Photodriven Samarium-Catalyzed Asymmetric Ketyl-Olefin Coupling
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Research Background
Samarium(II) iodide (SmI₂) is an important single-electron reductant in organic synthesis. Traditionally used in (super)stoichiometric amounts, its catalytic applications have been achieved in recent years. However, asymmetric reductive cross-couplings involving catalytic SmI₂ remain undeveloped. Existing enantioselective cross-couplings mediated by SmI₂ still require stoichiometric chiral ligands, and the high ligand loadings limit scalability. Developing a protocol where both samarium and the chiral ligand are used in catalytic quantities is therefore crucial. Recently, the research teams of Prof. Jonas C. Peters and Prof. Sarah E. Reisman at the California Institute of Technology developed a photodriven SmI₂-catalyzed asymmetric ketyl-olefin coupling. This represents the first example of such an asymmetric reaction using catalytic SmI₂, employing readily available PyBOX as the chiral ligand and an iridium photocatalyst as a cocatalyst. The reaction exhibits a broad substrate scope, tolerating various aryl ketones, heteroaryl ketones, and olefins with different electron-withdrawing groups. It can also be extended to intramolecular cyclizations. Mechanistic studies combining spectroscopy, electrochemistry, and DFT calculations confirmed that a samarium-stabilized PyBOX ketyl radical is the active species initiating the reductive coupling. The reaction proceeds via a synergistic interplay between an iridium photoredox cycle and a samarium-ligand complex catalytic cycle, providing a new direction for the development of SmI₂-catalyzed reductive cross-couplings.
Condition Screening
Substrate Scope
Proposed Reaction Mechanism
Highlights of the Chiral Bisoxazoline Ligand and Iridium Photocatalyst Used in This Reaction:
- Excellent Ligand Adaptability and Effective Stereocontrol The selected PyBOX ligand is a readily available chiral pyridine bisoxazoline ligand. The optimized ligand forms a 1:1 catalytic complex with Sm, enabling efficient stereochemical control of the reaction.
- Enhanced Economic Efficiency, Breaking Traditional Limitations The PyBOX ligand participates in the reaction in only catalytic amounts, overcoming the limitation of traditional SmI₂-mediated asymmetric reactions which require stoichiometric quantities of both the chiral ligand and SmI₂. This significantly reduces ligand cost and recycling difficulty, markedly improving the potential for scalable application.
- Iridium Photocatalyst Drives Efficient Catalytic Cycle Under Mild Conditions The commercial iridium photocatalyst [Ir(ppy)₂(dtbbpy)]PF₆ requires only a 2 mol% loading. Driven by 456 nm visible light, it enables a photoredox cycle that efficiently accomplishes the reductive regeneration of Sm(III) to Sm(II), eliminating the need for harsh stoichiometric reductants or extreme conditions. Efficient reactions proceed at -15 °C, and the light-driven mode offers enhanced controllability.
- Strong Synergy in Dual Catalytic System and Broad Substrate Compatibility The samarium-stabilized ketyl radical active species, formed from PyBOX and Sm, synergizes efficiently with the iridium photoredox cycle. This system not only achieves intermolecular coupling of ketones with acrylates but also tolerates functional groups like aryl halides and boronates, as well as heteroaryl ketones and olefins with various electron-withdrawing groups. It can also be extended to intramolecular cyclization reactions, significantly broadening the substrate scope.
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Publication Details
Authors: Li-Ming Chen, Drew E. Tarnopol, Sarah E. Reisman,* and Jonas C. Peters*
Title: Photodriven Sm-Catalyzed Asymmetric Ketyl-Olefin Coupling
Journal: Journal of the American Chemical Society (JACS)
DOI: 10.1021/jacs.5c20884