Visible‐Light‐Promoted Alkylation of Indoles with Tertiary Amines by the Oxidation of a sp³ C‐H Bond

Abstract

A visible-light driven reaction for the synthesis of 3-arylmethyl indole derivatives using tertiary amines and indoles was first reported. Corresponding products were obtained with yields of up to 70%, and various functional groups on the indoles were well tolerated when Rose Bengal was used as a photosensitizer and air was used as a green oxidant under mild reaction conditions.

Beyond Friedel and Crafts: Directed Alkylation of C−H Bonds in Arenes

“…In addition to alkenes,a lkyl halides,a nd cross-dehydrogenative coupling reactions,s ome other alkylating reagents have also been exploited for the direct and selective alkylation of electron-rich heteroarenes:t hese include alcohols, [155][156][157][158] carboxylic acids, [159] peroxides, [160] pyridinium salts, [90] N,N-dialkylanilines, [161] and carboxylic xanthates. [97,98,162] Theuse of alcohols as alkylating agents has been elegantly exploited by Yi for the ruthenium-catalyzed direct alkylation of alkenes with ac ationic ruthenium hydride complex [(C 6 H 6 )(PCy 3 )(CO)RuH] + BF 4 À .…”

“…[90] N,N-Dialkylanilines,u sed in excess,c an also be used for the introduction of 4-aminobenzyl groups at the C3-position of indoles upon activation with Rose Bengal and visible light. [161] Finally,r adical alkylation reactions of electron-rich heteroarenes have been promoted using carboxylic xanthates as alkylating agents.I nt his vein, Miranda reported ac ombination of Et 3 Band FeSO 4 ·7 H 2 Otobeefficient for promoting the oxidative cleavage of various xanthates possessing an a-electron-withdrawing group,w ith the corresponding radicals subsequently adding to indoles and pyrroles used in excess (Scheme 59). [162a] Theh eteroarenes have to be substituted with electron-withdrawing groups to achieve acceptable yields.M ore recently,M iranda developed ap hotoinduced, iridium-catalyzed system to promote the same transformation on some indoles and pyrroles.…”

Beyond Friedel and Crafts: Innate Alkylation of C−H Bonds in Arenes

“…In addition to alkenes, alkyl halides, and cross‐dehydrogenative coupling reactions, some other alkylating reagents have also been exploited for the direct and selective alkylation of electron‐rich heteroarenes: these include alcohols, carboxylic acids, peroxides, pyridinium salts, N , N ‐dialkylanilines, and carboxylic xanthates …”

“…The reaction could also be successfully extended to the direct C2‐alkylation of C3‐substituted indoles, with the corresponding alkylated heterocycles being obtained in moderate yields (Scheme ) . N , N ‐Dialkylanilines, used in excess, can also be used for the introduction of 4‐aminobenzyl groups at the C3‐position of indoles upon activation with Rose Bengal and visible light …”

Jenseits von Friedel und Crafts: dirigierte Alkylierung von C‐H‐Bindungen in Arenen

“…Neben Alkenen, Alkylhalogeniden und dehydrierenden Kreuzkupplungen wurden einige weitere Alkylierungsreagenzien fürd ie direkte und selektive Alkylierung elektronenreicher Heteroarene ausgenutzt:h ierzu gehçren Alkohole, [155][156][157][158] Carbonsäuren, [159] Peroxide, [160] Pyridiniumsalze, [90] N,N-Dialkylaniline [161] und Xanthogenate. [97,98,162] Die Umsetzung von Alkoholen als Alkylierungsmittel wurde auf elegante Weise von Yi fürd ie rutheniumkatalysierte direkte Alkylierung von Alkenen mithilfe des kationischen Rutheniumhydridkomplexes [(C 6 H 6 )(PCy 3 )-(CO)RuH] + BF 4 À verwendet.…”