Synthesis of 1λ⁶,2,4,6‐Thiatriazine‐1,3,5‐Trione Derivatives

Abstract

Mono N‐carbamoylation of 4‐methylbenzenesulfonimid‐amide with an isocyanate using pyridazine as the base, followed by N‐acylation on the other nitrogen in the sulfonimidamide with carbonyldiimidazole, and intramolecular cyclization in one‐pot, afforded 26 1λ6,2,4,6‐thiatriazine‐1,3,5‐trione derivatives in moderate to good yields. The protocol also works well for aliphatic sulfonimidamides, such as methylsulfonimidamide. Further functionalization on the triazinone scaffold was exemplified.

Data Science-Enabled Palladium-Catalyzed Enantioselective Aryl-Carbonylation of Sulfonimidamides

“…Pleasingly, sulfonimidamide 3aa reacted with 4-chlorophenyl isocyanate to form urea 5 in 82% yield while largely preserving enantiomeric enrichment at sulfur (94:6 er) (Figure a) . Similarly, a Mitsunobu reaction to form a piperidyl heterocyclic substituent at sulfur was successful when performed with 1,5-pentanediol ( 6 , 69%, 97:3 er) (Figure b) .…”

“…Pleasingly, sulfonimidamide 3aa reacted with 4-chlorophenyl isocyanate to form urea 5 in 82% yield while largely preserving enantiomeric enrichment at sulfur (94:6 er) (Figure 5a). 32 Similarly, a Mitsunobu reaction to form a piperidyl heterocyclic substituent at sulfur was successful when performed with 1,5-pentanediol (6, 69%, 97:3 er) (Figure 5b). 33 Furthermore, we found 3aa to be effective as a nucleophile in a Cu-catalyzed N-arylation with 4-iodotoluene, producing 7 in 83% yield while preserving the starting material's high enantiomeric enrichment (94:6 er) (Figure 5c).…”

An Improved Synthesis of 1λ6,2,4,6‐Thiatriazine‐1,3,5‐trione Derivatives – the Sulfonimidamide‐featured Triazinones

“…To prepare the mono‐acylated derivative, we developed a protocol using a mixture of acyl chloride and pyridazine as the acylating reagents [5b] . Inspired by these results, we used pyridazine as the base for mono N‐carbamoylation and reported a one‐pot approach to access 1λ 6 ,2,4,6‐thiatriazine‐1,3,5‐trione derivatives, the sulfonimidamide‐featured triazinones through a sequential carbamoylation‐acylation‐cyclization approach ( 5 , Scheme 1) in our previous work [5d] …”