Synergistic Mechanism Between Ir–Phosphinito Catalyst and HFIP Enables Asymmetric Hydrogenation of Ketones Under Acidic Conditions
A novel P*‐stereogenic phosphinito pincer iridium complex, in cooperation with hexafluoroisopropanol, enabled an unusually low‐energy pathway for hydrogen activation. Following the resolution of the racemic QuinSPO ligand (>99% ee) and its coordination to iridium, the resulting catalytic system demonstrated excellent performance and a broad scope in the asymmetric hydrogenation of ketones, achieving up to 96% ee and turnover numbers of 20 000. Remarkably, the reaction proceeded under mild acidic conditions without added base, enabling the reduction of substrates containing phenols and carboxylic acids, functionalities typically incompatible with conventional basic hydrogenation methodologies. Integrated experimental and DFT studies revealed that HFIP facilitates an alternative low‐energy hydrogen splitting mechanism responsible for the enhanced activity. Furthermore, noncovalent interaction analysis identified a critical π–π interaction in the transition state that governs enantioselectivity. These findings establish this system as a complementary strategy for the reduction of base‐sensitive substrates and introduce P*‐stereogenic phosphinito ligands as a powerful platform for asymmetric catalysis.
Authors
- Jordi Benet‐Buchholz (ORCID: https://orcid.org/0000-0003-3984-3550)
- María Vicent-Morales (ORCID: https://orcid.org/0000-0002-2198-2280)
- Giuseppe Sciortino (ORCID: https://orcid.org/0000-0001-9657-1788)
- Antoni Riéra (ORCID: https://orcid.org/0000-0001-7142-7675)
- Xavier Verdaguer (ORCID: https://orcid.org/0000-0002-9229-969X)
- Agustı́ Lledós (ORCID: https://orcid.org/0000-0001-7909-422X)
- Martí Sidro (ORCID: https://orcid.org/0000-0002-0817-2275)
Institutions
- Universitat Autònoma de Barcelona (ES)
- Institut Català d'Investigació Química (ES)
- Institute for Research in Biomedicine (ES)
- Instituto de Química Orgánica General (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Advanced Synthesis & Catalysis
- Published
- 2026-07-27
- DOI
- https://doi.org/10.1002/adsc.70666
- Primary Topic
- Asymmetric Hydrogenation and Catalysis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Institute for Research in Biomedicine
- Fundación Ramón Areces
- Ministerio de Ciencia, Innovación y Universidades
- Centres de Recerca de Catalunya
- Ministerio de Ciencia e Innovación
- Agencia Estatal de Investigación