Henneveld, Jackson S.Shiri, FarshadAriafard, AlirezaLucas, Nigel T.Bissember, Alex C.Hawkins, Bill C.2025-12-312025-12-310947-6539PubMed:37177913ORCID:/0000-0003-2383-6380/work/198195200https://hdl.handle.net/1885/733797361The 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 α-diazoisoindole and α-diazoisoquinoline substrates bearing the key secondary diazoalkane 1,3-dipole. N-Derivatisation of the intermediate α-diazoisoindole and α-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.The authors (JSH, NTL and BCH) thank the University of Otago for funding. We thank the Australian National Computational Infrastructure and the University of Tasmania for the generous allocation of computing time. ACB's contributions were supported by an ARC Future Fellowship (FT200100049). Open Access publishing facilitated by University of Otago, as part of the Wiley - University of Otago agreement via the Council of Australian University Librarians.7en© 2023 The Authors.AlkaloidsDiastereoselectivityDipolar cycloadditionsHeterocycles2023-07-2610.1002/chem.20230125485162060231