Sequence‐Defined Synthesis Enabled by Fast and Living Anionic Monoaddition of Vinyl Monomers

Abstract The selective monoaddition of polymerizable vinyl monomers like styrenes and methacrylates in a living manner has been achieved for the flash‐flow preparation of molecules in a defined sequence with high selectivity. We demonstrated the sequence‐defined synthesis of multifunctional molecules using an initiator, functionalized styrenes, diarylethylenes, various methacrylates, and an electrophilic trapping reagent at the living terminus (six‐component sequential connection at maximum) without any intermediate purification steps. The anionic living terminus of the vinyl monomers in the flow system described herein is active for polymerization, such that the styrene or methacrylate sequence can be expanded to afford highly dispersed oligomers without affecting other single units, which means that the unequivocal sequences were successfully inserted into the internal or terminal positions. The methodology described herein provides an adaptable method for the construction of new molecular spaces based on unimolecular sequence control and pinpoint functionalization.