Catalytic prenylation and reverse prenylation of aromatics

Prenylation and reverse prenylation are omnipresent in nearly all living organisms. In nature, these fundamental reactions rely on enzyme catalysis with dimethylallyl pyrophosphate (DMAPP) as the donor. Emulating biological process with chemical catalysis provides new opportunities to achieve prenylation and reverse prenylation of aromatics. The strategies include the Friedel–Crafts reaction, cross-coupling, C–H activation, the Tsuji–Trost reaction, addition reactions, and radical coupling. Because of the steric hindrance, prenylation is achieved in most cases, whereas reverse prenylation can be attained via Suzuki cross-coupling and the Tsuji–Trost reaction. From the viewpoint of step and atom economy, basic feedstock isoprene is an ideal donor for the incorporation of prenyl and reverse-prenyl groups. The regioselectivity can be diverted through modulation of the transition metals and ligands. Prenylated and reverse-prenylated aromatics are present in numerous natural terpenoids with a broad spectrum of pharmaceutical activity. In their biosynthesis, prenyl and reverse-prenyl motifs are selectively introduced via enzyme catalysis with dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP) as the precursors. In recent years, considerable efforts have been devoted to emulating the biological process with chemical catalysis via the intermediacy of π-prenyl species. A set of elegant strategies including the Friedel–Crafts reaction, cross-coupling, C–H activation, Tsuji–Trost-like reactions, addition reactions, and radical coupling have been demonstrated. This review aims to highlight these advances and discuss the regioselectivity issues, which will definitely further expand their applications and promote the development of this field. Prenylated and reverse-prenylated aromatics are present in numerous natural terpenoids with a broad spectrum of pharmaceutical activity. In their biosynthesis, prenyl and reverse-prenyl motifs are selectively introduced via enzyme catalysis with dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP) as the precursors. In recent years, considerable efforts have been devoted to emulating the biological process with chemical catalysis via the intermediacy of π-prenyl species. A set of elegant strategies including the Friedel–Crafts reaction, cross-coupling, C–H activation, Tsuji–Trost-like reactions, addition reactions, and radical coupling have been demonstrated. This review aims to highlight these advances and discuss the regioselectivity issues, which will definitely further expand their applications and promote the development of this field. the oxygen atom at the β-carbon position of the metal transfers to the metal via a four-membered transition state, producing an alkene and a metal-oxygen species. a metal/base-promoted C–H bond cleavage that proceeds through a simultaneous deprotonation and metalation process. excited PCs (*PCn) can be quenched by either a reductant (reductive quenching cycle) or an oxidant (oxidative quenching cycle) via single electron transfer to produce a reduced (PCn-1) or oxidized (PCn+1) PC. the synthesis of different regioisomers from the same starting materials just by varying the catalyst. with light irradiation, an electron is transferred from the t2g orbital (metal) to the π* orbital (ligand), which results in a triplet excited state. the allylic metal coordinates to the oxygen/nitrogen atom of the carbonyl/imine via a six-membered chair-type state, thereby guiding the attack of alkene to the carbonyl/imine carbon with good stereoselectivity.