Recent advances in the Nenitzescu indole synthesis (1990–2019)

This review, based on the literature published since 1990, highlights recent advances in the Nenitzescu 5-hydroxyindole synthesis—one of the most useful methods for obtaining of the 5-hydroxyindoles starting from 1,4-benzoquinones and β-enamines. The 5-hydroxyindole skeleton is an important component of many biologically active natural products, drug-like compounds and has high potential for advanced material applications, as demonstrated recently. Another significant feature of the Nenitzescu reaction is the formation of 5-hydroxybenzofurans. The extension of the Nenitzescu reaction, through variations in the structure of the quinone and/or the enamine used, has also proved a useful procedure for obtaining compounds incorporating the 5-hydroxyindole moiety, 6-hydroxyindoles, 5-hydroxyindazoles, and other structures. The ongoing interest for 5-hydroxyindole synthesis from 1,4-benzoquinone and enamines is due to the simple working procedures, mild reaction conditions, and easily accessible and structurally diverse starting materials. Also, the interesting biological properties observed for Nenitzescu reaction products and for their congeners obtained through subsequent modifications make 5-hydroxyindoles privileged structures in the quest to achieve structurally diverse compounds with unique biological properties.