Total Synthesis of Liangshanone.

The first total synthesis of liangshanone, a hexacyclic ent-kaurane diterpenoid alkaloid, has been completed. Its intricate cagelike framework was assembled through several key transformations, including an oxidative dearomatization/Diels-Alder (OD/DA) cycloaddition sequence, a tandem alkene cleavage/Mannich cyclization, a Robinson-type annulation, and an intramolecular aldol reaction. Notably, an organocatalytic enantioselective α-hydroxymethylation process allowed the preparation of an enantiomerically enriched tricyclic intermediate that should enable asymmetric access to the target natural product.

Asymmetric Michael Addition Induced by (R)-tert-Butanesulfinamide and Syntheses of Chiral Pyrazolidinone Derivatives.

A highly diastereoselective Michael addition of (R)-N-tert-butanesulfinyl imidates 8 to α,ß-unsaturated pyrazolidinone 3a has been developed to afford pyrazolidinones 10 possessing three contiguous stereocenters with good to excellent yield and excellent diastereoselectivity. A two-step conversion of reduction and cyclization provides the bicyclic pyrazolopiperidine 12 in a good yield. A series of pyrazolopiperidine derivatives 18 with a quaternary carbon center at C-3a are stereoselectively synthesized via alkylation or Michael addition.

Studies of a Diazo Cyclopropanation Strategy for the Total Synthesis of (-)-Lundurine†A.

The bioactive Kopsia alkaloids lundurines A-D are the only natural products known to contain indolylcyclopropane. Achieving their syntheses can provide important insights into their biogenesis, as well as novel synthetic routes for complex natural products. Asymmetric total synthesis of (-)-lundurine A has previously been achieved through a Simmons-Smith cyclopropanation strategy. Here, the total synthesis of (-)-lundurine A was carried out using a metal-catalyzed diazo cyclopropanation strategy. In order to avoid a carbene CH insertion side reaction during cyclopropanation of α-diazo- carboxylates or cyanides, a one-pot, copper-catalyzed Bamford-Stevens diazotization/diazo decomposition/cyclopropanation cascade was developed, involving hydrazone. This approach simultaneously generates the C/D/E ring system and the two chiral quaternary centers at C2 and C7.

Total syntheses of (-)-isoschizogamine and (-)-2-hydroxyisoschizogamine.

Total syntheses of (-)-isoschizogamine and (-)-2-hydroxyisoschizogamine are described. The synthesis employs two asymmetric Michael additions to establish chiral centers at C7 and the quaternary carbon C20. Regioselective reduction of the methylthioiminium cation rather than the enamine generates an isoschizogamine-type pentacyclic skeleton. Acidic hydrolysis of the isoschizogamine-type intermediate in the absence of oxygen provides natural (-)-isoschizogamine. Conducting the reaction in the presence of oxygen leads to a multistep oxidative hydrolysis cascade that affords unnatural (-)-2-hydroxyisoschizogamine.

One-pot synthesis of multisubstituted butyrolactonimidates: total synthesis of (-)-nephrosteranic Acid.

Multisubstituted chiral butyrolactonimidates have been synthesized via a one-pot, three-step cascade reaction in which (R)-N-tert-butanesulfinyl imidates and α,ß-unsaturated diesters undergo highly stereoselective Michael addition, anion-oxidative hydroxylation, and cyclization. The synthesized butyrolactonimidates are versatile intermediates for preparation of substituted butyrolactones and furans. The usefulness of this cascade reaction is demonstrated through the concise total synthesis of natural product (-)-nephrosteranic acid.