Recent Advances in the Catalytic Functionalization of “Electrophilic” Indoles

Abstract

When “dark” is bright: the scarcely explored electrophilic profile of the indolyl core (dark‐side) continues to inspire developments in organic synthesis by means of new catalytic methodologies. Recent advancements in the field enabled molecular diversity and complexity to be effectively realized within heterocyclic chemistry.

Reductive dearomative arylcarboxylation of indoles with CO2 via visible-light photoredox catalysis

“…The substrates with electron-donating groups or electron-withdrawing groups at the C5-position were all suitable for such a reaction to deliver the desired products in moderate to good yields. Many kinds of functional groups, such as methoxyl (14), fluoro (15), chloro (16), bromo (17), and ester group (18), were all tolerated well. The substrates bearing fluoro (19) and methoxyl (20) group at C6position also worked well.…”

“…Dearomatization of (hetero)arenes is an efficient and powerful method to provide 3D cyclic skeletons, which exist widely in pharmaceuticals and bioactive natural products [12][13][14][15][16] . Dearomative functionalization of indoles are particularly interesting to generate important indolines 15,16 .…”

“…Dearomatization of (hetero)arenes is an efficient and powerful method to provide 3D cyclic skeletons, which exist widely in pharmaceuticals and bioactive natural products [12][13][14][15][16] . Dearomative functionalization of indoles are particularly interesting to generate important indolines 15,16 . Although many methods have been developed in this field [17][18][19][20][21][22][23][24][25] , the dearomative reductive coupling of indoles with two electrophiles is still challenging due to the stability of carbon-carbon double bond within aromaticity and thus slow migratory insertion rate.…”

Dearomatization Reactions of Indoles to Access 3D Indoline Structures

“…10 Very interestingly in this reaction, the C3-position of N-Ac indole 6 could be formally considered as electrophilic. 9 This work was published in a journal 10a which is not widely accessed by the community of synthetic organic chemists and was unfortunately unnoticed despite its very high synthetic potential. Nevertheless, this method seemed well suited to access benzofuroindolines 11.…”

“…Rather than using the innate C3-nucleophilicity of indoles, our dearomatization strategies mainly relies on an umpolung process leading to the generation of electrophilic indolenium derivatives which can be further functionalized. 9…”