Gold-Catalyzed Annulations with Nucleophilic Nitrenoids Enabled by Heteroatom-Substituted Alkynes

The combination of a nucleophilic nitrene equivalent, a triple bond and a pi-acid catalyst has underpinned numerous efficient transformations for the preparation of azacycles. This personal account details our efforts in developing an annulation strategy. Adding a nucleophilic nitrenoid to an activated alkyne can generate carbenoid character that is then quenched by a cyclisation onto the nitrenoid substituent. The use and development of N-acyl and N-heterocyclic pyridinium-N-aminides as 1,3-N,O and 1,3-N,N-dipole equivalents is discussed in the context of oxazole and heterocycle-fused imidazole formation, respectively. The resulting processes are highly efficient, practically straightforward, and tolerate considerable structural and functional group variation. Our use of heteroatom-substituted alkynes as enabling tools for reaction discovery is discussed. The reactivity accessed from the strong donor-like properties of ynamides is complemented by that obtained from alkynyl thioethers, which are emerging as interesting substrates for pi-acid catalysis.

Automated summary

The combination of a nucleophilic nitrene equivalent, a triple bond, and a pi-acid catalyst has been utilized for efficient transformations to prepare azacycles. The development of an annulation strategy and the use of different N-acyl and N-heterocyclic pyridinium-N-aminides are discussed, showcasing highly efficient processes with structural and functional group tolerance. Additionally, the use of heteroatom-substituted alkynes and the reactivity of ynamides and alkynyl thioethers as enabling tools for reaction discovery are highlighted.