Studies On Synthesis Of Oragnophosphinates And Phosphinothioates Via Transformation Of P(O)-H Bonds

Phosphorothioates and phosphinates are important intermediates in organic synthesis, they are also widely applied in pesticides, pharmaceuticals, materials chemistry and other fields. Traditional procedures for their synthesis usually directly or indirectly depended on the transformation of the highly toxic and water-sensitive organohalides. These reactions usually suffer from hazardous conditions and low co-presence of functional groups.In this paper, we developed two efficient methods for the preparation of phosphorothioates and phosphinates via cross coupling of P(O)-H compounds with other nucleophilic coupling partners (alcohols, phenols, thiols, and selenophenols). The main results come as follows:1. Improvement on Atherton-Todd-type reaction.Atherton-Todd reaction is a powerful tool for constructing P-Z bonds. This reaction usually employs highly toxic CCl4 as the halogenating reagent and solvent. We find the phosphorylation of alcohols and thiols with hydrogen phosphoryl compounds can be accomplished in the cheaper and easy-to-handle chloroform, producing the corresponding phosphinothioates and phosphinates in high yields. This reaction is facile and complete in half an hour. It is well-known that aliphatic thiols cannot be phosphorylated by hydrogen phosphoryl compounds under the classic Artherton-Todd reaction conditions; however, aliphatic thiols are also applicable to this reaction to produce the corresponding products in high yields. Under similar reaction conditions, phosphoryl group can be introduced into bioactive molecules by using this strategy. For example, estrone and estradiol couple with diphenylphosphine oxide readily to produce the expected products in high yields.2. An efficient construction of P(O)-S Bonds via transition metal-catalyzed dehydrogenative coupling.An efficient Pd-catalyzed dehydrogenative phosphorylation of thiols with hydrogen phosphoryl compounds to produce the corresponding phosphorothioates in high yields is developed. Both aromatic and aliphatic thiols including those with functional groups like OH, NH2, SMe, OCF3, amide and etc. are applicable to this reaction. Mechanistic studies clearly show that this transformation would proceed via a Pd(0)/Pd(?) process involving oxidative addition, ligand exchange releasing dihydrogen and reductive elimination.