Silver-Catalyzed Oxidative C(sp~3)-H/P-H Cross-coupling Reactions

Organophosphorus compounds containing C(sp~3)–P bonds have been widely used as drug pharmacophores,agrochemicals,flame retardants,metal ligands and organic functional materials,due to their comprehensive biological activity,special chemical reactivity and outstanding photoelectronic performance.Considering the importance of organophosphorus compouds in modern chemistry,the development of more convenient and efficient methods for their synthesis holds particular significance,and has been the one of the hottest research topic in organic chemistry.So far,the construction of C–P bond mainly relys on the traditional Michaelis-Arbuzov,Michaelis-Becker reactions and transition-metal-catalyzed Hirao cross-coupling reactions.However,these protocols suffer from low substrate scopes,low yields,severe reaction conditions and toxicity.These limitations restrict their applications to some extent.Undoubtedly,from the viewpoint of atom economy and simplicity of synthetic route,the transition-metal-catalyzed oxidative C(sp~3)–H/P–H cross-coupling reaction would be the most concise,efficient and environmental-friendly strategy for C(sp~3)–P bonds formation.This novel method would not only avoid tedious multistep synthesis of the pre-activated substrates,but also reduce the cost of reaction and the waste discharge.Consequently,more and more attentions have been attracted to this area in recent years.In this dissertation,we have detailedly studied two different types of silver-catalyzed C(sp~3)–H/P–H oxidative cross-coupling reactions.In the first part,we have disclosed the silver-catelyzed C(sp~3)–H/P–H oxidative cross-coupling of 1,3-dicarbonyl compounds with H-phosphonates,followed by a chemo-and regioselective C(sp~3)–C(CO)bond cleavage step to provide heavily functionalizedβ-ketophosphonates.The current protocol features several key advantages,including(1)simple and readily available catalyst system;(2)base-,ligand-and additive-free;(3)wide substrate scope and good functional group tolerance;and(4)exclusive chemo-and regioselectivity.Notably,mechanistic studies based on situ NMR study and situ HRMS analysis have provided that a radical pathway may be involved in C(sp~3)–P bond formation and an nucleophilic attack by water may promote C(sp~3)–C(CO)bond cleavage.Compared to 1,3-dicarbonyl compound,simple ketones are more general and easily available in organic systhesis.In the second part,we have successfully developed a facile and efficient silver-catalyzed oxidative C(sp~3)–H/P–H cross-coupling reaction for the construction ofβ-ketophosphonates from H-phosphonates and simple ketones.Importantly,this transformation was not only amenable to methyl C(sp~3)–H bond of straight chain ketones,but aslo to methylene C(sp~3)–H bond in cyclic aliphatic ketones.Similarly,this reation displays high chemo-and region-selectivity,and provides an alternative approach for the versatile synthesis ofβ-ketophosphonates.