Urea Activation of Nitrimines: A Mild, Metal-Free Approach to Sterically Hindered Enamines

Abstract

Nitrimines have been identified as impressive starting points for the syntheses of otherwise inaccessible, sterically encumbered enamines. The activation of nitrimines with urea catalysts for reaction with a variety of amines enables the formation of highly substituted enamines in high yield. The reactions benefit from mild, metal-free conditions, high functional group tolerance, and straightforward scale up.

Nitrimines as Reagents for Metal‐Free Formal C(sp2)–C(sp2) Cross‐Coupling Reactions

“…As we became interested in exploiting the attractive reactivity of nitrimines in innovative, metal‐free procedures, we were inspired by their nitrogen‐based nucleophilic exchange reactions 9. To this end, we demonstrated that urea‐activated nitrimines provide access to an impressive array of sterically‐encumbered enamines 10. Our success with nitrimine‐based C–N cross‐coupling reactions prompted us to question the potential utility of nitrimines in more challenging metal‐free C–C cross‐coupling reactions.…”

Nitrimines as Reagents for Metal‐Free Formal C(sp2)–C(sp2) Cross‐Coupling Reactions

“…[9] To this end, we demonstrated that urea-activated nitrimines provide access to an impressive array of stericallyencumbered enamines. [10] Our success with nitrimine-based C-N cross-coupling reactions prompted us to question the potential utility of nitrimines in more challenging metal-free C-C cross-coupling reactions. To our knowledge, the unique reactivity of nitrimines had not been taken advantage of for formal C(sp 2 )-C(sp 2 ) coupling reactions prior to our investigations.…”