The diverse activity of flavoenzymes in organic transformations has fascinated researchers for a long time. However, when applied outside an enzyme environment, the isolated flavin cofactor only shows largely reduced activity. This highlights the importance of embedding the reactive flavin’s isoalloxazine core in defined surroundings. The latter include crucial non-covalent interactions with amino acid side chains or backbone as well as controlled access to reactants such as molecular oxygen. Nevertheless, molecular flavins are increasingly applied in the organic laboratory as valuable organocatalysts. Chemical modification of the parent isoalloxazine structure is of particular interest in this context in order to achieve reactivity and selectivity in transformations, which are so far only known with flavoenzymes or even unprecedented. This review aims to give a systematic overview of the reported designed flavin catalysts and highlights the impact of each structural alteration. It is intended to serve as a source of information when comparing the performance of known catalysts, but also when designing new flavins. Over the last decades, molecular flavin catalysis has emerged from proof-of-concept reactions to increasingly sophisticated transformations. This stimulates anticipating new flavin catalyst designs for solving contemporary challenges in organic synthesis.

In nature, the isoalloxazine heterocycle of flavin cofactors undergoes reversible covalent bond formation with a variety of different reaction partners. These intermediates play a crucial role inter alia as the...