A Fast-Slow-Fast Strategy for Exploring Three-Component Reactions of Formaldehyde.

To explore a fast/slow reactivity partitioning strategy for the design of multicomponent reactions (MCRs), the fast-slow-fast (FSF) approach was applied to formaldehyde-based systems. The assembly procedure of substrates to the MCR product was designed to be a fast-slow-fast (FSF) cascade process. The most reactive one among all the substrates was converted rapidly to a substable substance (the fast first step), which can be slowly transformed to a highly reactive intermediate (the slow second step), and finally, the intermediate was trapped by another substrate to form the MCR product (the fast third step). By using formaldehyde and ethyl 2-chloroacetylacetate as a proof of concept of the model substrates, some three-component reactions were found to be successful, demonstrating that the FSF strategy is indeed useful and inductive for the study of MCRs.