Developing an efficient and reliable catalytic protocol to access atropisomeric compounds, especially those bearing five-membered heteroaryl structures with lower rotation barriers, is a challenging task. Here, we disclose an unprecedented atropenantioselective Barton−Zard reaction via a central-to-axial chirality transfer strategy, by employing α-substituted nitroolefins with a β-ortho-substituted (hetero)aryl group and α-isocyano substrates with various electron-withdrawing groups, under the catalysis of Ag 2 O and a cinchona-derived phosphine ligand, providing a robust approach to construct axially chiral 3-(hetero)aryl pyrroles with a substantial skeleton and functionality versatility. An alternative asymmetric phase transfer catalysis protocol was also demonstrated to be practical for the direct construction of axially chiral bisphosphine dioxides. In addition, good conformational stability is generally observed for the obtained atropisomers, and their potential application as valuable organocatalysts has been well demonstrated in a highly stereoselective formal [4 + 2] cycloaddition reaction.

A previously unreported activation mode is developed through the generation of dearomatizative tetraenamine species between 5-allylic furfurals and a bifunctional amine-thiourea catalyst. The very remote ζ,η-alkenes perform as effective HOMO-raised dienophiles in inverse-electron-demand oxa-Diels-Alder cycloadditions with isatin-derived oxadiene substrates, delivering multifunctional spirocyclic oxindoles incorporating a dihydropyran skeleton in moderate to high yields with good to excellent enantio- and diastereoselectivity.

An asymmetric formal [3+3] cycloaddition process with diversely structured aliphatic ketones and electron-deficient cyclic 1-azadienes was developed by cascade enamine-enamine catalysis of a cinchona-based primary amine. This sequence involved a domino Michael addition-Mannich reaction to afford spirocyclic architectures in excellent diastereo- and enantioselectivity. Importantly, high regioselectivity was realized for a number of unsymmetrical aliphatic ketone substrates.

The discovery of a previously unreported activation mode and reaction pathway is important but challenging for the development of asymmetric organocatalysis. Here we disclosed a formal [5 + 3] cycloaddition reaction of unmodified Morita−Baylis− Hillman alcohols from 2-cyclopentenone and aldehydes with cyclic azomethine imines. A double catalytic system, combining chiral primary amine from cinchona alkaloid and achiral 2-mercaptobenzoic acid, has proved to be crucial for the chemoselectivity and enantioselectivity, through covalently dual activation of the sterically hindered enone substrates. A spectrum of tricyclic frameworks bearing substantial substitutions were produced in moderate to high yields with good stereoselectivity (up to 98% ee, >19:1 dr). Assisted by the experimental observations, a plausible catalytic mechanism is proposed; moreover, the key intermediates suggested have been detected and elucidated by high-resolution mass spectrometry analysis.

An asymmetric [4 + 2] cycloaddition reaction with 2-benzyl-3-furfurals and α-cyano-chalcones was developed to afford chiral tetrahydrobenzofurans having dense substitutions.