Origin of Stereoselectivity in Pd-Catalyzed Asymmetric Allylic Substitutions with Trost-Type Mixed Bidentate Phosphorus Ligands

• Published in: ACS catalysis 2024-07, Vol.14 (14), p.11113-11120
• Main Authors: Seo, Sanghyup, Shin, Taeil, Choi, Inkyu, Kim, Hyunwoo
• Format: Article
• Language: English
• ISSN: 2155-5435; 2155-5435
• DOI: 10.1021/acscatal.4c03726

In this study, we introduce a chiral, unsymmetrical bidentate phosphorus ligand, integrating features from bicyclic bridgehead phosphoramidite and Trost ligand structures, which forms a stable 1:1 complex with palladium without oligomerization, as confirmed by 31P­{1H} NMR spectroscopy and X-ray crystallography. This ligand exhibits exceptional performance in palladium-catalyzed allylic substitution reactions, achieving up to 99% yield and 99% ee. Our research includes an analysis of endo- and exo-allyl-Pd intermediates, identified by 31P­{1H} NMR spectroscopy, and investigates their distinct nucleophilic addition mechanisms. Steric map analysis of these intermediates reveals that the favored transition states involve minimal distortion in the allyl Pd species, leading to high enantioselectivity aligned with the energy profiles by DFT computation. This study not only offers a significant advance in ligand design but also enhances the understanding of mechanistic aspects of enantioselective palladium-catalyzed allylic substitution reactions.