Synthesis of Carbonyl-Containing Oxindoles via Ni-Catalyzed Reductive Aryl-Acylation and Aryl-Esterification of Alkenes.

Carbonyl-containing oxindoles are ubiquitous core structures present in many biologically active natural products and pharmaceutical molecules. Nickel-catalyzed reductive aryl-acylation of alkenes using aryl anhydrides or alkanoyl chlorides as acyl sources is developed, providing 3,3-disubstituted oxindoles bearing ketone functionality at the 3-position. Moreover, nickel-catalyzed reductive aryl-esterification of alkenes using chloroformate as ester sources is further developed, affording 3,3-disubstituted oxindoles bearing ester functionality at the 3-position. This strategy has the advantages of good yields and high functional group compatibility.

Diastereo- and Enantioselective Construction of Spirocycles by Nickel-Catalyzed Cascade Borrowing Hydrogen Cyclization.

Spirocycles play an important role in drug discovery and development owing to their inherent three-dimensionality and structural novelty. Despite the recent significant progress, the straightforward catalytic asymmetric assembly of spirocyclic scaffolds with multiple stereocenters from readily available starting materials remains a formidable challenge. Herein, we develop an unprecedented nickel-catalyzed one-pot synthesis of enantioenriched spiroindanones from easily available 1,6-enynes and o-formylarylboronic acids. The reaction proceeds smoothly under redox-neutral conditions, without the need for an additional hydrogen donor, and features a broad substrate scope and excellent regio-, enantio-, and diastereoselectivity.

Synthesis of Indanones and Spiroindanones by Diastereoselective Annulation Based on a Hydrogen Autotransfer Strategy.

An unprecedented nickel-catalyzed domino reductive cyclization of alkynes and o-bromoaryl aldehydes is described. The reaction features broad substrate scope and is tolerant of a variety of functional groups, providing straightforward access to biologically significant indanones and spiroindanone pyrrolidine derivatives in good yields with excellent regio- and diastereoselectivity. Preliminary mechanistic studies have shown that indanones are formed by the cyclization of o-bromoaryl aldehydes and alkynes to form indenol intermediates, followed by hydrogen autotransfer.

Synthesis of bridged tricyclo[5.2.1.01,5]decanes via nickel-catalyzed asymmetric domino cyclization of enynones.

The restricted availability, expense and toxicity of precious metal catalysts such as rhodium and palladium challenge the sustainability of synthetic chemistry. As such, nickel catalysts have garnered increasing attention as replacements for enyne cyclization reactions. On the other hand, bridged tricyclo[5.2.1.01,5]decanes are found as core structures in many biologically active natural products; however, the synthesis of such frameworks with high functionalities from readily available precursors remains a significant challenge. Herein, we report a nickel-catalyzed asymmetric domino cyclization reaction of enynones, providing rapid and modular synthesis of bridged tricyclo[5.2.1.01,5]decane skeletons with three quaternary stereocenters in good yields and remarkable high levels of regio- and enantioselectivities (92-99% ee).

Ni-Catalyzed Enantioselective Reductive Diarylation of Activated Alkenes by Domino Cyclization/Cross-Coupling.

A Ni-catalyzed enantioselective reductive diarylation of activated alkenes by domino cyclizative/cross-coupling of two aryl bromides is developed. This reaction proceeds under very mild conditions and shows broad substrate scope, without requiring the use of preformed organometallic reagents. Moreover, this approach provides direct access to various bis-heterocycles bearing all-carbon quaternary centers in synthetically useful yields (up to 81%) with excellent enantioselectivity (>30 examples, 90-99% ee).