerful new continuous process for the formation and use of donor/acceptor-substituted carbenes is described. The safety profile of diazo group transfer on methyl phenylacetate was determined including kinetic studies in batch and in flow using in-line IR analysis. Batch work-up and liquid chromatography were circumvented by developing an optimized liquid/liquid flow separation method providing aryl diazoacetates in high purity. Fast screening of reaction conditions in flow with in-line IR analysis allowed rapid reaction optimization. Finally, a multistep process of diazo group transfer, extraction, separation and subsequent diazo decomposition combined with multiple X-H insertion reactions was established.