RAFT Agent Design and Synthesis

This Perspective reviews the design and synthesis of RAFT agents. First, we briefly detail the basic design features that should be considered when selecting a RAFT agent or macro-RAFT agent for a given polymerization and set of reaction conditions. The RAFT agent should be chosen to have an optimal Ctr (in most circumstances higher is better) while at the same time it should exhibit minimal likelihood for retarding polymerization or undergoing side reactions. The RAFT agent should also have appropriate solubility in the reaction medium and possess the requisite end-group functionality for the intended application. In this light we critically evaluate the various methods that have been used for RAFT agent synthesis. These methods include reaction of a carbodithioate salt with an alkylating agent, various thioacylation procedures, thiation of a carboxylic acid or ester, the ketoform reaction, thiol exchange, radical substitution of a bis(thioacyl) disulfide, and radical-induced R-group exchange. We also consider methods for synthesis of functional RAFT agents and the preparation of macro-RAFT agents by modification of, or conjugation to, existing RAFT agents. The most used methods involve esterification of a carboxy functional RAFT agent, azide–alkyne 1,3-dipolar cycloaddition, the active ester–amine reaction, and RAFT single unit monomer insertion. While some of these processes are described as “click reactions”, most stray from that ideal. The synthetic method of choice is strongly dependent on the structure of the desired RAFT agent. Finally, we outline some of the current challenges in RAFT agent design and synthesis.