Photoredox Iridium Catalyst for Single Electron Transfer (SET) Cross-Coupling

Introduction

C(sp²)- and C(sp)-hybridized coupling reactions are established catalytic approaches. However, multi-step C(sp³)- and C(sp²)-coupling reactions of boronic acids and related derivatives are still limited by ineffective two-electron transmetalation reactions. These conventional protocols exhibit reactivity profiles related to heterocyclic C-B bond strengths, thereby greatly impeding progress toward efficient cross-coupling of C(sp³)-hybridized alkylboron nucleophiles.

Recently, a series of efficient, single-election transmetalation methods have been optimized for alkyl cross-coupling using a dual-catalyst system of nickel (244988) and iridium (804215) catalysts, whereby a potassium organotrifluoroborate is activated for cross-coupling via oxidative fragmentation to an alkyl radical. This mechanistic paradigm allows reactivity to be dictated by homolytic bond strengths, opening a new realm of possibilities in alkylboron cross-coupling. In collaboration with the Gary Molander group, we now offer a novel catalyst for high-yielding SET reactions.

Advantages

• Previously unrealistic C(sp³)-coupling reactions are now an efficient reality
• Reaction is performed at room temperature
• Possibilities for asymmetric coupling
• Reductive elimination using a chiral nickel catalyst allows stereoconvergent synthesis from racemic organotrifluoroborate substrates

Special thanks to Mr. John Tellis and Prof. Gary Molander for contributing this technology spotlight.

1. Tellis JC, Primer DN, Molander GA. 2014. Single-electron transmetalation in organoboron cross-coupling by photoredox/nickel dual catalysis. Science. 345(6195):433-436. https://doi.org/10.1126/science.1253647

2. Primer DN, Karakaya I, Tellis JC, Molander GA. 2015. Single-Electron Transmetalation: An Enabling Technology for Secondary Alkylboron Cross-Coupling. J. Am. Chem. Soc.. 137(6):2195-2198. https://doi.org/10.1021/ja512946e

3. Gutierrez O, Tellis JC, Primer DN, Molander GA, Kozlowski MC. 2015. Nickel-Catalyzed Cross-Coupling of Photoredox-Generated Radicals: Uncovering a General Manifold for Stereoconvergence in Nickel-Catalyzed Cross-Couplings. J. Am. Chem. Soc.. 137(15):4896-4899. https://doi.org/10.1021/ja513079r

4. Karakaya I, Primer DN, Molander GA. 2015. Photoredox Cross-Coupling: Ir/Ni Dual Catalysis for the Synthesis of Benzylic Ethers. Org. Lett.. 17(13):3294-3297. https://doi.org/10.1021/acs.orglett.5b01463