Study On The Construction Of S-alkyl/aryl Phosphorothioates And Polycyclic Compounds Containing P-C/P-N Bonds

Organophosphorus compounds,as the most important class of organic compounds,have attracted much attention in organic synthesis due to their unique biological activities in material chemistry and pharmaceutical biochemistry.In general,construction of the C(sp3)-SP(O)(OR)2 moiety mostly relies on Atherton-Todd-type reactions or nucleophilic substitution of the toxic and moisture sensitive RSX or P(O)X.Recently,the oxidative CDC coupling of odorous thiols and P(O)H compounds for accessing the C(sp3)-SP(O)(OR)2 moiety was reported by the groups of Han,Jiao,and Zhang.However,these approaches are relatively limited for the synthesis of phosphorothioates.Despite the significance of these reports,it is highly desirable to develop an efficient approach to synthesize phosphorothioates with an easily available catalyst,broad substrate scope,and an environmentally friendly reaction system.In general,construction of polycyclic phosphorus compounds containing C-P(O)bonds depends on the series cyclization of phosphorus positive ions or phosphorus free radicals with unsaturated compounds.Among them,the phosphonylation cyclization of phosphorus radicals and unsaturated compounds provides a convenient way to synthesize phosphorus-containing polycyclic compounds.Over the past few years,visible light driven photoredox catalysis in the exploration of P-centered radicals mediated reactions has been proven to be one of the powerful methods for the rapid and facile access to structurally diverse phosphorus-containing scaffolds under very mild reaction conditions with great atom-economy and step-economy.Compared with construction of polycyclic phosphorus compounds containing C-P(O)bonds depends,there are few reports of constructing N-P(O)bonded polycyclic phosphorus compounds.This paper is devoted to the diversified synthesis of organophosphorus compounds by efficiently constructing C-S-P(O)bonds,P-C bonds,and P-N bonds,which mainly include the following three parts:Part Ⅰ:The transition-metal-free one-pot direct synthesis of heterocyclic phosphorothioates involving indole or imidazo[1,2-a]pyridine derivatives,elemental sulfur,and P(O)H compounds is presented.The use of NaI or KI as a catalyst,tert-butyl hydroperoxide as an oxidant,Various indole and imidazo[1,2-a]pyridine derivatives were tolerated in cross-dehydrocoupling reactions,affording the corresponding products in good yields.Moreover,this method can be easily adapted to large-scale preparation.Part Ⅱ:We developed copper-catalyzed remote C(sp3)-H phosphorothiolation of sulfonamides and carboxamides in a multicomponent reaction involving a sequence of amidyl radical generation,1,5-HAT,and a Cu-catalyzed cross coupling of the resulting carbon radical with(RO)2P-(O)SH(generated in situ from(RO)2P(O)H and elemental sulfur).Moreover,the reaction showed broad substrate scope,good functional group tolerance,and high chemoselectivity and regioselectivity,Meanwhile,the reaction can be applied to late-stage functionalization of valuable complex molecules.Part Ⅲ:we developed the switchable and facile photocatalytic phosphorylation of cyanoaromatics with the 1,6-enyne moiety for the diverse and selective synthesis of potentially bioactive phosphorylated polyheterocycles,including not only phosphorylated ketones but also unprecedented phosphorylated aminophosphonates and iminophosphonates.The use of Ru(bpy)3Cl2 as the photocatalyst,potassium sulfate as the oxidant,and sodium bicarbonate as the base,the phosphorylated ketone was synthesized by the tandem cyclization of 1,6-enyne and Ph2P(O)H.When the base is replaced by cesium carbonate,the phosphorylated aminophosphonates are obtained by the radical coupling of phosphorus radicals with nitrogen radicals,wherein the nitrogen radicals are formed by the interaction of Ph2P(O)H with 1,6-enyne.Phosphonylated aminophosphine oxides were obtained in the reaction of 1,6-enyne and diphenylphosphine oxide when fac-Ir(ppy)3 was used as photocatalyst and NaHCO3 was used as base.These photocatalytic transformations,via radical cyclization and cross-coupling processes,selectively synthesize phosphorylated ketones,iminophosphonates,and aminophosphonates,accompanied by the formation of C-P and N-P bonds,highlighting the Atomic and step economics of the protocol.