Rapid mixing to race past rearrangement: Chemistry relies on encounters between reactive partners. Sometimes one of the partners changes shape during the wait, spoiling the desired outcome. Kim et al. designed a microfluidic device to keep such botched encounters from happening. The device operates at low temperatures to keep individual reactants from isomerizing. It also achieves fast flow rates to maximize encounters between reactants on a microsecond time scale. The authors showcase the device by achieving bimolecular carbon-carbon coupling before one of the reagents can undergo a Fries rearrangement that would shift a neighboring group to the coupling site. Science , this issue p. 691

Protecting-group-free synthesis has received significant recent research interest in the context of ideal synthesis and green sustainable chemistry. In general, organolithium species react with ketones very rapidly, and therefore ketone carbonyl groups should be protected before an organolithium reaction, if they are not involved in the desired transformation. If organolithium chemistry could be free from such a limitation, its power would be greatly enhanced. Here we show that a flow microreactor enables such protecting-group-free organolithium reactions by greatly reducing the residence time (0.003 s or less). Aryllithium species bearing ketone carbonyl groups are generated by iodine–lithium exchange reactions of the corresponding aryl iodides with mesityllithium and are reacted with various electrophiles using a flow-microreactor system. The present method has been successfully applied to the formal synthesis of Pauciflorol F.

We developed a microflow method for the generation and reactions of aryllithiums bearing a cyano group, including o-lithiobenzonitrile, m-lithiobenzonitrile and p-lithiobenzonitrile. The method was effective at much higher temperatures than are required for conventional macrobatch reactions, by virtue of rapid mixing, short residence time, and efficient temperature control. In addition, reactions of o-lithiobenzonitrile with carbonyl compounds followed by trapping of the resulting lithium alkoxides with electrophiles were achieved in an integrated microflow system.