Flowmicro In‐Line Analysis‐Driven Design of Reactions Mediated by Unstable Intermediates: Flash Monitoring Approach

Abstract

The direct observation of reactive intermediates is an important issue for organic synthesis. However, intermediates with an extreme instability are hard to be monitored by common spectroscopic methods such as FTIR. We have developed synthetic method utilizing flow microreactors, which enables a generation and reactions of unstable intermediates. Herein we report that, based on our flowmicro techniques, we developed an in‐line analysis method for reactive intermediates in increments of milliseconds. We demonstrated the direct observation of the living and dead species of the anionic polymerization of alkyl methacrylates. The direct information of the living species enabled the anionic polymerization and copolymerization of oligo(ethylene glycol) methyl ether methacrylates, which is the important but difficult reaction in the conventional method.

Defluorinative Functionalization Approach led by Difluoromethyl Anion Chemistry

“…No direct observation of such highly 25 unstable intermediates has been reported to date. Flow reaction systems allow for the in-line monitoring of products and have been used for a variety of analyses, such as our recently reported examples for observing unstable organolithium intermediates (40). A solution of 1a and KNp was mixed in a micromixer and subsequently passed through the tube reactor for 0.31 sec at -78 °C, followed by passing through the in-line IR device.…”