Chiral Ammonium Salts Meet Transition Metal Catalysis

The efficient and stereoselective construction of complex molecular architectures is one of the ultimate goals in chemistry and the use of small molecule organic catalysts (organocatalysts) has proven to be highly useful to achieve complex transformations starting from simple easily available starting materials in a large variety of different case studies. Hereby, non-covalent catalysis modes are amongst the most versatile approaches to mimic Nature, usually benefitting from mild and easy to handle reaction conditions, environmentally benign reagents, and high efficiencies. The use of chiral cations (especially chiral ammonium salt phase-transfer catalysts (PTCs)) as catalysts has obtained a prominent and outstanding position and has contributed significantly to the field of asymmetric catalysis. The enormous potential of these catalysts lies in the fact that (theoretically) every reaction involving anionic or even just highly Lewis basic intermediates (starting materials) can be affected and controlled by these cationic catalysts. Considering the high potential of chiral PTCs to facilitate reactions where other methods clearly fail, we are confident that the use of chiral PTCs holds much promise to facilitate a series of highly demanding complex transformations, thus addressing some longstanding synthesis challenges. Although the synergistic combination of complementary activation modes has emerged as a powerful tool for complex transformations, it comes as a surprise that so far only a few reports about the synergistic combination of chiral PTCs with complementary activation modes have been published. It is the main target of this project to carry out a systematic feasibility study of the combined use of chiral phase- transfer catalysts with complementary transition metal catalysts in a synergistic (or cascade) fashion. The high value of such an approach will be the benefit of employing the unique nucleophile-activation potential of chiral cation-based catalysts in combination with the well-described electrophile activating properties of transition metal catalysts. Accordingly, the successful implementation of the herein investigated reactions will broaden the field of asymmetric catalysis in general, as substrates which have so far not been useable in such approaches in a catalytic stereoselective manner can be directly employed to obtain valuable chiral compounds in just a single step. Thus this project should provide the community with outstanding new tools to solve longstanding problems and to get access to chiral building blocks that are otherwise only difficultly accessible in a stereoselective fashion under mild and environmentally friendly conditions by using easily tuneable and easy to handle catalysts.

The efficient and stereoselective construction of complex molecular architectures is one of the ultimate goals in chemistry and the use of small molecule organic catalysts (organocatalysts) has proven to be highly useful to achieve complex transformations starting from simple easily available starting materials in a large variety of different case studies. Hereby, non-covalent catalysis modes are amongst the most versatile approaches to mimic Nature, usually benefitting from mild and easy to handle reaction conditions, environmentally benign reagents, and high efficiencies. The use of chiral cationic catalysts (especially chiral ammonium salt phase-transfer catalysts (PTCs)) has obtained a prominent and outstanding position and has contributed significantly to the field of asymmetric catalysis. Although the synergistic combination of complementary activation modes has emerged as a powerful tool for complex transformations, it comes as a surprise that so far only a few reports about the synergistic combination of chiral PTCs with complementary activation modes have been published. Therefore it was the main target of this project to carry out a feasibility study of so far unprecedented reactions with a combined use of chiral phase-transfer catalysts and complementary activation modes. In the course of these studies we found that ammonium salt catalysts can be used to facilitate reactions of hypervalent iodine reagents. However, depending on the used species the herein observed enantioselectivities were rather low only, also when testing the synergistic combination with chiral transition metal catalysts. Nevertheless, we were able to develop the first moderately selective asymmetric ?-cyanation of ?-ketoesters using a chiral organocatalyst and a hypervalent iodine transfer reagent. These highly functionalized target molecules could so far only be accessed in a racemic manner and therefore the herein developed protocol holds promise for future development.