Beilstein Journal of Organic Chemistry (Dec 2020)

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

  • Giovanna Zanella,
  • Martina Petrović,
  • Dina Scarpi,
  • Ernesto G. Occhiato,
  • Enrique Gómez-Bengoa

DOI
https://doi.org/10.3762/bjoc.16.255
Journal volume & issue
Vol. 16, no. 1
pp. 3059 – 3068

Abstract

Read online

The tandem gold(I)-catalyzed rearrangement/Nazarov reaction of enynyl acetates in which the double bond is embedded in a piperidine ring was computationally and experimentally studied. The theoretical calculations predict that the position of the propargylic acetate substituent has a great impact on the reactivity. In contrast to our previous successful cyclization of the 2-substituted substrates, where the nitrogen favors the formation of the cyclized final product, the substitution at position 3 was computed to have a deleterious effect on the electronic properties of the molecules, increasing the activation barriers of the Nazarov reaction. The sluggish reactivity of 3-substituted piperidines predicted by the calculations was further confirmed by the results obtained with some designed substrates.

Keywords