Corcoran et al. of Professor MacMillan’s group at Princeton University, have made exciting headway into ligand free aryl amination using nickel salts with photoredox catalysis, and the Vapourtec UV-150 continuous flow photochemical reactor has been at the heart of the adaptation of this chemistry to continuous flow.
Corcoran et al. have demonstrated how nickel(II) salts can be used in place of the more traditional palladium for C-N coupling reactions, making use of an iridium photocatalyst to provide a route to the aniline motif, found in a diverse mix of complex products and medicinal compounds, as well as other aryl amines in a ligand free environment. The use of nickel(II) salts presents a more accessible route to nickel catalysed aryl aminations without the need for air and moisture sensitive nickel(0), using photochemical excitation to reduce the nickel(II) to nickel(0) in situ, and to also destabilise the nickel(II) product complex towards reductive elimination giving the aryl amine product. The method has been applied in batch to a variety of aryl bromides with range of functional groups tolerated, including nitriles, amides, esters and sulfonamides, among others, giving product yields of over 90% within a few hours, (although some of the less nucleophilic substrates required over 24 hours). The method has also been applied in continuous flow with comparable yields obtained within 15 – 30 minutes using the Vapourtec UV-150 continuous flow reactor. The photochemical excitation allows this method to be carried out under mild conditions, and Corcoran performed each of the reactions in this study at less than 60 °C.
The method has also been transferred to continuous flow in some preliminary experiments that have shown great promise. The Vapourtec UV-150 photochemical reactor has been used in the synthesis of N-(4-(trifluoromethyl) phenyl)pyrrolidine with yields of over 90% in residence times as short as 15 minutes. In the text, Corcoran comments “the initial evaluation of this C–N cross-coupling platform in flow chemistry has shown high efficiency in decreased reaction times”. This is a significant reduction in reaction time compared to the batch synthesis, and is an excellent demonstration of the capabilities of the UV-150 continuous flow photochemical reactor.
“The narrow diameter of the tubing inside the UV-150 photochemical reactor is one of the keys to its success” explains Dr Ryan Skilton, Vapourtec’s Research Scientist, “it ensures that there is always optimal light penetration through the reaction mixture. The reactor can also be supplied with LED arrays that emit at a specific wavelength, like the 425 nm array used by Corcoran, to allow for efficient and targeted activation of the photocatalyst”.