Invention:
This invention is a method for the synthesis of alpha arylation of inexpensive, unactivated carbonyl compounds with high yields at room temperature using any photocatalyst (PC) under visible light from blue to red.
Background:
Functionalization of the C-H bond has evolved as a fundamental principle that underpins both academic and industrial importance in conceptualization and actualization of challenging organic transformations. This ubiquitous but relatively inert bond, if converted to more valuable C-C bond, can greatly accelerate the construction of a wide variety of compounds. This transformation is particularly sought after in fine chemicals and pharmaceutical applications. Incorporation of an aryl substituents at the α-position of carbonyl compounds is a powerful and attractive method to construct a C(sp2)-C(sp3) bond; and its coupling products, especially α-aryl cyclic ketones are significant structural motifs that are often encountered in a wide range of biologically interesting natural and pharmaceutical products. A number of classical stoichiometric transformations have been employed for such a key transformation but suffered from complications in scale-up, either due to the need to use highly activated aryl halides as reactants or the use of stoichiometric amount of toxic reagents with harsh reaction conditions, e.g., a high reaction temperature. Significant efforts have been directed towards the development of alternative synthetic routes to this important scaffold. With the advances in metal-catalyzed transformations, palladium-catalyzed α-arylations of the carbonyl compounds appeared to be the most promising route due to its versatility. However, high cost of the catalyst and additives, as well as requiring a high reaction temperature limits the utility of this approach in the synthesis of α-aryl carbonyls as building block, especially for pharmaceutical applications.
Applications:
- Fine chemical synthesis
- Synthesis of pharmaceutical intermediates or products
- For example, isocoumarin compounds
Advantages:
- Start from less expensive reactants
- Wide variety of non-metal photocatalysts may be used
- Room temperature synthesis
- Environmentally friendly
- One pot synthesis
