Reversible C–C Bond Activation Enables Stereocontrol in Rh-Catalyzed Carbonylative Cycloadditions of Aminocyclopropanes

Upon exposure to neutral or cationic
Rh­(I)-catalyst systems, amino-substituted
cyclopropanes undergo carbonylative cycloaddition with tethered alkenes
to provide stereochemically complex N-heterocyclic scaffolds. These
processes rely upon the generation and trapping of rhodacyclopentanone
intermediates, which arise by regioselective, Cbz-directed insertion
of Rh and CO into one of the two proximal aminocyclopropane C–C
bonds. For cyclizations using cationic Rh­(I)-systems, synthetic and
mechanistic studies indicate that rhodacyclopentanone formation is
reversible and that the alkene insertion step determines product diastereoselectivity.
This regime facilitates high levels of stereocontrol with respect
to substituents on the alkene tether. The option of generating rhodacyclopentanones
dynamically provides a new facet to a growing area of catalysis and
may find use as a (stereo)­control strategy in other processes.