Trapping σ‐Alkyl–Palladium(II) Intermediates with Arynes Encompassing Intramolecular C−H Activation: Spirobiaryls through Pd‐Catalyzed Cascade Reactions

Abstract

Ap alladium-catalyzed cascade reaction based on the trapping of transient alkyl-Pd II intermediates with arynes encompassing aC ÀHactivation step has been developed. This synthetic pathwayg ives rise to hetero-spirocyclic scaffolds containing abiaryl motif,and opens up new synthetic strategies in the design of cascade reactions since it gathers several aspects of Pd chemistry,i .e., intra-and intermolecular carbopalladation of unsaturated species,C ÀHa ctivation and CÀCcoupling processes. Scheme 2. Optimized conditionsfor the cascade reaction. Scheme 3. Scope of the cascade reaction.Scheme 4. Scope of the cascade reaction with different arynes.

Palladium‐Catalyzed Spirocyclization through C−H Activation and Regioselective Alkyne Insertion

“…Recently,o ur group and the García-López group have employed C À Hf unctionalization in ad omino process to generate spirocycles through carbopalladation, C À Ha ctivation, and migratory insertion or direct reductive elimination. [11][12][13][14] Unfortunately,diastereo-and regioselective migratory insertion into the palladacycle involving highly reactive intermediates has proven to be challenging. In 2014, Garg and Houk [15] experimentally and computationally reported that unsymmetrical and electronically biased arynes show excellent regioselective addition reactions,w hereas in our study, [12,13] these arynes undergo the migratory insertion with poor regiocontrol (Scheme 1A).…”

“…[11][12][13][14] Unfortunately,diastereo-and regioselective migratory insertion into the palladacycle involving highly reactive intermediates has proven to be challenging. In 2014, Garg and Houk [15] experimentally and computationally reported that unsymmetrical and electronically biased arynes show excellent regioselective addition reactions,w hereas in our study, [12,13] these arynes undergo the migratory insertion with poor regiocontrol (Scheme 1A). Following this work, the García-López group reported spirocyclization involving a-diazocarbonyl compounds,albeit in modest diastereoselectivity (Scheme 1B).…”