New Class of Anion-Accelerated Amino-Cope Rearrangements as Gateway to Diverse Chiral Structures

We report useful
new lithium-assisted asymmetric anion-accelerated
amino-Cope rearrangement cascades. A strategic nitrogen atom chiral
auxiliary serves three critical roles, by (1) enabling in situ assembly
of the chiral 3-amino-1,5-diene precursor, (2) facilitating the rearrangement
via a lithium enolate chelate, and (3) imparting its influence on
consecutive inter- or intramolecular C–C or C–X bond-forming
events via resulting chiral enamide intermediates or imine products.
The mechanism of the amino-Cope rearrangement was explored with density
functional theory. A stepwise dissociation–recombination mechanism
was found to be favored. The stereochemistry of the chiral auxiliary
determines the stereochemistry of the Cope product by influencing
the orientation of the lithium dienolate and sulfinylimine fragments
in the recombination step. These robust asymmetric anion-accelerated
amino-Cope enabled cascades open the door for rapid and predictable
assembly of complex chiral acyclic and cyclic nitrogen-containing
motifs in one pot.