Reversal of Regioselectivity in Ynamide Chemistry

Ynamides are special alkynes bearing an electron-withdrawing group on the nitrogen atom, and they have been extensively studied over the past decade. However, the addition of functional groups across ynamides in these transformations typically occurs at the α-position of the ynamide because of the strong polarization of the alkynyl moiety. Studies of umpolung transformations in ynamide chemistry may not only discover organic reactions but also lead to divergent organic syntheses, thus significantly enriching ynamide chemistry. This review summarizes four main strategies utilized to achieve reversal of the regioselectivity, including the ring strain factor, metal–carbonyl (or sulfonyl) chelation, and base-mediated and radical-initiated addition.