Progress in the Chemistry of Phosphorothioates

Abstract

The present review focuses on the synthesis and applications of phosphorothioates (phosphorothioic esters) with the general structure R2P(O)SR', which are molecules belonging to the large family of organophosphorus compounds. They found important applications as biological active molecules, as well as synthetic intermediates to access valuable phosphorus and/or sulfur-containing structures. The reactivity of both heteroatoms, phosphorus and sulfur, is discussed by showing how they are involved as electrophilic, nucleophilic, or radicalar species in different transformations. The general methods for the preparation of phosphorothioates are described according to the various strategies involving P-S bond formation from one sulfur-reagent and one phosphorus-reagent, which include recent metalcatalyzed cross-coupling reactions. Particular attention is paid to synthetic applications of phosphorothioates occurring via the P-S bond cleavage, including for example anionic rearrangements and cascades, formation of sulfur-heterocycles, homolytic processes for olefins phosphorylation, and metal-catalyzed alkynes thiophosphorylation. The literature of the last two decades is covered, highlighting selected contributions in the chemistry of this class of compounds.

Gold-catalyzed alkenylation and arylation of phosphorothioates

“…5 Classical methods for synthesizing phosphorothioates are centered around the P–S bond formation through the nucleophilic substitution reactions of (RO) 2 P(O)X or R-SX. 6 However, this approach is associated with several drawbacks viz the use of toxic and moisture sensitive reagents, harsh reaction conditions and low functional group tolerability. As far as transition-metal catalysis is concerned, a new approach which employs copper-catalyzed reductive coupling of aryl sulfonyl chlorides/aryl sulfonyl hydrazides with H-phosphonates was developed (Scheme 1b, Path I).…”