Pd(II)-Catalyzed Enantioselective Iodination

The direct CH bond functionalization is a highly attractive and one of the most investigated but also most challenging topics in modern organic synthesis. The general aim of CH activation reactions is to introduce groups with a higher complexity to hydrocarbon structures. One of the most challenging quests is the development of enantioselective CH activation reactions. Although many direct functionalizations have been reported in recent years, there are only few examples of performing such a transformation in an enantioselective fashion. Yu and coworkers reported in this context an exceedingly practical palladium-catalyzed method for the direct alkylation of C(sp 2 )H and C(sp 3 )H bonds using monoprotected amino acids as effective chiral ligands. The goal of this project is now the "palladium-catalyzed enantioselective iodination of CH bonds using amino acids as chiral ligands". The direct substitution of hydrogen with iodine is a process of great significance and, overall, might result in new and distinctive synthetic features. Iodine labeled compounds can be used as radiopharamaceutical, for labeling proteins or clinical studies. Furthermore, iodine is an excellent leaving group and can therefore be converted to a vast number of functional groups. The enantioselective introduction of such a leaving group would be a superior starting point for the synthesis of more complex chiral compounds. In the course of the project an effective catalyst/ligand/oxidant/additive/solvent system has to be established for these transformations whereby preliminary results from the Yu group on related problems can be used as starting point. Furthermore, different starting materials with different directing groups (= DG) have to be synthesized. Subsequently, reactions shall be optimized with respect to yield, ligand, substrate scope, temperature and time. In the optimization process mechanistic studies will be included to get more detailed information on the reaction pathway. Tuning of the ligand will address special needs of the reaction regarding the enantioselectivity. Intelligent changing of the electronic and steric properties of the amino acid is expected to lead to an improved reaction outcome.

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