Background: Flavonoid is a family of compounds present in the everyday consumption plants and
fruits, contributing to a balanced diet and beneficial health effects. Being a scaffold for new drugs and presenting
a wide range of applicability in the treatment of illnesses give them also an impact in medicine. Among the several
types of flavonoids, flavone and isoflavone derivatives can be highlighted due to their prevalence in nature
and biological activities already established. The standard synthetic route to obtain both halogenated flavones and
isoflavones is through the use of already halogenated starting materials. Halogenation of the flavone and isoflavone
core is less common because it is more complicated and involves some selectivity issues.
Objective: Considering the importance of these flavonoids, we aim to present the main and more recent synthetic
approaches towards their halogenation.
Methods: The most prominent methodologies for the synthesis of halogenated flavones and isoflavones were reviewed.
A careful survey of the reported data, using mainly the Scopus database and halogenation, flavones and
isoflavones as keywords, was conducted.
Results: Herein, a review is provided on the latest and more efficient halogenation protocols of flavones and isoflavones.
Selective halogenation and the greener methodologies, including enzymatic and microbial halogenations,
were reported. Nevertheless, some interesting protocols that allowed the synthesis of halogenated flavone
and isoflavone derivatives in specific positions using halogenated reagents are also summarized.
Conclusion: Halogenated flavones and isoflavones have risen as noticeable structures; however, most of the
time, the synthetic procedures involve toxic reagents and harsh reaction conditions. Therefore, the development
of new synthetic routes with low environmental impact is desirable.