Versatile Method for the Synthesis of 4‐Aminocyclopentenones: Dysprosium(III) Triflate Catalyzed Aza‐Piancatelli Rearrangement

The Piancatelli Rearrangement: New Applications for an Intriguing Reaction

“…Recently Read de Alaniz's group employed 2-furylcarbinols and a series of anilines to access trans-4-amino-5-substituted-cyclopent-2-enones (35), appealing structures for the synthesis of biologically active compounds [44] This was allowed thanks to the identification of catalysts such as lanthanoid salts which were able to selectively activate 2-furaldehydes in the presence of an excess of nucleophilic amines [45]. Under optimized conditions, the aza-version of the Piancatelli rearrangement was carried out in acetonitrile at 80 °C, together with a catalytic amount (5 mol %) of Dy(OTf) 3 [46], preferred over Sc(OTf) 3 which gave similar results, but it is more expensive.…”

“…The authors worked with 2-furylcarbinols bearing an aminoalkyl chain at the 5 position of the furan ring (44)(45) and generated azaspirocyclic scaffolds (46-47, Scheme 19) [54]. This densely functionalized framework was obtained in only one step, as a single diastereomer, with high efficiency and in high yield, differently from the known procedures that require several synthetic steps for the construction of the tertiary carbon center bearing the nitrogen atom, and the formation of the spirocyclic ring [55,56].…”

“…This densely functionalized framework was obtained in only one step, as a single diastereomer, with high efficiency and in high yield, differently from the known procedures that require several synthetic steps for the construction of the tertiary carbon center bearing the nitrogen atom, and the formation of the spirocyclic ring [55,56]. The optimized conditions for the intermolecular rearrangement (Dy(OTf) 3 5 mol % in refluxing acetonitrile) [44] turned out to be suitable also for the intramolecular version, and the mechanism previously hypothesized was also assumed to be in action (Scheme 15). As shown in Table 3 for the formation of 5-azaspirocycles 46 (n = 1), the rearrangement worked equally well for most common substituents, but the nature of R 2 had a significant impact on the outcome of the reaction, both in terms of yield and reaction rate.…”

Recent applications of rare-earth metal(III) triflates in cycloaddition and cyclization reactions

“…83 They reported several inter-and intramolecular variants of the aza-Piancatelli reaction, which were promoted by Dy(OTf) 3 and gave rise to a number of complex, highly-functionalized molecular architectures. [84][85][86] A 2013 paper from the above-mentioned group disclosed an unprecedented Piancatelli rearrangement involving alcohols as nucleophiles. 87 The operationally simple reaction is catalyzed by Dy(OTf) 3 and proceeds in PhMe at 80 °C, affording structurally unique transsubstituted spirocyclic ether motif 111 (Scheme 32).…”

Lewis Acid Catalyzed Rearrangement of Furylcarbinols: The Aza- and Oxa-Piancatelli Cascade Reaction

“…To our delight, the rearrangement was efficient, trans-selective and amenable to a wide range of substitutions both on the aniline and on the furylcarbinol. 10 We were most encouraged by this initial study, that demonstrates that electron-rich, electron-poor, sterically bulky and even secondary anilines (16) 3 and La(OTf) 3 could also be used to catalyze the aza-Piancatelli reaction. 11…”