Oral Presentation Royal Australian Chemical Institute National Congress 2026

Trapped Cycloadducts of 1-Azabutadienes via Microwave-Assisted Ring Opening of N-acyl-2-Azetines (137107)

Jacob P Cameron 1 , Chuyi Su 1 , Paul V Bernhardt 1 , Timothy Clark 2 , Craig M Williams 1
  1. The University of Queensland, St Lucia, QLD, Australia
  2. Computer-Chemie-Centrum and Interdisciplinary Center for Molecular Materials, Friedrich-Alexander-Universität, Erlangen-Nürnberg, 91052 Erlangen, Germany

The Williams group has recently reported several highly-strained azahomocubanes such as 1-azahomocubane.1 The synthesis of the 5-azatriblattane skeleton, a seco-5-azahomocubane, used the Diels-Alder reaction of 2-azetines and cyclopentadiene as the key step in constructing the caged core.2 While further exploring the cycloaddition reactivity of the 2-azetine system, this unsaturated 4-membered heterocycle was found to undergo electrocyclic ring-opening to give N-substituted 1-azabutadienes. These nitrogenous analogues of butadiene have received much less study than their carbon counterpart, largely due to their instability, inaccessibility, and reactivity. Microwave irradiation at 110°C proved sufficient to generate these highly reactive dienes, which had only been obtained by flash vacuum pyrolysis previously  (<300°C).3 This talk shares the details of the discovery, observation of the intermediate azabutadiene, explores the tolerance of various N-protecting groups to this process, and investigates subsequent Diels-Alder reaction of intermediate azabutadienes with various dienophiles. Cycloaddition between the highly reactive azadiene intermediates and their parent systems gave hitherto unreported bicycles. Chemoreactivity of the intermediate N-acyl-1-azabutadiene trienes was strongly influenced by protecting group, affording both dihydro-1,3,-oxazines and tetrahydropyridines. Synthetically interesting aldehydes and tetrahydropyridones were obtained upon hydrolysis of obtained cycloadducts.

  1. Fahrenhorst-Jones, T., et al. 1-Azahomocubane. Chemical Science, 2023, 14(11): 2821-2825.
  2. Su, C., et al. The (±)-5-Aza[1.0]triblattane Skeleton via Azetine Cycloaddition. Organic Letters, 2024, 26(14): 2827-2831.
  3. Jung, M. E. and Y. M. Choi. New synthesis of 2-azetines and 1-azabutadienes and the use of the latter in Diels-Alder reactions: total synthesis of (.+-.)-.delta.-coniceine. The Journal of Organic Chemistry, 1991, 56(24): 6729-6730.