Transition-metal-free Phosphorylation Of Alkene C-H Bonds

Phosphonates and their derivatives are widely existed in many natural products, which play important roles to maintain normal life activities. Due to their unique properties, organophosphorus are widely used in medicine, pesticide, daily chemical, materials, etc. In this context, the reactions of organic phosphorus compounds are always a research subject in synthetic chemistry. With the development of organic phosphorus chemistry, particularly the development of biological phosphorus chemistry, the phosphorus drugs now play important roles in disease prevention and treatment. Therefore, explore the high efficient, high selectivity, and moderate reaction conditions for the synthesis of organic phosphorus are highly desirable. Since the first report by Hirao and co-workers in the 1980 using transition metal catalyzed cross coupling of aryl halide with organophosphorus reagent, numerous methods have been disclosed for the construction of C-P bonds, such as transition metal catalyzed phosphorus hydrogenation, phosphorus radical addition, nucleophilic addition etc. These methods provided simple and practical ways for organophosphorus synthesis.As a significant motif in organic chemistry, the C-H functionalization of alkenes has been intensively studied over the past years. Although the C-P coupling of aromatic C-H has been developed, the C-H phosphorylation of the alkene C-H bond has not yet been achieved due to the low reactivity of the alkene C-H bond(especially for internal alkenes) and the strong coordination of the phosphorus reagents to transition metal catalysts. C-H bond phosphorylation of ketene dithioacetals was achieved under transition-metal-free or AgNO3 mediated conditions. Synthetic transformations of the coupling product provided promising methods for the construction of highly functionalized phosphorylated N-heterocycles and tetrasubstituted alkenes. Considering the important function of phosphonates and their derivatives in physiology and medicine, this method will be applied in variety disciplines.