Ligand-Enabled Cu-Catalyzed Stereoselective Synthesis of P-Stereogenic ProTides.

Nucleoside analogues have seen significant advancements in treating viral infections and cancer through ProTide technology, leading to a series of FDA-approved drugs such as sofosbuvir, tenofovir alafenamide, and remdesivir. The stereochemical configuration at the phosphorus center of ProTides significantly influences their pharmacological properties, necessitating efficient stereoselective synthesis. Traditional methods using chiral auxiliaries or nonracemic phosphorylating agents are labor-intensive and inefficient, while recent organocatalytic approaches, despite their promise, still face limitations.

Synergistic -Heterocyclic Carbene/Palladium-Catalyzed [3 + 2] Annulation of Vinyl Enolates with 1-Tosyl-2-vinylaziridine.

The synergistic combination of -heterocyclic carbene organocatalysis and transition-metal catalysis for a formal [3 + 2] annulation between 3-substituted but-2-enoates and 1-tosyl-2-vinylaziridine was developed. This cooperative strategy provides a facile and efficient access to various functionalized ()-3-ethylidene-4-vinylpyrrolidin-2-ones in a regioselective and stereoselective manner. The preliminary asymmetric studies were also performed, which indicated a potential for enantioselective annulation of vinyl enolate intermediates with transition-metal-π-allyl species.

Redox-Neutral Borylation of Aryl Sulfonium Salts via C-S Activation Enabled by Light.

Reported here is a novel photoinduced strategy for the borylation of aryl sulfonium salts using bis(pinacolato)diboron as the boron source. This method exploits redox-neutral aryl sulfoniums to gain access to aryl radicals via C-S bond activation upon photoexcitation under transition-metal-free conditions. Therefore, it grants access to diverse arylboronate esters with good performance from easily available aryl sulfoniums accompanied by mild conditions, operational simplicity, and easy scalability.

Application of isatin-derived saturated esters in the synthesis of 3,3'-spirooxindole γ-butyrolactams.

Stable while reactive isatin-derived saturated esters have been utilized as 3-carbon synthons in a base-promoted formal [3 + 2] annulation with N-Boc imines. The developed protocol offers a direct pathway for the rapid and divergent construction of two classes of 3,3'-spirooxindole γ-butyrolactam skeletons that are recognized as the privileged structures of various bioactive compounds. This protocol also has the advantages of mild reaction conditions, scalability and wide reaction scope.

Asymmetric Synthesis of C2-Quaternary Indolin-3-ones Enabled by N-Heterocyclic Carbene Catalysis.

An N-heterocyclic carbene (NHC)-catalyzed formal [4 + 2] annulation of 2-aryl-3 H-indol-3-ones with α,β-unsaturated carboxylic acids bearing γ-H was developed via an in situ activation strategy. The reaction involves the γ-addition of vinyl enolates to the unique cyclic ketimines to afford chiral tricyclic indolin-3-ones with a quaternary carbon center at 2-position. This protocol provides a rapid and enantioselective pathway to access a novel class of structurally important C2-quaternary indolin-3-ones that might be useful for drug discovery.

N-Heterocyclic Carbene-Catalyzed Formal Conjugate Hydroacylation: An Atom-Economic Synthesis of 1 H-Indol-3-yl Esters.

An atom-economic synthesis of useful 1 H-indol-3-yl esters has been demonstrated by an N-heterocyclic carbene (NHC)-catalyzed formal conjugate hydroacylation of 2-phenyl-indol-3-ones with readily accessible aldehydes. This reaction involves a reductive hydride transfer process that was rarely investigated in the field of NHC catalysis. In this process, the hydrogen from the aldehydes was formally transferred to a heteroatom with NHC catalysis for the first time.