Arylation of α-Chiral Ketones by Palladium-Catalyzed Cross-Coupling Reactions of Tosylhydrazones with Aryl Halides

摘要

The carbonyl group is probably the most versatile functional group in organic synthesis, owing to its rich and highly developed chemistry. In particular, carbonyl compounds are extraordinary sources of enantiomerically pure compounds, that can be obtained from the chiral pool from terpenes, carbohydrates, and amino acids, and also through asymmetric catalysis and organocatalysis. However, carbonyl compounds bearing chirality at the a carbon can be difficult to manipulate owing to their configurational instability through enolization. Moreover, the typical formation of alkenes by nucleophilic-addition/elimination sequences usually affords the more-substituted olefin, with loss of the chiral information (Figure 1a), and the reactions that proceed through the formation of enolates, such as cross-coupling reactions through enol sulfonates, require tightly controlled kinetic conditions to avoid the equilibration of the chiral center (Figure 1 c). For these reasons, the development of meth- odologies that allow the manipulation of the carbonyl functionality with preservation of the a chirality are highly desirable.