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

• Published in: Beilstein journal of organic chemistry Vol. 16; no. 1; pp. 3059 - 3068
• Main Authors: Zanella, Giovanna, Petrović, Martina, Scarpi, Dina, Occhiato, Ernesto G, Gómez-Bengoa, Enrique
• Format: Journal Article
• Language: English
• Published: Germany Beilstein-Institut 15.12.2020
• Subjects: Chemistry; dft calculations; Full Research Paper; gold catalysis; n-heterocycles; nazarov reaction; gold catalysis; DFT calculations; N-heterocycles; Nazarov reaction
• ISSN: 1860-5397; 1860-5397
• DOI: 10.3762/bjoc.16.255

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.