Advances in the Iron-Catalyzed Direct Functionalizations of ­Heterocycles

Abstract

Direct functionalization of heterocycles is an advanced strategy for diversifying privileged and biorelevent heterocycle-containing molecules. Particularly, the most abundant transition metal, iron, as a catalyst makes this process highly cost-effective and sustainable. Recently, some progress has been realized towards the direct functionalization of heterocycles under iron catalysis. Herein, we present the developments in the C–H bond functionalizations and related reactions of various heterocycles by abundant iron salts. This Synpacts is categorized into different sections based on heterocycles being functionalized, and each section is discussed based on the type of reaction catalyzed by iron.

Advancement in the C–H bond alkylation of (hetero)arenes catalyzed by the most abundant transition metal–iron

“…[90][91][92][93][94][95] Particularly, the transition metal-catalyzed direct C-H functionalization, leading to diverse C-C and C-N bond-forming processes, is substantially explored. [96][97][98][99][100] Notably, installing an alkyl or methyl unit to indole and its derivatives represents a strategic development that enhances the lipophilicity of molecules. This modification is essential in drug development as the alkylated indole derivatives exhibit improved pharmacokinetic properties.…”

Iron-catalyzed selective construction of indole derivatives via oxidative C(sp3)–H functionalization of indolin-2-ones

“…For constructing carbon-carbon and carbon-heteroatom bonds in modern organic synthesis, iron, as the most abundant transition metal in the Earth's crust, has found extensive application as an ecofriendly and readily available catalyst. [1][2][3][4][5][6][7][8][9][10][11] Inspired by iron-containing enzyme catalysis, 12,13 the iron-catalyzed C(sp 3 )-H bond oxidation, coupled with the utilization of molecular oxygen, has emerged as a highly promising reaction over the past decade. [14][15][16][17][18][19][20][21][22][23][24] In 2015, Li's group pioneered the utilization of cross-dehydrogenative coupling (CDC) to develop an iron saltcatalyzed cross-dehydrogenative arylation between 3-substituted indolin-2-ones generating a series of 3,3′-disubstituted oxindole compounds.…”

Iron-catalyzed regioselective C–H alkylation of indoles: an additive-free approach in renewable solvent

“…7 Yoshikai and Shi independently showed Co-catalyzed hydroindolation to obtain C-2 alkylation. 8 In an important development on the most abundant transition metal, iron, 9 Yoshikai showed Fe( iii )-catalyzed alkylation of indoles via strong imine-chelation-assistance leading to a branch-selective product (Scheme 1a). 10 Unfortunately, this method needed an excess amount of Grignard reagent and TMEDA as additives, thus generating a large amount of waste.…”