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1,2-Addition versus homoconjugate addition reactions of indoles and electron-rich arenes to α-cyclopropyl N -acyliminium ions: Synthetic and computational studies

Journal Article


Abstract


  • An investigation of the reactivity of α-cyclopropyl N-acyliminium ions towards indoles has resulted in the unprecedented synthesis of 5-cyclopropyl-5-(3-indoyl)pyrrolidin-2-ones via 1,2-addition reactions and, in the case of highly electron deficient indoles and electron rich arenes, spiroheterocycles via sequential homoconjugate and 1,2-addition reactions with often high diastereoselective control at the C-5 quaternary stereocentres. Computational studies provided support for the proposed mechanisms and stereochemical outcome of these reactions, clearly showing that the 1,2-addition pathway is kinetically controlled. In reactions where the 1,2-adduct is destabilised, for example when the arene ring is less nucleophilic, the 1,2-addition is reversible and the thermodynamically preferred homoconjugate addition and subsequent rearrangement and cyclisation reactions become the major pathway.

UOW Authors


  •   Ryder, Gregory M. (external author)
  •   Wille, Uta (external author)
  •   Willis, Anthony C. (external author)
  •   Pyne, Stephen

Publication Date


  • 2019

Citation


  • Ryder, G. M., Wille, U., Willis, A. C. & Pyne, S. G. (2019). 1,2-Addition versus homoconjugate addition reactions of indoles and electron-rich arenes to α-cyclopropyl N -acyliminium ions: Synthetic and computational studies. Organic and Biomolecular Chemistry, 17 (29), 7025-7035.

Scopus Eid


  • 2-s2.0-85069759506

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers1/847

Number Of Pages


  • 10

Start Page


  • 7025

End Page


  • 7035

Volume


  • 17

Issue


  • 29

Place Of Publication


  • United Kingdom

Abstract


  • An investigation of the reactivity of α-cyclopropyl N-acyliminium ions towards indoles has resulted in the unprecedented synthesis of 5-cyclopropyl-5-(3-indoyl)pyrrolidin-2-ones via 1,2-addition reactions and, in the case of highly electron deficient indoles and electron rich arenes, spiroheterocycles via sequential homoconjugate and 1,2-addition reactions with often high diastereoselective control at the C-5 quaternary stereocentres. Computational studies provided support for the proposed mechanisms and stereochemical outcome of these reactions, clearly showing that the 1,2-addition pathway is kinetically controlled. In reactions where the 1,2-adduct is destabilised, for example when the arene ring is less nucleophilic, the 1,2-addition is reversible and the thermodynamically preferred homoconjugate addition and subsequent rearrangement and cyclisation reactions become the major pathway.

UOW Authors


  •   Ryder, Gregory M. (external author)
  •   Wille, Uta (external author)
  •   Willis, Anthony C. (external author)
  •   Pyne, Stephen

Publication Date


  • 2019

Citation


  • Ryder, G. M., Wille, U., Willis, A. C. & Pyne, S. G. (2019). 1,2-Addition versus homoconjugate addition reactions of indoles and electron-rich arenes to α-cyclopropyl N -acyliminium ions: Synthetic and computational studies. Organic and Biomolecular Chemistry, 17 (29), 7025-7035.

Scopus Eid


  • 2-s2.0-85069759506

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers1/847

Number Of Pages


  • 10

Start Page


  • 7025

End Page


  • 7035

Volume


  • 17

Issue


  • 29

Place Of Publication


  • United Kingdom