Date: 29 April 2020 | Category: News
Professor Stephen L. Buchwald’s team at MIT recently published a rapid, efficient and inexpensive photoredox arylamination for the synthesis of secondary and tertiary amines [1].
A photochemical approach to the Buchwald-Hartwig amination
Up until recently, chemists have had to rely on Pd-catalysed methods, such as the Buchwald-Hartwig amination, to generate C–N cross-couplings. The ability to carry out these couplings at scale is of vital importance for the synthesis of APIs.
Since the Macmillan group in 2016 reported a dual photoredox route for aryl aminations [2], the interest in this field has grown. This has greatly accelerated the use of photochemical processes for the preparation of novel pharmaceuticals.
The attractiveness of this approach are the mild reaction conditions and cheap reagents. The challenge however is that photochemical reactions are often problematic to scale in batch reactors.
This is a well-covered topic that lead the authors to the next logical step, the development of a flow photochemical approach to improve the efficiency of the photochemical process.
Monochromatic LEDs, maximising the irradiance power
The Vapourtec UV-150 photochemical reactor equipped with LEDs offers a precise and efficient solution to develop and scale up photochemical reactions. In this work, a Vapourtec Easy-Photochem system equipped with a range of LED light sources was used to study aryl aminations.
One of the biggest challenges in translating batch reaction conditions to continuous flow is dealing with precipitation of products and/or salts, as this could jeopardise the reaction. Buchwald’s team solved this problem by changing the system solvent and using organic bases, giving good handling characteristics.
High Power LED, new horizons
Vapourtec launched the UV-150 photochemical reactor in 2014, continual improvement of this reactor, has led Vapourtec to increase the irradiance power of our LEDs from 20 watts up to 70 watts.
Research Scientist Dr Manuel Nuño, explained: “The contribution of this research towards process development is invaluable; Buchwald’s team put a great effort to explore this chemistry. We recently published our work using the high power LED for a 2+2 cycloaddition, and we increased the throughput 230%.
“If they managed to reduce residence times to a range of 10-100 minutes using the standard LEDs of 24 W irradiance power, I can only imagine the further reduction in time that our new high power LEDs could provide.”
References
[1] B. Y. Park, M. T. Pirnot, and S. L. Buchwald, “Visible Light-Mediated (Hetero)aryl Amination Using Ni(II) Salts and Photoredox Catalysis in Flow: A Synthesis of Tetracaine,” J. Org. Chem., vol. 85, no. 5, pp. 3234–3244, Mar. 2020, doi: 10.1021/acs.joc.9b03107.
[2] E. B. Corcoran et al., “Aryl amination using ligand-free Ni(II) salts and photoredox catalysis,” Science (80-. )., vol. 353, no. 6296, pp. 279 LP – 283, Jul. 2016, doi: 10.1126/science.aag0209.
To read this publication by Professor Stephen L. Buchwald’s team click here
For more information on the UV-150 photochemical reactor click here