Access to S‑Stereogenic Free Sulfoximines via Bifunctional Phosphonium Salt-Catalyzed Desymmetrization of Bisphenols

Sulfur-stereogenic sulfoximines particularly
with a free N-H unit
exhibit intriguing chemical and biological activities, and thus have
received continuous attention from chemists. However, there are currently
no examples of guiding catalytic asymmetric strategies available to
directly access these molecules. Herein, we disclose an efficient
and practical protocol for the direct enantioenrichment of free N-H
sulfoximines, via a bifunctional phosphonium salt-catalyzed desymmetrization
triggered by the Atherton–Todd reaction together with a further
extended nucleophilic acyl substitution-type reaction. A series of
free N-H sulfoximines bearing an assortment of aromatic groups (70
examples) are tolerated in this desymmetrization with incidentally
involving minority kinetic resolution (KR). The desymmetrized products
can be easily transformed into chiral sulfoxides and other classes
of active sulfur-stereogenic compounds. Mechanistic studies provided
insights into the reaction pathway particularly suggesting a desymmetrization/KR
synergic process, and also offered support on hydrogen-bonding interactions
as the key elements to successful stereocontrol.