Rational Design of Highly Activating Ligands for Cu-Based Atom Transfer Radical Polymerization

Atom transfer radical polymerization (ATRP) is the most commonly utilized technique in controlled radical polymerization. However, the identification of more active catalysts could further increase its scope, both for polymerization and small-molecule synthesis more generally. To this end, a series of novel ligands were designed on the basis of two strategies: replacing nitrogen-based ligands with their phosphorus equivalents and rigidifying the ligand cap of nitrogen-based ligands so as to enforce short Cu-cap distances. Each ligand was assessed using accurate computational chemistry, which was used to compute the thermodynamics and, in selected cases, kinetics of an ATRP reaction with a model methyl methacrylate propagating radical. In principle, the use of phosphorus ligand caps was found to be a powerful strategy for increasing catalyst activity. Unfortunately, in practice, speciation issues sacrificed much of their advantage. In contrast, cap rigidification increases the activity of nitrogen-based ligands, well beyond existing ATRP ligands such as TPMA^NMe2. The effectiveness of these ligands was further demonstrated for hard-to-activate initiating systems based on ethylene, vinyl chloride, and vinyl acetate polymerization. Several of these improved ligands are synthetically accessible, with rigid piperidine or quinuclidine analogues of TPMA^NMe2 possessing improved thermodynamic and kinetic activity by 2 to 3 orders of magnitude.