A combination of polarity reversal, Diels–Alder cycloaddition and skeletal remodeling to access pyridine-fused nitrones

Abstract

An unprecedented cascade strategy consisting of piperidine-promoted polarity reversal, normal electron-demand Diels–Alder cycloaddition and skeletal remodeling was developed to construct structurally novel pyridine-fused nitrones in up to 82% yield.

Umpolung α-regioselective 1,3-dipolar cycloaddition and internal recycle of byproduct as two key strategies: access to diverse chiral bipyridines

“…In view of the above data and the previously disclosed work on umpolung regioselective addition, 6 we suspected that the in situ -generated azomethine ylides from aldehydes and perhydroindole-2-carboxylic acid have a strong tendency to undergo umpolung reaction, thus leading to the umpolung α-regioselective 1,3-dipolar cycloaddition to access two unexpected compounds 3a-1 and 3a-2 (Scheme 2). Furthermore, the two chiral diastereoisomers 3a-1 and 3a-2 can be isolated by column chromatography.…”

“…Recently, the application of the umpolung 6 of the reactivity of in situ -generated or prepared isatin-derived azomethine ylides by inverting the ketamine carbon from an electrophile to a nucleophile in the cycloaddition reaction for the construction of valuable nitrogen-containing spirooxindole molecules 7 has been reported. However, the umpolung α-regioselective 1,3-dipolar cycloaddition of the azomethine ylides in situ -generated from perhydroindole-2-carboxylic acid and aldehyde is still underdeveloped and remains a big challenge (Scheme 1a).…”

Mechanism of the phosphine‐catalyzed [3 + 3] annulation with MBH carbonates as the potential dipoles

“…The six-membered cycles, including the carbocycle and heterocycle, are commonly the key architectures embedded in various biologically and pharmaceutically active products [1][2][3]. Occurring as a concerted process, the Diels-Alder reaction is by far the best known and most widely applied [4][5][6][7][8][9][10][11][12][13][14] synthetic strategy. The [3 + 3]cycloaddition/annulation, which works as an important complementary, offers potential alternatives and tends to undergo the stepwise mechanism due to the symmetry disallowance [15][16][17].…”