Invention:
This invention is a new synthesis route for producing an alpha-aryl substituted cyclic ketone from a cyclic ketone compound using an aryl halide and an acridinium ion photocatalyst. The method of the invention is particularly useful in producing an alpha-aryl substituted cyclic ketone from an un-activated cyclic ketone compound. This is vast improvement to the synthesis of building blocks to many different fine chemicals and pharmaceuticals. This allows companies to perform the alpha arylation at room temperature, in the absence of expensive and toxic metals, and with commonly available white or green light.
Background:
The development of practical methods for the arylation of carbonyl compounds is, and has long been, a challenge in organic synthesis. Typically, this has been done through catalysis using expensive metals, such as palladium, and with temperatures exceeding 130°C or 266°F. All of this contributes to the difficulty of manufacturing commercial important intermediates for fine chemicals or pharmaceuticals. Pharmaceuticals especially face difficulty in manufacturing because of heavy regulation regarding the use of heavy metals in the manufacturing process.
For example, ketamine is one of the largest breakthroughs in severe depression in years when it was developed. Currently the process of synthesizing ketamine is an eight-step process that requires metal complexes and toxic reagents. With this synthesizing technique, Ketamine could be synthesized in four steps without any of the expensive metals or toxic reagents. Furthermore, the four steps now require much lower temperatures, around room temperature, and photosynthesizing agents instead of heavy metals.
Applications:
- Pharmaceutical chemical synthesis
- Fine Chemicals production
Advantages:
- Direct photoredox synthetic approach for alpha-carbonyl arylation from unactivated cyclic ketones
- Photocatatalyst effective at room temperature under green light
- Wide functional group tolerance
- Inexpensive precursors
- High yields
- Fewer synthetic steps
