Pd-Catalyzed Directed Thiocyanation Reaction by C-H Bond Activation

Abstract

The Pd-catalyzed directed thiocyanation reaction of arenes and heteroarenes by C-H bond activation was achieved. In the presence of an electrophilic SCN source, this original methodology offered an efficient tool to access a panel of functionalized thiocyanated compounds (21 examples, up to 78 % yield). Post-functionalization reactions further demonstrated the synthetic utility of the approach by converting the SCN-containing molecules into value-added scaffolds.

Keywords: C−H activation; homogeneous catalysis; palladium; synthetic methodology; thiocyanation.

Scheme 1

State of the art on transition metal catalyzed directed C−S bond formation by C(sp²)−H bond activation and the present work.

Scheme 2

Scope of the Pd‐catalyzed thiocyanation reaction of 2‐phenylpyridine derivatives. Reaction conditions: 1 (0.3 mmol), I (2 equiv), PdCl₂ (20 mol %), DMF (0.1 m), 100 °C, 16 h, Ar. Isolated yields were provided. [a] Reaction was run on 0.2 mmol scale. [b] Reaction was run on a gram scale. [c] The product was obtained with an inseparable impurity. [d] PdCl₂ (15 mol %), I (1.55 equiv). [e] No reaction occurred in the absence of PdCl₂.

Scheme 3

Extension to the thiocyanation of the N‐pyrimidine carbazole 3 and the benzo[h]quinoline 5. Reaction conditions: 3 or 5 (0.3 mmol), I (2 equiv), PdCl₂ (20 mol %), DMF (0.1 m), 100 °C, 16 h, Ar. Isolated yields were provided.

Scheme 4

Post‐functionalization reactions. Conditions: i. NaN₃ (1.2 equiv), ZnCl₂ (1 equiv), iPrOH (0.2 m), 50 °C, 1.5 h. ii. TMSCF₃ (2 equiv), Cs₂CO₃ (2 equiv), MeCN (0.1 m), 40 °C, 20 h. See Supporting Information for more details.

Scheme 5

Plausible mechanism. L=ligand.