Fellowship of the ring: The first total synthesis of (+)-crotogoudin, a 3,4-seco-atisane diterpenoid natural product, is reported. Asymmetric access to the bicyclo[2.2.2]octane core is achieved through a desymmetrization of a meso-diketone with baker's yeast (LG=leaving group, PG=protecting group). A SmI2 -induced radical cyclopropane-opening/annulation/elimination cascade affords the suitably decorated tetracyclic structure of (+)-crotogoudin. The synthesis led to revision of the reported optical rotation of the natural product and to assignment of its absolute configuration as an ent-atisane (5R,10R).

A facile synthesis of unsymmetrical N,N′-diaryl ureas is described. The utilization of the Pd-catalyzed arylation of ureas enables the synthesis of an array of diaryl ureas in good to excellent yields from benzylurea via a one-pot arylation-deprotection protocol, followed by a second arylation.

The coordination of chiral ligands to Lewis acid metal derivatives, a useful strategy for enantioselective, electrophilic catalysis, generally leads to a lower level of catalytic activity than that of the original uncomplexed compound. Activation by further attachment of a proton or strong Lewis acid to the complex provides a way to overcome the deactivating effect of a chiral ligand. The research described herein has demonstrated that further enhancement of catalytic activity is possible by the judicious placement of fluorine substituents in the chiral ligand. This approach has led to a new, second-generation family of chiral oxazaborolidinium cationic species which can be used to effect many Diels-Alder reactions in >95% yield and >95% ee using catalyst loadings at the 1-2 mol % level. The easy recovery of the chiral ligand makes the application of these new catalysts especially attractive for large-scale synthesis.

The use of formaldehyde N,N-dialkylhydrazones as neutral C1-nucleophiles in the iridium-catalyzed substitution of allylic carbonates is described for two processes. Kinetic resolution or, alternatively, stereospecific substitution affords configurationally stable α,α-disubstituted aldehyde hydrazones in high enantiomeric excess and yield. This umpolung approach allows for the construction of optically active allylic nitriles and dithiolanes as well as branched α-aryl aldehydes. A catalyst-controlled reaction with Enders' chiral hydrazone derivatives followed by diastereoselective nucleophilic addition to the hydrazone products constitutes a two-step stereodivergent synthesis of chiral amines.