Brønsted acid catalysts, such as phosphoric acids, have proven themselves to be highly versatile and efficient for many different transformations such as condensations, rearrangements and reductions. These catalysts activate the substrate via protonation and inducing stereochemical control through the chiral conjugate base that’s in close proximity. One important feature associated with the phosphoric acid catalyst is that the phosphoryl oxygen can also function as a Brønsted base. This gives the catalysts a Brønsted acid/base dual functionality that can be taken advantage of by several substrates. We have observed that enamides, 1, are ideal substrates for the chiral phosphoric acid catalyst system. A latent nucleophile is created in these substrates due to a hydrogen bond donation of the phosphoric acid, 2. This allows for a tautomerization, rendering the γ position nucleophilic. When electrophiles, such as imines, 3, are introduced, Mannich or Mannich-like reactivity will occur, generating a new C-C bond and two chiral centers as seen in the adduct, 4.

Chiral phosphoric acids as Brønsted acid promoters of latent nucleophile reactions

253rd National Meeting (2017)

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