Efficient Pd-Catalyzed Dehydrogenative Coupling of P(O)H with RSH: A Precise Construction of P(O)–S Bonds

Abstract

A Pd-catalyzed dehydrogenative phosphorylation of thiols is developed. A variety of thiols dehydrogenatively couple readily with all three kinds of P(O)-H compounds, i.e., H-phosphonates, H-phosphinates, and secondary phosphine oxides, providing a general access to the valuable phosphorothioates including the P-chiral compounds. A plausible mechanism is proposed.

NHC‐Catalyzed Metathesis and Phosphorylation Reactions of Disulfides: Development and Mechanistic Insights

“…Despite sulfur being an abundant element of the chalcogen group, organic reactions involving organosulfur compounds are relatively under‐investigated compared to their oxygen counterparts . The development of efficient metathesis and phosphorylation reactions of disulfides are of particular interest due to their synthetic values in polymer, medicinal, agricultural, and catalytic chemistry . Recently, these reactions have also become versatile tools for dynamic combinatorial and diversity‐oriented chemistry as they can rapidly generate molecular libraries for various applications .…”

“…With the establishment of this NHC‐promoted disulfide metathesis protocol, we turned our attention to the synthesis of phosphorothiolates from disulfide–phosphite coupling reactions. These organophosphorus–sulfur compounds serve as valuable intermediates in organic chemistry and precursors for important medicinal agents and agrochemicals . Current methods to produces these compounds normally involve toxic and moisture‐sensitive reagents or catalysts .…”

“…These organophosphorus–sulfur compounds serve as valuable intermediates in organic chemistry and precursors for important medicinal agents and agrochemicals . Current methods to produces these compounds normally involve toxic and moisture‐sensitive reagents or catalysts . NHC organocatalysts were previously known to also activate phosphites for a number of (1,ω)‐hydrophosphonylation to carbonyl compounds .…”

“…The limitation actually arose from less reactive disulfide substrates in which steric hindrance might be at play ( 5 ab , 5 cb , 5 db , 5 de , 5 ea , also see Scheme a) . In light of its overall good performance, this method could serve as a convenient and efficient organocatalytic alternative for the synthesis of synthetically valuable phosphorothiolates.…”

Reactions of Disulfides with Silyl Phosphites to Generate Thiophosphates Under Neat Conditions

“…[3] In 2013, Kaboudin and co-workersr eported that copper(I) iodide-catalyzed coupling of H-phosphine oxides/H-phosphonates with thiols proceeds effectively in the presence of triethylamine (Scheme 1B). [6] In 2017, Jiao andc o-workers presented the first example of direct oxidative cross-coupling of thiols with P(O)H compounds for the construction of SÀP(O)b onds catalyzed by Cs 2 CO 3 to produce phosphorothioate derivatives at 30 8Cu nder O 2 atmosphere (Scheme 1E). [3e, 5] Recently,H an and co-workers reported an efficient Pd-catalyzedd ehydrogenative phosphorylation of readily availableP (O)H compounds with thiols to produce phosphorothioates in high yields.…”