Carnegie Mellon University


The mechanistic aspects of atom transfer radical polymerization in the presence of zero-valent copper, Cu0, have been under discussion since 2006 when it was postulated that the alkyl halides could be exclusively activated by Cu0 via an outer sphere electron transfer (OSET) process.(1) CuI did not activate alkyl halides, instead it instantaneously disproportionated to form Cu0 and CuII, and the formed Cu0 activated the dormant initiator and CuII acted as the deactivator while there was minimal comproportionation to retain a suitable concentration of the Cu0 activator.(2)   The mechanism was termed single-electron transfer living radical polymerization (SET-LRP).  
This was surprising since the use of Cu0 in an ATRP was first disclosed in 1997.(3, 4)  At that time it was employed both to directly activate alkyl halide initiators and to reduce added CuII catalyst complexes to form the CuI activator in situ and to remain in the reaction medium to reduce the concentration of CuII formed by termination and increase the rate of polymerization.  Both Cu0 and Fe0 were also employed as sole source of the transition metal in the presence of excess ligand.  Me6TREN was used as a ligand for Cu based ATRP in 1998(5) and the role of polar solvents in increasing the rate of polymerization had already been discussed at that time.(6)  A paper in 2000 described optimization of an ATRP with a copper bromide complex with one equivalent of Me6TREN at low concentrations of catalyst in the reaction mixture for the preparation of well-defined poly(butyl acrylate) in bulk.(7)  So all of the components for SET-LRP had been introduced for use in an ATRP on or before 2000, but six years later the question was raised “was this procedure an ATRP with high values for KATRP or a novel mechanism employing exactly the same reagents, SET-LRP?”
Consequently the mechanism for reversible deactivation radical polymerization (RDRP) in the presence of Cu0 has been the subject of considerable interest since 2006, as a consequence of two differing interpretations on the role Cu0 and CuI catalyst complexes in the presence of polar solvents. One proposed mechanism, named supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) has Cu0 acting as a supplemental activator and a reducing agent with activation occurring via an inner-sphere electron transfer occurring during the slow activation step, while CuI acts as the major activator of the dormant alkyl halides. This occurs in the presence of a relatively slow comproportionation reaction between Cu0 and CuII and an even slower disproportionation of CuI to Cu0 and CuII.(8)  In SARA ATRP there is slow activation of alkyl halides by Cu0 and comproportionation of CuII with Cu0 that compensates for the small number of radicals lost to termination reactions. On the other hand SET-LRP assumes that the CuI species does not activate dormant alkyl halides, but undergoes instantaneous disproportionation forming Cu0 which activates alkyl halides through a fast outer sphere electron transfer (OSET) reaction between alkyl halides and the formed ‘nascent’ Cu0. The formed CuII, acts as in ATRP, and deactivates the propagating radical, the combination providing an ultra-fast controlled polymerization of (meth)acrylates, styrene and vinyl chloride.(9)  
The two competing models, SARA ATRP and SET-LRP actually use exactly the same components, although the proposed mechanisms are completely different.  The reactions involved in SARA ATRP and SET-LRP are shown in Scheme 1 where it can be observed that the same set of equilibria contribute to both SARA ATRP and SET-LRP, but the level of their contributions to the overall controlled polymerization process do differ dramatically.

mecanism of SARA
The differences between SARA ATRP and SET-LRP  were initially addressed in 2007,(8) when the role of Cu0 in the presence of Me6TREN in a series of solvents including DMSO, DMF and MeCN in a controlled radical polymerization was clearly defined.  Activation of alkyl halides by CuI/ Me6TREN was significantly faster than by Cu0 and disproportionation was slow in DMSO and comproportionation dominated. The role of Cu0 was to regenerate CuI and balance the ratio of [CuI] to [CuII].  However the discussion did not end with that clarification and recently a new set of experiments were carried out that was designed to provide additional rate and kinetic data to model the rate of each these potentially contributing reactions.(10)  The rate constant k, which has been determined experimentally, provides a practical route to deciding the most appropriate mechanism. The fundamentals of SARA ATRP were provided in a series of recent papers(11-14) and the experimental data agrees with the SARA ATRP mechanism, since the activation of alkyl halides by CuI species is significantly faster than activation with Cu0. The activation step involves inner sphere electron transfer rather than an outer sphere electron transfer. The analysis of an extensive set of data confirms that while comproportionation is slow in DMSO, it occurs faster than disproportionation. The rate of deactivation by CuII is essentially the same as the rate of activation by CuI and the system is controlled by the classic ATRP equilibrium. The role of Cu0 in this system is to slowly and continuously supply CuI activating species and radicals, by supplemental activation and comproportionation procedures to compensate for CuI lost due to the unavoidable radical termination reactions.(15)  
This conclusion was placed in a broader context of explaining unexpected data via competitive equilibria and processes in radical reactions with reversible deactivation where CuI was at the center of the competitive processes.(10)  It was confirmed that even though disproportionation is thermodynamically favored over comproportionation in polar media(1) and it is relatively fast(2, 15) in these highly polar media, CuI complexes are so ATRP active that they rapidly react with alkyl halides, and generate the CuII deactivator in the process, and push the CuI concentration to a very low level which decreases the rate of disproportionation, which is proportional to [CuI]2. Consequently, disproportionation is dominated by comproportionation.
With the mechanistic understanding gained by analyzing the experimental data in the literature, the reaction conditions in SARA ATRP can be tailored towards efficient synthesis of a new generation of complex architectures and functional materials.

(1)    Percec, V.;  Guliashvili, T.;  Ladislaw, J. S.;  Wistrand, A.;  Stjerndahl, A.;  Sienkowska, M. J.;  Monteiro, M. J.; Sahoo, S. J. Am. Chem. Soc. 2006, 128, 14156-14165.
(2)    Zhang, Q.;  Wilson, P.;  Li, Z.;  McHale, R.;  Godfrey, J.;  Anastasaki, A.;  Waldron, C.; Haddleton David, M. J Am Chem Soc 2013, 135, 7355-7363.
(3)    Matyjaszewski, K.;  Coca, S.;  Gaynor, S. G.;  Wei, M.; Woodworth, B. E. Macromolecules 1997, 30, 7348-7350.
(4)    Matyjaszewski, K.;  Gaynor, S. G.; Coca, S. In PCT Int. Appl.; (Carnegie Mellon University, USA). WO 9840415, 1998; p 230 pp.
(5)    Xia, J.;  Gaynor, S. G.; Matyjaszewski, K. Macromolecules 1998, 31, 5958-5959.
(6)    Matyjaszewski, K.;  Nakagawa, Y.; Jasieczek, C. B. Macromolecules 1998, 31, 1535-1541.
(7)    Queffelec, J.;  Gaynor, S. G.; Matyjaszewski, K. Macromolecules 2000, 33, 8629-8639.
(8)    Matyjaszewski, K.;  Tsarevsky, N. V.;  Braunecker, W. A.;  Dong, H.;  Huang, J.;  Jakubowski, W.;  Kwak, Y.;  Nicolay, R.;  Tang, W.; Yoon, J. A. Macromolecules 2007, 40, 7795-7806.
(9)    Rosen, B. M.; Percec, V. Chemical Reviews (Washington, DC, United States) 2009, 109, 5069-5119.
(10)    Konkolewicz, D.;  Krys, P.; Matyjaszewski, K. Accounts of Chemical Research 2014, 47, 3028-3036.
(11)    Wang, Y.;  Zhong, M.;  Zhu, W.;  Peng, C.-H.;  Zhang, Y.;  Konkolewicz, D.;  Bortolamei, N.;  Isse, A. A.;  Gennaro, A.; Matyjaszewski, K. Macromolecules (Washington, DC, U. S.) 2013, 46, 3793-3802.
(12)    Peng, C.-H.;  Zhong, M.;  Wang, Y.;  Kwak, Y.;  Zhang, Y.;  Zhu, W.;  Tonge, M.;  Buback, J.;  Park, S.;  Krys, P.;  Konkolewicz, D.;  Gennaro, A.; Matyjaszewski, K. Macromolecules (Washington, DC, U. S.) 2013, 46, 3803-3815.
(13)    Zhong, M.;  Wang, Y.;  Krys, P.;  Konkolewicz, D.; Matyjaszewski, K. Macromolecules (Washington, DC, U. S.) 2013, 46, 3816-3827.
(14)    Konkolewicz, D.;  Wang, Y.;  Zhong, M.;  Krys, P.;  Isse, A. A.;  Gennaro, A.; Matyjaszewski, K. Macromolecules (Washington, DC, U. S.) 2013, 46, 8749-8772.
(15)    Konkolewicz, D.;  Krys, P.;  Gois, J. R.;  Mendonca, P. V.;  Zhong, M.;  Wang, Y.;  Gennaro, A.;  Isse, A. A.;  Fantin, M.; Matyjaszewski, K. Macromolecules 2014, 47, 560-570.