Recent Advances in Visible-Light-Mediated Minisci Reactions

Abstract

N-Heteroarenes are present in a wide variety of natural products, small-molecule drugs, organic materials, and ligands. Therefore, the methods for selective C-H functionalization of N-heteroarenes are highly sought-after for late-stage modification of pharmaceuticals. A useful tool for the synthesis of alkyl-substituted nitrogen-containing aromatic rings is the Minisci reaction, in which a protonated N-heteroarene is attacked by an alkyl radical under oxidative and acidic conditions. Classic Minisci reactions often require the use of excess oxidant, excess acid, and high temperature, which greatly limits the scope of the substrates. With the rapid development of photocatalysis in organic synthesis, in recent years, a variety of photocatalytic Minisci reactions have been reported, and successfully been applied to the synthesis of drugs. In this paper, the visible light mediated Minisci reactions in recent years are briefly reviewed.

Catalyst-free photoinduced radical sulfonylation/cyclization of unactivated alkenes toward sulfone-containing quinazolinones

“…Given that nitrogen-containing heterocycles such as pyridine, quinoline, quinoxaline, quinoxalin-2one, quinazolinone, etc. could serve as general radical acceptors in the Minisci reaction, [46][47][48][49][50][51][52][53] we envisioned incorporating an unactivated CvC double bond into such a type of N-heterocyclic substrate and capturing the highly reactive alkyl radical species B via an intramolecular Minisci reaction as our solution to the above problem (Fig. 1d).…”

Visible‐Light‐Induced Cross‐Dehydrogenative Coupling of Heteroarenes with Aliphatic Alcohols Mediated by Iodobenzene Dichloride

“…[3] Some recent works successfully combined photochemistry to achieve Minisci couplings under mild conditions. [4] Compared with traditional methods to generate alkyl radicals by the cleavage of activated carbon-heteroatom bonds, it is more desirable to produce alkyl radicals through the selective hydrogen atom abstraction (HAT). [5] In 2015, the MacMillan group introduced a visible light-mediated Minisci reaction catalyzed with iridium photocatalyst at room temperature.…”

Photoredox-catalyzed direct C–H monofluoromethylation of heteroarenes

“…In recent years, diverse synthetic protocols and reagents have been developed for the synthesis of monofluoromethylated arenes and alkanes via radical cross-coupling 10 and alkene-difunctionalization reactions. 11 In particular, the synthetic methods for the radical C–H monofluoromethylation of heterocycles and their use for late-stage C–H functionalization 12 of drugs and drug-like compounds through a Minisci-like 13 process remain limited. 8–11…”