Journal of the American Chemical Society
Journal of the American Chemical Society
5 years ago

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

New Class of Anion-Accelerated Amino-Cope Rearrangements as Gateway to Diverse Chiral Structures
Jason S. Fell, Kevin A. Scott, K. N. Houk, Pradipta Das, Isaac Chogii, Jon T. Njardarson, Mark N. Crawford
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.

Publisher URL: http://dx.doi.org/10.1021/jacs.7b07319

DOI: 10.1021/jacs.7b07319

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