N-Heterocyclic Carbene Control over Multiple Stereogenicities: Atroposelective Synthesis of Axially Chiral Phthalimides

The design of a NHC-catalyzed methodology for the straightforward access to hitherto unknown axially chiral N-aryl phthalimides has provided a breakthrough in the field of multichirality control. Anticipating a formal (4+2) oxidative annulation, the use of NHC-derived chiral dienolate as ambident partner toward N-aryl maleimides unexpectedly yields original bis-succinimide-type compounds featuring a multichiral architecture with up to four stereogenic centers and two remote chiral axes. The overall pseudo-three components reaction between an enal and two equivalents of a N-aryl maleimide proceeds with excellent enantioselectivity and complete diastereoselectivity. This study illustrates the high synthetic potential of chiral NHC-activated dienolates for the rapid and highly diastereo- and enantioselective preparation of underexplored atropisomers in the pentatomic series, featuring multiple stereogenic elements including challenging Csp(2)-N chiral axes. The practicality of this reaction is highlighted by a broad substrate scope and a scaled-up synthesis. Moreover, the easy base-induced transformation of the chiral bis-succinimide precursors allows to prepare the initially planned N-aryl phthalimide atropisomers with excellent retention of enantiopurity.