Universität zu Köln

Brunen, Sebastian (2024). Asymmetric Catalytic Friedel–Crafts Reactions of Unactivated Arenes. PhD thesis, Universität zu Köln.

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Abstract

Aromatic scaffolds are crucial structural elements in all fields of chemical synthesis. The selective functionalization of simple arenes is therefore of vital importance for the preparation of more complex aromatic structures. The Friedel–Crafts reaction has proven to be a particularly powerful tool for this transformation, its dependence on electron-rich arenes, however, limits its scope significantly. The work reported herein describes the development of novel methods for the asymmetric catalytic Friedel–Crafts reaction of unactivated arenes using strong and confined Brønsted acid organocatalysts. To that end, simple alkylbenzene hydrocarbons but also more reactive alkoxybenzenes and heterocyclic arenes could be transformed with N,O-acetals to yield corresponding arylglycine esters with generally excellent regio- and enantiomeric ratios and high yields. Building up on the abovementioned studies and stimulated by the relevance of 3-arylpropanals for fragrance applications, the addition of unactivated arenes to simple enal derivates was studied subsequently. To this end, either preformed acylals or enals in combination with anhydrides as activating agents were used to deliver enantioenriched enol esters via asymmetric Brønsted acid-catalysis.