Early-Stage Organocatalysis

Organocatalysis has drastically advanced stereoselective chemical synthesis. From an underdeveloped niche area, it has become the most frequently applied approach to asymmetric synthesis. Organocatalysis is also developing into a technology, which can be used to make pharmaceuticals, scents, and other fine chemicals. However, the early stages of industrial chemistry, the upgrading of hydrocarbon-based alkenes, arenes, and alkanes, are still largely dominated by heterogeneous and transition metal catalysts. Here we will address the question if a selective, Early-Stage Organocatalysis (ESO) can be developed that directly delivers high-value substances from abundantly available hydrocarbon feedstock chemicals, while significantly saving energy and other resources. During the last few years, we have developed confined organic acids as a new catalyst class that features enzyme and zeolite-inspired active sites with well-defined pockets for selective substrate recognition and catalysis. These catalysts offer a widely tunable reactivity range, reaching extreme levels with turnover numbers exceeding 106 in challenging asymmetric carbon-carbon bond forming reactions, and approaching “magic acid” reactivity toward the activation of olefins. We now aim to take confined acid catalysis to another level by designing new, even more reactive acids that enable the utilization and valorization of steam-cracker-based hydrocarbons in selective organocatalysis. Specifically, we propose three aims: (1) Developing asymmetric olefin hydrofunctionalizations including hydrations and hydroarylations; (2) An early stage functionalization of simple arenes such as benzene and toluene via highly stereoselective and regioselective electrophilic aromatic substitution reactions; and, as the ultimate test of extreme reactivity, (3) we propose organocatalytic, asymmetric reactions of alkanes. The all-underlying goal will be the design and development of organocatalysts of the next generation.