Stereospecific alkene 1,2-aminofunctionalisation as a strategy towards complex heterocycles M.J .S. Smith 1 , Y. Zhu 1 , W. Tu 1,2 , J. F. Bower 1 1 Department of Chemistry, University of Liverpool, UK, 2 School of Chemistry, University of Bristol, UK 75% of small molecule drugs contain N-heterocycles, of which 65% contain saturated N-heterocycles (2021).1 Robust synthetic methods towards functionalised, saturated heterocycles often require expensive metal catalysts and/or lack stereocontrol. Work will be presented addressing these issues, employing a nitrene synthon equivalent (2, Scheme 1) which promotes aziridination of alkenes without the addition of metal catalysts and/or hazardous oxidants.2 Intramolecular (Section B, Scheme 1) and intermolecular (Section C, Scheme 1) alkene aziridination protocols which, followed by cascade intramolecular trapping, yielded complex heterocycles, stereospecifically, in a single step from linear precursors. Reaction scope, stereochemical considerations and mechanistic insight will all be discussed.
Scheme 1. (a) Synthetic strategy of 1,2-aminofunctionalisation towards complex heterocycles. (b) Intramolecular aziridination cascade approach to 1,2-aminofunctionalisation. (c) Intermolecular aziridination cascade approach to 1,2-aminofunctionalisation. Nu = Nucleophile. LG = Leaving Group. References
1. McGrath, N. A.; Brichacek, M.; Njardarson, J. T. Chem. Educ. 2010 , 87 , 1348–1349. 2. Farndon, J. F.; Young, T. A.; Bower, J. F. Am. Chem. Soc. 2018 , 140 , 17846−17850. 3. Zhu, Y.; Smith, M. J. S.; Tu, W.; Bower, J. F. Chem. Int. Ed. 2023 , 62 , e202301262.
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