Towards a More Sustainable Photocatalyzed α‐Arylation of Amines: Green Solvents, Catalyst Recycling and Low Loading

Abstract

A more sustainable and efficient protocol for the photocatalytic α-amino arylation promoted by fac-Ir(ppy) 3 was developed. Three noteworthy results were achieved: i) the replacement of toxic medium DMA with the greener solvents NBP and NHP, and the concurrent improvement of the process efficiency by lowering both the amine and the base amount; ii) the development of a recycling protocol for both the sustainable solvent NHP and the commercially available costly photocatalyst fac-Ir(ppy) 3 , achieving environmental and economic benefits. This approach to the photocatalyst recovery avoids very demanding catalyst structural modifications; iii) the protocol in green solvents proved to be scalable up to 10 mmol of limiting reagent, maintaining excellent performance also lowering the photocatalyst loading down to 0.05 mol%. This is the first example of photocatalytic α-arylation of amines promoted by such a low amount of catalyst. Lastly, the versatility of this approach was demonstrated by extending the use of the green solvent NBP to another photoredox process.

Green Metrics and Sustainability in Photocatalysis

“…As a consequence, one of the prevailing challenges is the recycling of rare metal-based photocatalysts, leading to environmental and economic benefits. [39] Recently, we contributed to this field by proposing an improved protocol for the photocatalytic α-amino arylation, [40] in which i) the toxic polar aprotic medium was replaced with the greener solvents 1-butyl-2-pyrrolidone (NBP) [41] or 2-pyrrolidone (NHP), [42] ii) the solvent NHP and the commercially available costly photocatalyst Ir(ppy) 3 were both recycled, iii) the photocatalyst loading was lowered to 0.05 mol% maintaining excellent performance (Scheme 3).…”

“…Comparison between the green chemistry metrics of the protocols for the synthesis of α-aryl amine 3. [a] Scheme 2 [34] Scheme 3 [40] Scheme 4 [43] AE 0.67 0.67 0.78 red flag). Regarding the tricomponent catalytic system, it must be noted that it represents 1 % of the waste mass, an unusually high value.…”

Sustainable Solvents in Metallaphotoredox Catalysis

“…14 In the past decades, an exponential number of methodologies based on photoredox catalysis have been disclosed, showcasing its synthetic significance. 15,16 Most key reports take advantage of undesirable, nonsustainable solvents, such as dipolar aprotic solvents like dimethylacetamide (DMAc), dimethylformamide (DMF), dimethyl sulfoxide (DMSO), or ethers such as dioxane and dimethoxyethane (DME). Its use in the academic setting is motivated by several distinct factors: (1) generally good performance in photoredox reactions, (2) availability and no constraint in its use, (3) scale of the reactions conducted, (4) overlooking solvent screening versus reagent optimization, and (5) optimal solubilization properties across a large variety of substrates.…”

“…However, the cumulative impact of numerous laboratories is noteworthy, underscoring the imperative need for the implementation of screening campaigns focused on greener approaches. These initiatives are crucial for identifying the most suitable sustainable solvents tailored to specific methodologies, ultimately playing a pivotal role in enabling technology in the pharmaceutical setting. , …”