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Preparation of visible-light-activated metal complexes and their use in photoredox/nickel dual catalysis

Nature Protocols volume 12, pages 472–492 (2017)Cite this article

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Abstract

Visible-light-activated photoredox catalysts provide synthetic chemists with the unprecedented capability to harness reactive radicals through discrete, single-electron transfer (SET) events. This protocol describes the synthesis of two transition metal complexes, [Ir{dF(CF3)2ppy}2(bpy)]PF6 (1a) and [Ru(bpy)3](PF6)2 (2a), that are activated by visible light. These photoredox catalysts are SET agents that can be used to facilitate transformations ranging from proton-coupled electron-transfer-mediated cyclizations to C–C bond constructions, dehalogenations, and H-atom abstractions. These photocatalysts have been used in the synthesis of medicinally relevant compounds for drug discovery, as well as the degradation of biological polymers to access fine chemicals. These catalysts are prepared from IrCl3 and RuCl3, respectively, in three chemical steps. These steps can be described as a series of two ligand modifications followed by an anion metathesis. Using the cost-effective, scalable procedures described here, the ruthenium-based photocatalyst 2a can be synthesized in a 78% overall yield (∼8.1 g), and the iridium-based photocatalyst 1a can be prepared in a 56% overall yield (∼4.4 g). The total time necessary for the complete protocols ranges from ∼2 d for 2a to 5–7 d for 1a. Procedures for applying each catalyst in representative photoredox/Ni cross-coupling to form Csp3–Csp2 bonds using the appropriate radical precursor—organotrifluoroborates with 1a and bis(catecholato)alkylsilicates with 2a—are described. In addition, more traditional photoredox-mediated transformations are included as diagnostic tests for catalytic activity.

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Figure 1
Figure 2: Redox reactions of photocatalysts.
Figure 3: Summary of representative Csp3–Csp2 bond formation processes via Ni, Cu, and Au photoredox cross-coupling dual catalysis.
Figure 4
Figure 5: Current progress made in photoredox dual catalytic cross-coupling reactions for the formation of Csp2–Csp2 and Csp2–Csp bonds.
Figure 6: Current progress made in photoredox dual catalysis cross-coupling reactions for the formation of Csp2–Y bonds.
Figure 7
Figure 8
Figure 9: Visual examples the two photocatalysts.

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Acknowledgements

The authors are grateful for the financial support provided by the National Institute of General Medical Sciences (R01 GM111465, R01-GM-113878), the National Science Foundation (CHE-1362841), Pfizer, and Eli Lilly. C.B.K. is grateful for a National Institutes of Health National Research Service Award postdoctoral fellowship (F32GM117634-01). J.C.T. is grateful for fellowship support from Bristol-Myers Squibb. In addition, the authors thank Sigma-Aldrich for the generous material donation of iridium(III) chloride and Johnson Matthey for the donations of iridium(III) chloride and ruthenium(III) chloride trihydrate.

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  1. Department of Chemistry, Roy and Diana Vagelos Laboratories, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Christopher B Kelly, Niki R Patel, David N Primer, Matthieu Jouffroy, John C Tellis & Gary A Molander

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  1. Christopher B Kelly
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Contributions

C.B.K. coordinated the project. C.B.K., N.R.P., D.N.P., M.J., and J.C.T. performed the reactions. C.B.K. and G.A.M. wrote the manuscript. N.R.P., D.N.P., M.J., J.C.T., and G.A.M. edited the manuscript.

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Correspondence to Gary A Molander.

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Kelly, C., Patel, N., Primer, D. et al. Preparation of visible-light-activated metal complexes and their use in photoredox/nickel dual catalysis. Nat Protoc 12, 472–492 (2017). https://doi.org/10.1038/nprot.2016.176

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