<i>N</i>‐Heterocyclic Carbene Control over Multiple Stereogenicities: Atroposelective Synthesis of Axially Chiral Phthalimides
Manuel Barday, Jéssica Ferreira Rodrigues, Pierre Bouillac, Jean Rodriguez, Muriel Amatore, Thierry Constantieux
Abstract
Abstract 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 C sp 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. magnified image