A Multi-Task Palladium Catalyst Involved in Heck-Reduction-Cyclization Sequences for the Preparation of 4-Benzyl-1,2-dihydroisoquinolin-3-ones: An Unusual Homogeneous-Heterogeneous Sustainable Approach

Abstract

A mixed homogeneous-heterogeneous catalysis that exploits a multi-task palladium catalyst has been developed for one-pot sequential Heck-reduction-cyclization (HRC) reactions leading to novel 4-benzyl-1,2-dihydroisoquinolin-3-ones. The HRC sequence requires mild conditions and allows the separation of the palladium residues under the form of an in situ generated Pd(0)/C catalyst by simple filtration. The homemade and recovered catalyst can be efficiently reused for Suzuki-Miyaura reactions and reductive processes making it useful for sustainable chemistry.

heterogeneous catalysis - heterocycles - palladium - Heck reaction - hydrogenation

References and Notes

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General Procedure for the Cyanation of Iodoaryls 7a,b: To a solution of iodoaryl 7a,b (7.00 mmol, 1 equiv) in DMF (7 mL) was added CuCN (689 mg, 7.7 mmol). The resulting mixture was stirred for 4-5 h at 130 ˚C and then filtered. The solution was diluted with CH₂Cl₂ (21 mL) and hydrolyzed with 5% aq NH₄OH solution. After being stirred for 30 min, the aqueous layer was extracted with CH₂Cl₂ (3 ×). The collected organic extracts were dried (MgSO₄) and concentrated under reduced pressure. Purification by flash chromatography gave the expected products 8a,b.

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General Procedure for the Preparation of Acrylates 1a,b: To a solution of ester 8a,b (10 mmol, 1 equiv) in toluene (13 mL) were added HCHO (28 mmol, 2.8 equiv), Bu₄NI (0.2 mmol, 0.04 equiv) and K₂CO₃ (30 mmol, 3 equiv) at r.t. The resulting mixture was stirred for 5 h at 50 ˚C. After cooling to r.t., H₂O (10 mL) was added and the aqueous phase was extracted with toluene (2 × 20 mL). The collected organic extracts were dried (MgSO₄), filtered and concentrated under reduced pressure to give the corresponding products 1a,b which were purified by flash chromatography.

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General Procedure for the Preparation of 4-Benzyl-1,2-dihydroisoquinolin-3-ones 5a-h: Acrylate 1a,b (1 mmol) and Pd(OAc)₂ (5 mol%) were added to a solution of diazonium salt (1.2 mmol) in MeOH (5 mL). The reaction was stirred for 12 h at 40 ˚C, charcoal (110 mg) was added and the resulting mixture was stirred under H₂ (balloon, 1 atm) for 24 h at 50 ˚C. After cooling to r.t., K₂CO₃ (2 mmol) was added in one portion and the heterogeneous mixture was stirred for 2 h, filtered, and purified by flash chromatography to give the corresponding 4-benzyl-1,2-dihydroisoquinolin-3-ones 5a-h.

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