Dipole-Transmissive 1,3-Dipolar Cycloadditions for the Rapid Construction of Polycyclic N-Heterocycles: Synthetic and Mechanistic Investigations

The investigation of distinctive dipole-transmissive dipolar cycloaddition (DTDC) methodology and the formalisation of this concept is reported. A DTDC procedure was able to be developed by taking advantage of the structural complementarity of azide and diazoalkane 1,3-dipoles. Intramolecular azide-alkene 1,3-DCs followed by spontaneous dipole transmission upon work-up furnished intermediate alpha-diazoisoindole and alpha-diazoisoquinoline substrates bearing the key secondary diazoalkane 1,3-dipole. N-Derivatisation of the intermediate alpha-diazoisoindole and alpha-diazoisoquinolines with a tethered secondary dipolarophile followed by a subsequent 1,3-DC allowed for rapid construction of a range of functionalised polycyclic N-heterocycles. Integrated experimental and theoretical studies established requirements for product formation and revealed the likely mechanistic basis of divergent reactivity observed.