Oxidative C(sp3)−N Cleavage Cascade Cyclization of N-Uracil Amidines and Tertiaryamines: Switchable Divergent Synthesis of Functionalized Pyrimidouracils and Dihydropyrimidouracils

The divergent synthesis of dihydropyrimidouracil and pyrimidouracil derivatives from N-uracil amidines and tertiaryamines by an oxidative C(sp³)−N cleavage cascade cyclization reaction is first described. This transformation enables the formation of new C(sp³)−N and C(sp²)−N bonds via the selection of different oxidation conditions. The features of this method include tunable product selectivity, excellent chemoselectivity, readily available starting materials, broad substrate scope, good tolerance of functional groups, and moderate to high yields.     

Versatile Biocatalytic C(sp3)−H Oxyfunctionalization for the Site- Selective and Stereodivergent Synthesis of α- and β-Hydroxy Acids

C(sp³)−H oxyfunctionalization, the insertion of an O-atom into C(sp³)−H bonds, streamlines the synthesis of complex molecules from easily accessible precursors and represents one of the most challenging tasks in organic chemistry with regard to site and stereoselectivity. Biocatalytic C(sp³)−H oxyfunctionalization has the potential to overcome limitations inherent to small-molecule-mediated approaches by delivering catalyst-controlled selectivity. Through enzyme repurposing and activity profiling of natural variants, we have developed a subfamily of α-ketoglutarate-dependent iron dioxygenases that catalyze the site- and stereodivergent oxyfunctionalization of secondary and tertiary C(sp³)−H bonds, providing concise synthetic routes towards four types of 92 α- and β-hydroxy acids with high efficiency and selectivity. This method provides a biocatalytic approach for the production of valuable but synthetically challenging chiral hydroxy acid building blocks.     

Ligand-Enabled Palladium(II)-Catalyzed Enantioselective β-C(sp3)−H Arylation of Aliphatic Tertiary Amides**

Amide is one of the most widespread functional groups in organic and bioorganic chemistry, and it would be valuable to achieve stereoselective C(sp³)−H functionalization in amide molecules. Palladium(II) catalysis has been prevalently used in the C−H activation chemistry in the past decades, however, due to the weakly-coordinating feature of simple amides, it is challenging to achieve their direct C(sp³)−H functionalization with enantiocontrol by Pd^II catalysis. Our group has developed sulfoxide-2-hydroxypridine (SOHP) ligands, which exhibited remarkable activity in Pd-catalyzed C(sp²)−H activation. In this work, we demonstrate that chiral SOHP ligands served as an ideal solution to enantioselective C(sp³)−H activation in simple amides. Herein, we report an efficient asymmetric Pd^II/SOHP-catalyzed β-C(sp³)−H arylation of aliphatic tertiary amides, in which the SOHP ligand plays a key role in the stereoselective C−H deprotonation-metalation step.