Dearomatization through Halofunctionalization Reactions

Abstract

Recent advances in dearomatization through halofunctionalization reactions are summarized in this Minireview. Two general categories of strategies are currently employed in this field. On one hand, the reaction can be initiated with electrophilic halogenation at an alkyne or alkene moiety. The resulting halonium ion intermediate is then captured by a pendant aromatic ring at the ipso position, affording the dearomatization product. On the other hand, electrophilic halogenation can directly take place at a substituted arene, and the final dearomatization product is furnished by deprotonation or intramolecular nucleophilic trap. Highly enantioselective variants have been realized in the latter case by organocatalysis or transition metal catalysis. By applying these methods, various valuable halogenated polycyclic molecular architectures have been obtained from readily available starting materials.

Catalytic Asymmetric Dearomatization by Transition-Metal Catalysis: A Method for Transformations of Aromatic Compounds

“…Reactions with substituted phenols, naphthols and indoles, benzothiophenes, and benzofurans have been studied. 98 Usually, the reactions are catalyzed by chiral tertiary amines or chiral anion phase-transfer catalysts, whereas transition-metal complexes have seldom been utilized as catalysts in this area.…”

Anthracene‐Based Cyclophanes with Selective Fluorescent Responses for TTP and GTP: Insights into Recognition and Sensing Mechanisms

“…Consecutively, the free amine might attack the 9‐position of anthracene, leading to dearomatization of the central ring and to the formation of intermediate C . Nucleophilic dearomatization reactions of the anthracene ring are well‐documented; however, they usually require organometallic reagents and/or low temperatures. Intermediate C may possess both cis ‐ and trans ‐orientations of the aldehyde and the bicyclic amine.…”

“…Ap ossible mechanism for the formationo fa mine 4 is presented in Scheme 1. Condensation of the aldehyde with the amine leads to the formation of intermediate A,f ollowed by cyclization to produce five-membered cyclic amine B.Consecutively,t he free amine might attack the 9-position of anthracene, leadingt od earomatization of the central ring and to the formation of intermediate C.N ucleophilic dearomatization reactions of the anthracene ring are well-documented; [36,37] however,t hey usually require organometallic reagents and/or low temperatures. Intermediate C mayp ossessb oth cis-a nd transorientations of the aldehyde and the bicyclic amine.…”

Asymmetric Dearomatization of Indole Derivatives with N‐Hydroxycarbamates Enabled by Photoredox Catalysis

“…[1] Of particular note,c atalytic asymmetric dearomatization (CADA) reactions of indoles and their derivatives allow easy access to enantioenriched fused indolines,aprivileged scaffold in alkaloid natural products and biologically active molecules. [2] There have been many elegant asymmetric dearomatization reactions of indoles,such as Friedel-Crafts-type alkylations, [3,4] oxidations, [5] and halogenations [6] in the presence of catalysts including enzymes,t ransition-metal complexes,a nd organocatalysts. Despite the great achievements made to date,m ost of these methods exploit the inherent nucleophilicity of indoles by reacting with electrophiles (Scheme 1a).…”