- Computational Study of Benzosultam Formation through Gold(I)-Catalyzed Ammoniumation/Nucleophilic Substitution Reaction
Pertschi, R.; de Aguirre, A.; Pale, P.; Blanc, A.; Poblador Bahamonde, A. I.
Helv. Chim. Acta 2021, 104, e2100133
The Au(I)-catalyzed reactions of (2-alkynyl)phenylsulfonyl azetidines bearing terminal and non-terminal alkynes in the presence of methanol as protic nucleophile were studied by density functional theory (DFT) calculations. Our study highlights that gold(I) catalyze nucleophilic addition of the nitrogen on the alkyne is favored over the direct ring opening of the azetidine by methanol, confirming the ammonium-based mechanism. In addition, the revers regioselectivity observed experimentally where non-terminal alkynes favor the formation of 6- endo -dig-benzosultams while terminal alkynes favor 5- exo -dig products is also explored via two different scenarios. The first one embraces the classical activation of the alkyne by a single Au(I) species while the second one tackle the formation of a σ,π-digold acetylide complex. Calculations identify both pathways as competitive although only mono Au(I) complexes can lead to final products, in good agreement with experimental observation. Further details on the importance of the presence of an excess of the protic nucleophile on the protodemetallation step and the final aminal formation is also discussed.
Dedicated to Prof. E. Peter Kündig on the occasion of his 75th birthday.
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