p‐Substituted Tris(2‐pyridylmethyl)amines as Ligands for Highly Active ATRP Catalysts: Facile Synthesis and Characterization

Abstract

A facile and efficient two‐step synthesis of p‐substituted tris(2‐pyridylmethyl)amine (TPMA) ligands to form Cu complexes with the highest activity to date in atom transfer radical polymerization (ATRP) is presented. In the divergent synthesis, p‐Cl substituents in tris(4‐chloro‐2‐pyridylmethyl)amine (TPMA3Cl) were replaced in one step and high yield by electron‐donating cyclic amines (pyrrolidine (TPMAPYR), piperidine (TPMAPIP), and morpholine (TPMAMOR)) by nucleophilic aromatic substitution. The [CuII(TPMANR2)Br]+ complexes exhibited larger energy gaps between frontier molecular orbitals and >0.2 V more negative reduction potentials than [CuII(TPMA)Br]+, indicating >3 orders of magnitude higher ATRP activity. [CuI(TPMAPYR)]+ exhibited the highest reported activity for Br‐capped acrylate chain ends in DMF, and moderate activity toward C−F bonds at room temperature. ATRP of n‐butyl acrylate using only 10–25 part per million loadings of [CuII(TPMANR2)Br]+ exhibited excellent control.

A mechanistic perspective on atom transfer radical polymerization

“…More recently a series of new ligands based upon the TPMA backbone, such as TPMA NMe2 , have been developed with activities unparalleled by any from the previous generation of ATRP catalysts. 51,52 Computational studies suggest that this activity could be further improved by capping of the amine ligand (e.g. using quin, ((2R,6R,7R)-quinuclidine-2,6,7-triyl) trimethanamine) so as to destabilize the Cu I and lower its oxidation potential.…”

“…11 Figure 1 shows experimental k act values for CH 3 CH 2 (COOCH 3 )Br with Cu I Br in MeCN at 22°C and a wide range of ligands. 51,52,58 These values range over 10 orders of magnitude for available ligands, 51,52,58 with another 3 orders of magnitude improvement in activity possible if the computationally designed ligands are considered as well. 15 A number of experimental and computational structure-reactivity studies have been published and the structure-reactivity trends are reasonably well understood.…”

“…[58][59][60] Some of the most active ligands, such as TPMA NMe2 , are then further substituted with electron donating amine or methoxy substituents. 51,52 However, within these broad trends, there is still considerable variation with chemical structure that is best understood by examining the molecular orbitals of the Cu I complex (Fig. 2).…”

“…Selected experimental activation rate constants k act (L mol −1 s −1 ) for ATRP with various N-based ligands with the initiator CH 3 CH 2 (COOCH 3 )Br in the presence of Cu I Br in MeCN at 22°C. Experimental data taken from references51,52,58 . The species in green boxes are computationally predicted values for new ligands taken from reference 15; other more active ligands are also predicted in this paper but these are the ones with synthetic precedent.…”

Atom Transfer Radical Polymerization-Inspired Room Temperature (sp3)C–N Coupling

“…Originally based on atom transfer radical addition (ATRA) methodologies, successive generations of Cu­(I) catalysts have led to an improvement in activity of more than seven orders of magnitude simply by varying the ligand (Figure ). − As a result, currently available catalysts can trigger the reversible cleavage of relatively strong (sp 3 )­C–X bonds at room temperature at low catalytic loading . Until now, these catalysts have been used to generate radicals exclusively for ATRP and ATRA processes.…”