Asymmetric catalytic conjugate addition of acetaldehyde to nitrodienynes/nitroenynes: applications to the syntheses of (+)-α-lycorane and chiral ß-alkynyl acids.

The catalytic enantioselective conjugate addition of acetaldehyde to polyconjugated substrates, nitrodienynes and nitroenynes, has been accomplished using organocatalysis. Various functionalized 1,3-enynes and propargylic compounds were obtained in moderate to good yields with high enantioselectivity. The synthetic utilities of the conjugate addition reactions have been highlighted in the concise total synthesis of (+)-α-lycorane and the metal-free synthesis of chiral ß-alkynyl acids.

Catalytic enantioselective and divergent total synthesis of (+)-10-oxocylindrocarpidine, (+)-cylindrocarpidine, (-)-N-acetylcylindrocarpinol, and (+)-aspidospermine.

The catalytic enantioselective and divergent total syntheses of Aspidosperma alkaloids (+)-10-oxocylindrocarpidine 7, (+)-cylindrocarpidine 1, (-)-N-acetylcylindrocarpinol 6, and (+)-aspidospermine 8 have been accomplished in 11 steps from a common precursor (15) on the basis of a highly concise route. The route features three metal-catalyzed reactions, including the key Pd-catalyzed decarboxylative asymmetric allylation of carbazolones developed in our laboratory. Our syntheses, using a combination of C-H activation, enantioselective catalysis, and collective synthesis, represent the first total synthesis of 10-oxocylindrocarpidine and the first asymmetric total synthesis of cylindrocarpidine and N-acetylcylindrocarpinol.

Enantioselective conjugate addition of both aromatic ketones and acetone to nitroolefins catalyzed by chiral primary amines bearing multiple hydrogen-bonding donors.

A new class of chiral primary amine catalysts bearing multiple hydrogen-bonding donors have been designed and synthesized. The newly developed bifunctional organocatalysts efficiently catalyzed not only enantioselective conjugate addition of aromatic ketones to nitroolefins in good yields (up to 87%) with excellent enantioselectivities (97→99% ee) but also enantioselective conjugate addition of acetone to nitroolefins in excellent yields (90-96%) with high enantioselectivities (up to 97% ee).

Catalytic asymmetric construction of spirocyclopentaneoxindoles by a combined Ru-catalyzed cross-metathesis/double Michael addition sequence.

Biologically important and synthetically challenging spirocyclopentaneoxindoles with four contiguous stereocenters including one spiroquaternary stereocenter have been constructed in good yields (72-87%) with excellent diastereoselectivity (16:1→30:1 dr) and enantioselectivity (93→99% ee) by a combined Ru-catalyzed cross-metathesis/organocatalyzed asymmetric double-Michael addition sequence.

Highly enantioselective one-pot synthesis of spirocyclopentaneoxindoles containing the oxime group by organocatalyzed Michael addition/ISOC/fragmentation sequence.

A highly diastereo- and enantioselective organocatalytic protocol for the synthesis of biologically important spirocyclopentaneoxindoles containing the oxime functional group from easily accessible 3-allyl-substituted oxindoles and nitroolefins has been developed by a one-pot Michael addition/ISOC/fragmentation sequence.

Enantioselective and regioselective organocatalytic conjugate addition of malonates to nitroenynes.

The first catalytic asymmetric conjugate addition of 1,3-dicarbonyl compounds to nitroenynes catalyzed by cinchona alkaloid-based thiourea organocatalysts has been developed. The 1,4-addition adducts were obtained solely, in moderate to good yields (up to 93%) with good enantioselectivities (up to 99% ee). This protocol affords a conceptually different entry to the precursors of pharmaceutically important chiral ß-alkynyl acid derivatives and synthetically useful chiral nitroalkynes. Notably, the protocol worked well with both aryl- and alkyl-substituted alkynyl substrates.

Ligand-controlled enantioselective [2 + 2] cycloaddition of oxabicyclic alkenes with terminal alkynes using chiral iridium catalysts.

The first catalytic asymmetric [2 + 2] cycloaddition of oxabicyclic alkenes and terminal alkynes has been developed. This iridium-catalyzed enantioselective [2 + 2] cycloaddition allows the formation of four stereocenters in a single step with excellent enantioselectivity (94-->99% ee).

Organocatalytic enantioselective Michael addition of 2,4-pentandione to nitroalkenes promoted by bifunctional thioureas with central and axial chiral elements.

Two novel bifunctional amine-thiourea organocatalysts 1 and 2, which both bear central and axial chiral elements, have been developed to promote enantioselective Michael reaction between 1,3-dicarbonyl compounds and nitro olefins. The catalyst 2 afforded the desired products with good levels of enantioselectivity (up to 96% ee), showing clearly that two chiral elements of 2 are matched, and enhance the stereochemical control.