Stereospecific nickel-catalyzed [4+2] heteroannulation of alkynes with aminophosphanes

Abstract

Enantioenriched phosphorus compounds play crucial roles in many fields ranging from catalyst to materials science to drug development. Despite advances in the construction of phosphacycles, incorporation of a P-chirogenic center into heterocycles remains challenging. Here, we report an effective method for the preparation of phosphacycles through nickel-catalyzed [4+2] heteroannulation of internal alkynes with aminophosphanes derived from o -haloanilines. Notably, chiral 2-λ5-phosphaquinolines can be prepared from P-stereogenic substrates via NH/PH tautomeric equilibrium without loss of stereochemical integrity. The strategy is found to exhibit a broad scope in terms of both reaction components, enabling modular construction of libraries of 2-λ5-phosphaquinolines with different steric and electronic properties for fine-tuning photophysical properties, where some of these compounds showed distinct fluorescence with high quantum yields. A series of mechanistic studies further shed light on the pathway of the heteroannulation and reasons for stereospecificity.

Azaphosphinines and their derivatives

“…98 Instead of the typical approach, which until this point has involved P V starting materials that are then incorporated into the final azaphosphinine, this publication used P III phosphanamines 126 . Much like the similar work from Shi and coworkers 62 published in 2023, the trivalent phosphorus starting materials are oxidized to the pentavalent state during the heteroannulation. However, unlike Shi and coworkers the reaction explored in this work did not involve any intermolecular condensations or additions to furnish the final azaphosphinines.…”

“…Very recently in 2023, Shi and coworkers reported similar transition-metal catalyzed [4+2] heteroannulation reactions on phosphanamines 48 and functionalized alkynes. 62 There are several important distinctions that separate this work from earlier publications. The design of the starting material is quite different, notably that the phosphorus atom of the phosphanamines is trivalent and is oxidized to pentavalence during the reaction.…”