Modular Sulfondiimine Synthesis Using a Stable Sulfinylamine Reagent

Sulfondiiminesthe double
aza-analogues of sulfoneshold
significant potential as leads in discovery chemistry, yet their application
in this arena has been held back by the scarcity of appropriate synthetic
routes. Existing methods employ sulfides as substrates, and rely on
consecutive imination reactions using the hazardous reagent O-mesitylenesulfonyl hydroxylamine. Here we report a method
for sulfondiimine synthesis that does not begin with a sulfide or
a thiol, and instead employs two Grignard reagents and a bespoke sulfinylamine
(RNSO) reagent as starting materials. Lewis
acid-mediated assembly of these three components provides efficient
access to a series of sulfilimine intermediates. A novel rhodium-catalyzed
imination of these electron-rich sulfilimines then delivers a varied
range of sulfondiimines featuring orthogonal N-functionalization.
Conditions for the selective manipulation of both N-atoms of the sulfondiimines are reported, allowing access to a broad
range of mono- and difunctionalized products. The oxidation of the
sulfilimine intermediates is also described, and provides a complementary
route to sulfoximines.