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. 2022 Aug 8;61(32):e202205562.
doi: 10.1002/anie.202205562. Epub 2022 Jun 10.

Photo-Induced Ruthenium-Catalyzed Double Remote C(sp2 )-H / C(sp3 )-H Functionalizations by Radical Relay

Yulei Wang  1 , Shan Chen  1 , Xinran Chen  1   2 , Agnese Zangarelli  1 , Lutz Ackermann  1
Affiliations

Photo-Induced Ruthenium-Catalyzed Double Remote C(sp2 )-H / C(sp3 )-H Functionalizations by Radical Relay

Yulei Wang et al. Angew Chem Int Ed Engl. .

Abstract

Distal C(sp2 )-H and C(sp3 )-H functionalizations have recently emerged as step-economical tools for molecular synthesis. However, while the C(sp2 )-C(sp3 ) construction is of fundamental importance, its formation through double remote C(sp2 )-H/C(sp3 )-H activation has proven elusive. By merging the ruthenium-catalyzed meta-C(sp2 )-H functionalization with an aliphatic hydrogen atom transfer (HAT) process, we, herein, describe the catalyzed twofold remote C(sp2 )-H/C(sp3 )-H functionalizations via photo-induced ruthenium-mediated radical relay. Thus, meta-C(sp2 )-H arene bonds and remote C(sp3 )-H alkane bonds were activated by a single catalyst in a single operation. This process was accomplished at room temperature by visible light-notably without exogenous photocatalysts. Experimental and computational theory studies uncovered a manifold comprising ortho-C-H activation, single-electron-transfer (SET), 1,n-HAT (n=5-7) and σ-activation by means of a single ruthenium(II) catalyst.

Keywords: C−H Activation; Hydrogen Atom Transfer; Photocatalysis; Ruthenium; meta-Functionalization.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Design of transition‐metal‐catalyzed double remote C(sp2)−H/C(sp3)−H functionalizations via radical relay.
Scheme 2
Scheme 2
Ruthenium‐catalyzed double remote C(sp2)−H/C(sp3)−H functionalization. Reaction conditions: Arene (0.5 mmol), alcohol derivative (1.0 mmol), [RuCl2(p‐cymene)]2 (0.025 mmol), (PhO)2PO2H (0.15 mmol), K2CO3 (1.0 mmol), 1,4‐dioxane (2.0 mL), blue light, RT, N2, 24–48 h. [a] Work‐up with TBAF (1.0 M in THF, 4.0 mL), see Supporting Information. [b] Arene (0.5 mmol), alcohol derivative (1.0 mmol), Ru(OAc)2(p‐cymene)2 (0.05 mmol), K2CO3 (1.0 mmol), 1,4‐dioxane (2.0 mL), 90 °C, N2, 24 h. [c] Mixture.
Scheme 3
Scheme 3
Gram‐scale synthesis and late‐stage derivatization.
Scheme 4
Scheme 4
Summary of key mechanistic findings.
Figure 1
Figure 1
Computed free energy surface. Computational methods: PBE0‐D3(BJ)/6–311+G(d,p)‐SDD‐SMD(1,4‐Dioxane)//B3LYP‐D3(BJ)/6‐31G(d)‐LANL2DZ.
Figure 2
Figure 2
Proposed catalytic cycle.
See this image and copyright information in PMC

References

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