Stereoselective Kinugasa/Aldol Cyclization: Synthesis of Enantioenriched Spirocyclic ß-Lactams.

We report an enantioselective copper-catalyzed Kinugasa/aldol domino reaction. This strategy enables access to a range of spirocyclic ß-lactam pyrrolidinones in a stereoselective fashion. Under mild reaction conditions, prochiral alkyne-tethered ketones are coupled with nitrones to enable the facile construction of two spirofused ring systems containing three continuous stereocenters with excellent enantioselectivity. Also disclosed are post-transformation modifications demonstrating potential downstream functionalization of the spirocyclic molecules.

Pd-Catalyzed Domino Narasaka-Heck/C-H Activation/Amination Reactions: Synthesis of Bis-heterocyclic Spirocycles.

The palladium-catalyzed synthesis of bis-heterocyclic spirocycles containing both pyrroline and indoline motifs is reported. Di-tert-butyldiaziridinone is used to functionalize palladacycles generated in situ via domino Narasaka-Heck/C-H activation reactions. The reaction is readily scalable, and the spirocyclic products can undergo deprotection, reduction, and (3 + 2) cycloadditions, highlighting their synthetic utility. Additionally, kinetic isotope effect experiments support a turnover-limiting C-H functionalization step in the catalytic cycle.

Asymmetric Gold(I)-Catalyzed Prins-Type Cyclization for the Construction of Tricyclic Scaffolds.

Gold-catalyzed Prins-type cyclizations are interesting strategies for synthesizing complex molecules with excellent diastereoselectivity. We developed a novel and efficient system for such processes (13 examples, ≤89% yield) and reported the first enantioselective version of a gold-catalyzed Prins-type cyclization using a new chiral TADDOL-based Au(I) phosphonite complex. After crystallization, highly enantiomerically enriched products were obtained with >99% ee.

Gold-Catalyzed Domino Cycloisomerization/Alkoxylation: An Entry to 3,4-Dihydro-1H-[1,4]oxazino[4,3-a]indole.

A novel and mild synthetic route for the preparation of functionalized polycyclic indole skeletons via a gold-mediated cycloisomerization/alkoxylation of 1,6-aldehyde-yne has been developed. This atom-economical catalytic process that associates IPrAu(MeCN)BF4 and an alcohol demonstrated remarkable selectivity in accessing functionalized 3,4-dihydro-1H-[1,4]oxazino[4,3-a]indole derivatives of high synthetic utility (21 examples, yields of ≤96%) and could be optimized under asymmetric conditions with an enantiomeric excess of ≤86%.

Catalytic Gold Chemistry: From Simple Salts to Complexes for Regioselective C-H Bond Functionalization.

Gold coordinated to neutral phosphines (R3 P), N-heterocyclic carbenes (NHCs) or anionic ligands is catalytically active in functionalizing various C-H bonds with high selectivity. The sterics/electronic nature of the studied C-H bond, oxidation state of gold and stereoelectronic capacity of the coordinated auxiliary ligand are some of the associated selectivity factors in gold-catalyzed C-H bond functionalization reactions. Hence, in this review a comprehensive update about the action of different types of gold catalysts, from simple to sophisticated ones, on C-H bond reactions and their regiochemical outcome is disclosed. This review also highlights the catalytic applications of Au(I)- and Au(III)-species in creating new opportunities for the regio- and site-selective activation of challenging C-H bonds. Finally, it also intends to stress the potential applications in selective C-H bond activation associated with a variety of heterocycles recently described in the literature.