Gold(I)-Catalyzed Cyclization/Nucleophilic Substitution of 1-(N-Sulfonylazetidin-2-yl) Ynones into N-Sulfonylpyrrolin-4-ones

Abstract

Polysubstituted pyrrolin-4-ones have been efficiently synthesized from readily available 1-(N-sulfonylazetidin-2-yl) ynones via gold(I)-catalyzed cyclization/nucleophilic substitution in the presence of various nucleophiles, such as water, alcohols, or indoles. Additionally, 3-iodopyrrolin-4-one derivatives have also been obtained under the same reaction conditions upon addition of 1.2 equiv of N-iodosuccinimide.

Auto‐Tandem Catalysis: Activation of Multiple, Mechanistically Distinct Process by a Single Catalyst

“…A gold-catalysed cyclisation/nucleophilic substitution reaction was recently used by Blanc et al for the synthesis of Nsulfonylpyrroin-4-ones 29 (Scheme 7). [22] Subjection of ynoneazetidines 26 to the reaction condition allowed for an intramolecular cyclisation to form azetidinium intermediates 28. Nucleophilic ring opening of azetidiniums 28 gave the desired N-sulfonylpyrroin-4-ones 29 in moderate to excellent yields.…”

Gold(I)‐Catalyzed N‐Desulfonylative Amination versus N‐to‐O 1,5‐Sulfonyl Migration: A Versatile Approach to 1‐Azabicycloalkanes

“…[Cy 3 PAu] BF 4 promoted the formation of 2 a in 87 % yield in only 0.5 h (Table , entry 10). Control experiments confirmed that the transformation did not occur in the absence of a gold catalyst, whereas silver tetrafluoroborate alone afforded a minor amount of pyrrolin‐4‐one ( 3 a ) (product type in Scheme , top) along with degradation products (Table , entries 11 and 12). Phenyl 4‐methylbenzenesulfonate was always produced concomitantly in these reactions, thus supporting our mechanistic hypothesis (Scheme ).…”

“…We recently demonstrated that bicyclic vinylgold ammonium intermediates, formed by the gold activation of ynones A substituted at the 1‐position with an N ‐sulfonyl azacycle, can be opened regioselectively by oxygenated nucleophiles. This reaction allowed the exclusive formation of pyrrolin‐4‐ones in high yields (Scheme , top) . On this basis, an alternative pathway could be envisaged through nucleophilic attack, either inter‐ or intramolecularly, on the sulfonyl group on the ammonium intermediate B .…”

“…With this aim, we chose the readily available 1‐( N ‐tosylazetidinyl) ynone 1 a as a model substrate to evaluate the first strategy, that is, the N‐desulfonylative cyclization reaction with phenol as a selective nucleophile. N‐to‐O sulfonyl migration should be minimized with this model compound because the strained azetidinium intermediate formed upon gold activation ( B in Scheme ) should be less prone to enolization.…”

“…[f] No conversion was observed. [g] The pyrrolin‐4‐one 3 a was obtained in 10 % yield (see the Supporting Information) . Cy=cyclohexyl, JohnPhos=2‐(di‐ tert ‐butylphosphanyl)biphenyl, Tf=trifluoromethanesulfonyl, Ts= para ‐toluenesulfonyl.…”