Tin-Free Radical Reactions Using the Persistent Radical Effect

The Persistent Radical Effect (PRE) is a general principle that explains the highly specific formation of the cross-coupling product (R1-R2) between two radicals R1 and R2 when one species is persistent (long lived) and the other transient, and the two radicals are formed at equal rates. The initial build up in concentration of the persistent species, caused by the self-termination of the transient radical, steers the reaction subsequently to follow a single pathway the cross reaction.
The PRE is meanwhile very important in the field of free radical polymerization. It was Studer who early recognized the importance of the PRE for synthetic radical chemistry. The PRE has been elegantly used to conduct environmentally benign radical cyclization reactions. Nitroxides have been used as persistent radicals for these processes.

 

New nitroxides have been designed and tested in radical isomerization reactions. Recently, the PRE has been successfully applied to conduct more difficult intermolecular addition reactions. Alkoxyamines of type 1, which are readily prepared from commercially available starting materials, undergo thermal additions to various nonactivated double bonds to provide γ-functionalized malonates 2, which are synthetically highly useful building blocks. These reactions are very easy to conduct and show perfect atom economy according to Trost. The addition reactions can be combined with radical cyclization and fragmentation processes.

 

Recently it has been shown that the PRE-mediated processes could be performed under microwave irradiation. The reactions could be conducted in a short time with high yields representing one of the first examples on the use of microwave irradiation to conduct radical reactions. The Studer group has also exploited cascade reactions where PRE-mediated processes have been combined with ionic as well as transition-metal mediated processes. The new methods are currently applied for the preparation of biologically interesting compounds.
It is important to note that the Studer group is also interested in physical organic chemistry. For example, kinetics of the various processes involved in the PRE-mediated radical reactions have been investigated using state of the art techniques. For example, kinetic EPR-experiments have been used to determine the C-O-bond energies of the various new alkoxyamines studied. Along with the kinetics, the dynamic processes have been simulated using Predici, a program for modeling nonlinear dynamic processes.

Papers on this and related topics: No. 19, 25, 35, 42, 43, 46, 48, 4, 50, 57, 61, 64, 65 and 67.


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