HKUST Team Led by Sun Jianwei and Zhang Chaoshen Reports JACS Study on PHOX Ligands
Created on 11.25
Introduction
Chiral phosphino-oxazoline (PHOX) ligands represent an important class of P,N-ligands. Their structure combines the strong coordination ability of phosphorus atoms with the rigid chiral framework of oxazoline rings: the phosphorus atom ensures catalytic activity by stabilizing transition metals, while the chiral center of the oxazoline precisely controls reaction selectivity. This design addresses the limitations of single-type ligands and balances reactivity with selectivity.
Innovative Methodology
Recently, a team led by Professor Sun Jianwei and Professor Zhang Chaoshen at the Hong Kong University of Science and Technology achieved the first copper-catalyzed enantioselective ring-opening of azetidiniums using ferrocene-derived chiral PHOX ligands. Starting from enone-tethered azetidinium substrates, the team efficiently constructed multifunctionalized tetrahydropyran and piperidine compounds bearing three contiguous stereocenters via a boronylation/cyclization cascade. The developed catalytic system is also applicable to intermolecular reactions between azomethine ylides and azetidiniums.
Condition Optimization
Advantages of PHOX Ligands
- High Stereocontrol: PHOX ligands are crucial for enantioselectivity, achieving up to 92% ee in intramolecular reactions and 99% ee in intermolecular reactions, with diastereoselectivity >20:1.
- Broad Compatibility: Effective in both intramolecular boronylation/cyclization and intermolecular bond-forming reactions, adaptable to various copper salts and substrates without ligand modification.
- Structure-Driven Synergy: The ferrocene backbone provides a stable chiral environment, bidentate coordination optimizes copper intermediates, and tert-butyl groups steer favored transition states.
- Versatile Product Utility: Intramolecular products can be converted to trifluoroborate salts or secondary alcohols; intermolecular ornithine derivatives are suitable for deprotection, hydrogenation, and reduction to amino alcohols, serving as key intermediates for chiral amines and natural product synthesis.
Reference
- Authors: Minghui Zhu, Chaoshen Zhang, Jianwei Sun
- Title: Copper-Catalyzed Enantioselective Intra- and Intermolecular Desymmetrization of Azetidiniums by Carbon Nucleophiles
- DOI: 10.1021/jacs.5c17131