Directed Evolution of a Ketone Synthase for Efficient and Highly Selective Functionalization of Internal Alkenes by Accessing Reactive Carbocation Intermediates

The direct regioselective oxidation of internal alkenes to ketones could simplify synthetic routes and solve a longstanding challenge in synthesis. This reaction is of particular importance because ketones are predominant moieties in valuable products as well as crucial intermediates in synthesis. Here we report the directed evolution of a ketone synthase that oxidizes internal alkenes directly to ketones with several thousand turnovers. The evolved ketone synthase benefits from more than a dozen crucial mutations, most of them distal to the active site. Computational analysis reveals that all these mutations collaborate to facilitate the formation of a highly reactive carbocation intermediate by generating a confined, rigid and preorganized active site through an enhanced dynamical network. The evolved ketone synthase fully exploits a catalytic cycle that has largely eluded small molecule catalysis and consequently enables various challenging functionalization reactions of internal alkenes. This includes the first catalytic, enantioselective oxidation of internal alkenes to ketones, as well as the formal asymmetric hydration and hydroamination of unactivated internal alkenes in combination with other biocatalysts.

Selective functionalization of benzylic C-H bonds of two different benzylic ethers by bowl-shaped N-hydroxyimide derivatives as efficient organoradical catalysts

A highly efficient, site-selective benzylic C-H bond amination of two different benzylic ether substrates was described by using bowl-shaped N-hydroxyimide organoradical catalysts with diethyl azodicarboxylate. The synthetic utility of this...

A C-to-O atom-swapping reaction sequence enabled by Ni-catalyzed decarbonylation of lactones

Advances in site-selective functionalization reactions have enabled single atom changes on the periphery of a complex molecule, but reaction manifolds that enable such changes on the core framework of the...

Metal-Free Allylic C-H Nitrogenation, Oxygenation, and Carbonation of Alkenes by Thianthrenation

Selective functionalization of allylic C-H bonds into other chemical bonds are among the most straightforward and attractive, yet challenging transformations. Herein, a transition-metal-free protocol for direct allylic C-H nitrogenation, oxygenation,...

A General Strategy for the Synthesis of Rare Sugars via Ru(II)-catalyzed and Boron-mediated Selective Epimerization of 1,2-trans-diols to 1,2-cis-diols

Human glycans are primarily composed of nine common sugar building blocks. On the other hand, several hundred monosaccharides have been discovered in bacteria and most of them are not readily available. The ability to access these rare sugars and the corresponding glycocon-jugates can facilitate the studies of various fundamentally important biological processes in bacteria, including interactions between microbiota and the human host. Many rare sugars also exist in a variety of natural products and pharmaceutical reagents with significant biological activi-ties. Although methods have been developed for the synthesis of rare monosaccharides, most of them involve lengthy steps. Herein we report an efficient and general strategy that can provide access to rare sugars from commercially available common monosaccharides via a one-step Ru(II)-catalyzed and boron-mediated selective epimerization of 1,2-trans-diols to 1,2-cis-diols. The formation of boronate esters drives the equilibrium towards 1,2-cis-diol products, which can be immediately used for further selective functionalization and glycosylation. The utility of this strategy was demonstrated by the efficient construction of glycoside skeletons in natural products or bioactive compounds.