MnBr₂-Catalyzed Direct and Site-Selective Alkylation of Indoles and Benzo[h]quinoline

Abstract

Manganese-catalyzed regioselective C−H alkylation of indoles and benzo[h]quinoline with a variety of unactivated alkyl iodides is reported. Unlike other Mn-catalyzed C−H functionalization, this protocol does not require a Grignard reagent base and employs a simple and inexpensive MnBr 2 as a catalyst. This method tolerates diverse functionalities, including fluoro, chloro, bromo, iodo, alkenyl, alkynyl, pyrrolyl, and carbazolyl groups. The alkylation proceeds through a single-electron transfer pathway comprising reversible C−H manganesation and involving an alkyl radical intermediate.

Manganese‐Catalyzed C(sp2)−H Alkylation of Indolines and Arenes with Unactivated Alkyl Bromides

“…The attempted alkylation of 1 a was completely quenched in the presence of radical scavengers, TEMPO, galvinoxyl or BHT, wherein the compound 1 a was recovered in 95%, 84% and 92%, respectively (Scheme 4a). These findings highlighted the involvement of a radical species during the alkylation [11,16] . Furthermore, the exclusive rearranged/cyclized products 3 aC and 5 aC were obtained in the reaction of 6‐brormohex‐1‐ene with 1 a and 4 a , respectively (Scheme 4b).…”

“…These findings highlighted the involvement of a radical species during the alkylation. [11,16] Furthermore, the exclusive rearranged/cyclized products 3 aC and 5 aC were obtained in the reaction of 6-brormohex-1-ene with 1 a and 4 a, respectively (Scheme 4b). All this experimental evidence suggested the participation of an alkyl radical intermediate during the alkylation.…”

“…Reaction optimization . The demonstrated Mn‐catalyzed C‐2 alkylation of indoles with alkyl iodides proceeds through a favorable five‐membered metallacycle (Scheme 1b); [11] whereas the C‐7 alkylation of indoline ( 1 a ) would occur via a less favored six‐membered metallacycle intermediate (Scheme 1c). In searching for a more facile and straightforward Mn‐catalyst for the C‐7 alkylation of indoline, we initiated the reaction of 1 a with different 1‐octyl halides using 10 mol% of MnBr 2 at 120 °C (Table 1 and Table S1 in the SI).…”

“…Therefore, developing Mn‐catalyzed C−H functionalization methodologies with organic halides using a simple inorganic base is highly attractive. In that direction, recently, we demonstrated the C(2)−H alkylation of indoles with alkyl iodides using a user‐friendly LiHMDS, without the Grignard reagent (Scheme 1b) [11] …”

Rhodium(I)‐Catalyzed C2‐Selective Decarbonylative C−H Alkylation of Indoles with Alkyl Carboxylic Acids and Anhydrides

“…A variety of C2−H alkylation of indoles with alkenes catalyzed by Ni, Co, Ir, Rh, Ru and Fe complexes have been established by the groups of Hiyama, [4a] Yoshikai, [4b,h,i] Shibata, [4c,j] Hartwig, [4d,l] Glorius, [4e] Ackermann [4f,o,q,r] and others [4g,k,m,n,p,s–u] . Meanwhile, the groups of Bach, [5a,c,e] Ackermann, [5b,d,f] Punji [5g,i,j] and Shi [5h] have independently developed C2−H alkylation of indoles with alkyl halides using Pd, Ni, Co and Mn catalysts. Such a transformation has also been successfully implemented by using 2‐vinyloxiranes, [6a] alkyltrifluoroborates, [6b,h,i] diazo compounds, [6c,g] alkylarenes, [6d,j] cyclopropanols, [6e] carbonyl compounds, [6f] imines [6k] and acetonitrile derivatives [6l] .…”