Ruthenium-Catalyzed Dehydrogenation Through an Intermolecular Hydrogen Atom Transfer Mechanism

Abstract

The direct dehydrogenation of alkanes is among the most efficient ways to access valuable alkene products. Although several catalysts have been designed to promote this transformation, they have unfortunately found limited applications in fine chemical synthesis. Here, we report a conceptually novel strategy for the catalytic, intermolecular dehydrogenation of alkanes using a ruthenium catalyst. The combination of a redox-active ligand and a sterically hindered aryl radical intermediate has unleashed this novel strategy. Importantly, mechanistic investigations have been performed to provide a conceptual framework for the further development of this new catalytic dehydrogenation system.

Keywords: alkenes; aryl radicals; dehydrogenation; hydrogenation atom transfer; redox-active ligands.

Scheme 1

Previous works: a) Pincer‐ligated metal catalytic dehydrogenation, b) Intramolecular desaturation, c) Cooperative desaturation (cHAT), and d) Our hypothesis and design.

Scheme 2

Intermolecular dehydrogenation scope of alkanes, ethers and aliphatic amines. Reaction conditions: Ru₃(CO)₁₂ (3 mol %), L₄ (18 mol %), 1 (0.5 mmol), 2 n (2.5 mmol), Cs₂CO₃ (1 mmol), PhCl (1 mL), 150 °C, 24 h, ¹H‐NMR yields using CH₂Br₂ as the internal standard. [a] Ru₃(CO)₁₂ (6 mol %), L₄ (36 mol %), 2 n (10 mmol). [b] Ru₃(CO)₁₂ (5 mol %), L₄ (30 mol %). [c] Ru₃(CO)₁₂ (6 mol %), L₄ (36 mol %), 2 n (5 mmol). [d] Ru₃(CO)₁₂ (6 mol %), L₄ (36 mol %), 2 n (5 mmol), 1‐iodo‐2‐methylbenzene (1 b, 0.5 mmol).

Scheme 3

Intermolecular dehydrogenation scope of alkanes, ethers and aliphatic amines. Reaction conditions: Ru₃(CO)₁₂ (3 mol %), L₄ (18 mol %), 1 (0.6 mmol), 5 n (0.5 mmol), Cs₂CO₃ (1 mmol), PhCl (1 mL), 150 °C, 16 h, isolated yields. [a] Ru₃(CO)₁₂ (5 mol %), L₄ (30 mol %), 1 (1.1 mmol), 5 n (0.5 mmol). [b] PhCl (0.1 mL), 18 h.

Scheme 4

Intermolecular dehydrogenation scope of aryl alkanes. Reaction conditions: Ru₃(CO)₁₂ (3 mol %), dppp (10 mol %), L₁₃ (30 mol %), 1 (0.5 mmol), 8 n (7.5 mmol), Cs₂CO₃ (1 mmol), PhCl (1 mL), 150 °C, 24 h, ¹H‐NMR yields using CH₂Br₂ as the internal standard. [a] reaction conditions from Scheme 2. [b] 8 n (2.5 mmol).

Scheme 5

Applicability and scalability of our dehydrogenation protocol.

Scheme 6

Radical coupling and trap reactions and kinetic isotope effect study. Reactions were performed under optimum conditions (0.5 mmol scales). GC yield using dodecane as the internal standard. ¹H NMR yields using CH₂Br₂ as the internal standard.

Figure 1

Mechanistic and organometallic studies. For more details, see the Supporting Information.