Latent nucleophiles in Lewis base catalysis: Enantioselective allylation of nitrogen nucleophiles

• Applicant: Professor Ivan Vilotijevic, Ph.D.
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 445755502

A common problem in Lewis base catalysis is the narrow substrate scope for the nucleophile. One of the reasons for this is the competition between the nucleophile and the catalyst. To address this and related issue and enable expanded scope in Lewis base catalyzed allylic substitutions, we introduced the concept of latent nucleophiles in Lewis base catalysis. Latent nucleophiles are molecules that are not nucleophilic until activated to react as a nucleophile. If activation of nucleophile depends on the activation of electrophile by the Lewis base, the activated nucleophile would be produced only when the activated electrophile is already present in the mixture thus enabling the fast reaction between the two activated species to out-compete other pathways. In this project we apply this concept to various N-centered nucleophiles with the goals of (i) developing efficient organocatalytic protocols for N-allylation of a wide range of N-containing compounds and (ii) conducting a detailed evaluation of the concept and it’s limits. The model latent nucleophiles are N-silyl compounds where latency is imposed on the molecule by steric bulk of the silyl group. A detailed study of the different classes of N-nucleophiles will allow for enantioselective N-allylation using Morita Baylis Hillman fluorides. The products of these reactions are derivatives of β-amino acids often utilized in synthesis of various bioactive compounds. The overarching goal of the project is to develop a general methods for effective synthesis of chiral allylic amines and enable their more common use in medicinal chemistry and synthesis.

• DFG Programme: Research Grants