The research in Liu’s group focused on the difunctionalization of alkenes using transition metal (TM) catalyst, including the following three parts:

Part I: TM-catalyzed fluorination and related transformations

Introducing fluorine (F) and fluorine-containing groups (Rf) into bio-molecules could usually change their reactivity dramatically, while only limited practical strategies are existed with high selectivity and efficiency. To achieve these goals, palladium-catalyzed oxidative difunctionalization of alkene was studied, in which high-valent palladium species was responded for the C-F and C-Rf bond formation. Distinct from previous studies, combination of commercial available strong oxidant with nucleophilic fluorine and fluorine-containing reagents were employed as oxidative system. A series of transformations, such as aminofluorination, aryltrifluoromethylation, and aminotrifluoromethoxylation, were achieved under mild reaction condition, and a variety of fluorine-containing heterocycles was synthesized efficiently.

Based on the above studies, high-valent palladium strategy could be extended to other transition metal, which can be used to achieve fluorination of aromatic compounds.

Part II: TM-Catalyzed oxidation of alkenes with green oxidants

Palladium-catalyzed oxidation reactions that involve PdIV complexes as key intermediates have been demonstrated as efficient strategy for the difunctionalization of alkenes, in which the involvement of alkyl–PdIV intermediates can readily undergo reductive elimination reactions to form new chemical bonds. Strong oxidants, such as PhI(OAc)2, Oxone, NXS, and PhICl2, were required to generate PdIV complexes, which often produce a large amount of byproducts. Compared to these oxidants, hydrogen peroxide would be preferred because it is inexpensive, environmental benign, and readily available. Our groups revealed that H2O2 can be used as green oxidant to achieve palladium oxidation to high-valent palladium species, led to the successful oxidative amination of alkenes, such as aminochlorination, aminoacetoxylation as well as aminohydroxylations, under simple catalytic systems.

Part III:TM-catalyzed highly-selective radical reactions

Radical chemistry is a powerful strategy for the difunctionalizaiton of alkenes, especial for the intermolecular reactions. For example, atom transfer radical addition (ATRA) has received much attention. However, the highly selective reaction is very challenging due to the insurmountable control on the selectivity of free radical chemistry. Trapping alkyl radical by transition metal complex was used as our strategy to control highly selectivity of radical reactions by tunable ligands. We have demonstrated that this is an effective way to achieve highly selective transformation of alkenes, such as diastereoselective radical fluorination, enantioselective radical cyanation reactions, and so on. And this strategy could also be applied to the C-H functionalization, and a highly enantioselective benzylic C-H cyanation was achieved in the presence of chiral copper catalyst.