Design principles for site-selective hydroxylation by a Rieske oxygenase

Rieske oxygenases exploit the reactivity of iron to perform chemically challenging C–H bond functionalization reactions. Thus far, only a handful of Rieske oxygenases have been structurally characterized and remarkably little information exists regarding how these enzymes use a common architecture and set of metallocenters to facilitate a diverse range of reactions. Herein, we detail how two Rieske oxygenases SxtT and GxtA use different protein regions to influence the site-selectivity of their catalyzed monohydroxylation reactions. We present high resolution crystal structures of SxtT and GxtA with the native β-saxitoxinol and saxitoxin substrates bound in addition to a Xenon-pressurized structure of GxtA that reveals the location of a substrate access tunnel to the active site. Ultimately, this structural information allowed for the identification of six residues distributed between three regions of SxtT that together control the selectivity of the C–H hydroxylation event. Substitution of these residues produces a SxtT variant that is fully adapted to exhibit the non-native site-selectivity and substrate scope of GxtA. Importantly, we also found that these selectivity regions are conserved in other structurally characterized Rieske oxygenases, providing a framework for predictively repurposing and manipulating Rieske oxygenases as biocatalysts.

Enantioselective C–H Functionalization toward Silicon-Stereogenic Silanes

In recent years, transition-metal-catalyzed enantioselective C–H bond functionalization has emerged as a powerful and attractive synthetic approach to access silicon-stereogenic centers, which continues to give impetus for the innovation of chiral organosilicon chemistry. This short review is aimed to summarize recent advances in the construction of silicon-stereogenic silanes via transition-metal-catalyzed enantioselective C–H functionalization. We have endeavored to highlight the great potential of this methodology and hope that this review will shed light on new perspectives, inspire further research in this emerging area.

The Application of C-H bond Functionalization in Total Syntheses of Indole Natural Products

The direct functionalization of unactivated C–H bonds is a rapidly growing field in organic chemistry in recent years because of its indisputable advantages in bond forming reactions in terms of...

Unorthodox cascade reaction of arynes and N-nitrosamides leading to indazole scaffolds

An unusual cascade annulation of arynes with N-alkyl-N-nitrosamides is developed by leveraging aryne σ-insertion and C(sp3)–H bond functionalization strategies under transition-metal-free conditions at ambient temperature, offering functionalized indazoles in high...

Solvent-Controlled Regioselective Arylation of Indoles and Mechanistic Explorations

The ability to manipulate the site selectivity in C–H bond functionalization reactions is an important goal in modern chemistry. Herein, we report a new reaction strategy for the regioselective arylation...