Unprecedented three-dimensional 1,2,6-thiadiazine 1oxides have been prepared by an aza-Michael-addition/cyclization/ condensation reaction sequence starting from sulfonimidamides and propargyl ketones. The products have been further functionalized by standard cross-coupling reactions, selective bromination of the heterocyclic ring, and conversion into a β-hydroxy substituted derivative. A representative product was characterized by single-crystal X-ray structure analysis. cross-coupling reactions and bromination of the heterocyclic ring in addition to functionalization of the endo-cyclic sulfur substituent. ■ ASSOCIATED CONTENT* sı Supporting InformationThe Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.0c00666.Experimental procedures, characterization data, NMR spectra for new compounds, X-ray crystallography data (PDF)

Structural analogues of PFI-1 varying at the sulfur core were prepared, and their activities as BET inhibitors in myeloid cell lines and primary cells from patients with acute myeloid leukemia were studied. Docking calculations followed by molecular dynamics simulations revealed the binding mode of the newly prepared inhibitors, suggesting explanations for the observed high enantiospecificity of the inhibitory activity.

Sulfondiimines are aza-analogues of sulfones and sulfoximines. Understanding their syntheses and derivatisations shall lead to more applications in medicinal and crop protecting chemistry.

Unprecedented 1,2‐benzothiazine 1‐imines have been prepared from sulfondiimines by regioselective rhodium‐catalyzed annulation reactions with diazo keto esters and α‐substituted (pseudo)halo acetophenones as coupling partners. A representative product was characterized by single crystal X‐ray structure analysis, and the applicability of the resulting three‐dimensional heterocycles to Buchwald‐Hartwig‐type amination reactions is shown.magnified image

A solvent-free mechanochemical synthesis for 1,2,6thiadiazine 1-oxides starting from NH-sulfonimidamides and propargyl ketones has been developed. Lewis acids affect these one-pot aza-Michael-addition/cyclization/dehydration reaction sequences. The photophysical properties of the resulting heterocyclic sulfonimidamide derivatives were characterized.