Asymmetric synthesis of bicyclic diol derivatives through metal and enzyme catalysis: application to the formal synthesis of sertraline.

Enzyme- and ruthenium-catalyzed dynamic kinetic asymmetric transformation (DYKAT) of bicyclic diols to their diacetates was highly enantio- and diastereoselective to give the corresponding diacetates in high yield with high enantioselectivity (99.9 % ee). The enantiomerically pure diols are accessible by simple hydrolysis (NaOH, MeOH), but an alternative enzyme-catalyzed ester cleavage was also used to give the trans-diol (R,R)-1 b in extremely high diastereomeric purity (trans/cis=99.

Synthesis of a neonicotinoide pesticide derivative via chemoenzymatic dynamic kinetic resolution.

Chemoenzymatic dynamic kinetic resolution (DKR) via combined ruthenium and enzyme catalysis was used in the key step of a synthesis of a neonicotinoid pesticide derivative (S)-3. The DKR was carried out under mild conditions with low catalyst loading. The method gives (S)-3 in high enantiomeric excess (98%).

Directed evolution and axial chirality: optimization of the enantioselectivity of Pseudomonas aeruginosa lipase towards the kinetic resolution of a racemic allene.

Directed evolution of Pseudomonas aeruginosa lipase by the use of combinatorial active site saturation test (CAST) criteria provided a highly enantioselective mutant (Leu162Phe) for kinetic resolution of an axially chiral allene, p-nitrophenyl 4-cyclohexyl-2-methylbuta-2,3-dienoate (E=111); the high enantioselectivity of the Leu162Phe mutant was rationalized by pi-pi stacking.

Gold-catalyzed cyclization of allene-substituted malonate esters: synthesis of beta,gamma-unsaturated delta-lactones.

An efficient method for the preparation of beta,gamma-unsaturated delta-lactones has been developed. The starting materials for the synthesis of these compounds are allene-substituted malonates which undergo gold-catalyzed cyclization by means of nucleophilic attack of the ester moiety on the allene. It is worth mentioning that this is the first example where an ester group attacks as a nucleophile in a gold-catalyzed transformation of allenes.