Metal Iridium Photocatalyst in Photodriven SmI2-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. Although catalytic applications have been achieved in recent years, catalytic asymmetric reductive cross-coupling reactions involving SmI2 have not yet been developed. Existing SmI2-mediated enantioselective cross-couplings still require stoichiometric amounts of chiral ligands. The high ligand loading limits their scalability. Developing protocols where both samarium and the chiral ligand are used in catalytic quantities has become a key research goal. Recently, the research teams of Jonas C. Peters and Sarah E. Reisman at the California Institute of Technology have developed a photodriven, SmI2-catalyzed asymmetric ketyl-olefin coupling reaction. This is the first reported example of an asymmetric reaction of this type involving catalytic amounts of SmI2. The reaction employs readily available PyBOX as the chiral ligand and an iridium photocatalyst as a cocatalyst. The reaction exhibits good substrate scope, tolerating various aryl ketones, heteroaryl ketones, and olefins bearing different electron-withdrawing groups. The reaction can also be extended to intramolecular cyclizations. Mechanistic studies combining spectroscopy, electrochemistry, and DFT calculations confirm that the samarium-stabilized PyBOX radical is the active species that initiates the reductive coupling. The reaction is completed through a synergistic cycle involving an iridium photoredox catalytic cycle and a samarium-ligand complex catalytic cycle. This work provides a new direction for the development of SmI2-catalyzed reductive cross-coupling reactions.
Condition Screening
*Determined by ¹H NMR using 1,3,5-trimethoxybenzene as an internal standard. *Determined by SFC using a chiral stationary phase. *(R)-3 was obtained in 69% yield and 80% ee. *(R)-3 was obtained in 3% yield. *Racemic 3 was formed in 34% yield.
Substrate Scope
Proposed Reaction Mechanism
Highlights of the Chiral Bis(oxazoline) Ligand and Iridium Photocatalyst Used in This Reaction
- Excellent Ligand Compatibility and Effective Stereocontrol: The selected PyBOX ligand is a readily available chiral pyridine bis(oxazoline) ligand. The optimized 1:1 catalyst-ligand complex formed with Sm efficiently achieves stereochemical control of the reaction.
- Enhanced Economic Feasibility, Breaking Traditional Limitations: The PyBOX ligand participates in the reaction in only catalytic amounts, breaking through the limitations of traditional SmI2-mediated asymmetric reactions, which require stoichiometric amounts of both the chiral ligand and SmI2. This significantly reduces ligand costs and recovery difficulties, markedly enhancing the potential for large-scale application of the reaction.
- Iridium Photocatalyst Drives Efficient Catalytic Cycle under Mild Conditions: The commercial iridium photocatalyst [Ir(ppy)2(dtbbpy)]PF6 is used at a low loading of only 2 mol%. Driven by 456 nm visible light, it enables the photoredox cycle, efficiently regenerating Sm(II) from Sm(III). This eliminates the need for harsh stoichiometric reductants or extreme reaction conditions. The reaction proceeds efficiently at -15°C, and the light-driven mode offers greater controllability.
- Strong Synergy in the Dual Catalytic System and Broad Substrate Compatibility: The samarium-stabilized radical active species formed by PyBOX and Sm works in efficient synergy with the iridium photoredox cycle. This system not only enables the intermolecular coupling of ketones and acrylates but also tolerates functional groups such as aryl halides and boronates, as well as heteroaryl ketones and olefins with different electron-withdrawing groups. The reaction can also be extended to intramolecular cyclization, 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
DOI: 10.1021/jacs.5c20884